Anthaquinones Active components of many crude drugs with purgative properties Colored compounds traditionally used as dyes Mostly glycosides (mainly glucosides or rhamnosides) Sugar residue is prerequisite for pharmacological effects 9,10-anthraquinone as basic st.

Classes of Anthraquinones Based on degree of oxidation status oxid. red.

Biosynthesis of Anthraquinones Mainly produced via acylpolymalonate (acetate-malonate) pathway in Polygonaceae & Rhamnaceae & Leguminosae…. Starts with acetyl CoA carboxylation to malonly CoA then continues in the usual way of formation of the poly-keto-methylene-chain with simultaneous loss of CO2 followed by cyclisation Shikimate-mediated in Rutaceae, Rubiaceae & Gesneriaceae ACP= Acyl carrying protein

In the biosynthesis of the anthraquinones for the formation of the poly-keto-methylene-chain : 1 acetyl CoA and 7 Malonyl CoA are used.

Anthraquinones from Shikimic Acid Shikimic acid reacts with alpha ketoglutaric acid which can be formed either by deamination of glutamic acid or via the citric acid cycle Succinylbenzoic acid intermediate binds with mevalonic acid (formed from aceteate) to prduce anthraquinones

Important anthraquinones: OH at C-1 and C-8 R at C-3: CH3………………Chrysophanol R at C-3: CH2OH………….Aloe-emodine R at C-3: COOH…………. Rhein R at C-3: CH3 and at C-6 OH Frangula-emodine R at C-3: CH3 and at C-6 OCH3 Phycion

Natural Sources Widespread in plant kingdom Produced by microorganimsms e.g. Penicillium & Aspergillus spp Anthraquinone-rich plant families: Liliaceae, Polygonaceae, Rhamnaceae, Rubiaceae, Fabaceae, Rutaceae Animals produce anthraquinones e.g. cochineal insect

Medicinal Use of Antharquinones Purgatives Pure compounds are rarely prescribed Mostly used as simple extracts of crude drugs Sugar moiety increases solubility & facilitates transport to the site of action Aglycone is active part Anthrone is the most effective form Normal flora in colon liberates aglycone to stimulate peristalsis Too much anthrones in crude drugs are not suitable for use (frangula bark storing to allow {O} to anthraquinone

Frangula Bark Dried bark of Rhamnus frangula L. (Rhamnaceae) Fresh frangula rich anthrones (too strong) Storing for one year to oxidize (mild activity and widely used) 2-4% glucofrangulins Frangulin A & B are minor

Dried bark of Rhamnus purshiana (Rhamnaceae) Cascara Bark Dried bark of Rhamnus purshiana (Rhamnaceae) Cascara (Spanish word from cascara sagrada=sacred bark) Fresh cascara like frangula (must be stored before use) 6-9% Anthraquinones mainly Cascarosides A-D A & B aloe-emodine anthrone (aglycone) C & D chrysophanol anthrone (aglycone) Crude bark from west coast of North America, British Columbia & Canada Cascarosides of 2 steroisomeric pairs differ in their aglycones

Aloe spp (Liliaceae) Aloe barbadensis, A. ferox dried juice from the leaves (from leave base) Strong purgative Barbaloin A & B (stereoisomers) Aloinosides A & B (stereoisomers) Aloin= H2O-sol. components of aloe Aloin might be used for barbaloin Best avoid aloin (ambiguous term)

Other Aloe Preparations Aloe vera leaf mucilage from parenchymatous layer Herbal remedy for sunburn Cosmetic industry FREE FROM ANTHRAQUINONES

Rhubarb radix الرواند Dried rhizomes & roots of Rheum palmatum (Polygonaceae) Active Ingredients: mixture of complex anthraquinone glycosides. Aglycone classification Noncarboxyllated chrysophanol, aloe-emodin, emodin & physcion COOH-containing e.g. rhein Anthrones & dianthrones of the above Hetero-dianthrones of anthrones Tannins of rhubarb responsible for mild activity

Raponticin: A stilbene glucoside from Rheum raponticum, R Raponticin: A stilbene glucoside from Rheum raponticum, R. undulatum; estrogenic action, treatment of menopausol symptoms; Alzheimer’s disease(?)

Senna Folium Dried leaves of Cassia angustifolia or Cassia senna = C. acutifolia (Fabaceae) Sennosides A-D Sennosides A & B (Homodiantrone) Sennosides C & D (heterodianthrone) Sennosides A & B are ingredients of many products in the market

Senna fructus Dried fruit of C. senna or C. angustifolia Same active ingredients as leaves in addition to rhein dianthrones containing up to 10-sugar molecules Milder laxative than leaves