Anthaquinones

1. 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.

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

3. 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

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

5. Anthraquinones from Shikimic Acid

6. Important anthraquinones: OH at C-1 and C-8R at C-3: CH3………………ChrysophanolR at C-3: CH2OH………….Aloe-emodineR at C-3: COOH…………. RheinR at C-3: CH3 and at C-6 OH Frangula-emodineR at C-3: CH3 and at C-6 OCH3 Phycion

7. 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

8. 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 • Anthroneis 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

9. 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

10. Cascara Bark Dried bark of Rhamnuspurshiana(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-emodineanthrone (aglycone) • C & D chrysophanolanthrone (aglycone)

11. Aloe spp (Liliaceae) • Aloe barbadensis, A. feroxdried 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)

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

13. 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

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

15. Senna Folium • Dried leaves of Cassia angustifoliaor 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

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