NAME: Maria Hashim

CLASS: Pharmacy 5th PROFF (9TH semester)

SUBJECT: Medicinal Chemistry Theory
Assignment: Papaver nudicaule L. & Swertia petiolate d.don
PAPAVER NUDICAULE L.

SCIENTIFIC CLASSIFICATION:
KINGDOM: Plantae
CLADE: Tracheophytes
CLADE: Angiosperms
CLADE: Eudicots
ORDER: Ranunculales
FAMILY: Papaveraceae
GENUS: Papaver
SPECIES: P.nudicaule
BINOMIAL NAME: Papaver nudicaule L.

BOTANICAL DESCRIPTION:
COMMON NAME: Iceland poppy, Arctic poppy
NATIVE TO: Subpolar regions of North America & Asia, & the mountains of Central Asia as well
as temperate China
USDA Hardiness: 4-10
HABITATS: Perennial plants prefer light, well-drained soil & full sun. It can live 2 to 3 seasons in
cool summer, well-drained soil flowering from early spring to fall.
HAZARDS: Toxic in mammals but toxicity is low
CULTIVARS: Come in shades of orange, yellow, salmon, pink, rose, cream, white & bicolored
varieties. Of this white is dominant one.
PHYSICAL CHARACTERISTICS: large, papery, bowl-shaped, lightly fragrant flowers supported by
curved stems, one foot, & feathery blue-green foliage of 1 to 6 inches.
FIRST DESCRIBED: In 1759

USES:
The plants belonging to this genus are mostly used for ornamental purposes. Red & beige dyes
are obtained from flowers while brown & yellow dyes obtained from flower pods. Its leaves can
be cooked & agreeable to taste as they are good source of Vitamin C (although caution is
advised for toxicity). Its seeds also can be eaten raw or cooked & are agreeable to taste.

PHYTOCHEMISTRY:
Almost all the plant parts contain abundance of alkaloids (mostly toxic) in them. In particular, it
contains isoquinoline alkaloid (especially benzophenanthidine alkaloid) & chelidonine. It
contains a newly known promorphinane alkaloid (−)-8,14-dihydroflavinantine isolated from the
aerial parts of Papaver nudicaule L. Six other known isoquinoline alkaloids (+)-amuronine,
pseudoprotopine, allocryptopine, (−)-dihydroamuronine, (−)-amurensinine N-oxide A and (−)-
amurensinine N-oxide B also present. Nudicaulins, flavonoid-derived indole alkaloids, along
with pelargonidin, kaempferol (major secondary metabolite in capsule), and gossypetin (in
basal spots of cultivars) glycosides are responsible for white, red, orange, and yellow color in
petals of different Papaver nudicaule cultivars.

PHARMACOLOGICAL ACTIVITY:
 ANTI-INFLAMMATORY:
In a study published in April 2019 by Oh, JH., Yun, M., Park, D. et al. investigated Papaver
nudicaule extracts for anti-inflammatory activity & its action mechanism on RAW264.7
macrophage cells. Firstly all 5 cultivars (NW: white, NO: orange, NY: yellow, NS: scarlet, NP:
pink) of Papaver nudicaule were tested for its cytotoxicity on RAW264.7 cells. Then all 5 were
examined for anti-inflammatory effects by evaluating NO (nitric oxide) production in RAW264.7
cells when treated with LPS (lipopolysaccharide-induced inflammation) in absence/presence of
each extract. And it was noticed that only NW90 (Papaver nudicaule extract with white flower)
showed most effective result in decreasing LPS-induced NO production. This NW90 further
went through experiments. When examined levels of NOS2 & COX2 (which are key enzymes in
regulation of PGE2 & NO) in RAW264.7 cells (for understanding underlying molecular
mechanism), NW90 effectively reduced PGE2 (prostaglandin E2) & NO by decreasing expression
of NOS2 (nitric oxide synthase 2) & COX2. NW90 also showed anti-inflammatory effects by
decreasing production & secretion of LPS-induced inflammatory cytokines (IL-1β & IL-6). NW90
reduced LPS-induced phosphorylation levels of IκBα, p65 and STAT3 (signal transducer and
activator of transcription 3), indicating NW90-mediated inactivation of transcription factors i.e.
NF-κB (nuclear factor-kappa-light-chain-enhancer of activated B) and STAT3 signaling pathways
and showing that it is potent inhibitor of these transcription factors. Hence, these results
suggest that Papaver nudicaule extracts have the potency to be developed into an anti-
inflammatory agent. They can help in inflammation to a great extent as transcription factor NF-
κB majorly regulates expression of inflammation-related genes due to induction via
inflammatory stimuli such as LPS & is associated with chronic inflammatory diseases like atopic
dermatitis, IBD (inflammatory bowel disease), and rheumatoid arthritis. Therefore, anti-
inflammatory activity of Papaver nudicaule through NF-κB regulation can be effectively applied
to chronic inflammatory diseases. STAT3 is another important transcription factor which
collaborates with NF-κB to control inflammation. There dual inhibition is an attractive
therapeutic strategy for treating inflammatory diseases.
 BIA (BIOSYNTHESIS OF ISOQUINOLONE ALKALOID):
Isoquinolone alkaloid is the most important metabolite obtained from plants as it contributes to a wide
range of expensive drugs responsible to wellbeing of humans like morphine, codeine, sanguinarine,
noscapine & berberine. As Papaver species are well known to contain alkaloids in abundance, a study in
Int J Mol Sci. 2018 generated a heat map of secondary metabolite biosynthesis transcripts. It showed
that Papaver nudicaule had higher quantity of alkaloids in metabolite quantitative analysis, as compared
to Papaver rhoeas spp. And alkaloids from morphine to tetrahydropapaverine were highly accumulated
in 90 days plant.

 CHELIDONINE:
An article by Zhongguo Zhong Yao Za Zhi. 1997 Isolated minor alkaloids from capsule of Papaver
nudicaule based on physicochemical methods & spectroscopic analysis which were identified as
chelidonine & 5-hydroxy-2-hydroxymethylpyridine. Chelidonine is an isolate of Papaveraceae family
having acetylcholinesterase (ACHE) and butyrylcholinesterase (a nonspecific cholinesterase) inhibitory
activity. ACHE inhibitors work by inhibiting cholinesterase enzyme from breaking acetylcholine
neurotransmitter, & hence increases both its level and duration of neurotransmitter action. These
inhibitors are used in treatment & diagnosis of various diseases like myasthenia gravis, post-operative
ileus, AD, glaucoma, bladder distention, also as antidote to anticholinergic overdose. In recent times,
chelidonine has been known as important anticancer drug.

SWERTIA PETIOLATA D. DON

SCIENTIFIC & BOTANICAL DESCRIPTION:

KINGDOM: Plantae
CLADE: Tracheophytes
CLADE: Angiosperms
FAMILY: Gentianaceae
TRIBE: Gentianeae
SUB-TRIBE: Swertiinae
GENUS: Swertia
LOCAL NAME: Momiran
URDU NAME: Charita
FOUND: In Afghanistan, Kashmir, China, W. Nepal, Pakistan, Himalaya, S.E. Tibet.
PHYSICAL CHARACTERISTICS: Perennial herb grows upto 1m tall. Its basal leaves are obovate-
oblong to elliptic-spthulate, upto 20 cm long. Cauline leaves opposite, connate at base & upto
10 cm long & 2 cm broad.
FLOWER CHARACTERISTICS: Flowers are greenish-yellow or lurid grey, 5-merous; calyx lobes
linear, longer than corolla in bud; corolla lobes elliptic oblong to nearly lancelate, each with two
green glands at base of each lobe, fringed by white hairs; filaments free; capsule 8-10 mm long.
USDA Hardiness zone: 7
FLOWERING TIME: Its flowers from July to September.

USES:
This plant has been used in Tibetan medicine. Its taste is bitter & extremely cooling potency. It
is used for its anti-inflammatory activity, as febrifuge & liver tonic in treatment of liver
inflammation, hypertension, scleritis, & stomach inflammation. Its herbs are used in Kashmir,
for toothaches, rheumatic diseases & to heal wounds caused from infections by Bakerwal &
Gujjar community, locally called as ‘momram’.

PHYTOCHEMISTRY:
The main constituent found in Swertia genus is xanthonoids which are responsible for most of
the medicinal activities of plant. Besides this, iridoid & seco-iridoid glycosides (21 constituents
are known), flavonoids (some eleven isolated flavonoids isolated) & terpenoids (nearly 30
terpenoids isolated), alkaloids (few known) & some lignans, lactones etc. are also metabolites
found producing biological action.
PHARMACOLOGICAL ACTION:
 HEPATOPROTECTIVE & ANTIOXIDANT ACTION:
In a study done by Bader et al. in 2017 on thioacetamide induced liver damage in rats, which
screened Swertia petiolata for its hepatoprotective activity. Firstly, two extracts are prepared
from S.petiolata which are aqueous extracts & hydroalcoholic extracts. To study effect of these
extracts on liver, thioacetamide is administered intraperitoneally. Thioacetamide significantly
increases liver enzymes like ALT/AST (serum aminotransferases), ALP (alkaline phosphatase), &
GGT (gamma glutamyl transpeptidase) which act as biochemical markers of hepatic injury. By
Swertia extracts, these levels are decreased. Which indicates towards protective nature of
extracts. Also, hepatic lipid peroxidation was measured with the help of MDA levels (hepatic
malondialdehyde) in tissue. MDA (index of oxidative stress) was increased after induction of
liver necrosis but it decreased in extract treated rats. A marked reduction was seen in levels of
glutathione in necrotic group while extracts helped increase the glutathione levels i.e.
glutathione reductase, glutathione catalase & peroxidase. Hence, this denotes towards Swerta
extract antioxidant role. In test involving TAA produced necrosis which provoked xanthine
oxidase & generating ROS, showing its part in liver injury, was decreased significantly in group
pre-treated with extract. All these findings suggest that Swertia extracts can protect from liver
necrosis by reducing production of ROS and this is because of extract ability to strengthen
antioxidant status of tissues.
Glycosides like sweroside & gentiopicroside present in S.petiolata are both used as anti-
hepatitis drugs because of hepatoprotective activity.

 BITTERS:
The plants in this specie is known to have bitter taste because of iridoid compound present
especially amarogentin. Bitters have been used in traditional medicine for loss of appetite &
fever & are still involved in many ‘tonic’ formulations.

 CNS STIMULATION, ANTI-INFLAMMATORY, ANALGESIC, HYPOGLYCEMIC ACTION:

Xanthones present (especially mangiferin) stimulates CNS & action is cause of its MAO
inhibitory activity (Bhattacharya et al). A xanthone called norathyriol produces anti-
inflammatory & analgesic action as it is a cyclooxygenase & lipoxygenase pathway blocker. It
also helps suppress inflammation related edema because of suppression of mast cell
degranulation & hence reduction in chemical mediator release. Other xanthones like bellidifolin
& swerchirin have got strong hypoglycemic action.

 SEDATIVE:
The flavan glycosides have been reported (Ghosal et al) to contain sedative effects.

 ANTIPSYCHOTIC ACTIVITY:
This activity has been reported (Bhattacharya et al) for gentianine which antagonizes
amphetamine & decreases aggressiveness.