Guggulipid: ancient medicine for new therapeutic targets
Gum resin from the tree Commiphora mukul Engl. is one of the most popular therapeutic agents in Ayurveda, the traditional Indian system of practicing medicine. The Sushruta Samhita (600 B.C) a well-known Ayurvedic medical text, describes the usefulness of the gum resin from the tree C. mukul in the treatment of number of ailments, including arthritis, inflammation, obesity and disorders of lipid metabolism.
C. mukul, a member of the Burseraceae family, is found in arid areas of India, Bangladesh and Pakistan. A small busty tree with thorny branches, it produces a yellowish gum resin in small ducts located throughout its bark. Each collecting season a guggul tree yields between 250 – 500 grams of dry resin, which is extracted from the bark through a process called tapping. The tree is tapped in the months of November to January and the resin is collected from May to June.
The ethyl acetate extract of gum guggul, reported to have hypolipidemic and anti-inflammatory activities, was subjected to further study by separating it into basic, acidic and neutral fractions. In these studies the acidic fraction retained anti-inflammatory activity, while the neutral fraction retained hypolipidemic activity. Additional studies on the neutral fraction revealed that it could be further separated into ketonic and non-ketonic fractions. In the ketonic fraction, a number of steroids were identified, including isomers of E and Z – Guggulsterone, which were found to be responsible for the hypolipidemic activity. Since receiving regulatory approval in India in 1987, this extract termed Guggulipid, has been widely and effectively used to treat Hyperlipidemia.
Clinical studies have demonstrated that administration of guggulipid, the ethyl extract of gum guggul, significantly lowers LDL-cholesterol and triglyceride levels in patients with Hyperlipidemia. In the largest reported study of 205 patients with cholesterol levels greater than 220 mg/dl and/or triglyceride levels greater than 150 mg/dl, Guggulipid administered at a dose of 500 mg daily for 12 weeks significantly decreased serum cholesterol (24%) and triglyceride (23%). In addition to a hypolipidemic effect, gum guggul has been reported to have a beneficial effect on obesity, inflammation, and acne, and stimulatory effects on the thyroid gland and drug metabolism. A recent study also suggests guggulipid may be a potential anti-dementia drug.
Studies have shown that the isomers E and Z – Guggulsterone are effective antagonists of the bile acid receptor farnesoid X receptor (FXR), a ligand-dependent transcription factor that regulates the expression of genes involved in maintaining cholesterol / bile acid homeostasis. Importantly, expression of FXR is required for the lipid-lowering activity of guggulsterone in mice, which suggests that guggulsterone may lower lipid levels by inhibiting the transcription activity of FXR. A protective affect against streptozotocin induced memory deficits model of dementia can be attributed to anti-oxidant and anti-AChE activity of guggulipid. In clinical studies, gum guggul did show some side effects, including headache, diarrhoea and skin rashes. Purification of gum guggul decreased the incidence of these symptoms. From a medical perspective, guggulsterone is likely to interact with the many drugs whose metabolism is increased in response to PXR activation. Therefore, guggulipid should be used only with caution in combination with other drugs.
Further reading:
Urizar, N. L. and D. D. Moore (2003). "Guggulipid: A natural Cholesterol-lowering agent." Annu. Rev. Nutr., 23: 303-313.
Panda, S. and A. Kar (2005). "Guggulu (Commiphora mukul) potentially ameliorates hypothyroidism in female mice." Phytotherapy Research 19(1): 78-80.
Deng, R. (2007). "Therapeutic effects of guggul and its constituent guggulsterone: cardiovascular benefits." Cardiovascular Drug Reviews 25(4): 375-390.
Saxena, G., P. Singh Sheelendra, R. Pal, S. Singh, R. Pratap and C. Nath (2007). "Gugulipid, an extract of Commiphora whighitii with lipid-lowering properties, has protective effects against streptozotocin-induced memory deficits in mice." Pharmacology, biochemistry, and behavior 86(4): 797-805.
Ahn, S.-I. and H.-S. Youn (2008). "Guggulsterone suppresses the activation of NF-kB and expression of COX-2 induced by toll-like receptor 2, 3, and 4 agonists." Food Science and Biotechnology 17(6): 1294-1298.
Shishodia, S., K. B. Harikumar, S. Dass, K. G. Ramawat and B. B. Aggarwal (2008). "The guggul for chronic diseases: ancient medicine, modern targets.":Anticancer Research 28(6A): 3647-3664.
By Thirumurugan Rathinasabapathy
