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Tsubokusa and Bacopa monnieri :

herbs with pharmaceutical potential in the treatment of Alzheimer's disease and neurodegenerations
LightningIce, Aug, 2015

Alzheimers disease initiated by apolipoprotein E < Johnson, et al, 2006 >, amyloid precursor
protein < Citron, et al, 1992 > and presenilin i and ii mutations < De Strooper, 2007 > impair
cognitions and memory faculties, resulting in degenerating cerebral conditions, destroying cellular
structures and impairing functions. Initial memory declines spiral towards total loss of cognitive
capabilities till the eventual death many years after onset. Classical findings include loss of basal
forebrain cholinergic neurons, declines in acetylcholine, dopamine, serotonin and norepinephrine
quantums, deficiencies in vitamin b xii, folate and increases in homocysteine quantums.
Pathological findings include white matter degenerations, tau peptides, neurofibrillary tangles,
amyloid plaques, copper and zinc high affinity accumulates within amyloid plaques further
contributing to neuraltoxicities, when not overexpressed amyloid functions in copper bindings
thus shielding the brain from heavy metal induced oxidative stressors < Smith, et al, 2006 >, likewise
both amyloid and prion proteins in their natural well regulated, moderately expressed forms
enhance and moderate neurogenesis of neural stem cells < Collins, et al, 2015 >; medial temporal
lobe atrophies < Burton, et al, 2009 >, inferolateral temporal lobe atrophies < Scahill, et al, 2002 >,
parahippocampal gyrus atrophies < Echvarri, et al, 2010 >, whole brain and hippocampus atrophies
< Henneman, et al, 2009 >; cortical thinning < Sabuncu, et al, 2001 >, hippocampus volume declines
< Visser, et al, 2001 >, hippocampal lesions < Struble, et al, 1991 >, frontal and parieto occipital
white matter leisions < de Leeuw, et al, 2004 >, diminishing cortical cholinergic innervations <
Mesulam, 2004 >, along with progressing global neuronal atrophies along the various disease stages
< Scahill, et al, 2002 > and apoptosis of glia and neurons < Mines, et al, 2011 >.
A prolonged and debilitating illness still yet to be curable. Progress has been made with novel
research still currently ongoing to facilitate amyloid beta clearances < Wildsmith, et al, 2013 > along
with disease biomarkers < Hltt et al, 2013 > developed for early detections at initial onsets though
measurements of clusterin quantums within plasma < van Dijk, et al 2013 >, or before onsets via
locations of low mitochondria dna within cerebrospinal fluid < csf > which often surfaces before
ailment starts < Podlesniy, et al, 2013 > thus indicative of metabolic declines. Further clinical trails
are required to look deeper into it and affirm that their effectiveness and efficacy apply to most.
Once applicable to a clinical setting, early screenings can be carried out and a window of treatment
time frame in between would come into existence, thus improving the conditions and decelerating
disease progressions and symptom severities. There are many facets to alzheimer's disease, when indepth explorations have been sufficiently carried out into the myriad of mechanisms that trigger it
and occurrences during its progression, a preventive vaccine can be developed. In the meanwhile,
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we can also focus on attenuating the existing situation with various cures and their potential
medicinal developments.
Neuroregenerative herbs Tsubokusa and Bacopa monniera are discussed along with their
applications towards attenuating the injuries, imbalances and dysfunctions brought about in
alzheimers disease and other cognitive impairment / degenerative ailments. They have the potential
to be further looked into and developed into pharmacological medications for ailment treatment that
can halt progressions, lessening ailment severities, attenuating the symptoms and disease. Coupled
with regenerative techniques and circuitry fine tunings to heal neurons and cognitive sectors along
with impaired brain circuit pathways afflicted / disrupted by tangles and plaques.
Tsubokusa
Other names of this herb include Centella asiatica, Gotu kola and Indian Pennywort.
Applicable in treatments of neurodegenerative conditions such as Alzheimer's disease, as it enhances
neuroregenerations < Soumyanath, et al, 2005 >, neuroprotection < Kumar, et al, 2009 >, protections
against amyloid induced apoptosis while reducing their tau expression and phosphorylation
changes by i, v- dicaffeoylquinic acid and isochlorogenic acid A < Gray, et al, 2014 >, facilitating
amyloid clearances < Patil, et al, 2010 >, attenuating neurotoxicities < Prakash, et al, 2013 >,
mitochondria dysfunctions < Kumar, et al, 2011 > whilst enhancing neuronal growths and
developments.
A small aquatic, wetland, evergreen, frost resistant, perennial medicinal herb from the
Mackinlayoideae family of plants. Growth often occurs within ditches, wetlands, marshes, swampy,
lowland, wet tropical climates. Often found located in tropical climate regions such as Japan, South
Pacific, South Africa, Madagascar < which contains the highest asiatic acid amongst the other
geographic regions >,Sri Lanka, India and Southeast Asia
Consist of creeping, lean and slender stems in colors of green, shades of red to reddish green tints
that intricately intertwine with each other forming a delicate meshwork of stolons. Grows to a
height of about xv cm and ranges in widths of between xii to xvii cm. Tasteless and produces no
odor when consumed or scented. With the leaves and stem regions often exhibiting medicinal
properties.
Green stalks are long with smooth, rounded, veined apices arranged in a spread net format.
Pericladial petioles give rise to green fan shaped leaves that are about ii cm in size. Vertical white to
cream colored rhizomes emerge from the root regions, they are coated with fine root hairs and have
a downward growing pattern.
Hermaphrodite flowers blossom at the soil surface regions, emerging in small clusters, each tiny
flower no more than iii mm in size, delicately enclosed by a pair of green bracts and are in shades of
whites, violets, reds, pinks and reddish pink hues. Flowers consist of about ii styles, v stamens and
between v to vi corolla lobes, they blossom wildly. Reticulate dense, oval fruits are borne by this
herb.
Densely concentrated with mainly basal endothelia specific collagen type i and fibronectin synthesis
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enhancing, cancer cytotoxic, antimicrobial phytoanticipins of bioactive pentacyclic triterpenoids


such as : brahmoside < Joseph, et al, 2001 > and antioxidative, antibacterial against Staphylococcus
spp, Proteus spp < Dash, et al, 2011 >, Pseudomonas spp, Escherichia spp, Bacillus spp <
Arumugam, et al, 2011 >; fungicidal against Candida albicans, Aspergillus niger < Dash, et al, 2011
>, antiinflammatory, collagen synthesis enhancing, fibroblast upregulating, extracellular matrix
remodeling and collagen accumulating, effective in treatments of tuberculosis along with multi drug
resistant strains < Radji, et al, 2014 > and leprosy < Barnosa-Filho, et al, 2007 >; antibiotic, glycoside
asiaticoside < Tiwari, et al, 2010 > .
Consist of strongly antiinflammatory, antiaging, upregulating epidermis homeostasis thus leading to
wounds and epidermis reconstructive effects, keratinocytes renewal and differentiation equilibrium
balancing and regulations mediating, collagen type i and iii synthesis regulating and enhancing <
Bont, et al, 1995 >, wound healing facilitating glycoside, madecassoside acid < Wu, et al, 2012 >.
Along with triterpene anticancer < Tang, et al, 2009 >, smaller amyloid fibrils formation inhibiting
and dementia effective < Hossain, et al, 2015 > asiatic acids which will aid in attenuating the
accumulations and oxidative damages caused by these small amyloid plaques in alzheimer's
disease : other asiatic acids include madecassic acid < also known as brahmic acid > and madecassic
acid saponins, madasiatic acid, asiaticoside F-G, quadranoside iv and sceffoleoside A, thankuniside
and glycoside isothankuniside.
Pentacyclic triterpene asiatic acids, after isoprenoid pathway synthesis occurs with theses secondary
plant metabolites, an asiaticoside aglycone form emerges. These aglycones consist of a hydrophobic
triterpenoid structure and hydrophilic sugar chain, are blood brain barrier permeable < Jger, et al,
2011 >, cancer cell cytotoxic, disrupts the endoplasmic reticulum and increases intra cytoplasmic
quantums of calcium, downregulates mitochondria membrane potentials, caspase iii activations <
Bunpo, et al, 2005 > along with increasing p liii quantums < Lee, et al, 2002 > thus enhancing
apoptosis and necrosis of tumor cells, downregulates angiogenesis which prevents tumor and glioma
cell growths, glioma glial cell proliferations have been found to be inhibited by its nitric oxide
generating donors S-nitroso-N-acetyl-penicillamine < SNAP > and sodium nitroprusside < SNP >.
Neuroprotective as ATP upregulating caffeoylquinic acids within decreases neurotoxicity of beta
amyloid < Miyamae, et al, 2011 > accumulates of hyperphosphorylated tau aggregations during
ailments like alzheimers disease < Miyamae, et al, 2012 > through BACE i downregulations and
stimulates maturations of ADAM x in cortical neurons, reducing amyloid within cortical neurons
and hippocampal regions that lead to extensive neuronal loss, atrophies, apoptosis, pathological
spreads within the brain, cytotoxicities, neuroinflammations, oxidative stress increases, declines /
loss of functions of dendrites and loss of synapses along with their synaptic transmissions and
connections thus leading to cognitive declines, impairments and memory loss.
While isochlorogenic acid A downregulates tau phosphorylations < Gray, et al, 2014 > along with
microtubule loss brought about by amyloid protein filament accumulations which occur via GSKiii and CDK v kinase pathway activations resulting in phosphorylations occurring mainly at
regions of Ser cccxciii / cdiv thus attenuated by isochlorogenic acid A. Effects of downregulating tau
phosphorylations were also found to occur partially at the region of Ser xxvi, thus reducing these
overall tangle forming tau hyperphosphorylations. Tau phosphorylating pro apoptotic protein
glycogen synthase kinase iii also lead to enhanced neurocytotoxicities and cellular death, thus
potentiating the negative effects of tau hyperphosphorylations which are axon located, together their
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overall reductions decrease alzheimer's disease severities and symptoms.


Bioactive effects are vulnerary, antiseptic, antibacterial, antifungal, antioxidative, collagen
producing enhancing / modulating, thus giving rise to a tissue regenerative and dermis
reconstruction result often leading to skin healing whilst accelerating and hastening edge closures of
open wounds; increases connective tissue vascularization, hair and nail growth stimuli, reinforcing
skin connective tissues's tenacity thus strengthening fragile wounds or previously scarred regions
and functioning as an overall dermal antiaging; enhances the synthesis of structural
glycosaminoglycans such as hyaluronic acid and chondroitin sulfate, with dermal increases of
keratinization and tensile strength restoring skin's protective barrier functions.
Downregulation of inflammations occur through reducing free radical, vasodilating, nitric oxide <
NO > synthesis, NO synthesis is further enhances during malignant glioma growths due to their
high quantums of inducible nitric oxide synthase < iNOS > from high quantums of angiogenic tumor
vasculatures, these enhance productions of vascular endothelial growth factor < VEGF > which
promote vasculogenesis and the further angiogenic formations that enhance glioma growths; but
they are downregulated by asiatic acids thus preventing brain ischemia, cerebral reperfusion injuries
from NO combinations with superoxides thus producing dna and protein oxidizing peroxynitrites
which damages cells, and further angiogenesis and glioma developments, neuronal cytotoxicities,
lysis or damages. Enhances collagen productions which speed the healing of wounds without
excessive glial scars forming and hasten recovery of injured or atrophied neurons from gliomas /
neurodegenerative conditions.
Epithelial cells are also protected from the effects of hydrogen peroxide which enhances cellular
damages and death, upregulating expressions of Bax and caspase iii while downregulating Bcl ii
expressions, whilst asiatic acid upregulates Bcl ii preventing enhanced apoptotic signals which occur
during neurodegenerative conditions, thus preventing oxidative stress, inflammations and apoptosis
from resulting. Antioxidative functions attenuate the increased generations of reactive oxygen
species, free radicals, prostaglandin E ii interleukin vi and tumor necrosis factor-. Cellular
Na+K+ATPase activity along with the normal mitochondrial membrane potentials are also
conserved. Downregulations of excessive expressions of superoxide initiating p xlvii phox,
inflammatory mediating cyclooxygenase <COX> ii, immune stimulating and inflammatory
upregulating NF-B p lxv declines of which also decreases viral replications, as the virus utilizes its
apoptosis suppressing effects, to maintain viabilities within the cells infected thus increasing their
viral loads < Gregory, et al, 2004 > / being able to undergo latency, and pp xxxviii stimuli for an
antiinflammatory effect are also carried out.
Diuretic, corticosterone synthesis downregulating saponin glycosides, central nervous system
depressant, motor activity downregulating, pentacyclic triterpenoids brahmoside and brahminoside
reduce cortisol synthesis during periods of stress, effective in attenuating anxiety, protecting
neurons from harm and are mildly sedative when dosages are high.
Mechanisms of action include activations of p xxxviii mitogen activated signaling protein kinase
pathways along with extracellular signaling regulated kinases thus halting cellular signaling during
S to G ii/ M phrase of cell cycle replications inducing apoptosis and growth halts of cancer cells.
Apoptotic cascades are also upregulated as caspase ix and iii is upregulated, cytochrome c releases
enhanced while Bax and Bcl ii rations are also changed, these events induce mitochondria apoptotic
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pathways to be upregulated and apoptosis of cancerous cells further initiated. Venous distensibility
is improved, peritumoral edema and edemas are reduced, blood pressures lowered and it functions
well as an adaptogen.
Polyphenol rosmarinic acid is a iii-<iii,iv-dihydroxyphenyl>lactic acid and caffeic acid ester an
antiviral, antimicrobial < Swarup, et al, 2007 >, antilipidperoxidation, antiinflammatory through
inhibitions of v-lipoxygenase and v-HETE synthesis, anxiolytic and a strong antioxidant,
annticancer < Yesil-Celiktas, et al, 2010 >, chemopreventive, protective and preventive against
developments of skin carcinogenesis via antagonizing cancer's activator protein-i-dependent
activation of proinflammatory cyclooxygenase < COX > ii expressions < Scheckel, et al, 2008 > ,
inhibits cancer migrations and metastasis, prevents metastasis of breast to bone cancers by
decreasing expressions of interleukin viii < IL viii > and targeting receptor activator of NF kappaB
ligand < RANKL >/RANK/osteoprotegerin < OPG > pathway.
Exhibits cancer cytotoxicity, induces cancer cell apoptosis, increases activities of alkaline
phosphatase < ALP > resulting in mineralizations of cancerous nodules occurring within bone < Xu,
et al, 2010 >, decreases the activity of acetylcholinesterase < Mushtaq, et al, 2014 > which aids in
ailments with declines in acetylcholine quantums thus affecting cognitions, memory or spatial
learning abilities; effectively functioning as an antiepileptic, Alzheimer's disease preventive,
attenuates cognition dysfunctions, reduces anxiety, effective against herpes simplex virus < HSV-i >
preventing cellular viral attachments < Astani, et al, 2012 >, culex mosquitoes transmitted Japanese
encephalitis virus < Swarup, et al, 2007 >, cardioprotective, cancer chemopreventive and aids in the
treatment of excessive edema < Osakabe, et al, 2004 >, swellings, cataract, bronchial asthma,
rheumatoid arthritis, synovitis, arthritis, peptic ulcers and kidney ailments.
Bioactivity includes enhancements of glutamic acid decarboxylase activities < Awad, et al, 2007 >,
inhibitions of iv-aminobutyrate transaminase, a -aminobutyric acid < GABA > transaminase <
GABA-T >. Thus preventing its enzymatic degradations and catabolism of GABA substrates, an
inhibiting, neuronal hyperpolarization inducing and nerve relaxing neurotransmitter; leading to an
increase in cerebral concentrations and quantums which also lead to anticonvulsant action and is an
effective treatment for epilepsy. Increases in GABAnergic neurotransmissions at the basolateral
amygdala results in potent anxiolytic effects as well, thus reducing anxiety and panic disorders.
Inhibitions of collagen degrading matrix metalloproteinase i < Nema, et al, 2013 > and xiii are also
carried out, thus this aids in treatments of carcinomas so as prevent cancer cell migrations and
metastasis from occurring along with preserving cartilage regions affected by autoimmune ailments
that destroy collagen type ii excessively such as arthritis and osteoarthritis.
Tryptophan < L-Trp > catabolizing indoleamine ii,iii-dioxygenase expressions are inhibited by
cyclooxygenase inhibiting functions, these are can also be partially carried out by maitake
mushrooms, thus preventing tumor cells from escaping immune surveillance while inhibiting the
growth and proliferations of microbes such as chlamydia and parasitic Toxoplasma spp; due to
amino acid tryptophan insufficiencies.
End product of this rate limiting enzyme forms N-formylkynurenine along with downstream
neurotoxic kynurenine metabolites such as free radical superoxide anion producing nitric oxide
synthase. Other toxic downstream metabolite produced include quinolinic acid < QUIN > an Nv

methyl-D-aspartate < NMDA > receptor agonist, productions of which upregulated during episodes
of fatigue, exacerbated by brain inflammatory conditions such as post ischemia, as direct
conversions occur by macrophages; with high affinity towards receptors with NRiiA and NRiiB
subunits, initiating overstimulation of NMDA, a massive calcium < Ca ii+ >influx occurring within
L-type voltage-dependent Ca ii+ channels as well, thus resulting in damages and dysfunctions of
endoplasmic reticulum Ca ii+-ATPase < SERCA > pump along with influencing the membrane
potential and increasing firings.
When in excess it brings about inhibitions of tau phosphatase expressions thus resulting in
upregulations of tau phosphorylations, impaired and dysfunctional intracellular Ca ii+ signaling,
inhibitions of astrocytic, serotonergic and histaminergic neuronal outer leaflet located synaptosomal
mitochondria B monoamine oxidase < MAO-B > densely found within striatal terminals thus
resulting in decreased synaptosomal dopamine catabolisms, inhibitor of gluconeogenesis
phosphoenolpyruvate carboxykinase, activity inhibitions of succinate dehydrogenase and creatine
kinase thus affecting cellular ATP energy transfers and intracellular respirations, resulting in energy
declines; this situation is worsen as ATP requirements are increased by the constant potentiations
induced by QUIN bindings to NMDA receptors thus leading to accelerated dips in ATP quantums,
Na + accumulations, followed by increased intracellular water concentrations which lead to
depolymerization of microtubules and the subsequent mitochondrial collapses along with dendritic
swellings.
Quin mediates organelle decreases, cytoskeletal disruptions, intermediate filament
hyperphosphorylations, microtubular disruptions, mitochondrial dysfunctions along with the
consequential dendritic beadings, cholinergic neuronal apoptosis, necrosis, is a neurotoxic and
excitotoxin. It is quickly synthesized but metabolic degradations and removals are slow, thus
resulting in saturations occurring at neurons and the resultant damages; concentrations of which are
twice more within cerebral cortex than hippocampal regions injuring pyramidal neurons. Substance
P and GABA neurotransmitting striatal spiny neurons, neurons and astrocytes within striatum
regions are also affected by increases in quantums, while dopaminergic neurons are also affected by
QUIN uptakes from the cerebral environments.
Apart from occupying glutamate binding sites thus leading to excessive glutamate within the
cerebral microenvironments, QUIN also inhibits astrocytic glutamate reuptakes by decreasing
glutamine synthetase activity thus further saturating the neurons with glutamate, these increases in
excitory neurotransmitter can lead to over excitations and the subsequent convulsions, epilepsy,
neurotoxicities, neuronal lesions, mitochondrial damages, dendritic beadings, apoptosis, neuronal
damages or depressions occurring whilst neuronal regenerating and excitotoxicity neuronal
protecting brain-derived neurotrophic factor < BDNF > synthesis is decreased.
Another downstream neurotoxic and carcinogenic product is iii-hydroxy-kynurenine < iii OHKY >
metabolite; it damages cortical and striatal neurons during uptakes, produces oxidative stressors and
causes the downstream apoptotic events. Excess quantums have been found in ailments such as
Alzheimer's disease, kynurenine pathway's tryptophan metabolism dysfunctions in Huntington's
disease and heightened activities of kynurenic metabolic pathways in human immunodeficiency
virus < HIV > type i associated dementia.
Excess of these kynurenine pathway metabolites, bring about the neuronal damages that surface in
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ailments such as schizophrenia. Thus their inhibitions results in neuroprotective effects and prevents
neurodegenerations or ailments from occurring.
Bioactive antioxidative flavonoid, apigenin, an antiinflammatory, downregulating cluster of
differentiation xxxviii < CD xxxviii > < Escande, et al, 2013 > which functions to increase cytokine
synthesis and expressions, an inflammatory moiety upregulator, thus it's inhibitions prevents onsets
of post focal cerebral ischemia brain injuries, post ischemic inflammations or reperfusion injures.
Along with beta pancreatic cells, intracranial neurons also express high quantums of calcium
mobilizer CD xxxviii, a type ii transmembrane glycoproteins is also present upon outer
mitochondria membranes, their reduced expressions lowers the quantums of intracellular
mitochondria calcium. Ca ii+activated hydrolyzing enzymes are thus reduced, the mitochondria

permeability transmembrane pore stays closed thus preventing releases of pro apoptotic molecules
and subsequent swellings leading to apoptosis, whilst the neurons are protected from necrosis and
these organelle swellings or apoptotic events, along with being shielded from excitotoxicities and
complement induced cellular deaths. During ailments like Alzheimers disease, Ca ii + homeostasis is
disrupted resulting in excessive Ca ii + influxes within neurons, dendrites and mitochondria. Thus
this attenuation of CD xxxviii leading to mitochondria Ca ii + quantum decreases, enables a better
cellular condition in the mist of disease onsets, protecting cells from undergoing the typical Ca ii +
excess symptoms of swellings and apoptosis.
Effective as an anticancer, cancer preventive, anticonvulsion glycoside, decreases anxiety as it
functions as a benzodiazepine ligand, inhibiting neurotransmissions as it mediates
hyperpolarizations and brings about sedative effects, protecting neurons from excitotoxicities. It
inhibits pro apoptotic Bcl ii thus decreasing the occurrence of apoptosis and is cellular protective
especially within renal cellular regions.
An activator of monoamine transporter, while moderating receptors of GABA A , blocking NMDA
resulting in mild dissociative anesthesia effects and antagonizing opioid -, - and receptors
resulting in abilities to attenuate morphine overdoses, along with neurprotective functions against
ailments such as ischemia induced injuries, reducing food palatability, reducing intake and
decreasing the habits of compulsive and disproportionate binge eating.

Neuronal differentiations of stem cells along with neurite outgrowths < Wanakhachornkrai, et al,
2013 > are also initiated along with neurogenesis which aid in the stimuli of stem cells within the
cerebral subventricular zone, striatal interneurons, nucleus accumbens and subgranular zone within
dentate gyrus of hippocampal regions thus healing cognitive dysfunctions and memory impairments
in neurodegenerative ailments. When guided by targeted regional morphogen expressions, these
stem cell niches can potentially repair regions that have undergone necrotic or apoptotic events,
lesions or regions with extensive neuronal damages can also be repaired by these mechanisms.
These can thus aid in the regenerative procedures required when neuronal loss occurs,
compromising cerebral functions. Such as during lesion occurrences mediated by cerebral
infarctions, von Hippel-Lindau syndrome, brain regeneration via stem cells carried out after the
clearances of gliomas, epilepsy, transmissible spongiform encephalopathies, meningitis, pathogen
induced encephalitis such as infections caused by HIV, neurosyphilis affecting the medial temporal
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lobe, lesions arising within this region affect long term declarative semantic and episodic memories.
Effective against other cns permeable pathogenic infections such as cerebral candidiasis transmitted
by volatile membranous < sexual or otherwise > contact, Lyssavirus spp, Neisseria spp, Toxoplasma
spp, Streptococcus spp, Haemophilus spp, parasitic pork tapeworm or round worms. Brain
granulomas tend to occur during the infections and inflammations as they wall in the pathogens thus
condoning further spreads within the cerebral system and facilitating immune system attacks.
However regions with granulomas or their subsequent calcifications affecting cohesive neuronal
circuitry networks along with overall connectivities would result in impaired cerebral function,
seriousness of which involves the specific region/s they arise at. If functions are impair, inductions of
stem cell differentiating, growth and migrations is a good way to repair the impaired regions thus
restoring cohesive function and network integrity once again.
Other lesion inductions include allergy, Pick's disease, neurofibromatosis, migraines, strokes,
hypoxia, brain hemorrhage, arteriovenous malformations, cerebral palsy, toxins, excessive alcohol
consumptions, illicit drug overdose which impair blood glucose control along with harming
cardiovascular, cerebrovascular and pathological conditions, of which methamphetamine causes the
most extensive brain degenerations and damages; ionizing radiation, degenerative ailments such as
Alzheimers disease, various types of dementias, Parkinson's disease, Huntingtons disease and
motor neuron disorders.
Diabetic neuropathy < Lou, et al, 2012 >, insulin and non insulin dependent diabetes mellitus is also
attenuated < Mutayabarwa, et al, 2003 > as glucose transporter GLUT iv translocation is improved,
blood glucose levels are reduced, along with exerting cellular protective effects thus cells and organs
are protected from ailments such as diabetic nephropathy that arise due to downstream effects,
glucose insufficiencies and metabolic effects of the ailment.
Rutin is another bioactive bioflavanoid constituent of Centella asiatica, functions include
antioxidative activities < Azevedo, et al, 2013 >, as a heavy metal chelator it binds iron ions thus
prevent their bindings to hydrogen peroxide and the Fenton reactions downstream with high
quantum generations of free radicals; vitamin C is stabilized thus enhancing its effects. When
coupled together, antiinflammatory effective against arthritis, antimicrobial, lowering cholesterol
levels, cardioprotective, anticancer as it inhibits G ii/M of the cell cycle phase < Chen, et al, 2013 >,
enhancers cancer cell apoptosis, prevents occurrences of angiogenesis by downregulations and
inhibitions of vascular endothelial growth factor < VEGF >, reduces activation of phospholipase C,
inhibits protein kinase C activity and thromboxane A ii platelet formation, leading to declines in P
xlvii phosphorylation and intracellular Ca ii+ mobilizations along with reducing extracellular
coagulation forming protein disulfide isomerase. Thus inhibiting the aggregation of platelets
resulting in vasculature, cerebralvasculature and cardiovascular protection.
This prevents the formation of embolisms, thrombosis, arterial clots and the consequential strokes
and heart attacks; blood pressure and fluid mobilities are also improved as the capillary
permeabilities are decreased, attenuating and stabilizing capillary fragility and thus enhancing
shunting and a smooth circulation, this prevents deep vein thrombosis, reducing glaucoma's
intraocular pressure, excessive or extensive bleedings or bruisings, venous edema, edemas, ascites,
swellings, excessive inflammations, autoimmune conditions whereby poor blood circulations
contribute to additional damages as immune cells are concentrated at the region mediating serious
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inflammatory conditions, good perfusions along with smooth blood circulations enable even
distributions of the immune cells thus reducing their localized concentrations along with facilitating
clearances of antibody complexes thus aiding in conditions such a arthritis; varicosis,
microangiopathy and blood stagnancy within organs or pooling at distal regions along with their
accompanying symptoms such as lower limb tingling sensations or numbness.
Aldose reductase an oxidoreductase involved in the polyol pathway of glucose metabolism is
inhibited preventing the conversions of glucose to alcohol sugar, sorbitol. This aids in reducing
diabetic complications especially within regions whereby they are intracellular located; organ
systems are vulnerable to damage due to their high baseline metabolic requirements. In diabetic
conditions sugars are saturated and stuck within the vasculatures unable to permeate within these
cells for optimal metabolisms for tissue and organ health to occur, leaving them more prone to
metabolic dysfunctions and imbalances thus leading to complications when imbalances within their
chemical pathways occur. Intracellular aldose reductase are organ localized mainly within eye
regions of the cornea, retina, lens; kidneys, along with neuronal myelin sheaths.
As high blood glucose within vessels that innervate these organs in the hyperglycemia state of
diabetes upregulates these pathways, coupled along with excessive blood sugar quantums, these also
lead to lowering of the ability of erythrocytes to pass through capillary filtration pores. Thus
excessive conversions and low filtrations results in high quantums of intracellular sorbitol
accumulations leading to diabetic complications such as microvasculature damages, retinopathy,
blindness, cardiovascular ailments, kidney failures and neuropathies afflicting these organs; rutin is
thus protective and preventive against these accumulates in diabetic states.
Centellin and centellicin < Siddiqui, et al, 2007 > upregulate the formations of cellular antioxidants
such as catalase, superoxide dismutase, ascorbic acid vitamin E and glutathione peroxidase. These
function protectively towards cells preventing them from free radical damages along with
upregulating cellular regenerations, enhances dna synthesis, protein expressions, increases collagen
productions, enhances cross linkages and maturations of newly synthesized collagen, increases the
speed of epithelia productions, improves microcirculations and vasculature flows, enhances the
closures of fresh wounds, overall cellular and tissue wound healing, circulatory improvements,
preventing agings, attenuating excessive scar formations and downregulating excessive
inflammatory reactions through lowering free radicals during such events producing a healing and
soothing effect; effectively attenuating excessive cellular apoptosis, tissue or organ damages,
cognitive declines, cerebral reperfusion injuries whereby high quantums of free radicals are often
liberated thus leading to these injuries, stroke, ischemia, swellings, itch, redness, pain or other
cellular irritations from occurring.
Cardioprotective lipophilic pentacyclic triterpenoid ursolic acid < a triterpenoid > carries out JNK
and signal transduction and activator of transcription < STAT iii > activation pathways inhibition <
Pathak, et al, 2007 >. When excessively and concurrently expressed cancer growths are initiated and
amplified proliferations occur. STAT iii is growth factor responsive towards bone morphogenetic
protein ii < BMP ii >, hepatocyte growth factor < HGF >, epidermal growth factor < EGF >,
leukemia inhibitory factor < LIF >, interferons, interleukin < IL > v, vi, x and leptin; mediating
signaling pathways that lead to cellular proliferations or apoptosis, bone developments, along with
aiding in differentiations of T helper xvii cells, when excessive these lead to onsets of autoimmune
conditions, intestinal inflammations, diabetes, low blood counts and thyroid disease.
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STAT iii expressions and functions are dependent upon phosphatase and tensin homolog < PTEN >
regulator , when PTEN/mammalian target of rapamycin < mTOR > /STAT iii signaling occurs it
leads to cancer malignancy, however when PTEN pathway activates protein kinase B < Akt > /
catenin beta i < -catenin > / transcription activator forkhead box O < Foxo1 > axis it upregulates
inflammations thus preventing further oncogenicity and destroying tumor cells, it also functions as a
tumor suppressor and inhibits excess STAT iii expressions thus leading to antitumor states; along
with being able to regulate AKT/FoxO iii a/ pro apoptotic activating, BCL ii interacting mediator of
cell death < Bim > which is able to directly activate Bax and Bak thus initiating mitochondrial
apoptotic cascades and enhancing tumor apoptosis, maintaining eukaryote homeostasis and
preventing spontaneous autoimmunity conditions from developing.
Other functions include inducing cancer cell apoptosis whilst downregulating their proliferations
and upregulating cytokine productions such as IL ii < Punturee, et al, 2005 >, enhances the
biosynthesis of potent anticancer molecules. Increases the synthesis of myocytes and the
accumulations of muscle mass, functions as a moderate aromatase inhibitor reducing estrogen
synthesis aiding in attenuating excessive quantums of estrogen related cancers such as
postmenopausal breast carcinomas, lung, ovarian and endometrial cancer, while enhancing
testosterone quantums in males attenuating the late puberty and maturation disorders of ailments
such as gonadotropin independent precocious puberty; attenuates glucose intolerance and
upregulates brown fat while decreasing white fat thus reducing conditions such as fatty liver disease,
decreases fat accumulates within organs such as arteries or the cardiac and obesity. Eryptosis of
dysfunctional red blood cells are also carried out thus aiding in vasculature health and enhances
blood circulations.
Antioxidative, anticancer and antiinflammatory phenolic polyphenol, cinnamic acid derivatives :
chlorogenic acid protects dopaminergic neurons from excess neuroinflammations < Shen, et al, 2012
>, has mild blood pressure lowering effects which aids in hypertensions, upregulates expression of
DNA repair enzymes, apoptotic inducing intranucleus poly < ADP-ribose > polymerase < PARP >
which detects single strand breaks upon the double helix and initiates signaling cascades that
mediate its repair, longevity occurs when there are high quantums of PARP present within an
organism as errors are mended resulting in correct protein expressions along with optimal cellular
health; and chromosome vii encoded, spermatogenesis inducing and dna protective, mismatch repair
endonuclease < PMS ii > thus preventing cancerous conditions from occurring, stimulates flows of
bile, enhancing and regulating proper lipid metabolism lowering quantums of cholesterol and
triglycerides, visceral fat mass and body weight while slowing the rates of glucose adsorptions after
intakes, thus aiding in reducing obesity, lipidoses, atherosclerosis, cardiovascular disease, circulatory
disorders, fatty liver disease, hypertension and conditions arising from high cholesterol.
Other bioactive phenolic acid constituents include isochlorogenic acid, antiaging irbic acid < iii,v-Odicaffeoyl-iv-O-malonilquinic acid >, i,v-di-O-caffeoyl quinic acid; iii,v-di-O-caffeoyl quinic acid;
iii,v-di-O-caffeoyl quinic acid and iv,v-di-O-caffeoyl quinic acid.
Antihistamine, antiinflammatory and anticancer flavonol quercetin exhibits an antidiabetic effect as
it activates L type channels within pancreatic cells enhancing natural secretions of insulin < Youl,
et al, 2010 >; inhibits advances glycation end product < AGE > formations < Alam, et al, 2015 >,
reduces high blood pressure, lowers high cholesterol quantums, attenuates and prevents occurrences
of cardiovascular ailments, inhibits cortisol synthesis attenuating the detrimental effects of stress
x

thus functioning as a neuroprotective regent. Other effective flavanols include quercetin-iii-O--Dglucoside and castillicetin < quercetin-iii-caffeate >.
Post menopausal bone loss preventive flavonoid, phytoestrogen kaempferol, a selective estrogen
receptor modulator < Zoechling, et al, 2009 >, functions as polyphenol antidiabetic with enhanced
sensitivity towards insulin < Alkhalidy, et al, 2015 >, stimuli of thyroid hormones < da-Silva, et al,
2007 >, antioxidant, anxiolytic, antiinflammatory, antiallergic, analgesic, antimicrobial, angiogenic,
antimetastatic, antiproliferative, anticancer, neuroprotective, cardioprotective and biphasic ER
pathway mediated estrogenic / antiestrogenic. It upregulates tumor suppressor P liii expressions
while altering estrogen signaling by functioning as an inverse agonist and downregulating estrogen
receptor alpha and gamma < ERR and ERR > expressions, inhibiting their interactions with
coactivator peroxisome proliferator-activated receptor coactivator i (PGC i ); thus effective in
estrogen affected ailments such as postmenopausal symptoms along with endometrial, ovarian and
breast cancer growth halts, reduces blood clotting and the formations of aneurysms, thrombosis,
strokes, blood sugar regulation which excessive estrogen interferes with, reduces fat storage which
excessive estrogen upregulates, as estrogen thickens the uterine lining decreases in high quantums
secreted would normalize and maintain it, attenuations of thyroid hormone secretions are also
carried out as estrogen inhibits it, mediates cancer cells apoptosis.
Other functions include inhibitions of osteoclastic bone resorptions thus preventing onsets or
occurrences of osteoporosis, mineralizations of osteoblasts and enhancing initiations of osteogenic
differentiations by estrogen receptor signaling, targeting ER signaling cascades; through initiations
of phosphorylations of ER and subsequent ERE transcriptions. Kaempferol glycosides astragalin <
kaempferol-iii-O--D-glucoside > and castilliferol < kaempferol-iii-p-coumarate> are also contained
within.
Acetylenic polyacetylene cadiyenol which functions as an antioxidative and antineoplastic regent,
initiating apoptotic events within cancerous cells, alkaloids hydrochotine and hydrocotyline, ursanetype triterpene saponins : centellosides A and B, centellasaponins B, C and D, along with other
triterpenoids such as corosolic acid, pomolic acid, ii , iii , xx, xxiii-tetrahydroxyurs-xxviii-oic
acid,xi,xii dehydroursolic acid lactone, ii , iii -dihydroxyurs-xii-en-xxviii-oic acid and iiiepimaslinic acid are the other components. Bioactive centella asiatica unique ginsenosides Mc, Rk i,
Rg v, Rd ii, and Y, < xx S>-ginsenoside Rg iii, < xx R >-ginsenoside Rg iii and notoginsenoside ST iv
and Fe. While other constituents include viii-acetoxy-i,ix-pentadecadiene-iv,vi-diyn-iii-ol and
gypenoside i and .
Phytosterols, precursors of anabolic steroid, boldenone undecylenate include stigmasterol,
campesterol and -sitosterol iii-O-glucopyranoside which lowers high cholesterol and low density
lipoprotein through competitive bindings with receptors, enhances immunity, antiinflammatory and
functions as an antiviral and anticancer.
Other components include high blood oxygenating and detoxifying chlorophyll, trans violaxanthin,
trans neoxanthin, trans lutein, carotene, mental deterioration preventing thiamine found in high
quantums within the leaves; psychosis, schizophrenia, confusion, mood swings, psychomotor
retardation and hallucination attenuating pyridoxine, vitamins B, C, K; magnesium, calcium, iron,
sodium, potassium, manganese, cobalt, copper, zinc, anthocyanins, antioxidant flavonoids :
quercitin, naringin, cathecin, kampeferol; tannins, phytosterols, volatile oils camphor, cineole,
xi

vallerin and amino acids.


They upregulated productions of hydroxyproline, glycosaminoglycan along with enhancing
angiogenesis to aid in revascularizations of the injured tissue along with enhancing the wound
healing and immuno clearance process.
Downregulations of inflammations are also brought about along with reductions in the quantums of
scar forming myofibroblast thus reducing the inlaying of thick, dense scar tissue or keloids. These
mechanisms of action aid in would healing along with the synthesis and formations of adequate
collagen as the foundation of scar tissue synthesis which would close the injured regions. Consist of
centellose, centelloside, and madecassoside.
This herb has been found to enhance dna synthesis thus increasing the speed and quantums of
epithelia formations which help to increase wound's tensile strength, enhance the healing speed
along with closing of gash margins. The also give rise to increases in antioxidants due to its natural
concentrates of polyphenolic antioxidants: quercetin, myricetin, and kaempferol increasing
quantums of free radical scavengers such as superoxide dismutase, catalase, glutathione peroxidase,
vitamin E, and ascorbic acid while enhancing nitric oxide scavengings, bring about decreases in lipid
peroxidations. It also has metal chelating properties and is an effective iron chelator.
Skin tightening functions occur as it enhances the cross linkages of collagen to set in within layers of
epithelia and cellular regenerative as it enhances the healing of wounds and cells.
Usage
Applicable in neuroregenerations, neuroprotection, nerve injuries, cognitive enhancements,
reversals of cognitive impairments, epilepsy mainly absence seizures and tonic clonic; amnesia,
Alzheimer's disease, Parkinson's Disease, schizophrenia, protects hippocampus from the effects of
oxidative stress, attention deficit hyperactivity disorder, improves / enhances alertness, trauma, post
traumatic stress disorder, stress, anxiety, enhances relaxation, nervous breakdown, mood
fluctuation, mild depression, sleep disturbances, insomnia, mental fatigue, fatigue, adaptogen, for
enhanced calmness, depression, mental retardation, improves cognitions, inhibits the decrease in
hippocampal Mg ii+-ATPase pump and Na+/K+-ATPase activity brought about by hyperglycemia in
diabetes and conditions such as seizures, thus restoring hippocampal functions resulting in memory
improvements and normalities.
Function in the improvements of vision, diabetes related complications, improves metabolism,
cardiovascular ailments, strengthens cardiomusculatures, congestive cardiac failure, pulmonary
fibrosis, high blood pressures, hypertension, varicose veins, hemorrhoids, strengthening vascular
tones, connective tissue sheaths ensheathing the vasculature networks are reinforced and
strengthen, increases tensile strength of arteries, capillaries, veins and venules, Raynaud's disease,
circulatory disorders, neutralize blood acids cramps, tingling sensation experienced at extremities
from low blood circulations and perfusions to the regions, improves overall blood circulations, blood
purifications, antihypertensive, cancer, gliomas, skin wounds, scleroderma, keloids, prevents
excessive scarring as it balances the overall collagen productions, synthesis of collagen within
vascular networks, lymphatics, lymphoid tissue, skin and cartilage; skin and membranous ulcers,
stasis ulceration, gastric ulcers, stomach ulcers, improves conditions of mucous membrane, gastritis,
xii

varicose ulcers, skin ulcers, canker sores, lesions, inhibitions of UVA mediated photoaging, eczema,
stasis dermatitis, acne, psoriasis, baldness, in the treatment of second and third degree burn injuries
and enhances hair and nail growth, while it enhances repairs of connective tissue.
Effective in blood detoxifications and purification which will aid in viremia and bacteremia / in
pathogenic conditions as clearances of microbes, pathogenic secretions/ metabolites /molecules are
facilitated / enhanced, attenuates arsenic induced cytotoxicity < Kulshrestha, et al, 2014 >, enhanced
blood circulations, peripheral vasodilator, chronic venous insufficiency, venotonic, varicose veins,
edema, lymphedema, exerts adrenal strengthening effects, attenuates deficient pancreatic function,
as a mediator of anti inflammations, immunomoderations, systemic lupus erythematosus,
rheumatism, asthma, swelling, lupus, longevity, anti aging, longevity tonic, herpes simplex viruses <
HSV i > and < HSV ii > mediated by its asiaticosides, syphilis, hepatitis, leprosy, swine flue,
tuberculosis, bronchitis, rhinitis, phlebitis, cystitis, urinary tract infections, a general antiallergenic,
antimycobacerial, antimicrobial, antiviral, antihelminthic, schistosomiasis, elephantiasis, antioxidant,
detoxification, lymph cleansing, diarrhea, fever, influenza, whooping cough, tonsillitis, swollen
glands, sore throat, asthma, sedative, analgesic, fibrocystic breasts, endometriosis, improves
hypochloric acid states as it enhances hydrochloric acid productions, aids in eradication of kidney
stones, improves bile synthesis, cirrhosis, hepatoprotective and as an antihepatofibric.
Contraindication
Non toxic when taken in accordance to dosage and instructions. At recommended dosages there are
no known adverse side effects, so far discovered. Long term topical applications are to be avoided
due to carcinogenic concerns as it upregulates collagen synthesis and angiogenesis thus mediating
wound healing, but in healthy balanced, uninjured tissue any long duration / excessive applications
might be harmful.
Contact dermatitis occurs if applied topically by anyone that is allergic to it. In rare case, some
experience photosensitization with heightened sensitivity to sunlight or headaches. Decreases in
dosage or to stop taking it altogether is advisable.
Sedative effects, hyperglycemia, headache, decreased fertility and non fatal liver toxicity occurs if
dosages exceed the recommended and are taken in excessively high quantums.
Contraceptive properties are inherent thus it is not recommended for woman planning pregnancies,
those that are already pregnant or lactating.
Interacts with cholesterol lowering drugs, thus they should not be taken together. As with most
herbs, interaction with drugs often occurs thus the mixed effects / excessive potentiations have to be
known, before ascertaining if ingest is safe / suitable.
Not suitable for those with an overactive thyroid and it is not to be mixed with other sedatives or
tranquilizers so as to prevent excessively amplified effects.
Dosage
Recommended oral consumption is 60-180 mg per day.
xiii

When weight is 150 lb, dosage involves 2100 - 3300 mg; at 200 lb, dosage is 2900 - 4400 mg and for
weights of 250 lb, dosage is 3600 5500 mg.
When taken as a tincture : 10 ml, taken twice per day. Taken in the form of tea : ii-iii cups per day.
When applied topically as a paste with mixtures of dried herb powder with some water : ii tsp.
Bacopa monnieri
Also know as herb of grace, water hyssop, brahmi and thyme leafed grlaatio.
Effective in neurodegenerative conditions and in improvements of Alzheimer's disease, mechanisms
of action functions in attenuating the ailment along with improving it's various neurodegenerative
symptoms.
Creeping, perennial plant blooming naturally in warm climates of wetland or aquatic environments,
this herb is from the Scrophulariaceae family. Found in brackish water, estuaries, shallow watery
regions, marshlands, bogs, swamps within countries such as North and South America, Europe,
Australia, Africa and Asia. Oblanceolate, succulent leaves range from about iv to vi mm in
thickness. Small flowers emerge from the apical region of stem, they are white to whitish violet
shades, with iv to v small petals emerging circularly.
Functions as an acetylcholine enhancer, dopamine and serotonin modulator < Rauf, et al, 2013 >,
prevents degenerations of dopaminergic neurons, upregulates dopamine D i and D ii receptors thus
attenuating dopamine dysfunctions in hypoglycemia < Thomas, et al, 2013 >, antidiabetic along with
attenuating the accompanying spatial memory impairments brought about by the ailment, though
increasing hippocampal expressions of excitatory, fast synaptic transmission mediating -amino-iiihydroxy-v-methyl-iv-isoxazolepropionic acid receptor < AMPA > one of it's tetramer subunits
glutamate receptor ii < GluR ii > < Pandey, et al, 2015 >, thus improving glutamate dysfunctions in
amyotrophic lateral sclerosis < Van Damme, et al, 2005 > as well, attenuating calcium mediated
excitotoxicities and preventing neurodegenerations; clinical trial have found that it improves
attention speed, cognitions < Kongkeaw, et al, 2013 >, heightens the retention of newly acquired
memory < Roodenrys, et al, 2002 > and improves free recall < Pase, et al, 2012 >.
Effective as an antioxidant, stimulating innate productions of other free radical neutralizers, along
with aluminum < in sulphate form, a common tap water pollutant < Bloomberg, 2009> > and other
heavy metal chelating functions thus exerting neuroprotective effects, as free radicals are prevented
from destroying bonds and molecular structures of neurons. Functions well as an adaptogen,
alleviating excessive cortisol synthesis during stressful episodes < Benson, et al, 2014 > thus
neuroprotective as neurons and circuit pathways will not be injured or affected by cortisol surges.
Decreases storages of neurodegenerative proteins : amyloid accumulates and facilitates their
clearances, preventing their initial formations into masses of tangles while dissipating tangle fibrils;
inhibits synthesis of amyloid precursor protein, inhibits phospho tau expressions < Ramachandran,
et al, 2014 >, decreases build ups of synclein accumulates; enhances synaptic plasticity via
enhancing gene expressions and upregulations of neuropeptide transcripting cAMP response
xiv

element binding protein < CREB > cellular transcription factor, thus upregulating quantums of
downstream brain derived neurotrophic factor, dopamine's precursor L-DOPA catalyzing tyrosine
hydroxylase, VGF nerve growth factor inducible precursor often found decreased in alzheimer's
disease, frontotemporal dementia the initial stage of alzheimers disease with high quantum of tau
accumulates, acute encephalopathy, parietal cortex of parkinson's disease, and Lou Gehrig's disease
< amyotrophic lateral sclerosis >; enhances synthesis of enkephalin, somatostatin, c-Fos and
attention increasing corticotropin releasing hormone.
One of its downstream products antiglucocorticoid emerges, which enhances new neuronal stem cell
growths as glucocorticoids inhibit their proliferations, antioxidative < Simpson, et al, 2015 >,
enhances longevity < Phulara, et al, 2015 >, improves synaptic plasticity while restoring
hippocampus hypoxia induced spatial memory and learning impairments by upregulating Fmr i
expressions with downregulations of Hif i expressions < Rani, et al, 2015 >; antiinflammatory,
mediates synaptic plasticity though N-methyl-D-aspartate receptor < NMDAR > modulations thus
improving spatial memory and learning, attenuating effects of amnesia with increases in NMDAR
expressions at prefrontal cortex and hippocampal regions < Rai, et al, 2015 >, preventing
excitotoxicities, glutamate toxicities whilst further preventing cerebellum impairments and
attenuating encephalopathies < Mondal, et, al, 2015 >; while increases synthesis of blood brain
barrier permeable neurosteroid, dehydroepiandrosterone < DHEA >.
DHEA is often synthesized by hypothalamic astrocytes via cytochrome P cdl cvii hydroxylase
gene expression which perform active metabolisms converting them into estradiol and to a lesser
extend cortical astrocytes which are however not as active in estradiol conversions, which gives rise
to longevity < Schwartz, et al, 2004 >. Expressions are also upregulated during physical exercise and
in calorie restrictive < Roth, et al, 2002 > or fasting type of diets.
Exerting neuroprotective, neurogenesis effects upon the cerebral system along with enhancing
neural survival, regulating neural stem cell progenitor pools within subgranular zone of
hippocampus's dentate gyrus, increasing their growths, differentiations and proliferations;
enhancing neurite growths, elongations, branching and extensions thus improving cohesiveness of
neural connectivities, facilitating enhance neural plasticity occurrences. DHEA further modulates
and upregulates synthesis of neuroprotective, growth stimulating and enhancing, mainly localized
within basal forebrain cholinergic neural region, nerve growth factors < NGF > and hypothalamus
brain derived neurotrophic factors < BDNF > thus enhancing neuritogenesis, plasticity, preventing
cholinergic cell loss while enhancing their viabilities; regulating apoptosis and synthesis and
secretions of catecholamines dopamine, epinephrine and norepinephrine.
Hypoglycemia occurs in hypothalamic corticotropin deficiencies, while excessive upregulations of
corticotropin releasing hormone receptor i leads to anxiety, depression and suicidal tendencies, in
alcoholics this results in upregulated alcohol induced euphorias, thus increasing alcohol dependence
tendencies.
Quantums of DHEA decline through the years < Perrini, et al, 2005 > affecting brain metabolism,
eventually resulting in neurodegenerations, memory impairments or cognitive dysfunctions. High
utility of cognitive resources coupled with minimal sleep, might bring about optimal brain
functioning on a daily basis as high and regular firings lead to good perfusions and the resultant
neuronal developments along with expansions of grey matter reservoirs, however with time
xv

neuronal health declines and cognition might be affected if brain metabolism is unable to keep up
with function / utility. When mental activities exceed metabolism capacities, neuronal injuries /
damages occur.
Cerebrospinal fluid < csf > keeps the brain sufficiently moist and cool from the high firing activities,
it is composed mainly of glucose, electrolytes and solutes, likewise blood perfusions aid in supplying
the brain with adequate glucose for ATP production. However the consumption of meat is unable to
provide the brain with glucose, to meet its metabolic requirements honey nourishes both the
cerebral system and cardiac cells facilitating good pumping activity adequately perfusing the brain.
Oxygenation is important as well, a high platelet quantum delivers sufficient oxygenations to the
cerebral system, this is reflected in blood that is dark red rather than red or lighter shades and hues.
Iron is best obtained from shitake mushrooms due to its extremely high iron quantums.
Vessel and capillary diameters influences the rates and quantums of perfusions within the cerebral
system. If vessels are too dilated, leakages of neurotransmitters out from the tongue circulations
occur as seen in ailments like psychosis / schizophrenia, these leakages also affect the cerebral
circulations leading to impaired cognitions and if severe, conditions such as hydrocephalus arise
along with the resulting accumulates of intracranial pressures surfacing as severe headaches and
projectile vomiting episodes, cumulating in eventual brain damages. However excessively
constricted vessels impede smooth blood circulations leading to inadequate blood flows reaching
neurons thus affecting metabolisms and decreasing them along with neuronal health. Thus the
condition of cerebral vasculatures along with their perfusions and regions affected have to be
properly ascertained and diagnosed when ailments affecting cognitions and memory occur or in
neurodegenerations.
These provide insights into brain metabolic conditions which is also a key underlaying /
accompanying factor behind most neuronal ailments. Attenuating of imbalances can subsequently be
carried out once the conditions of cerebral vasculatures and perfusions are brought to light. Physical
systemic symptoms such as prolapsed vessels or varicose veins are signs of excessive vasodilatations,
while numbness or tingling sensations at extremities indicate vasoconstrictions impeding smooth
perfusions and circulations. Cerebral symptoms of perfusion and electrolyte imbalances include
syncope, fainting, memory impairments, brain fog, mild confusions, mental fatigue along with all the
various varying degrees of headaches and migraines. When cerebral perfusions / perfusion
distributions are left untreated, they affect brain circuit pathways and accumulate into conditions
such as dementia, psychosis or schizophrenia.
Cerebral vasodilations can be mediated with intakes of l carnosine, while vasoconstrictions occur
with intakes of ruscus aculeatus. Metabolism can be enhanced in low metabolic conditions with
capsicum and camellia sinensis, while ATP mitochondria productions are enhanced by l carnitine
and coenzymeQ x. Infertility due to immobile spermatozoons can also be attenuated with
coenzymeQ x as they provide mitochondria energy for adequate mobilities.
Events of cerebral metabolic exhaustions would lead to the very abrupt and sudden cognitive
faculty halts of the respective cognitive unit involved, often without any warning signs apart from
the occasional mental fatigue and exhaustion here and there sometimes experienced upon initial
waking, especially when its nearing to the point of irreversible neuronal fatigue stage. These events
arise if one gets by on just iii to iv hrs of sleep per night, coupled with intensive long duration mental
xvi

activities, as firings can no longer take place as neurons undergo damages, atrophies and eventual
silencing from extreme usages without the proper maintenances and energy requirements. Another
occurrence leading to that, is when cognition is carried out so intensely or prolonged, pushed way
past the brink of metal exhaustion yet it still carries on, further potentiated by coupled events such
as sleep deprivations, that metabolic requirements can no longer be met, all of a sudden the
cognitive sector involves just shuts down. When neuronal units undergo these type of overused
silencing, they go dormant long term and undergo extreme atrophies over time from these
consequential disuse, yet years later, they are still cellularly viable, just no longer effectively
functional for cognitions any longer.
If activated in such a condition whether though electric stimuli innate or external, of which
perfusions would follow, they might be weakly marginally functional < provided serious damages or
apoptosis to some cells within the neural network have yet to occur > for a short duration; but once
their remaining metabolic reserves are finished coupled with firings in that weakened state which
would wear them out further, they can never be cognitively utilized again, the silencing is permanent
this time round; thus it takes ii rounds of silencing for permanency to occur. The initial silencing
weakens them leading to serious atrophies eventually, the second deactivates them permanently
sending the cells towards a sate whereby firings as a cohesive cognitive unit are no longer possible.
Reactivations of previously once silenced cognitive sectors could be carried out, but they are best
left as it is, in their dormant states. Years later when brought back to active firing states and
reopened, some might reflect neurodegenerative conditions and ailments depending upon the
severity of neuronal damage already sustained previously and through its period of dormancy. If
these damaged cognitive sectors that reflect neurodegenerative states and ailments continue firing,
or being cognitively functional; perfusions may eventually end up being shunted towards these
sectors instead, quantums of cerebral blood is more or less fixed, if perfusions are taken away and
channeled somewhere else, it cannot be sustained this way, the balance would be disrupted; thus
leaving the preexisting healthy sectors with minimal perfusions which will eventually send them into
silenced states instead which leaves healthy cognitive sectors dormant and the dysfunctional ones
dominant instead; a situation best totally avoided.
However in cases of neuroplasticity occurring whereby new cognitive sectors are formed, viability
in the long run may be possible without affecting functions or cellular conditions of preexisting
cognitive sector/s, if these newly activated and developing cognitive sectors are situated very close to
the current dominant ones.
Likewise the way cerebral cognitive sector developments tend to be genetically determined from
hereditary patterns, neonates will have the same cognitive sectors as their parents, one / both; or
similar close by cognitive sectors to paternal. But as plasticity takes place through life coupled with
environmental influences or trauma, some sectors may change or be developed through the years,
Though the birth hemispheres they are found within initially will remain constant, unless in rare
cases or exceptions of physical trauma / events that brought about extensive neuronal damages /
apoptosis / necrosis within a certain hemisphere. These developmental / life progression changes will
in turn affect gene and protein expressions.
If all possible cognitive sectors viable within a cerebral structure are discovered through mapping of
their exact circuitry pathways and electric quantum distributions / densities within the cerebral
xvii

system; with data and results properly classified, these can subsequently be correlated to the
respective dna sequences that give rise to them. Thus, the known sequences bringing about the
exact cognitive sectors and circuitries will be clearly defined. These known pathways will function
as control against circuitries in neurodysfunctions / ailments which once mapped and known, when
compared, the imbalances in distributions and dysfunctions within pathways will be brought to
light, so too the respective healing procedures which can then be carried out via circuitry
corrections to attenuate these ailments, thus curing them of the cerebral ailment.
Apart from stem cells, optogenetics and regenerative techniques, gene therapy and precision
medicine can be applied if neurodegenerative events / ailments occur, for precisely targeted
treatments along with functional plasticity developments if required in serious cases of cellular loss
inhibiting normal cognitive sector function < such as in : Pick's disease, seizures, Alzheimer's
disease, dementias which leave at least about 1 cc of cell loss, strokes, prion diseases, excessive
formations of glial scars > for cognitions to be restored once again. An interesting area with immense
treatment potential for neurodegenerations and neurological ailments, still very early in its infancy
and yet to be fully explored, elucidated, developed or perfected.
President Obama's BRAIN Initiative, committed efforts, knowledge, skills, expertise and beautiful
team work heralding ongoing novel discovers and many break throughs so far have been most
spectacular, enlightening and exciting; it brings us closer to the day when incurable
neurodegenerative conditions and ailments will be a thing of the past.
The ideal situation if silenced sectors are reactivated dysfunctional or too young in terms of the year
they were silenced and thus currently cognitively incapable of carry out the functions of the present
day matured dominant cognitive sectors, would be to silence them permanently. A brain sector that
was once silenced when an entity was aged v, would still reflect the same v year old's maturity and
previous cognitive development, even if reactivated x or xx years later. This can be carried out in
some ways, fast fix methods of which there are quite a variety; but redirection of perfusions back to
the dominant cognitive sectors would attenuate part of the problem in the meanwhile, while the low
perfusions of the dysfunction reactivated sectors wane and naturally undergo permanent dormancy
with time thus solving the entire issue.
Apart from enough hydrations for smooth cerebral vascular perfusions, adequate sleep to facilitate
clearances and repairs when firings are low and neurons relaxed, brain metabolisms affected by
mitochondria health, energy productions and quantums of DHEA have to be maintained for optimal
long term utility and durable functions. Extremely low DHEA quantums have been discovered in
ailments such as major depressive disorders and schizophrenia, whereby detection of their sharp
declines within posterior media frontal cortex correlated with schizophrenia's negative symptom
occurrences.
Bacopa monnieri functions as an anxiolytic < Bhattacharya, et al, 1998 >, antioxidant along with
reducing cerebral lipid peroxidation < Tripathi, et al, 1996 > while enhancing vitamins A, C, E
quantums within the cerebral system, enhances glutathione reductase and glutathione peroxidase
leading to increases in dna synthesizing and repair, iron metabolisms facilitating and antioxidative
cellular tripeptide, glutathione quantums; heavy metal chelating, increases quantums of zinc and
selenium which are co factors of catalase and superoxide dismutase thus enhancing and
upregulating their antioxidative abilities and activities; antiinflammatory, antimicrobial, neurological
xviii

tonic, neurorejuvenating, cognitive enhancement, improvements for memory and attenuations of


their impairments.
Enhances acetylcholine < ACh > activities, improves long term potentiation and heightens
activations of cholinergic circuit pathways as it is a acetlycholinesterase inhibitor < Peth-Nui,et al,
2012 > while coupled with choline acetyltransferase activations which enhances ACh synthesis.
During Alzheimer's disease, when complex with amyloid peptides, acetylcholinesterase results in
high neurotoxicity and the formation of more fibrils, higher densities of neurofibrillary tangles and
plagues; inhibitions of their activities can halt severities as ailment progresses.
These functions are applicable in attenuating ailments such as Alzheimer's disease, provided
permanent neocortex lesions have yet to occur, as progressions herald neocortex cholinergic
innervations decline, circuitry start to wane leading to declining and the eventual complete loss of
semantic memories, affecting conscious cognitions, analytical skills, logic, socialization skills,
awareness and recognition of space, sensory perceptions, analysis of visual, auditory or tactile
inputs, visual-spatial abilities along with language. As verbal abilities of females are dependent upon
these abilities more so then males, coupled with lower gender based visual spatial abilities < Blough,
et al, 1987 > depending upon the dominant cognitive hemispheres, < left hemisphere females tend to
be more verbal as perfusions are strong in that cognitive dominant region, where left situated
Broca's and Wernicke's region is located > thus these verbal declines would emerge more often in
female Alzheimer's disease patients; learning dependent upon cholinergic activities are also impacted
and decreased.
When dopamine D i receptors are dysfunctional and their respective signaling pathways affected,
spatial learnings and memory decline occur. Neuroactive Bacoside A attenuate these dysfunctions
by upregulating D i receptor expressions thus restoring its natural balance < Thomas, et al, 2013 >.
Neural connections and communications are also restored and enhanced, as dendritic growths are
increased within hippocampal regions and basal amygdala < Vollala, et al, 2011 > thus aiding in
memory improvements and speed of early information processing.
Hindbrain serotonin transporter expressions are upregulated < Charles, et al, 2011 > enhancing
selective transports of v-hydroxytryptamine < v HT > into neurons with synapses at limbic and
forebrain regions, thus downregulating the occurrences of seizures and increasing resistance, v HT
quantums are also upregulated within regions of hippocampus, cerebral cortex and hypothalamus;
these effects also aid in attenuating v HT degenerations such as serotonergic cytoskeleton damages
and cellular loss mainly at the midbrain of Parkinson's disease and serotonergic neuronal
degenerations in Alzheimer's disease < Mssner, et al, 2000 > which often exhibit sharp dips in
serotonin, dopamine and norepinephrine, while serotonin declines were greatest in dementia with
lewy bodies when coupled with depression these declines mainly affected the prefrontal lobes, limbic
system, temporal lobes, hippocampus and occipital lobes. Loss of serotonergic pathways in late stage
alzheimer's disease affects right dorsolateral prefrontal cortex < Ouchi, et al, 2009 >, hindering
higher cognitive functions and emotions, these are often coupled with onsets of declines in serotonin
uptakes in depression. While serotonin bindings to 5HT 2 receptors along with releases of oxytocin
facilitate empathy, thus a lack thereof will post a certain degree of danger to others especially if
forced interactions in tight situations occur.
Glutamate quantums are also upregulated with increases of prefrontal vesicular glutamate
xix

transporter type ii densities thus attenuating schizophrenia < Piyabhan, et al, 2014 > glutamate
modulations and upregulations also lead to enhanced synthesis of platelet activating factor, thus
improving cerebral blood perfusions which improves memory formations, retrievals and cognitive
dysfunctions. Enhancements of cerebral blood perfusions also occur due to the vasodilating effects
and upregulations of nitric oxide functions, enhancing endothelia nitric oxide secretions while
preventing calcium fluctuations from occurring on both membraneous sides of the sarcoplasmic
reticulum. These effects aid in improving neuronal oxygenation, health, growth, synaptic
transmissions and cognitive functions.
In Alzheimer's disease along with onsets of psychosis, dopamine is decreased within the amygdala
region < Vermeiren, et al, 2015 > but heightened within locations of locus coeruleus and mesolimbic
regions, accompanied by symptoms of frequent severe headaches, syncopes and fainting occurrences
these reflect dysfunctions in blood quantums, flows and regional perfusion distributions, conditions
of which can be thus improved by enhanced blood regulations, upregulated cerebral flows and
evenly balancing the distributions of perfusions thus attenuating the intracranial pressures which
would have been imbalanced by these conditions. Likewise psychosis occurrences in dementia with
lewy bodies affect mainly the right hemispheres due to the high perfusion requirements.
Blood distribution imbalances are common in neurodegenerative ailments as neurotransmissions are
reduced in injured neurons which may eventually undergo atrophies or apoptotic events, as
transmissions diminishes, these are accompanied by reduction in perfusions as blood flows are
highest at regions with peak neural activities. Thus a negative cycle emerges : degenerations lead to
reductions in cellular perfusions at their specific locations; as these injuries occur at various cerebral
regions, blood perfusion redistributions inevitably occurs and eventual imbalances arise, these
would lead to further imbalances in neurotransmitters as their mobilities and locations within
vasculatures are also dependent upon capillary diameters, permeabilities, blood densities and
carriage.
Prevents hippocampus neuronal apoptosis thus enhancing storages of newly acquired data and
memories, preventing further degenerations, preserving long term memory storage, improving
anterograde memory formations and retrievals, attenuating retrograde amnesia, spatial navigations
and learnings. Upon Alzheimer's disease onsets, the hippocampus is often one of the first regions to
be affected, with the median eminence being one of the iv regions unprotected by the blood brain
barrier along with pineal gland, toxin detecting and subsequent nausea inducing postrema along
with posterior pituitary gland, thus leaving it vulnerable to neurotoxins such as heavy metals and
pathogens; however medication that in unable to transverse the blood brain barrier can be shunted
to the cerebral circuits through these vessel regions.
Damages to neurons within hippocampus affect key neurocircuits involved in memory and
cognition, leading to learning impairments, inabilities to concentrate, thought disruptions, inhibited
motor acquisitions, learnings and retentions; dips in memory consolidations, cognitive halts,
amnesia, disorientations, awareness and orientations of present time and space are void, inabilities to
form memories or recollections about events especially pertaining to time and space.
Contains antidepressant dammarane type triterpenoid saponins bacosides A < Gubbannavar, et al,
2013 > and B which stimulate cholinergic and GABAnergic pathways inducing calmness and
removing anxiety, along with increasing information retention and concentrative capabilities; upon
xx

stomach acid hydrolysis they result in formations of bacogenins A i, A ii, A iii, jujubogenin aglycone
units, pseudojujubogenin glycoside, pseudojujubogenin isomers : antidepressant saponins
bacopasides i which activates neuroprotective, enhanced protein synthesis, facilitates glucose
transport, neuronal growth, differential and survival, antiapoptotic protein kinase B pathways,
phosphokinase C and phosphoinositide iii kinase.
Bioactive saponins isolated include bacopasides ii; bacopasides iii, iv, v < Chakravarty, et al, 2003 >
and N ii, antidepressant bacopasaponin C and jujubogenins : bacopasaponin E, F, bacopasides iv, N
i, X; bacopa A iii, alkaloid brahmine, bacosine, bacosterols, betulinic acid, beta sitosterol glucoside,
cucurbitacin, nicotinine, plantainoside B, luteolin. luteolin, apigenin, quercertin, herpestine,
hersaponins, D mannitol, stigmasterol, stigmastanol, sitosterol, saponins A, B, C; phenylethanoid
glycosides monnierasides i, ii, iii < Chakravarty, et al, 2002 >; titerpenoid saponins and antioxidative
phenols and flavonoids.
Usage
Applicable to attenuations of neurodegenerative ailments such as epilepsy, dementia < all the various
types, onsets of which could be due to : lewy bodies, vascular, Creutzfeldt-Jakob disease, Pick's
disease, Parkinson's disease, Huntingtons chorea, motor neuronal disease, AIDS, alcoholism,
dementia dialytica or brain trauma from a physical impact >, Alzheimer's disease, Parkinson's
disease < Jansen, et al, 2014 >, schizophrenia as it aids in balancing neurotransmitters which might
restore the disrupted and truncated circuitries inherent in this disorder. Other effects include
decreasing of its accompanying psychopathologies < Sarkar, et al, 2012 > thus improving the overall
condition while reducing symptoms, cognitive dysfunctions, memory impairments, mild cognitive
impairments < Zanotta, et al, 2014 >, depression, anxiety, cerebral ischemia < Thi Le, et al, 2015 >,
neuroinflammations, neuroprotective from after effects of stroke, neuroprotective against
hypoglycemic damages, neuroprotective against neurotoxins, reperfusion injuries, cerebral injuries
that give rise to high quantums of free radical releases, reduces cerebral inflammations with mild
sedative properties.
Functions in decreasing lipid peroxidations thus protective in ailments such as diabetes,
neurodegenerations, myelin injuries, multiple sclerosis, encephalomyelitis, preserves integrity of
phospholipid cell membranes, metabolic syndrome, high cholesterol, peripheral vascular disease,
atherosclerosis, coronary heart disease, anemia, decreases inflammations within arteries, ascites,
edema; antimicrobial, leprosy, cancers, allergy reactions, vasodilating effect aids in
bronchoconstriction, enhances activities of vascular musculatures and thrombolytic action which
attenuates atherothrombotic ailments < Emran, et al, 2015 >.
Enhances vasodilating nitric oxide utilization, normalizes imbalances blood pressures, hypertension,
bradycardia, hypotension, blood disorders, protection and damage preventions from neurotoxins,
poisons and heavy metals along with enhancing detoxifications; attenuated excessive spasms,
irritable bowel syndrome; enlarges spleen, hyperbilirubinemia, hepatic dysfunctions, gastric
ulcerations, enhances thyroid functions through upregulations of T iv hormones, functions to
attenuate toxicity as a calcium antagonist and anticholinergic, decreases morphine toxicity, liver
dysfunctions, protects systemic organs from opiate toxicities, protects against stomach ulcers,
repairs membranous cells of internal linings and antimicrobial against Staphylococcus aureus <
Emran, et al, 2015 >
xxi

Contraindication
Safe for short term intake of about xii weeks. Seldom associated with any adverse side effects. No
genotoxicity that bring about events such as micronuclei formations, chromosomal aberrations or
exchanges of sister chromatids < Giri, et al, 1996 >. Non toxic when taken within standard dosage
limits.
Some side effects might occur in susceptible entities, especially when taken unaccompanied by
meals, these include dry mouth, fatigue, nausea, stomach cramps, bloating or increased bowel
movements < Morgan, et al, 2010 >.
Dosage
Standard dose in oral intakes is : 300 mg / day.
In extracts standardized to yield xx % bacosides A and B, when spread between divided doses, an
adult standard dosage is : 200 - 400 mg / day. While the kid's standard dosage is : 100 - 200 mg / day.
When take in the form of non standardized powder, dosage is : 5 - 10 g.
In the form of an infusion, dosage is : 8 - 16 ml.
When drank in syrup form, standard dose is : 30 ml / day.
In the form of a i : ii fluid extract, adult dosage is : 5 - 12 ml / day, while dosage for kids < aged
between vi to vii > is : 2.5 - 6 ml / per day.

xxii

References
Ajit Kumar Chakravarty, Tapas Sarkar, Takahisa Nakane, Nobuo Kawahara and Kazuo Masuda.
New Phenylethanoid Glycosides from Bacopa monniera. Chemical and Pharmaceutical Bulletin.Vol.
50 (2002) No. 12 P 1616-1618
Ajit Kumar Chakravarty, Saraswati Garai, Kazuo Masuda, Takahisa Nakane and Nobuo Kawahara.
Bacopasides IIIV: Three New Triterpenoid Glycosides from Bacopa monniera. Chemical and
Pharmaceutical Bulletin. Vol. 51 (2003) No. 2 P 215-217
Alam MM, Ahmad I, Naseem I. Inhibitory effect of quercetin in the formation of advance glycation
end products of human serum albumin: An in vitro and molecular interaction study. Int J Biol
Macromol. 2015 Aug;79:336-43. doi: 10.1016/j.ijbiomac.2015.05.004. Epub 2015 May 14.
Alfred Zoechling, Evelyne Reiter, Reinhard Eder, Silvia Wendelin, Falk Liebner, and Alois
Jungbauer. The Flavonoid Kaempferol Is Responsible for the Majority of Estrogenic Activity in
Red Wine Am. J. Enol. Vitic. June 2009 60:223-232
Anil Kumar, Samrita Dogra, and Atish Prakash. Neuroprotective Effects of Centella asiatica against
Intracerebroventricular Colchicine-Induced Cognitive Impairment and Oxidative Stress.
International Journal of Alzheimers Disease. Volume 2009 (2009), Article ID 972178, 8 pages
Anil Kumar, Atish Prakash, and Samrita Dogra. Centella asiatica Attenuates D-Galactose-Induced
Cognitive Impairment, Oxidative and Mitochondrial Dysfunction in Mice. International Journal of
Alzheimers Disease. Volume 2011 (2011), Article ID 347569, 9 pages
Anna K. Jger and Lasse Saaby. Flavonoids and the CNS. Molecules 2011, 16, 1471-1485;
doi:10.3390/molecules16021471
Anupama Rani and S. Prasad. A Special Extract of Bacopa monnieri (CDRI-08)-Restored Memory
in CoCl2-Hypoxia Mimetic Mice Is Associated with Upregulation of Fmr-1 Gene Expression in
Hippocampus. Evidence-Based Complementary and Alternative Medicine, Article ID 347978
Archana Kulshrestha, Urmila Jarouliya, GBKS Prasad, SJS Flora and Prakash S Bisen. Arsenicinduced abnormalities in glucose metabolism: Biochemical basis and potential therapeutic and
nutritional interventions. World J Transl Med. 2014 August 12; 3(2): 96-111.
doi:10.5528/wjtm.v3.i2.96.
Ashok Kumar Giri and Kaleem Ahmed Khan. Chromosome Aberrations, Sister Chromatid
Exchange and Micronuclei Formation Analysis in Mice after in vivo Exposure to Bacoside A and B.
Cytologia. Vol. 61 (1996) No. 1 P 99-103
Astani A, Reichling J, Schnitzler P. Melissa officinalis extract inhibits attachment of herpes simplex
xxiii

virus in vitro. Chemotherapy. 2012;58(1):70-7. doi: 10.1159/000335590. Epub 2012 Feb 23.
Awad R, Levac D, Cybulska P, Merali Z, Trudeau VL, Arnason JT. Effects of traditionally used
anxiolytic botanicals on enzymes of the -aminobutyric acid (GABA) system. Can J Physiol
Pharmacol. 2007 Sep;85(9):933-42.
B. S. Siddiquia, H. Aslama, S. T. Alia, S. Khana and S. Begum. Chemical constituents of Centella
asiatica. Journal of Asian Natural Products Research. Volume 9, Issue 4, 2007.
DOI:10.1080/10286020600782454
BK Dash, HM Faruquee, SK Biswas, MK Alam,SM Sisir and UK Prodhan. Antibacterial and
Antifungal Activities of Several Extracts of Centalla asiatica L. against Some Human Pathogenic
Microbes. Life Sciences and Medicine Research, Volume 2011: LSMR-35
Benson S, Downey LA, Stough C, Wetherell M, Zangara A and Scholey A. An acute, double-blind,
placebo-controlled cross-over study of 320 mg and 640 mg doses of Bacopa monnieri (CDRI 08) on
multitasking stress reactivity and mood. Phytother Res. 2014 Apr;28(4):551-9. doi:
10.1002/ptr.5029. Epub 2013 Jun 21.
Bhattacharya SK, Ghosal S. Anxiolytic activity of a standardized extract of Bacopa monniera: an
experimental study. Phytomedicine. 1998 Apr;5(2):77-82. doi: 10.1016/S0944-7113(98)80001-9.
Bont F, Dumas M, Chaudagne C, Meybeck A. Comparative activity of asiaticoside and
madecassoside on type I and III collagen synthesis by cultured human fibroblasts. Ann Pharm Fr.
1995;53(1):38-42. French
Burton EJ, Barber R, Mukaetova-Ladinska EB, Robson J, Perry RH, Jaros E, Kalaria RN,
O'Brien JT. Medial temporal lobe atrophy on MRI differentiates Alzheimer's disease from dementia
with Lewy bodies and vascular cognitive impairment: a prospective study with pathological
verification of diagnosis. Brain. 2009 Jan;132(Pt 1):195-203. doi: 10.1093/brain/awn298. Epub 2008
Nov 20.
C. Echvarri, P. Aalten, H. B. M. Uylings, H. I. L. Jacobs, P. J. Visser, E. H. B. M. Gronenschild,
F. R. J. Verhey, S. Burgmans. Atrophy in the parahippocampal gyrus as an early biomarker of
Alzheimers disease. Brain Structure and Function, Jan, 2011, Volume 215, Issue 3-4, Page 265
271
CK Mutayabarwa, JGM Sayi and M Dande. Hypoglycaemic Activity of Centella Asiatica (L) Urb.
East and Central African Journal of Pharmaceutical Sciences. Vol 6, No 2 (2003).
Charles PD, Ambigapathy G, Geraldine P, Akbarsha MA, Rajan KE. Bacopa monniera leaf extract
up-regulates tryptophan hydroxylase (TPH2) and serotonin transporter (SERT) expression:
xxiv

implications in memory formation. J Ethnopharmacol. 2011 Mar 8;134(1):55-61. doi:


10.1016/j.jep.2010.11.045.
Cheppail Ramachandran, Karl-Werner Quirin, Enrique Escalon and Steven Melnick. NT-28
Neuroprotective effects of Bacopa Monnieri and Rosmarinus Officinalis Supercritical CO2
Extracts. Neuro Oncol (2014) 16 (suppl 5): v164. doi: 10.1093/neuonc/nou265.26
Chuenjid Kongkeaw, Piyameth Dilokthornsakula, Phurit Thanarangsarita, Nanteetip
Limpeanchoba and C. Norman Scholfielda. Meta-analysis of randomized controlled trials on
cognitive effects of Bacopa monnieri extract. Journal of Ethnopharmacology. Volume 151, Issue 1,
10 January 2014, Pages 528535
David P. Smith, Danielle G. Smith, Cyril C. Curtain, John F. Boas, John R. Pilbrow, Giuseppe D.
Ciccotosto, Tong-Lay Lau, Deborah J. Tew, Keyla Perez, John D. Wade, Ashley I. Bush, Simon C.
Drew, Frances Separovic, Colin L. Masters, Roberto Cappai and Kevin J. Barnham. Coppermediated Amyloid- Toxicity Is Associated with an Intermolecular Histidine Bridge J. Biol. Chem.
2006 281: 15145-15154. First Published on April 4, 2006, doi:10.1074/jbc.M600417200
de Leeuw FE, Barkhof F, Scheltens P. White matter lesions and hippocampal atrophy in Alzheimer's
disease. Neurology. 2004 Jan 27;62(2):310-2.PMID: 14745078
De Strooper B. Loss-of-function presenilin mutations in Alzheimer disease. Talking Point on the
role of presenilin mutations in Alzheimer disease. EMBO Reports. 2007;8(2):141-146.
doi:10.1038/sj.embor.7400897.
Citron M, Oltersdorf T, Haass C, McConlogue L, Hung AY, Seubert P, Vigo-Pelfrey C, Lieberburg
I, Selkoe DJ. Mutation of the beta-amyloid precursor protein in familial Alzheimer's disease
increases beta-protein production. Nature. 1992 Dec 17;360(6405):672-4. PMID: 1465129
Emran TB, Rahman MA, Uddin MM, Rahman MM, Uddin MZ, Dash R, Layzu C. Effects of
organic extracts and their different fractions of five Bangladeshi plants on in vitro thrombolysis.
BMC Complement Altern Med. 2015 Apr 23;15:128. doi: 10.1186/s12906-015-0643-2.
Emran TB, Rahman MA, Uddin MM, Dash R, Hossen MF, Mohiuddin M, Alam MR. Molecular
docking and inhibition studies on the interactions of Bacopa monnieri's potent phytochemicals
against pathogenic Staphylococcus aureus. Daru. 2015 Apr 17;23:26. doi: 10.1186/s40199-015-01069.
Escande C, Nin V, Price NL, Capellini V, Gomes AP, Barbosa MT, O'Neil L, White TA, Sinclair
DA, Chini EN. Flavonoid apigenin is an inhibitor of the NAD+ ase CD38: implications for cellular
NAD+ metabolism, protein acetylation, and treatment of metabolic syndrome. Diabetes. 2013
Apr;62(4):1084-93. doi: 10.2337/db12-1139. Epub 2012 Nov 19.
xxv

G.V.R. Joseph, Sachin Chaturvedi and Deokule S.S. Standardisation and Quality Evaluation of
Centella asiatica Linn. Ancient Science of Life. Vol No XX(4) April 2001
Gray NE, Morr J, Kelley J, Maier CS, Stevens JF, Quinn JF, Soumyanath A. Caffeoylquinic
acids in Centella asiatica protect against amyloid- toxicity. J Alzheimers Dis. 2014;40(2):359-73.
doi: 10.3233/JAD-131913.
Gubbannavar JS, Chandola HM, Harisha CR, Khanpara K, Shukla VJ. A comparative
pharmacognostical and preliminary physico-chemical analysis of stem and leaf of Bacopa monnieri
(L.) Pennel and Bacopa floribunda (R.BR.) Wettst. Ayu. 2013 Jan;34(1):95-102. Doi:
10.4103/0974-8520.115441.
Hana Alkhalidy, William Moore, Yanling Zhang, Ryan McMillan, Aihua Wang, Mostafa Ali,
Kyung-Shin Suh, Wei Zhen, Zhiyong Cheng, Zhenquan Jia, Matthew Hulver and Dongmin Liu.
Small Molecule Kaempferol Promotes Insulin Sensitivity and Preserved Pancreatic -Cell Mass in
Middle-Aged Obese Diabetic Mice. Journal of Diabetes Research, vol. 2015, Article ID 532984, 14
pages, 2015. doi:10.1155/2015/532984
Hltt M, Hansson O, Andreasson U, Hertze J, Minthon L, Ngga K, et al. (2013) Evaluating
Amyloid- Oligomers in Cerebrospinal Fluid as a Biomarker for Alzheimers Disease. PLoS ONE
8(6): e66381. doi:10.1371/journal.pone.0066381
Hongyan Chen, Qing Miao, Miao Geng, Jing Liu, Yazhuo Hu, Lei Tian, Jingkun Pan and Yi Yang.
Anti-Tumor Effect of Rutin on Human Neuroblastoma Cell Lines through Inducing G2/M Cell
Cycle Arrest and Promoting Apoptosis. The Scientific World Journal, vol. 2013, Article ID 269165,
8 pages, 2013. doi:10.1155/2013/269165
Jansen RL, Brogan B, Whitworth AJ, Okello EJ. Effects of five Ayurvedic herbs on locomotor
behaviour in a Drosophila melanogaster Parkinson's disease model. Phytother Res. 2014
Dec;28(12):1789-95. doi: 10.1002/ptr.5199.
Jau-Shin Lou, Diana Dimitrova, Amala Soumyanath, Heather Belding, Ngoc Le, Nick Seifer and
Grace Arnold. Centella Asiatica Triterpene Extract Is Effective in Treating Diabetic Neuropathy
A Pilot Study (P03.192). doi:10.1212/WNL.78.1_MeetingAbstracts.P03.192Neurology April 24,
2012; 78(Meeting Abstracts 1): P03.192
Jos M. Barbosa-Filho; Francisco A. do Nascimento Jnior, Anna Cludia de Andrade Tomaz,
Petrnio F. de Athayde-Filho, Marcelo S. da Silva, Emdio V. Leito da Cunha, Maria de F.
Vanderlei de Souza, Lenia M. Batista and Margareth F.F. Melo Diniz. Natural products with
antileprotic activity. Rev. bras. farmacogn.vol.17.no.1.Joo Pessoa.Jan./Mar.2007

xxvi

Karin van Dijk, Wesley Jongbloed, Wilma van de Bergh, Philip Scheltens, Sandra Mulder, Piet
Eikelenboom, Marinus A. Blankenstein, Wiesje Van der Flier, and Rob Veerhuis. Clusterin: An
early biomarker for Alzheimer's disease? Alzheimer's & Dementia: The Journal of the Alzheimer's
Association , Volume 9 , Issue 4 , P198 - P199
Lee YS, Jin DQ, Kwon EJ, Park SH, Lee ES, Jeong TC, Nam DH, Huh K, Kim JA. Asiatic acid,
a triterpene, induces apoptosis through intracellular Ca2+ release and enhanced expression of p53 in
HepG2 human hepatoma cells. Cancer Lett. 2002 Dec 1;186(1):83-91.
Maksum Radji, Marita Kurniati and Ariyani Kiranasari. Comparative antimycobacterial activity of
some Indonesian medicinal plants against multi-drug resistant Mycobacterium tuberculosis. Journal
of Applied Pharmaceutical Science Vol. 5(01), pp. 019-022,January, 2015
DOI:10.7324/JAPS.2015.50104
Maria Isabel Azevedo, Anamaria Falco Pereira, Ricardo Braz Nogueira, Flvio Esmeraldo Rolim,
Gerly AC Brito, Deysi Viviana T Wong, Roberto CP Lima-Jnior, Ronaldo de Albuquerque
Ribeiro and Mariana Lima Vale. The antioxidant effects of the flavonoids rutin and quercetin inhibit
oxaliplatin-induced chronic painful peripheral neuropathy. Molecular Pain 2013, 9:53
doi:10.1186/1744-8069-9-53
Marjelo A. Mines, Eleonore Beurel, and Richard S. Jope. Regulation of Cell Survival Mechanisms
in Alzheimer's Disease by Glycogen Synthase Kinase-3. International Journal of Alzheimers
Disease. Volume 2011 (2011), Article ID 861072, 11 pages
Marsel Mesulam. The Cholinergic Lesion of Alzheimer's Disease: Pivotal Factor or Side Show?
Learn. Mem. 2004. 11: 43-49. doi: 10.1101/lm.69204
Matthew P. Pase, James Kean, Jerome Sarris, Chris Neale, Andrew B. Scholey and Con Stough.
The Cognitive-Enhancing Effects of Bacopa monnieri : A Systematic Review of Randomized,
Controlled Human Clinical Trials. The Journal of Alternative and Complementary Medicine.
Volume 18, Number 7, 2012, pp. 16. DOI: 10.1089/acm.2011.0367
Michael R. Bloomberg. New York City 2009 Drinking Water Supply and Quality Report. NYC
Environmental protection. Pages 1- 16.
Miyamae Y, Kurisu M, Han J, Isoda H and Shigemori H. Structure-activity relationship of
caffeoylquinic acids on the accelerating activity on ATP production. Chem Pharm Bull (Tokyo).
2011;59(4):502-7.
Miyamae Y, Kurisu M, Murakami K, Han J, Isoda H, Irie K and Shigemori H. Protective effects of
caffeoylquinic acids on the aggregation and neurotoxicity of the 42-residue amyloid -protein.
Bioorg Med Chem. 2012 Oct 1;20(19):5844-9. doi: 10.1016/j.bmc.2012.08.001. Epub 2012 Aug 12.
xxvii

Morgan A, Stevens J. Does Bacopa monnieri improve memory performance in older persons?
Results of a randomized, placebo-controlled, double-blind trial. J Altern Complement Med. 2010
Jul;16(7):753-9. doi: 10.1089/acm.2009.0342.
Mssner R, Schmitt A, Syagailo Y, Gerlach M, Riederer P, Lesch KP. The serotonin transporter in
Alzheimer's and Parkinson's disease. J Neural Transm Suppl. 2000;(60):345-50.
Mushtaq, N., Schmatz, R., Pereira, L. B., Ahmad, M., Stefanello, N., Vieira, J. M., Abdalla, F.,
Rodrigues, M. V., Baldissarelli, J., Pelinson, L. P., Dalenogare, D. P., Reichert, K. P., Dutra, E. M.,
Mulinacci, N., Innocenti, M., Bellumori, M., Morsch, V. M. and Schetinger, M. R. (2014),
Rosmarinic acid prevents lipid peroxidation and increase in acetylcholinesterase activity in brain of
streptozotocin-induced diabetic rats. Cell Biochem. Funct., 32:287293. doi:10.1002/cbf.3014
Nema NK, Maity N, Sarkar BK, Mukherjee PK. Matrix metalloproteinase, hyaluronidase and
elastase inhibitory potential of standardized extract of Centella asiatica. Pharm Biol. 2013
Sep;51(9):1182-7. doi: 10.3109/13880209.2013.782505.
Osakabe N, Takano H, Sanbongi C, Yasuda A, Yanagisawa R, Inoue K, Yoshikawa T. Antiinflammatory and anti-allergic effect of rosmarinic acid (RA); inhibition of seasonal allergic
rhinoconjunctivitis (SAR) and its mechanism. Biofactors. 2004;21(1-4):127-31.
P J Visser, F R J Verhey, P A M Hofman, P Scheltens, J Jolles. Medial temporal lobe atrophy
predicts Alzheimer's disease in patients with minor cognitive impairment. J Neurol Neurosurg
Psychiatry 2002;72:4 491-497 doi:10.1136/jnnp.72.4.491
P. Piyabhan and T. Wetchateng. EPA-0094 Cognitive enhancement effect of bacopa monnieri on
vesicular glutamate transporter 2, vglut2, in the prefrontal cortex, striatum and hippocampus of
schizophrenia rat model. European Psychiatry. Volume 29, Supplement 1, 2014, Pages 1.
Pandey SP, Singh HK, Prasad S. PLoS One. Alterations in Hippocampal Oxidative Stress,
Expression of AMPA Receptor GluR2 Subunit and Associated Spatial Memory Loss by Bacopa
monnieri Extract (CDRI-08) in Streptozotocin-Induced Diabetes Mellitus Type 2 Mice.
2015 Jul 10;10(7):e0131862. doi: 10.1371/journal.pone.0131862. eCollection 2015.
Papia Mondal and Surendra Kumar Trigun. Bacopa monnieri Extract (CDRI-08) Modulates the
NMDA Receptor Subunits and nNOS-Apoptosis Axis in Cerebellum of Hepatic Encephalopathy
Rats. Evidence-Based Complementary and Alternative Medicine, Article ID 535013
Pathak AK, Bhutani M, Nair AS, Ahn KS, Chakraborty A, Kadara H, Guha S, Sethi G and
Aggarwal BB. Ursolic acid inhibits STAT3 activation pathway leading to suppression of
proliferation and chemosensitization of human multiple myeloma cells. Mol Cancer Res. 2007
Sep;5(9):943-55.
xxviii

Patil SP, Maki S, Khedkar SA, Rigby AC, Chan C. Withanolide A and Asiatic Acid Modulate
Multiple Targets Associated with Amyloid- Precursor Protein Processing and Amyloid- Protein
Clearance. Journal of natural products. 2010;73(7):1196-1202. doi:10.1021/np900633j.
Perrini S, Laviola L, Natalicchio A, Giorgino F. Associated hormonal declines in aging: DHEAS. J
Endocrinol Invest. 2005;28(3 Suppl):85-93.
Phulara SC, Shukla V, Tiwari S, Pandey R. Bacopa monnieri promotes longevity in Caenorhabditis
elegans under stress conditions. Pharmacogn Mag. 2015 Apr-Jun;11(42):410-6. Doi: 10.4103/09731296.153097.
Piyawan Bunpo, Keiko Kataoka, Hideki Arimochi, Haruyuki Nakayama, Tomomi Kuwahara,
Usanee Vinitketkumnuen, Yoshinari Ohnishi. Inhibitory effects of asiatic acid and CPT-11 on
growth of HT-29 cells. The Journal of Medical Investigation. Vol. 52 (2005) No. 1,2 P 65-73
Podlesniy, P., Figueiro-Silva, J., Llado, A., Antonell, A., Sanchez-Valle, R., Alcolea, D., Lleo, A.,
Molinuevo, J. L., Serra, N. and Trullas, R. (2013), Low cerebrospinal fluid concentration of
mitochondrial DNA in preclinical Alzheimer disease. Ann Neurol., 74:655668.
doi:10.1002/ana.23955
Patricia M Blough and L Kady Slavin. Reaction time assessments of gender differences in visualspatial performance. Perception & Psychophysics. 1987, 41(3),276-281
Prakash A, Kumar A. Mitoprotective effect of Centella asiatica against aluminum-induced
neurotoxicity in rats: possible relevance to its anti-oxidant and anti-apoptosis mechanism. Neurol
Sci. 2013 Aug;34(8):1403-9. doi: 10.1007/s10072-012-1252-1. Epub 2012 Dec 8. PMID: 23224641
Punturee K, Wild CP, Kasinrerk W, Vinitketkumnuen U. Immunomodulatory activities of Centella
asiatica and Rhinacanthus nasutus extracts. Asian Pac J Cancer Prev. 2005 Jul-Sep;6(3):396-400.
R.K Tiwari, S.Chanda, M. Deepak, B. Murli and A. Agarwal. HPLC method validation for
simultaneous estimation of madecassoside, asiaticoside and asiatic acid in Centella asiatica. J. Chem.
Pharm. Res., 2010, 2(3):223-229
Rakesh Rai, Hemant K. Singh, and S. Prasad. A Special Extract of Bacopa monnieri (CDRI-08)
Restores Learning and Memory by Upregulating Expression of the NMDA Receptor Subunit
GluN2B in the Brain of Scopolamine-Induced Amnesic Mice. Evidence-Based Complementary and
Alternative Medicine, Article ID 254303.

xxix

Rauf K, Subhan F, Sewell RD. A Bacoside containing Bacopa monnieri extract reduces both
morphine hyperactivity plus the elevated striatal dopamine and serotonin turnover. Phytother Res.
2012 May;26(5):758-63. doi: 10.1002/ptr.3631. Epub 2011 Nov 22.
Roodenrys S, Booth D, Bulzomi S, Phipps A, Micallef C, Smoker J. Neuropsychopharmacology.
Chronic effects of Brahmi (Bacopa monnieri) on human memory. 2002 Aug;27(2):279-81.
Roshni Baby Thomas, Shilpa Joy, M. S. Ajayan and C. S. Paulose. Neuroprotective Potential of
Bacopa monnieri and Bacoside A Against Dopamine Receptor Dysfunction in the Cerebral Cortex
of Neonatal Hypoglycaemic Rats Cellular and Molecular Neurobiology. November 2013, Volume
33, Issue 8, pp 1065-1074
Roth GS, Lane MA, Ingram DK, Mattison JA, Elahi D, Tobin JD, Muller D, Metter EJ.
Biomarkers of caloric restriction may predict longevity in humans. Science. 2002 Aug
2;297(5582):811.
Sabuncu MR, Desikan RS, Sepulcre J, Yeo BT, Liu H, Schmansky NJ, Reuter M, Weiner MW,
Buckner RL, Sperling RA, Fischl B; Alzheimer's Disease Neuroimaging Initiative. Arch Neurol.
2011 Aug;68(8):1040-8. doi: 10.1001/archneurol.2011.167.
Sarkar S, Mishra BR, Praharaj SK, Nizamie SH. Add-on effect of Brahmi in the management of
schizophrenia. J Ayurveda Integr Med. 2012 Oct;3(4):223-5. doi: 10.4103/0975-9476.104448.
Scahill RI, Schott JM, Stevens JM, Rossor MN, Fox NC. Mapping the evolution of regional
atrophy in Alzheimer's disease: unbiased analysis of fluid-registered serial MRI. Proc Natl Acad Sci
U S A. 2002 Apr 2;99(7):4703-7. PMID: 11930016
Scheckel KA, Degner SC, Romagnolo DF. Rosmarinic Acid Antagonizes Activator Protein-1
Dependent Activation of Cyclooxygenase-2 Expression in Human Cancer and Nonmalignant Cell
Lines. The Journal of Nutrition. 2008;138(11):2098-2105. doi:10.3945/jn.108.090431.
Schwartz AG, Pashko LL. Dehydroepiandrosterone, glucose-6-phosphate dehydrogenase, and
longevity. Ageing Res Rev. 2004 Apr;3(2):171-87.
Shahdat Hossain, Michio Hashimoto, Masanori Katakura, Abdullah Al Mamun and Osamu Shido.
Medicinal value of asiaticoside for Alzheimers disease as assessed using single-molecule-detection
fluorescence correlation spectroscopy, laser-scanning microscopy, transmission electron microscopy,
and in silico docking. BMC Complementary and Alternative Medicine 2015, 15:118.
doi:10.1186/s12906-015-0620-9
xxx

Shen W, Qi R, Zhang J, Wang Z, Wang H, Hu C, Zhao Y, Bie M, Wang Y, Fu Y, Chen M, Lu D.


Chlorogenic acid inhibits LPS-induced microglial activation and improves survival of dopaminergic
neurons. Brain Res Bull. 2012 Aug 1;88(5):487-94. doi: 10.1016/j.brainresbull.2012.04.010. Epub
2012 May 2.
Soumyanath A, Zhong YP, Gold SA, Yu X, Koop DR, Bourdette D, Gold BG. Centella asiatica
accelerates nerve regeneration upon oral administration and contains multiple active fractions
increasing neurite elongation in-vitro. J Pharm Pharmacol. 2005 Sep;57(9):1221-9.PMID: 161052
Sterling C. Johnson, Taylor W. Schmitz, Mehul A. Trivedi, Michele L. Ries, Britta M. Torgerson,
Cynthia M. Carlsson, Sanjay Asthana, Bruce P. Hermann and Mark A. Sager. The Influence of
Alzheimer Disease Family History and Apolipoprotein E 4 on Mesial Temporal Lobe Activation.
The Journal of Neuroscience. N26(22): 6069-6076; doi: 10.1523/JNEUROSCI.0959-06.2006
Steven J Collins, Carolin Tumpach, Qiao-Xin Li, Victoria Lewis, Timothy M Ryan, Blaine Roberts,
Simon C Drew, Victoria A Lawson and Cathryn L Haigh. The prion protein regulates beta-amyloidmediated self-renewal of neural stem cells in vitro. Stem Cell Research & Therapy(2015) 6:60 DOI
10.1186/s13287-015-0067-4
Struble RG, Polinsky RJ, Hedreen JC, Nee LE, Frommelt P, Feldman RG, Price DL.
Hippocampal lesions in dominantly inherited Alzheimer's disease.J Neuropathol Exp Neurol. 1991
Jan;50(1):82-94. PMID: 1985156
Swarup V, Ghosh J, Ghosh S, Saxena A, Basu A. Antiviral and Anti-Inflammatory Effects of
Rosmarinic Acid in an Experimental Murine Model of Japanese Encephalitis. Antimicrobial Agents
and Chemotherapy. 2007;51(9):3367-3370. doi:10.1128/AAC.00041-07.
Tamara Simpson, Matthew Pase, and Con Stough. Bacopa monnieri as an Antioxidant Therapy to
Reduce Oxidative Stress in the Aging Brain. Evidence-Based Complementary and Alternative
Medicine, Article ID 615384
Tang XL, Yang XY, Jung HJ, Kim SY, Jung SY, Choi DY, Park WC, Park H. Asiatic acid induces
colon cancer cell growth inhibition and apoptosis through mitochondrial death cascade. Biol Pharm
Bull. 2009 Aug;32(8):1399-405.
Tatimah Peth-Nui, Jintanaporn Wattanathorn, Supaporn Muchimapura, Terdthai Tong-Un,
Nawanant Piyavhatkul, Poonsri Rangseekajee, Kornkanok Ingkaninan and Sakchai Vittayaareekul. Effects of 12-Week Bacopa monnieri Consumption on Attention, Cognitive Processing,
Working Memory, and Functions of Both Cholinergic and Monoaminergic Systems in Healthy
Elderly Volunteers. Evidence-Based Complementary and Alternative Medicine, vol. 2012, Article
ID 606424, 10 pages, 2012. doi:10.1155/2012/606424
xxxi

Thangavel Arumugam, Muniappan Ayyanar, Yesudason Justin Koil Pillai and Thangavel Sekar.
Phytochemical screening and antibacterial activity of leaf and callus extracts of Centella asiatica.
Bangladesh Journal of Pharmacology. Vol 6, No 1 (2011)
Thomas RB, Joy S, Ajayan MS, Paulose CS. Neuroprotective potential of Bacopa monnieri and
Bacoside A against dopamine receptor dysfunction in the cerebral cortex of neonatal hypoglycaemic
rats. Cell Mol Neurobiol. 2013 Nov;33(8):1065-74. doi: 10.1007/s10571-013-9973-0. Epub 2013
Aug 22.
Tripathi YB, Chaurasia S, Tripathi E, Upadhyay A, Dubey GP. Bacopa monniera Linn. as an
antioxidant: mechanism of action. Indian J Exp Biol. 1996 Jun;34(6):523-6.
Van Damme P, Braeken D, Callewaert G, Robberecht W, Van Den Bosch L. GluR2 deficiency
accelerates motor neuron degeneration in a mouse model of amyotrophic lateral sclerosis. J
Neuropathol Exp Neurol. 2005 Jul;64(7):605-12.
Venkata Ramana Vollala, Subramanya Upadhya, and Satheesha Nayak. Enhancement of
Basolateral Amygdaloid Neuronal Dendritic Arborization Following Bacopa Monniera Extract
Treatment in Adult Rats. Clinics 66.4 (2011): 663671.doi:10.1590/S1807-59322011000400023
W.J.P. Henneman, J. D. Sluimer, J. Barnes, W. M. van der Flier, I. C. Sluimer, N. C. Fox, P.
Scheltens, H. Vrenken and F. Barkhof. Hippocampal atrophy rates in Alzheimer disease. Added
value over whole brain volume measures. Neurology March 17, 2009 vol. 72 no. 11 999-1007.
doi:10.1212/01.wnl.0000344568.09360.31
Wagner S. da-Silva, John W. Harney, Brian W. Kim, Jing Li, Suzy D.C. Bianco, Alessandra
Crescenzi, Marcelo A. Christoffolete, Stephen A. Huang, and Antonio C. Bianco. The Small
Polyphenolic Molecule Kaempferol Increases Cellular Energy Expenditure and Thyroid Hormone
Activation. Diabetes. March 2007. 56:3 767-776; doi:10.2337/db06-1488
Wanakhachornkrai O, Pongrakhananon V, Chunhacha P, Wanasuntronwong A, Vattanajun A,
Tantisira B, Chanvorachote P, Tantisira MH. Neuritogenic effect of standardized extract of Centella
asiatica ECa233 on human neuroblastoma cells. BMC Complementary and Alternative Medicine.
2013;13:204. doi:10.1186/1472-6882-13-204.
Wildsmith KR, Holley M, Savage JC, Skerrett R, Landreth GE. Evidence for impaired amyloid
clearance in Alzheimers disease. Alzheimers Research & Therapy.
2013;5(4):33.doi:10.1186/alzrt187.
Wu F, Bian D, Xia Y, et al. Identification of Major Active Ingredients Responsible for Burn Wound
xxxii

Healing of Centella asiatica Herbs. Evidence-based Complementary and Alternative Medicine:


eCAM. 2012;2012:848093. doi:10.1155/2012/848093.
Xoan Thi Le, Hang Thi Nguyet Phama, Tai Van Nguyenb, Khoi Minh Nguyenb, Ken Tanakac,
Hironori Fujiwaraa and Kinzo Matsumoto. Protective effects of Bacopa monnieri on ischemiainduced cognitive deficits in mice: The possible contribution of bacopaside I and underlying
mechanism. Journal of Ethnopharmacology. Volume 164, 22 April 2015, Pages 3745
Yannick Vermeiren, Debby Van Dam, Tony Aerts, Sebastiaan Engelborghs, Jean-Jacques Martin
and Peter P De Deyn. The monoaminergic footprint of depression and psychosis in dementia with
Lewy bodies compared to Alzheimers disease. Alzheimer's Research & Therapy 2015, 7:7
doi:10.1186/s13195-014-0090-1
Yasuomi Ouchi, Etsuji Yoshikawa, Masami Futatsubashi, Shunsuke Yagi, Takatoshi Ueki and
Kazuhiko Nakamura. Altered brain serotonin transporter and associated glucose metabolism in
Alzheimer disease. J Nucl Med. 2009 Aug;50(8):1260-6. doi: 10.2967/jnumed.109.063008.
Yesil-Celiktas O, Sevimli C, Bedir E, Vardar-Sukan F. Yesil-Celiktas O, Sevimli C, Bedir E and
Vardar-Sukan F. Inhibitory effects of rosemary extracts, carnosic acid and rosmarinic acid on the
growth of various human cancer cell lines. Plant Foods Hum Nutr. 2010 Jun;65(2):158-63. doi:
10.1007/s11130-010-0166-4.
Yichun Xu, Zijing Jiang, Guang Ji and Jianwen Liu. Inhibition of Bone Metastasis from Breast
Carcinoma by Rosmarinic Acid. Planta Med 2010; 76(10):956-962. DOI: 10.1055/s-0029-1240893
Youl, E., Bardy, G., Magous, R., Cros, G., Sejalon, F., Virsolvy, A., S Richard, JF Quignard, R
Gross, P Petit, D Bataille and Oiry, C. (2010). Quercetin potentiates insulin secretion and protects
INS-1 pancreatic -cells against oxidative damage via the ERK1/2 pathway. British Journal of
Pharmacology, 161(4), 799814. doi:10.1111/j.1476-5381.2010.00910.x
Zanotta D, Puricelli S, Bonoldi G. Cognitive effects of a dietary supplement made from extract of
Bacopa monnieri, astaxanthin, phosphatidylserine, and vitamin E in subjects with mild cognitive
impairment: a noncomparative, exploratory clinical study. Neuropsychiatr Dis Treat. 2014 Feb
3;10:225-30. doi: 10.2147/NDT.S51092. eCollection 2014.

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