Phytopharmacology: Primary Metabolism in Plants

Alejandro Pino, PhD. Class 4

Lectins: Derivatives From Proteins Glycoproteins Specific binding to cell glycoproteins Phytoaglutinines Mitogenic activity Cytostatic activity

Mistletoe (Viscum album L.) Parasitic plant on trees Branches might be as long as 1 m Leaves of 8 cm

History of Mistletoe First used by original civilizations in Germany Ornamental in Europe In 1917 the anticancer effect was demonstrated

Chemical Composition
Lectin: Viscumin or ML-1 Viscotoxins I,II,III,IV (Proteins) Alkaloids:
Viscalbina

Phenylpropanes Lignans Flavonoids

Viscum album - Pharmacology

Anticancer effect: Lectins, Lignans and Viscotoxins Immunomodulating effect: Alkaloids and Polysaccharides Estrogenic effect: Lignans Hipotensive effect: Viscotoxins

Viscumin (ML-1)
Mr = 60,000 (by gel electrophoresis) Two chains 34,000 (B) and 28,000 (A) Inhibit protein synthesis in cell free systems Chain A is responsible of inhibition Ribosomal subunit 60 S is selectively inactivated by chain A Chain B is responsible of binding to cells

Viscotoxins
Basic proteins Low molecular weight Agonists of acetyl-choline receptors Capable to interact with DNA

Medical Applications and Dosage Forms Treatment of Cancer Iscador: Fermented plant juice administered orally (2 ml BID, 2.5 mg of Viscumin) Eurixor: Viscumin (ML-1) administered intravenously or SC close to the place of tumor (No reported dose) (Twice a week) Under clinical trial in Europe

Toxicities and Adverse Effects

GIT effects Cardiovascular toxicity by interfering Ca2+ ions at the membrane Viscotoxins LD50 in rats = 0.7 mg/Kg Iscador LD50 in rats = 276 mg/Kg

Polysaccharides
Homo-polysaccharides Hetero-polysaccharides Glucans (glucose) Mannans (mannose) Hemicellulose (Xylose) Levans (Fructose)

Glucose isomers

Hemiacetal forms

Xanthan gum

Aloe (Aloe vera L.)

Succulent plant growing to 1 m tall Leaves are lanceolate, thick and fleshy Flowers on a spike up to 90 cm tall

History
Egipt: Evers Papyrus, Century XVI b.C. = Long life elixir Used by soldiers to heal wounds Century I: Dioscorides refers to the internal and external use of aloe juice Century XV: Barbados. 1932: Declared officinal drug in England 1973: Declared protected spice in USA

Chemical Composition
Anthraquinones: Aloins
Nataloins Barbaloins

Polysaccharide Gel
Mucopolysaccharides: Acemannan (Acetylated mannans)

Pharmacology of Mannans
Inhibit cholesterol absorption (Orally) Mannose binding proteins in cell surface macrophage activation and interleukin-l release inhibit viral replication stimulate bone marrow activity promote wound healing inhibit tumor growth

Effects on Skin and Mucoses

Restorative effect on the skin Wound healing (Activation of fibroblasts) Anti-inflammatory effect (Inhibition of phospholipases = less release of araquidonic acid).

Mode of action
Activation of membrane mannan receptors influences the activity of T-lynphocytes, fibroblasts, B-lynphocytes, and endothelial cells. Stimulates phagocytosis. Increases antibody production Inhibit the enzyme lipooxygenase Possible activation of beta-cells in pancreas.

Applications of the Gel

Cosmetic applications (Topic) Wound healing (Topic) Ulcers and gastritis (Orally) Diabetes (Orally) Treatment of Fibrosarcoma in dogs and cats (Acemannan) (IV) Inhalation solutions of acemannan in asthma (under study)

Toxicities and Adverse Effects Anthraquinones:

Irritation of mucoses Diarrhoea Hypokalemia Colon cancer

Doses and Dosage Forms

Gel orally 30 ml/dose BID Gel topically 2 10 %

Sulfoxides
S-Propyl-cysteine sulfoxide S-Propenyl-cysteine sulfoxide S-Methyl-cysteine sulfoxide Alliin (S-Allyl-cysteine sulfoxide) Zwiebelane

Thiosulfinates Allyl-methane-thiosulfinate Methyl-methane-thiosulfinate Diallyl-thiosulfinate (Allicin?) Dipropenyl-thiosulfinate (Allicin)

Derivatives from Allicin

Ajoenes
Z-ajoene E-ajoene

Dithiins
2-vynyl-1,3-dithiin 3-vynyl-1,2-dithiin

Pharmacology of sulfur compounds

Hypocholesterolemic effect Anti-atherosclerosis Inhibit platelet aggregation, anti-thrombotic Anti-infections, antibiotic activity Hypoglycemic effect Antitumoral effect Antioxidant effect

Garlic (Allium sativum) Food and medicine for 4000 years Egyptian Codex Evers year 1550 b.C. indicating garlic remedies for heart, headache, bites, worms and tumors Dioscorides century I, vermifuge Louis Pasteur 1858, antibacterial Effective against Atherosclerosis and platelet aggregation

Top supplements used in USA in 1997

Garlic plant Leaves long, narrow and flat Bulb consisting of numerous bulblets (cloves), enclosed within a whitish skin, which holds them as in a sac Flowers placed at the end of a stalk, grouped in a globular head or umbel Plant 50 cm tall

Allium sativum L

Chemical composition
Gamma-glutamyl-cysteine Alliin (80 % of sulfated compounds) Alliinase Allicin Other sulfoxides Other thiosulfinates Saponins Flavonoids

Toluene:Ethylacetate (100:30) Paladium II chloride reagent

T1=diallylsulfide, T2=allicin, T3=dipropylthiosulfinate, T4=dimethylthiosulfinate 1=Allium sativum, 2=Allium ursinum, 3=Allium cepa

Vanillin-Acetic acid reagent

T1=diallylsulfide, T2=allicin, T3=dipropylthiosulfinate, T4=dimethylthiosulfinate 1=Allium sativum, 2=Allium ursinum, 3=Allium cepa

Pharmacology of garlic
Anticoagulant and thrombolytic Decrease the synthesis of cholesterol Prevents atherosclerosis Antithrombotic Chemopreventive and antitumoral Antimutagenic activity Antimicrobial effect Prevents nephrotoxicity

Mode of action
Inhibition of lipooxigenase and cyclooxigenase Increase superoxide dismutase activity Increase glutathione peroxidase activity Increase catalase activity in vascular endothelial cells Inhibition of platelet aggregation (Aggregin, ADP) Increase of HDL cholesterol level in blood Allicin scavenges free radicals Inhibition of OH-Methyl-glutaryl-Co-A reductase

TOXICITY OF GARLIC (The dose makes the poison)

Glucosinolates
Sulfated thioglycosides Characteristic odor and taste of plants from Brassicaceae family (Mustard, radish, cabbage, Brussels sprout ) They produce isothiocyanates, nitriles or thiocyanates Soluble in water

GLUCOSINOLATES

Glucotropaeolin 4-Methoxybenzyl glucosinolate Glucoalyssin 4-Hydroxybenzyl glucosinolate Glucobrassicanapin Glucobrassicin 4-Methoxyindolyl-3-methyl glucosinolate 3-Methoxyglucotropaeolin

AROMATIC ISOTHIOCYANATES

Benzylisothiocyanate 4-Methoxybenzylisothiocyanate 3-Methoxybenzylisothiocyanate

Pharmacological properties of Glucosinolates

Protective effect against tumorigenic compounds Activation of Liver enzymes for fase II metabolism
NADPH reductase Glutathion S-transferase

Respiratory tract protection Aphrodisiac effect

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