Terpenes A. Introduction What are terpenes? General structural characteristics? Storage and synthesis?

- largest class of secondary metabolites. - linear or cyclic; formed from combining 5 carbon units and prenyltransferases. - mevalonic acid pathway: acetyl CoA > mevalonic acid > isopentenyl diphosphate (IPP) & dimethylallyldiphosphate (DMAPP). - isolated from conifer turpentine but distributed in all plan parts; chemical modification produces terpenoids. B. Terpene function What is their function in plants? - protection from predators (neem & azadirachtin), attraction of pollinators (fragrance), allelopathy (black walnuts & juglone) - cell growth modulation, light harvesting, photoprotection, control of membrane fluidity. What are their medicinal and economic / commercial uses? - medicinal: antiseptics, expectorants, mild anesthetic, sedative, anti-spasmodic, cognitive enhancer, antidepressants. - commercial: volatile oil of terpenes used in perfumes, cosmetics, spices, flavouring, aromatherapy. C. Terpene Structure What is the role of isoprene in terpene synthesis? - isoprene is a 5 C molecule produced during terpene breakdown, not used to produce them; IPP and DMAPP synthesize terpenes. What are the different types of terpenes (their names) and what are the corresponding number of carbons for each? o Terpenes are cyclic and acyclic (linear) within each class - hemiterpene (C5), monoterpene (C10), sesquiterpene (C15), diterpene (C20), triterpene (C30), tetraterpene (C40). - larger terpenes formed from C10-C20 parent skeletons and terpene synthases. D. Monoterpenes - volatile, aromatic, colorless, oily, hydrophobic compounds; constituents of volatile oils. Linear: - geraniol & geraniums (characteristic smell), - citronellal & citronella grass (lemon oil aroma and insecticide) Cyclical: - limonene & orange peels (paint solids, fragrance, cleaning solvents, anticancer) - camphor & camphor tree (allelopathic agent, rosemary oil) - eucalyptol (cold medications, reduces pain and inflammation, rosemary oil) - thymol & Thymus vulgaris (stimulant, antiseptic, expectorant, antifungal, antibacterial, lotions and ointments) - menthol & Mentha piperita, M. spicata (stimulant, antiseptic, treat indigestion, rheumatism, flavoring, cold medication, pain relief) E. Sesquiterpenes - fulfill ecological roles in allelopathy, pheromone secretion, and defense; constituents of volatile oils. Linear: - farnesol & rose (used perfumes) Cyclical: - bisabolene & myrrh (sunscreen for myrhh) - abscisic acid (non-volatile, inhibitory developmental hormone, tolerance to dessication) *deficiency yields wilted phenotype*

produce lycopene at the expense of other terpenes like GA. absorbing UV to reduce DNA damage and photooxidation of chlorophylls. detergent causes lysis via disruption of cell membranes.not volatile oils. ginseng. antioxidant.stevioside & Stevia rebaudiana (sweetener. Polyterpene thousands of 5 carbon units combine to make rubber . . carotenes are produced. licorice. I. long structure accounts for high MP and viscosity. cycloaudenol & opium. .salvinorin A & Salvia divinorum (hallucinogen) . plants show dwarf phenotype. . compounds that become soapy when added to water. soaps.squalene is linear precursor found in resin. Diterpenes: . Triterpenes . treat diabetes. eg.phytoene synthase (GGDP > enzyme > phytoene > lycopene) transformation with Agrobacterium . congestive heart failure) H.contains digitalis. cardiac glycosides: that are steroid forms of saponins § increase force of contraction. Tetraterpene . converted to vitamin A in the liver Biosynthesis of carotenoids . § Digitalis purpurea (foxglove) produces digitalis . single leaf can cause paralysis and heart failure. resins Cyclical: . digitonin described by William Withering in order to treat dropsy (edema. digoxin.F.golden rice from rice transgenics for PSY and CRT1 genes plants store lycopene in grain. slows heart rate. infections) G.cyclic versions are based on three cyclohexane rings and one pentane ring (steroid structure).glycoside: sugar units are added to cyclic triterpene molecules plant glycosides: can be saponins. § non-sugar portion of saponin is called aglycone or sapognenin § glycosylated triterpene is steroid glycoside or saponin § saponins found in detergents. azadirachtin & neem tree . both ends F-carotene. .vitamins (derivatives of diterpenes) . § inhibits Na+/K+ ATPases of heart muscle membranes. skin abrasions. aim to combat vitamin A deficiency. anti-cancer. cyclization at one end makes K-carotene.carotenoids are pigments. narrow therapeutic index.derived from lycopene.gibberellins (initiating developmental hormone) .taxol & Taxus brevifolia (anticancer drug) . high BP.attract pollinators.

plant compounds act as CNS depressants. NSAIDs and estrogen may work too. Generally describe the symptoms. Sedatives.chamomile & Matricaria recutita. 3. sesquiterpenes (valerenol). Chamaemelum nobile: o flowering tops. now for insomnia and anxiety o inhibits uptake and breakdown. Antidepressants (many contain terpene compounds) Note: for most of the plants in this topic.Alzhemier s disease o symptoms: episodic memory. attention.Parkinson s disease o symptoms: motor. block voltage gated ion channels (Na+ or Ca2+). effects. language problems. reduce anxiety > behavioural disinhibition. neurofibrillary tangles of tau proteins. o treatment: NT replacement strategies (anti ACh-esterases means more ACh available. alertness. . effects occur in dose dependant manner o compounds include: monoterpenes (valenol). optimize mental functioning 5.valerian & Valerian officinalis: o roots and rhizome. antispasmodic. problem solving) . sedation. . and compounds found in the following sedative producing plants: . pathologies. increase in cognitive function) or neuroprotective strategies (antioxidants. used to treat epilepsy and stress.Cognitive Enhancers. . o treatment: compensate for dopamine loss (anticholinergic drugs. You should be aware of any mechanisms that are described. Keep in mind that many plants have multiple compounds. relaxation. vitamin E prevents B-amyloid toxicity and memory deficits) or selegiline: inhibitor of MAO (increases monoamine signaling). you should be able to provide at least one compound that is found in that plant as an example. dopamine modulation. minimal effects on cognition o enhances ligand receptor binding of GABA. the specific compound and related mechanism of action is really not well understood. what are the non-herbal treatments? What is the mechanism for these drugs (If known)? . sleep > respiratory suppression. loss of nigrostriatal projections. and possible signaling pathways associated with two diseases where cognitive function is disrupted: Alzheimer s disease and Parkinson s disease. carbidopa (inhibits enzymes that produce dopamine peripherally). or ergot alkaloid compounds (agonists at dopamine receptors). ACh antagonizes dopamine). and it is unclear which compounds and affected pathways may be applicable to different physiological responses. loss of ACh enzymes. Describe the relationship of sedatives to anxiety and insomnia. Review the mechanisms of action. gauinolide lactone (matricin).kava & Piper methysticum: o roots. inability to function in daily activities o pathology: neuritic plaques (B-amyloid and apolipoprotein E). . vegetative state.nootropics to treat dementia. What is cognition? What are cognitive enhancing drugs (nootropics) used to treat? . mild calming effects o apigenin binding to benzodiazepine receptors. For each of the diseases. mental imagery. 2. What are the general cellular mechanisms of action that might be related to increasing neuronal sedation? . perception. increase release. kavalactone and terpenoid mixture. and alkaloids (valeranine) .cognition: ability to intelligently process information (memory. emotional effects o pathology: degneration of neurons in the substantia nigra.neuronal inhibition: increase GABA activity. inhibit cyclooxygenase and thromboxane A2 synthesis (shown to inhibit GABA receptors) . cognitive. promotes release of GABA. ion channel receptor has allosteric binding sites OR block reuptake. action. or L-Dopa (increased dopamine synthesis and release). inhibits voltage gated ion channels. If the specific active compound for a plant is unknown. anti-inflammatory. flavonoids (apigenins) 4. possible version of GABA receptors o compounds include: terpenoid (a-bisabolol and a-bisbololoxides). 1.inhibition of neuronal excitation: block glutamate at NMDA receptors.

MAO inhibitors. agonists at GABA receptors. Hypericum perforatum as an herbal anti-depressant (St. General description of depression and anxiety . John s-Wort) Folklore: . atypical. tomato. facilitates ACh release.Anxiety: subjective feelings of dread. increase mental resistant to stress. breathing ailments Active compounds: . kava. panaxosides). xanthones Mechanism of action: . o Solanaceae family members (potato. panaxadiols and panaxatriols. low Rg-1 (insomnia.CNS inhib and stim effects. direct receptor effects. General description of the different kinds of ginseng Vary in location and preparation. affect AA neurotransmission (inhibit GABA reuptake and activation). SSRIs. o Fava beans contains significant amoutns of L-dopa. o non-herbal antidepressants: . prevent scopolamine-induced memory deficits and amnesia. cognitive impairment. improvement in memory. and hormonal levels (distinguished by duration and severity of symptoms). myricetin. insomnia. biflavones. anemia.hypericin is MAO inhibitor . worry. bilobalide (sesquiterpene). Panax ginseng and Panax quinquefolius (Cold-FX) are most widely used and researched species.inhibits reuptake of monoamines. phloroglucinols. . .cure-all. 9.cyclic triterpene glycosides (saponins. tricyclic antidepressants. many herbals for anxiety also associated with depression. proanthocyanidins (antioxidant effects) Mechanism of action: . ginsenosides. overcome fatigue.6. low Rb-1 (health promoting.Rb-1 increases choline uptake. rescues neurons from ischemic damage and delays neuronal death.napthodianthrones (hypericin and pseudohypericin have MAO inhibiting properties).flavonols inhibit COMT activity that would degrate NTs . motor impairment. aphrodisiac. . terpene lactones (ginkolides. increase serotonin uptake. BP.prevent degradation. ward off evil spirits Active compounds: . . sweating. dry mouth. inhibit MAOs (more monoamines available) Physiological effects: . emotional tension. comparable effects to prescribed drugs with cholinergic mechanisms 7. stress). add R groups to saponin. flavonoids. avoidance. maintain energy.high Rb-1. cognitive impairments in concentration. Mechanism of action: . high Rg-1. opioid receptors. chamomile may be useful for anxiety. toothaches). Active compounds: . lowered self-esteem.Depression: sadness. kaemferol). anxiety. Historical uses: . Other herbal nootropics and their mechanisms for enhancing cognitive function o Ergot alkaloids hydergine & Claviceps purpurea (cholinergic and monoamine signaling) may have antioxidant effects.vasodilation antioxidant. eggplant) cholinesterase inhibiting effects. sleep. increase number of muscarinic receptors.valerian.leaves to treat memory loss. treat asthma. lower back pain.increase uptake of choline (more ACh released). terpenes. dizziness. o Areca catechu arecoline improves memory in rats. increased HR. pessimism. block reuptake.flavonoid glycosides (apigenin. indigestion. General description of Ginkgo biloba Historical uses: . diterpenes). worry. 10. sex drive.for depression. changes in appetite. phenolic acids. Physiological effects: . 8. nausea.

stroke. related to pain and reduction of inflammation (thromboxanes. oil extract contains terpenoids (bisabolene. antiemetic.serotonin receptor antagonism. treat rhinitis. toothache. inhibits platelet aggregation. .divine drink.harvested from rhizome. root of india . antiulcer. Active compounds: . gingivitis.increases bile emptying and gastric motility. Zingiber officinale Historical use: . substance P release (both may result in analgesia) Physiological effects: . analgesia. Mechanism of action: . zingiberol). ant-inflammatory. leukotrienes. gingerol as pungent chemical. cramps. antispasmodic. antipyretic.11. prostaglandins) . diabetes.eicosanoid inhibition.

phytochemicals such as phenolics. antioxidant. antibacterial properties .cabbage (phenethyl isothiocyanate. antioxidant Mechanisms: .blocks cell growthn by stimulating apoptosis and inhibiting angiogenesis.Soy products & Glycine max Compounds: . lung. antiestrogenic agent . similar mechanism to tamoxifen C.cruciferous vegetables: broccoli. Uses: . starter for many nutritious foods Mechanisms: . .I3C modifies estradiol (not sulfur containing) B. partial agonist.Cancer 1. aflavins.broccoli and brussels (indole 3-carbinol.blocks VEGF receptor activity related to initiation of angiogenesis D. and mechanisms A. liver. thearubigins. involved in breast and prostate cancers Uses: . and sulfur containing compounds appear to be chemopreventative.contain glucosinolates that are broken down into isothiocyantes to reduce the risk of cancer Uses: . Herbal drugs and cancer: chemoprevention o What is chemoprevention and what are some treatment approaches that are used to achieve it? . antithrombotic.cultivated for nitrogen fixing properties.curcumin Uses: . pancreas. inhibits cellular damage Mechanisms: . 2. cauliflower. reduces cholesterol. I3C) protects from breast.prevents cancer initiation and promotion. stomach. compounds. Plants: . Plants: . 3. and uterine cancers Mechanisms: .Turmeric & Curcuma longa Compounds: .soy isoflavones and phytoestrogens. o What are some general mechanisms thought to be involved with herbal chemoprevention? . Plants: . colon.used to make green tea. terpenes.herbal compounds may be used in chemoprevention but active compounds can be used as treatment. anticarcinogenic effects in skin. Plants: .contains polyphenols including catechins. What is cancer? read the first few slides.broccoli (sulforaphane) has antioxidant effects . cabbage Compounds: . uses. cervical.PEITC induces apoptosis of cancer cells . Herbal chemoprevention examples: know plants. esophagus. inhibits cyclooxygenase 2. EGCG inhibits cancer growth cells.Green tea & Camelia sinensis Compounds: . PEITC) protects animals from cancers caused by toxins .sulforaphane triggers apoptosis of cancer cells.genistein competes with estrogen for its receptor.

prevent the activation of carcinogenic substances into toxins and inhibit VEGF and PDGF F. proanthocyanidins. chocolate. chiles Compounds: .stimulates rapid recovery of cellular immunity damaged by radiation. delphinidin.Berries & raspberries. inhibit VEGF activity Mechanisms: . reduce EGF receptor seen in angiogenesis. Catharanthus rosea (vincristine and vinblastine) o How did C.antioxidant. phenolic stilbene Uses: . and surgery Mehcanisms: . Plants: . capsaicin Uses: . blackberries. vitamin C.Pacific yew contains taxine throughout the plant.anthocyanidins (polyphenols).preventing scurvy through anti-inflammatory processes. stimulate apoptosis in cancer cells .Schizophyllum commune Compounds: . vinblastine and vincristine? o How are the vinca alkaloids produced/harvested? C. slows down drug metabolism . ellagic acid Uses: . G. Podophyllum peltatum (podophyllotoxin and palatatins) o What is the mechanism of action of podophyllotoxin? . Taxus brevifolia (paclitaxel or taxol) o Toxic properties of yews . reduces risk of heart disease. taxol is more concentrated in the bark o How was taxol s chemotherapeutic action discovered ? . reduction in DNA synthesis leading to apoptosis.E. antioxidant Mechanisms: .antitumor activity mediated by T-cells and macrophages 4. Plants: . induce macrophages involved with immune resp.carotenoid reduces prostate cancer.resveratrol. Plant: . citrus.allin and allicin. stimulate enzymes to eliminate carcinogens. lycopene. Compounds: .rosea s historical uses lead to its discovery as a chemotherapeutic agent? o What are the specific anticancer uses of the active compounds? o What is the mechanism of action of the vinca alkaloids.lowers cholesterol. tomato. chemotherapy. Plants: . from woot rotting basidiomycete Uses: . H.garlic. Use of plants to treat cancer A.sizofiran. possibly antioxidant activity .wine and grapes Compounds: .prevent cancers initiated by nitrosamines.antioxidant effects related to reduction in cardiovascular disease.induces an enzyme that detoxifies carcinogens. inhibits cyclooxygenase. strawberries.random collection program o What is taxol s mechanism of action? o What is the problem and possible solutions with the supply of taxol? B.

Unsubstantiated cures o What is laetrile? How is it supposed to work? o What is essiac? What is the folklore and and proposed effects for essiac? . Camptotheca acuminata (camptothecin) o How was camptothecin discovered as an anti-cancer agent? o What is the mechanism of action of camptothecin? o Is camptothecin used to treat cancer? E. Indigofera tinctoria (indirubin) o Based on traditional Chinese medicine o What is the mechanism of action and cancers that seem to be affected? 5.D.

results in lack of muscle contraction . Poisonous plants Listed are the plants that you should obviously know. Datura metel. This is a developmental pathway where the transcription of specific genes leads to formation of the cerebral hemispheres and leads to correct patterning of the midline and bilateral symmetry.Toxins 1. A. Cardiac Glycosides: Digitalis purpurea Have specific action on heart muscle Acokanthera and Strophanthus species § Produce oubain and strophanthidin .results in an increase of acetylcholine in the neuromuscular junction and more muscle contraction § Used to treat myasthenia gravis. Hyoscyamous niger. o Similar birth defects seen in other living organisms are due to disruption/alteration of the same signaling pathway (not because they ate cyclopamine) o Strychnos nux-vomica (produces strychnine) o Low dose is stimulant/ High dose is convulsant. common names. active compounds. physiological effects. including scientific names. Mandragora officinarum Nicotiana tabacum Lupinus polyphyllus Claviceps purpurea o Aconitum napellus (produces aconitine) o Mechanism: reduces ion selectivity of sodium channels. Alteration/disruption of the transcription of these genes during development may lead to cycoplegia (one eye in middle) or milder phenotypes. Birth defects like these occur when grazing animals ingest cyclopamine during pregnancy. etc. Not all of these facets are relevant for every plant. Plants covered in previous lectures were described in more detail elsewhere and the expectation is that you are still familiar with them. at high dose can kill due to sustained muscle contraction § Solanum tuberosum produces solanine . What is a toxin? o How can plants be toxins as well as useful for other purposes? 2. Only those plants that are being introduced for the first time in this lecture topic are described in detail below. history.used as arrow poisons § Inhibit the sodium/potassium ATPase that maintains ion gradients in heart muscle cells . Alkaloids Conium maculatum Atropa belladonna. resulting in sodium influx and production of cardiac arrhythmias leading to death o Veratrum californicum (produces cyclopamine) o Mechanism: cyclopamine binds to the smoothened protein in the sonic hedgehog signaling pathway. contracts all muscles breathing is disupted . mechanism of action.in particular this affects the ability to breathe leads to death o Physostigma venenosum (produces physostigmine) o Mechanism: inhibits acetylcholinesterase .leads to death o Used in rat poisons and on arrows for hunting o Chondrodendron tomentosum (produces curare) o Mechanism: competitive inhibitor of nicotinic acetylcholine receptors § At neuromuscular junction.also inhibits acetylcholinesterase to a lesser degree B. History of poisons o Who created poisonous plants? o What are some techniques for poisoning? o What are some antidotes/ways to avoid poisoning? o What is the relevance of Mithridates? o What are some specific historical examples of documented poisonings? o What is the relationship of women to poisoning? 3.

thought to be the most toxic naturally occurring compound o Mechanism: inhibits mRNA translation by binding to subunits of ribosomes o Recorded use in espionage murders . resulting in mutation and cancer o Camellia sinensis (produces tannins) § Mechanism: bind proteins and precipitates them out of solution .C.results in rash D. Phenolics o Aspergillus sp. (produces aflatoxin) § Mechanism: intercalates and alkylates DNA.used to treat liver damage and disease Lectins o Toxic proteins of non-immune origin. cause agglutination and precipitation of sugar molecule complexes o Ricinus communis: produces ricin. a compound that suppresses the action of the toxic compounds from Amanita sp. § Is hepatoprotective. Amino acids and proteins o Coprinus atramentarius (fungi): produces amino acid that interferes with the ability to metabolize alcohol o Amanita phalloides and Amanita virosa (fungi): both contain amatoxins and phallotoxins that cause extensive liver damage and lead to death § Amatoxins are specifically absorbed by hepatocytes and inhibit RNA polymerase II § Phallotoxins bind to proteins on cell surface. causing membrane leakiness o Also bind to actin subunits o Silybum marianum (milk thistle) produces silymarin.can be oncogenic or anti-oncogenic o Toxicodendron radicans (produces urushiol) § Mechanism: induces immune system .