Herbal Medicines for Neurologic disorders

1. Herbal Medicines for Neurologic disorders Hamid R. Sadeghnia Department of Pharmacology, School of Medicine, MUMS

2. US dietary supplement market (Rea & Ooyen 2009) US $23.7 billion with a predicted compound annual growth rate of 5%

3. Outlines • ANALGESIC AGENTS • ANTIANXIETY AGENTS, SEDATIVES & HYPNOTICS • ANTICONVULSANTS • ANTIDEPRESSANTS • APPETITE STIMULANTS • CENTRAL NERVOUS SYSTEM STIMULANTS • CHOLINESTERASE INHIBITORS &COGNITIVE ENHANCING AGENTS • MIGRAINE PREPARATIONS • VERTIGO AGENTS

4. Barberry (Berberis vulgaris) • The medicinal part is the fruit and the root bark • Isoquinoline alkaloids (berberine) & vit. C • Berberin • Competitive α1& α2 adrenergic blocking effects • Anticonvulsant and  antispasmodic effects • Daily Dosage: up to 2 g • Opiate withdrawal symptoms • Barberry root bark

5. Boswellia (Boswellia serrata) • The resin gum exuded when incisions are made in the bark of the trunk • Pentacyclictriterpene acids: Boswellic acids • Brain vascular insufficiency (memory loss, cognitive decline, Alzheimer’s disease) • Increase CBF • Inflammatory conditions (rheumatoid arthritis, MS, Asthma) • Anti-inflammatory effect (inhibition of LOX & LTs production) • Sedative & analgesic properties

6. Chamomile • German Chamomile (MatricariaRecutita): the entire flowering herb or only the flowers • Volatile oil: alpha-bisabolol (levomenol) • Flavonoids: apigenin, luteolin, quercetin • Anxiolytic Effects • Flavonoids: Apigenin is a ligand for the central BDZ receptors • Daily dosage: 3 g at the main meals • Caution: Anaphylactic Reactions • Drug Interactions: • Coumarin Anticoagulants: additive effects due to the hydroxycoumarins in chamomile

7. Chamomile • English Chamomile or Roman Chamomile (Chamaemelumnobile): flowers & aerial parts • Sedative • Daily dosage: 1.5 g at the main meals • The drug is not to be used during pregnancy

8. Cinnamon (Cinnamomumverum) • The dried tree bark, the cinnamon oil extracted from the bark • Volatile oil: cinnamaldehyde, cinnamicacid, eugenol • Diterpenes: cinnzeylanin, cinnzeylanol • Alzheimer’s disease, Loss of appetite • Daily Dosage: 2 to 4 g drug

9. Esfand or Harmal(Peganumharmala) • CNS stimulant & antidepressant activity • Harmala alkaloids: harmane, harmine, harmaline, harmalol • β-carboline • Reversible inhibitor of MAO-A (RIMA) • Acetylcholinesterase inhibitor • Histamine N-methyltransferase inhibitor (wakefulness-promoting effects) • Daily dosage: 1 g

10. Fennel (Foeniculum vulgare) • Fennel oil extracted from the fruit and seeds • Trans-anethols, Fenchone, Estragole, Hydroxycoumarins • Central analgesic effect, memory-strengthening effect (anti-acetylcholinestrase activity) • Daily Dosage: 0.1-0.6 ml of Fennel oil (5-7 g fennel seed) رازیانه

11. Ginger (Zingiber officinale) • The root • Volatile oil: zingiberene, zingiberol, linalool • Gingerols • Shogaols • Anti-emetic Effects (Motion Sickness, Postoperative Nausea and Vomiting) • Local gastrointestinal actions • Positive inotropic, antithrombotic & platelet aggregation inhibitory (inhibit thromboxane synthesis), anti-lipidemic effects • Anti-dyspepsia زنجفيل

12. Ginger (Zingiber officinale) • Anti-migraine • Anti-Inflammatory Effects • Inhibition of COX & 5-LOX • Immunomodulation (RHEUMATOID ARTHRITIS, OSTEOARTHRITIS) • Drug interactions: anticoagulants • Daily dosage: 2-4 g

13. Ginkgo (Ginkgo biloba) • The fresh or dried leaves, and the seeds • Flavonoids & Biflavonoides: quercetin, ginkgetin • Trilactonicditerpenes: ginkgolides • Trilactonicsesquiterpene: bilobalids • Platelet-activating factor (PAF) receptor antagonist (GinkgolideB) • Inhibition of PAF-induced platelet aggregation, inflammation, extravasation, bconchoconstriction and airway hyperactivity and T-lymphocyte proliferation and cytokine production • The antioxidant (free radical scavenging), membrane-stabilizing & increase CBF • Ischemic Dementia

14. Ginkgo (Ginkgo biloba) • Indications: • Dementia & Symptomatic relief of organic brain dysfunction • Peripheral Occlusive Arterial Disease (Intermittent claudication) • Vascular Vestibular Disorders (vertigo, tinnitus) • ADVERSE REACTIONS: • Subarachnoid hemorrhage and an increase in bleeding time

15. Ginkgo (Ginkgo biloba) • Anticoagulants, Antiplatelet Agents, Low Molecular Weight Heparins, and Thrombolytic Agents/NSAIDs • Increased risk of bleeding • Buspirone & SSRI • Precipitation of hypomanic episodes (serotonin syndrome) • Insulin • Ginkgo increase insulin levels • Monoamine Oxidase Inhibitors (MAOIs) • Potentiation effect (Ginkgo may inhibit monoamine oxidase) • Anticonvulsants • ↓ efficacy (lowering seizure threshold) • CYP2B 1/2, CYP3A1, and CYP3A2 induction by ginkgo

16. Ginseng (Panax ginseng) • The dried root • Triterpenesaponins(25ginsenosides) • Improve performance, stamina, cognitive function, Cerebrovascular deficits • Used also for loss of appetite, cachexia, anxiety, impotence, neuralgia and insomnia • Increase plasma ACTH and corticosteroids • Stimulate insulin release and increase insulin receptors

17. Ginseng (Panax ginseng) • Adverse reactions: • Insomnia, headache, nervousness • Hypertension • Mastalgia • Pregnancy/Lactation: • Maternal use of Ginseng has been associated with neonatal androgenization, thus it is not recommended for use during pregnancy or lactation

18. Ginseng (Panax ginseng) • Drug interactions: • Anticoagulants (Warfarin, Antiplatelet Agents)/NSAIDS: Increased risk of bleeding • Antidiabetic agents/Insulin: Additive hypoglycemic effects • Estrogens: ↑ estrogenic symptoms such as mastalgia & breakthrough menstrual bleeding • Monoamine Oxidase Inhibitors (MAOIs): Manic-type symptoms (insomnia, tremor, headache, agitation) • Daily dosage: 1-2 g of root

19. Siberian ginseng (Eleutherococcussenticosus) • Dried roots and/or rhizome • Caffeicacid derivatives • Hydroxycoumarins • Triterpenesaponins (eleutherosides) • Immune-stimulating/immune-modulating & antiviral effect • Hypoglycemic & platelet aggregation-inhibiting effects • Indications: Lack of stamina, Tendency to infection, tonic • Daily dosage: 2-3 g of root

20. Lavender (Lavandula angustifolia) • The essential oil extracted from the fresh flowers • Volatile oil: linalool, linalylacetate • Hydroxycoumarins: umbelliferone • Caffeicacid derivatives: rosmaric acid • Nervousness and insomnia, migraine prophylaxis, Loss of appetite

21. Lemon Balm (Melissa officinalis) • The oil, the dried leaves, the fresh leaves and the whole plant • Volatile oil: geranial, linalool, geraniol, eugenol • Flavonoids & Caffeicacid derivatives: rosmaricacid • Triterpene acids: ursolicacid • Nervousness & insomnia • Daily Dosage: 1.5-4.5 g بادرنجبويه

22. Sweet Orange (Citrus sinensis) • The fresh and dried fruit peel and the extracted essential oil • Volatile oil: Jimonene, citronellal, linalyl acetate • Flavonoids: naringin, tangeretin • Nervous tension & sleeplessness, Loss of appetite

23. Bitter Orange (Citrus aurantium) • The fresh and dried fruit peel, the flowers, the seeds and the extracted essential oil • Volatile oil: linalool, linalyl acetate, limonene • Limonoids(triterpenoide bitter principles) • Flavonoids: naringin, tangeretin • Nervous tension & sleeplessness, Loss of appetite نارنج

24. Passion Flower (Passiflora incarnata) • The whole dried herb and the fresh aerial parts • Flavonoids • Cyanogenic glycosides: gynocardine • Nervousness and insomnia, depressive states گل ساعت

25. Saffron (Crocus sativus) • The stigma and style • Carotinoids: crocins& crocetin • Picrocrocin • Volatile oil: safranal (4,5-dehydro-betacyclocitral) • Antidepressant, anti-anxiety, anti-convulsant • Daily Dosage: 2 to 4 g drug

26. St. John's Wort (Hypericum perforatum) • The entire flowering plant, flowers and aerial parts • Hypericins (Anthracene derivatives): hypericin, pseudohypericin, hyperforin • Flavonoids: hyperoside, quercitrin, rutin • Xanthones: 1,3,6,7-tetrahydroxyxanthone • Mild antidepressant, sedative and anxiolytic action • MAO inhibitory activity: hypericin • 5-HT, NE & DA re-uptake inhibition: hyperforin • down-regulation of cortical beta-adrenoceptorsand 5HT-2 receptors گل راعي، علـــف چای، هوفاريقون

27. St. John's Wort (Hypericum perforatum) • Side Effects: • CNS: Restlessness & headache • GIT: Anorexia, nausea, gastrointestinal pain, dry mouth, Constipation • Dermatologic: Photosensitization (Hypericism, the hypericumpigments) • Dosage: 2-4 g (dried herb) or 300 mg (the standardized extract) 3 times daily • Drug interactions: • MAOIs: Hypertensive crisis • SSRIs: serotonin syndrome • Induce CYP 450: ↓ bioavailability of cyclosporine, Indinavir, OCP گل راعي، علـــف چای، هوفاريقون

28. Valerian (Valerianaofficinalis) • The dried roots • Alkaloids: Valerine, Valerianine, Valtrate • Iridoids:valepotriates • Sesquiterpenes: valerenic acid • Volatile oil: valerenal, Valerenol, isoeugenylvalerenate, (-)-bornylisovalerenate • Nervousness & insomnia • Centrally depressive, sedative, anxiolytic, spasmolytic & muscle relaxing سنبل الطيبطبي

29. Valerian (Valerianaofficinalis) • ↑ GABA • ↓ GABA degradation • GABA Re-uptake inhibition • ↑ GABA synthesis & release (glutamine) • Daily Dosage: 100-3800 mg سنبل الطيبطبي

30. Thank you