PHARM. DChemical Pharmacognosy- I

Lecture 18April 7th, 2011

GLYCOSIDESSAPONIN GLYCOSIDES

M. M. AhsanAhsan KhalidKhalid, , B.PharmB.Pharm, Pharm. D, Pharm. DM.PhilM.Phil Scholar (RIPS/RIU)Scholar (RIPS/RIU)

HIPSHIPS--HUKICHUKIC

Saponins are a class of chemical compounds, one of many secondary metabolites found in natural sources, with saponins found in particular abundance in various plant species.

Specifically, they are amphipathic glycosides grouped phenomenologically by the soap-like foaming they produce when shaken in aqueous solutions, and structurally by their composition of one or more hydrophilic glycoside moieties combined with a lipophilic triterpene derivative

These compounds give a permanent froth when shaken with water. They also cause hemolysis of red blood cells.

Their medicinal value is due to their expectorant, and corticoid and anti-inflammatory effects.

Steroid saponins for example in Dioscorea wild yam, the sapogenin diosgenin, in form of its glycoside dioscin, is an important starting material for production of semi-synthetic glucocorticoidsand other steroid hormones such as progesterone.

In general, the use of the term saponin in organic chemistry is discouraged, because many plant constituents can produce foam, and many triterpene-glycosides are amphipolar under certain conditions acting as a tenside. More modern uses of saponins in biotechnology are as adjuvants in vaccines, Quil A and its derivatives QS-21, isolated from the bark of Quillaja saponaria, to stimulate both the Th1 immune response and the production of cytotoxic T-lymphocytes (CTLs) against exogenous antigens makes them ideal for use in subunit vaccines and vaccines directed against intracellular pathogens as well as for therapeutic cancer vaccines but with the aforementioned side effects of hemolysis.

Saponin glycosides are divided into 2 types based on theChemical structure of their aglycones (sapogenins).

Saponins on hydrolysis yield an aglycone known as "sapogenin".

The so-called NEUTRAL saponins are derivatives of STEROIDSwith spiroketal side chains.

The ACID saponins possess triterpenoid structures.

• The main pathway leading to both types of sapogenins is similar and involves the head-to-tail coupling of acetate units. However, a branch occurs, after the formation of the triterpenoid hydrocarbon, squalene, that leads to steroids in one direction and to cyclic triterpenoids in the other.

Glycyrrhiza is the dried rhizome and roots of Glycyrrhiza glabra. Glycyrrhiza contains: 1. A saponin glycoside called Glycyrrhizin (glycyrrhizinic acid).

Glycyrrhizin is the Ca2+ and K+ salts of glycyrrhizinic acid.

Glycyrrhizinic acid is 50 times sweeter than sugar (sucrose). Upon hydrolysis, the glycoside loses its sweet taste and is converted to the aglycone glycyrrhetinic acid plus two molecules of glucuronic acid.

Glycyrrhetinic acid is a pentacyclic triterpenoid derivative of the beta-amyrin type.

It has expectorant and antitussive properties (Chandler,1985).

Expectorants are used to decrease the viscosity of tenacious mucus, or to increasethe secretion of mucus in dry irritant unproductive cough, thereby, lubricatingthe air passages and making coughing more productive.

It is used considerably as a flavoring agent and is frequentlyemployed to mask the taste of bitter drugs such as aloe, quinine etc.

Glycyrrhetinic acid inhibits the enzymes (15-hydroxyprostaglandin dehydrogenase & delta 13-prostaglandin) that metabolise the prostaglandins, PGE2 and PGF2alpha to their respective 15 keto-13,14-dihydro metabolites which are INACTIVE.

This causes an increased level of prostaglandins in the digestive system.

Prostaglandins inhibit gastric secretion but stimulate pancreatic secretion and mucous secretion in the intestines and markedly increase intestinal motility.

They also cause cell proliferation in the stomach. The effect on gastric acid secretion, promotion of mucous secretion and cell proliferation shows why licorice has potential in treating peptic ulcer

PGF2alpha stimulates activity of the uterus during pregnancyand can cause abortion, therefore, licorice should notbe taken during pregnancy.

The structure of glycyrrhetinic acid is similar to that of cortisone.

Both molecules are flat and similar at position 3 and 11.

This might be the basis for licorice's anti-inflammatory action.

3-Beta-D-(monoglucuronyl)18-beta-glycyrrhetinic acid, a metabolite of glycyrrhetinic acid inhibits 11-beta-hydroxysteroid dehydrogenase which converts ACTIVE cortisol to INACTIVE cortisone in the kidneys.

The increased amounts of cortisol binds to the unprotected, unspecific mineralocorticoid receptors and induce sodium and fluid retention, hypokalaemia, hypertension and inhibition of the RENIN-ANGIOTENSIN-ALDOSTERONE system.

Licorice should not be given to patients with a known history of high blood pressure. A prolonged usage of licorice can also cause the formation of cataracts.

Glycyrrhizin inhibits liver cell injury caused by many chemicals and is used in the treatment of chronic hepatitis and cirrhosis in Japan.

It also inhibits the growth of several DNA and RNA viruses, inactivating herpes simplex virus particles irreversibly.