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Guggul (Commiphora mukul)


Commiphora mukul
Synonyms / Common Names / Related Terms
African myrrh, Arabian myrrh, Commiphora myrrha, guggal, Guggulu, guggulsterone (4,17(20)-pregnadiene-3,16-dione), gum guggul, gum guggulu, guggulsterone, gugulimax, guggulipid C+, guglip, gum myrrh, fraction A, myrrha, Somali myrrh, yemen myrhh.






Mechanism of Action

Pharmacology:

  • Lipid-lowering effects: Guggul (gum guggul) is a resin produced by the mukul mirth tree. Guggulipid is extracted from guggul using ethyl acetate. The preparation produced by extraction with petroleum ether is called a fraction A. Typical guggulipid preparations contain 2.5-5% of the plant sterols guggulsterones E and Z. These two components have been reported to exert effects on lipids.12,13 Several hypotheses have been advanced to explain these effects on lipids. Guggulsterones, particularly guggulsterone (4,17(20)-pregnadiene-3,16-dione), have been reported to function as antagonists of the farsenoid X receptor (FXR) and the bile acid receptor (BAR), nuclear hormones which are involved with cholesterol metabolism and bile acid regulation.1,4,5 It has been reported that guggulsterone does not exert its lipid effects on mice lacking FXR. Other publications have proposed that guggul may inhibit lipogenic enzymes and HMG-Co A reductase in the liver.14,15 increase uptake of cholesterol by the liver via stimulation of LDL receptor binding.13 directly activate the thyroid gland.7,6,8,16 and/or increase biliary and fecal excretion of cholesterol.15
  • Antioxidant effects: Guggul extracts have been reported to possess antioxidant properties17 possibly mediating protection against myocardial necrosis18,19.
  • Platelet effects: Guggulipid has been found to inhibit platelet aggregation and increase fibrinolysis.9,2,10,11
  • Anti-inflammatory: the results of several studies suggest possible anti-inflammatory and antiarthritic activities of guggul.20,21,22,23,24,25,26,27,28 On a per-microgram basis, guggulipid appears to be significantly less potent than indomethacin or hydrocortisone.23 Possible effects on high-sensitivity C-reactive protein (hs-CRP) have recently been observed in a clinical trial.3

Pharmacodynamics/Kinetics:

  • Insufficient available evidence.

References
  1. Urizar NL, Liverman AB, Dodds DT et al. A natural product that lowers cholesterol as an antagonist ligand for the FXR. Science (Science Express Reports) 2002 (May 3).
  2. Gaur SP, Garg RK, Kar AM, et al. Guggulipid, a new hypolipidaemic agent, in patients of acute ischaemic stroke: effect on clinical outcome, platelet function and serum lipids. Asia Pacif J Pharm 1997;12:65-69.
  3. Szapary PO, Wolfe ML, Bloedon LT, et al. Guggulipid for the treatment of hypercholesterolemia: a randomized controlled trial. JAMA 2003;290(6):765-772. 12915429
  4. Cui J, Huang L, Zhao A, et al. Guggulsterone is a farnesoid X receptor antagonist in coactivator association assays but acts to enhance transcription of bile salt export pump. J Biol Chem 2003;278(12):10214-10220. 12525500
  5. Wu J, Xia C, Meier J, et al. The hypolipidemic natural product guggulsterone acts as an antagonist of the bile acid receptor. Mol Endocrinol 2002;16(7):1590-1597. 12089353
  6. Tripathi YB, Malhotra OP, Tripathi SN. Thyroid stimulating action of Z-guggulsterone obtained from Commiphora mukul. Planta Med 1984;(1):78-80. 6739577
  7. Tripathi SN, Gupta M, Sen SP, et al. Effect of a keto-steroid of Commifora mukul L. on hypercholesterolemia & hyperlipidemia induced by neomercazole & cholesterol mixture in chicks. Indian J Exp Biol 1975;13(1):15-18. 1158393
  8. Tripathi YB, Tripathi P, Malhotra OP, et al. Thyroid stimulatory action of (Z)-guggulsterone: mechanism of action. Planta Med 1988;54(4):271-277. 3222368
  9. Mester L, Mester M, Nityanand S. Inhibition of platelet aggregation by "guggulu" steroids. Planta Med 1979;37(4):367-369. 538109
  10. Baldwa VS, Sharma RC, Ranka PC, et al. Effect of Commiphora mukul (guggul) on fibrinolytic activity and platelet aggregation in coronary artery disease. Rajas Med J 1980;19(2):84-86.
  11. Bordia A, Chuttani SK. Effect of gum guggulu on fibrinolysis and platelet adhesiveness in coronary heart disease. Indian J Med Res 1979;70:992-996. 396237
  12. Nityanand S, Kapoor NK. Hypocholesterolemic effect of Commiphora mukul resin (guggal). Indian J Exp Biol 1971;9(3):376-377. 5144338
  13. Singh V, Kaul S, Chander R, et al. Stimulation of low density lipoprotein receptor activity in liver membrane of guggulsterone treated rats. Pharmacol Res 1990;22(1):37-44. 2330337
  14. Nityanand S, Kapoor NK. Cholesterol lowering activity of the various fractions of the guggal. Indian J Exp Biol 1973;11(5):395-396. 4793249
  15. Sheela CG, Augusti KT. Effects of S-allyl cysteine sulfoxide isolated from Allium sativum Linn and guggulipid on some enzymes and fecal excretions of bile acids and sterols in cholesterol fed rats. Indian J Exp Biol 1995;33(10):749-751. 8575806
  16. Panda S, Kar A. Gugulu (Commiphora mukul) induces triiodothyronine production: possible involvement of lipid peroxidation. Life Sci 1999;65(12):L137-L141. 10503949
  17. Singh K, Chander R, Kapoor NK. Guggulsterone, a potent hypolipidaemic, prevents oxidation of low density lipoprotein. Phytother Res 1997;11:291-294.
  18. Kaul S, Kapoor NK. Reversal of changes of lipid peroxide, xanthine oxidase and superoxide dismutase by cardio-protective drugs in isoproterenol induced myocardial necrosis in rats. Indian J Exp Biol 1989;27(7):625-627. 2632388
  19. Kaul S, Kapoor NK. Cardiac sarcolemma enzymes & liver microsomal cytochrome P450 in isoproterenol treated rats. Indian J Med Res 1989;90:62-68. 2722218
  20. Arora RB, Kapoor V, Gupta SK, et al. Isolation of a crystalline steroidal compound from Commiphora mukul & its anti-inflammatory activity. Indian J Exp Biol 1971;9(3):403-404. 5144347
  21. Arora RB, Taneja V, Sharma RC, et al. Anti-inflammatory studies on a crystalline steroid isolated from Commiphora mukul. Indian J Med Res 1972;60(6):929-931. 4660307
  22. Singh GB, Atal CK. Pharmacology of an extract of salai guggal ex-Boswellia serrata, a new non-steroidal anti-inflammatory agent. Agents Actions 1986;18(3-4):407-412. 3751752
  23. Sosa S, Tubaro R, Della Loggia R, et al. Anti-inflammatory activity of Commiphora mukul extracts. Pharmacol Res 1993;27(suppl 1):89-90.
  24. Duwiejua M, Zeitlin IJ, Waterman PG, et al. Anti-inflammatory activity of resins from some species of the plant family Burseraceae. Planta Med 1993;59(1):12-16. 8441773
  25. Gujral ML, Sareen K, Reddy GS, et al. Endocrinological studies on the oleo resin of gum guggul. Indian J Med Sci 1962;16:847-851.
  26. Kesava RG, Dhar SC. Effect of a new non-steroidal anti-inflammatory agent on lysosomal stability in adjuvant induced arthritis. Ital J Biochem 1987;36(4):205-217. 3429205
  27. Kesava RG, Dhar SC, Singh GB. Urinary excretion of connective tissue metabolites under the influence of a new non-steroidal anti-inflammatory agent in adjuvant induced arthritis. Agents Actions 1987;22(1-2):99-105. 3687602
  28. Sharma JN, Sharma JN. Comparison of the anti-inflammatory activity of Commiphora mukul (an indigenous drug) with those of phenylbutazone and ibuprofen in experimental arthritis induced by mycobacterial adjuvant. Arzneimittelforschung 1977;27(7):1455-1457. 578471




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