Herbal Medicines for Neurologic disorders

Hamid R. SadeghniaDepartment of Pharmacology, School of Medicine, MUMS

US dietary supplement market(Rea & Ooyen 2009)

US $23.7 billion with a predicted compound annual growth rate of 5%

Outlines

• ANALGESIC AGENTS

• ANTIANXIETY AGENTS, SEDATIVES & HYPNOTICS

• ANTICONVULSANTS

• ANTIDEPRESSANTS

• APPETITE STIMULANTS

• CENTRAL NERVOUS SYSTEM STIMULANTS• CHOLINESTERASE INHIBITORS &COGNITIVE ENHANCING AGENTS

• MIGRAINE PREPARATIONS

• VERTIGO AGENTS

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

Boswellia (Boswellia serrata)

• The resin gum exuded when incisions are made in the bark of the trunk

• Pentacyclic triterpene 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

Chamomile

• German Chamomile (Matricaria Recutita): 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

Chamomile

• English Chamomile or Roman Chamomile (Chamaemelum nobile): flowers & aerial parts

• Sedative

• Daily dosage: 1.5 g at the main meals

• The drug is not to be used during pregnancy

Cinnamon (Cinnamomum verum)

• The dried tree bark, the cinnamon oil extracted from the bark

• Volatile oil: cinnamaldehyde, cinnamic acid, eugenol

• Diterpenes: cinnzeylanin, cinnzeylanol

• Alzheimer’s disease, Loss of appetite

• Daily Dosage: 2 to 4 g drug

Esfand or Harmal (Peganum harmala)

• 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

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

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

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

Ginkgo (Ginkgo biloba)

• The fresh or dried leaves, and the seeds

• Flavonoids & Biflavonoides: quercetin, ginkgetin

• Trilactonic diterpenes: ginkgolides

• Trilactonic sesquiterpene: bilobalids

• Platelet-activating factor (PAF) receptor antagonist (Ginkgolide B)• 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

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

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

Ginseng (Panax ginseng)

• The dried root

• Triterpene saponins (25 ginsenosides)

• 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

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

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

Siberian ginseng (Eleutherococcus senticosus)

• Dried roots and/or rhizome

• Caffeic acid derivatives

• Hydroxycoumarins

• Triterpene saponins (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

Lavender (Lavandula angustifolia)

• The essential oil extracted from the fresh flowers

• Volatile oil: linalool, linalyl acetate

• Hydroxycoumarins: umbelliferone

• Caffeic acid derivatives: rosmaric acid

• Nervousness and insomnia, migraine prophylaxis, Loss of appetite

Lemon Balm (Melissa officinalis)

• The oil, the dried leaves, the fresh leaves and the whole plant

• Volatile oil: geranial, linalool, geraniol, eugenol

• Flavonoids & Caffeic acid derivatives: rosmaric acid

• Triterpene acids: ursolic acid

• Nervousness & insomnia

• Daily Dosage: 1.5-4.5 g

بادرنجبويه

• 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

Sweet Orange (Citrus sinensis)

• 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 appetiteنارنج

Bitter Orange (Citrus aurantium)

Passion Flower (Passiflora incarnata)

• The whole dried herb and the fresh aerial parts

• Flavonoids

• Cyanogenic glycosides: gynocardine

• Nervousness and insomnia, depressive statesگل ساعت

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

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-adrenoceptors and 5HT-2 receptors گل راعي، علـــف چای، هوفاريقون

St. John's Wort (Hypericum perforatum)

• Side Effects:• CNS: Restlessness & headache

• GIT: Anorexia, nausea, gastrointestinal pain, dry mouth, Constipation

• Dermatologic: Photosensitization (Hypericism, the hypericum pigments)

• 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

Valerian (Valeriana officinalis)

• The dried roots

• Alkaloids: Valerine, Valerianine, Valtrate

• Iridoids: valepotriates

• Sesquiterpenes: valerenic acid

• Volatile oil: valerenal, Valerenol, isoeugenyl valerenate, (-)-bornyl isovalerenate

• Nervousness & insomnia• Centrally depressive, sedative, anxiolytic, spasmolytic & muscle relaxing

سنبل الطيب طبي

Valerian (Valeriana officinalis)

• ↑ GABA• ↓ GABA degradation• GABA Re-uptake inhibition• ↑ GABA synthesis & release (glutamine)

• Daily Dosage: 100-3800 mg سنبل الطيب طبي

Thank you