phytopharmacology class 4 (primary metabolism in plants)

8/13/2019 Phytopharmacology Class 4 (Primary Metabolism in Plants)

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Phytopharmacology:

Primary Metabolism in Plants

Alejandro Pino, PhD.

Class 4


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Lectins: Derivatives From Proteins

Glycoproteins

Specific binding to cell glycoproteins

Phytoaglutinines

Mitogenic activity

Cytostatic activity


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Mistletoe (Viscum album L.)

Parasitic plant on trees

Branches might be as long as 1 m

Leaves of 8 cm


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History of Mistletoe

First used by original civilizations in Germany

Ornamental in Europe

In 1917 the anticancer effect wasdemonstrated


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Chemical Composition

Lectin: Viscumin or ML-1

Viscotoxins I,II,III,IV (Proteins)

Alkaloids:

Viscalbina

Phenylpropanes

Lignans

Flavonoids


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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


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Viscotoxins

Basic proteins

Low molecular weight

Agonists of acetyl-choline receptors

Capable to interact with DNA


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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


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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


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Polysaccharides

Homo-polysaccharides

Hetero-polysaccharides

Glucans (glucose)

Mannans (mannose)

Hemicellulose (Xylose)

Levans (Fructose)


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Glucose isomers

Hemiacetal forms


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Xanthan gum


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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


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History

Egipt: Evers Papyrus, Century XVI b.C. = Long life

elixir

Used by soldiers to heal wounds

Century I: Dioscorides refers to the internal andexternal use of aloe juice

Century XV: Barbados.

1932: Declared officinal drug in England 1973: Declared protected spice in USA


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Chemical Composition

Anthraquinones: Aloins

Nataloins

Barbaloins

Polysaccharide Gel Mucopolysaccharides: Acemannan (Acetylated mannans)


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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


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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).


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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.


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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 (understudy)


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Toxicities and Adverse Effects

Anthraquinones:

Irritation of mucoses

Diarrhoea

Hypokalemia

Colon cancer


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Doses and Dosage Forms

Gel orally 30 ml/dose BID

Gel topically 2 10 %


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Sulfoxides

S-Propyl-cysteine sulfoxide

S-Propenyl-cysteine sulfoxide

S-Methyl-cysteine sulfoxide

Alliin (S-Allyl-cysteine sulfoxide)

Zwiebelane


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Thiosulfinates

Allyl-methane-thiosulfinate

Methyl-methane-thiosulfinate

Diallyl-thiosulfinate (Allicin?)

Dipropenyl-thiosulfinate (Allicin)


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Derivatives from Allicin

Ajoenes

Z-ajoene

E-ajoene

Dithiins 2-vynyl-1,3-dithiin

3-vynyl-1,2-dithiin


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Pharmacology of sulfur compounds

Hypocholesterolemic effect

Anti-atherosclerosis

Inhibit platelet aggregation, anti-thrombotic

Anti-infections, antibiotic activity

Hypoglycemic effect

Antitumoral effect

Antioxidant effect


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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


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Top supplements used in USA in 1997


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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


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Allium sativum L


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Chemical composition

Gamma-glutamyl-cysteine

Alliin (80 % of sulfated compounds)

Alliinase

Allicin

Other sulfoxides

Other thiosulfinates

Saponins

Flavonoids


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T1=diallylsulfide, T2=allicin, T3=dipropylthiosulfinate, T4=dimethylthiosulfinate

1=Allium sativum, 2=Allium ursinum, 3=Allium cepa

Toluene:Ethylacetate

(100:30)

Paladium II chloride

reagent


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T1=diallylsulfide, T2=allicin, T3=dipropylthiosulfinate, T4=dimethylthiosulfinate

1=Allium sativum, 2=Allium ursinum, 3=Allium cepa

Vanillin-Acetic acid

reagent


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Pharmacology of garlic

Anticoagulant and thrombolytic

Decrease the synthesis of cholesterol

Prevents atherosclerosis

Antithrombotic

Chemopreventive and antitumoral

Antimutagenic activity

Antimicrobial effect

Prevents nephrotoxicity


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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


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http://en.wikipedia.org/wiki/Image:Eicosanoid_synthesis.svg


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TOXICITY OF GARLIC (The dose makes the poison)


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GLUCOSINOLATES

Glucotropaeolin4-Methoxybenzyl glucosinolate

Glucoalyssin

4-Hydroxybenzyl glucosinolate

Glucobrassicanapin

Glucobrassicin

4-Methoxyindolyl-3-methyl glucosinolate

3-Methoxyglucotropaeolin


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AROMATIC ISOTHIOCYANATES

Benzylisothiocyanate

4-Methoxybenzylisothiocyanate

3-Methoxybenzylisothiocyanate


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End of presentation

Thank you!

phytopharmacology class 4 (primary metabolism in plants)

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