Commiphora mukul (Guggul)

commiphora-mukul

NOME COMUNE

Commiphora mukul (Guggul)

NOME SCIENTIFICO

Commiphora wightii (Hook. ex Stocks)

FAMIGLIA

Burseraceae

HABITAT

Commiphora mukul è una pianta spinosa che cresce in terreni poveri dell’India, Bangladesh e Pakistan, ma può essere trovato dal Nord Africa all’Asia centrale . Predilige i climi aridi e semi-aridi. Attraverso l’incisione della corteccia nella parte bassa della pianta si ricava una resina, chiamata gomma gugul. [1]

PARTE USATA

Gommoresina

PREPARAZIONI FARMACEUTICHE CONSIGLIATE

Estratto secco titolato in Guggulsteroni Z ed E min.2,5 %

COMPOSIZIONE CHIMICA

La frazione resinosa contiene lignani diarilfuranici come la sesamina e altri composti simili, diterpeni macrociclici detti cembrani, esteri dell’acido ferulico e carburi saturi poliidrossilati in C18, C 19 e C 20 detti guggultretoli e steroidi derivati dal colestano e dal pregnano. I composti principali sono i guggulsteroni E e Z, , che sono isomeri geometrici del pregnan-4,17(20)-diene-3,16-one. Essi sono accompagnati dai guggulsteroli. Nella frazione gommosa si ritrova un polisaccaride con molecola molto ramificata, costituito da D-galattosio, da L-arabinosio e dall’etere metilico in 4 dell’acido D-glicuronico.
Esiste anche una frazione volatile, costituita soprattutto da monoterpeni e in particolare da mircene, ma anche da alfa pinene, beta pinene, sabinene, alfa tuiene, limonene, 3-carene e beta elemene. [2]

PROPRIETA’ SALUTISTICHE

Azione su colesterolo e trigliceridi

Utilizzato per secoli nei principali sistemi di Medicina Tradizionale, in particolar modo nell’Ayurveda[5,32,33], secondo letteratura scientifica il guggulipide possiede capacità ipolipemizzanti e soprattutto ipocolesterolemizzanti, contribuendo a ridurre il colesterolo totale e il colesterolo LDL, aumentando la ratio colesterolo HDL/colesterolo totale [5,-6,9,12,13,14,15,16,19,20].
Questa azione è dovuta in parte ad un aumento del numero dei recettori per le LDL posti sulla superficie degli epatociti e quindi ad un aumento del legame colesterolo/recettore [7], in parte ad uno stimolo sulla funzionalità della tiroide [11,49,50], i cui ormoni hanno notoriamente un effetto ipocolesterolemizzante e in parte anche ad un aumento dell’attività dell’enzima dopamina-beta-idrossilasi.
Dati recenti indicano che i guggulsteroni sono antagonisti del recettore X farnesoide, un recettore ormonale nucleare che è attivato dagli acidi biliari, e che provoca un aumento del colesterolo [9-35-36-37-51-52].

Dalla fine degli anni ’80 un crescente interesse scientifico per Guggul ha prodotto numerosi studi clinici per approfondirne i razionali di utilizzo nell’iperlipidemia, nell’ipercolesterolemia anche correlata a situazioni di obesità. Questi studi sono concordi nell’evidenziare che dopo assunzione per alcune settimane di estratto di guggul, si può osservare un’attività ipolipemizzante, con una riduzione media dei valori di colesterolo totale, colesterolo LDL e trigliceridi di circa il 13.5% [12,13,15,19]. Esami di laboratorio dimostrano anche che Guggul è in grado di prevenire l’ossidazione lipidica e di ridurre i fenomeni infiammatori, a carico delle cellule dei vasi sanguigni, che concorrono all’insorgenza delle malattie cardio-vascolari [5,7,22]. Secondo questi studi guggul dimostrerebbe la capacità di ridurre i livelli lipidici circolanti, determinando indirettamente un effetto cardioprotettivo [5].

Azione prevalente

  • Ipolipidemizzante
  • Ipocolesterolemizzante

Altre azioni

  • Antinfiammatoria
  • Antiossidante

Indicazioni principali

Trattamento coadiuvante dell’ipercolesterolemia moderata anche correlata a stati di sovrappeso ed obesità

EFFETTI COLLATERALI

In alcuni pazienti può provocare nausea, eruttazioni e singhiozzo. A dosi elevate, come per l’assunzione di elevati dosaggi, in genere, di gommoresine, può causare diarrea, che regredisce prontamente con la sospensione del trattamento.

CONTROINDICAZIONI

Non è consigliabile in gravidanza e durante l’allattamento

INTERAZIONI CON FARMACI

Questa droga potrebbe ridurre l’assorbimento intestinale del propranololo e del diltiazem

DATI TOSSICOLOGICI

Dati non disponibili

Bibliografia

1. Sultanul Abedin And S.I. Ali. “Commiphora wightii”. Flora of Pakistan. 26.

2. Jain Anurekha and Gupta.
Chemistry and pharmacological profile of guggul-A review. Indian journal of Traditional Knowledge pages 478{483, October 2006.

3. Urizar NL, Moore DD. GUGULIPID: a natural cholesterol-lowering agent. Annu Rev Nutr. 2003;23. 303-313.

4. Shishodia S, Harikumar KB, Dass S, Ramawat KG, Aggarwal BB.The guggul for chronic diseases: ancient medicine, modern targets. Anticancer Res. 2008 Nov-Dec;28(6A):3647-64. -.

5. Deng R. Therapeutic effects of guggul and its constituent guggulsterone: cardiovascular benefits. Cardiovasc Drug Rev. 2007 Winter;25(4):375-90.

6. Gupta A, Kapoor NK and Nityanand S: Mechanism of hypolipidemic action of standardized extract. Indian J Pharmacol 14: 1982.

7. Singh V, Kaul S, Chander R and Kapoor NK: Simultaneous low density lipoprotein receptor activity in liver membrane of guggulsterone treated rats. Pharmacology Research 22: 37-44, 1990.

8. Chander R, Khanna AK and Kapoor NK: Lipid-lowering activity of guggulsterone from Commiphora mukul in hyperlipidemic rats. Phytother Res 10: 508-511, 1996.

9. Cui J, Huang L, Zhao A, Lew JL, Yu J, Sahoo S, Meinke PT, Royo I, Pelaez F and Wright SD: Guggulsterone is a farnesoid X receptor antagonist in coactivator association assays but acts to enhance transcription of bile salt export pump. J Biol Chem 278: 10214-10220, 2003.

10. Urizar NL et al.A natural product that lowers cholesterol as an antagonist ligand for FXR. Science. 2002 May 31;296(5573):1703-6.

11. Tripathi YB, Malhotra OP and Tripathi SN: Thyroid-stimulating action of Z-guggulsterone obtained from Commiphora mukul. Planta Med 50: 78-80, 1984.

12. Kuppurajan K, Rajagopalan SS, Rao TK and Sitaraman R: Effect of guggul (Commiphora mukul–Engl.) on serum lipids in obese subjects. J Res India Med 8: 1-8, 1973.

13. Kuppurajan K, Rajagopalan SS, Rao TK and Sitaraman R: Effect of guggul (Commiphora mukul–Engl.) on serum lipids in obese, hypercholesterolemic and hyperlipemic cases. J Assoc Physicians India 26: 367-373, 1978.

14. Ghorai M, Mandal SC, Pal M, Pal SP and Saha BP: A comparative study on hypocholesterolaemic effect of allicin, whole germinated seeds of bengal gram and guggulipid of gum guggul. Phytother Res 14: 200-202, 2000.

15. Kotiyal JP, Bisht DB and Singh DS: Double cross-over trial of gum guggul (Commiphora mukul) fraction A in hypercholesterolemia. J Res India Med Yoga Hom 14: 11-16, 1979.

16. Verma SK and Bordia A: Effect of Commiphora mukul (gum guggulu) in patients of hyperlipidemia with special reference to HDL-cholesterol. Indian J Med Res 87: 356-360, 1988.

17. Nityanand S, Srivastava JS and Asthana OP: Clinical trials with guggulipid. A new hypolipidemic agent. J Assoc Physicians India 37: 323-328, 1989.

18. Singh RB, Niaz MA, Ghosh S. Hypolipidemic and antioxidant effects of Commiphora mukul as an adjunct to dietary therapy in patients with hypercholesterolemia. Cardiovasc Drugs Ther. 1994 Aug;8(4):659-64.

19. Nohr LA, Rasmussen LB, Straand J. Resin from the mukul myrrh tree, guggul, can it be used for treating hypercholesterolemia? A randomized, controlled study. Complement Ther Med. 2009 Jan;17(1):16-22. Epub 2008 Aug 15.

20. Singh K, Chander R and Kapoor NK: Guggulsterone, a potent hypolipidemic, prevents oxidation of low-density lipoprotein. Phytother Res 11: 291-294, 1997.

21. Wang X, Greilberger J, Ledinski G, Kager G, Paigen B and Jurgens G: The hypolipidemic natural product Commiphora mukul and its component guggulsterone inhibit oxidative modification of LDL. Atherosclerosis 172: 239-246, 2004.

22. Gebhard C. Guggulsterone, an anti-inflammatory phytosterol, inhibits tissue factor and arterial thrombosis. Basic Res Cardiol. 2009 May;104(3):285-94. Epub 2008 Oct 24.

23. Shishodia S and Aggarwal BB: Guggulsterone inhibits NFkappaB and IkappaBalpha kinase activation, suppresses expression of anti-apoptotic gene products, and enhances apoptosis. J Biol Chem 279: 47148-47158, 2004.

24. Kimura I, et al. New triterpenes, myrrhanol A and myrrhanone A, from guggul-gum resins, and their potent anti-inflammatory effect on adjuvant-induced air-pouch granuloma of mice. Bioorg Med Chem Lett. 2001 Apr 23;11(8):985-9.

25. Mencarelli A, Renga B, Palladino G, Distrutti E, Fiorucci S.The plant sterol guggulsterone attenuates inflammation and immune dysfunction in murine models of inflammatory bowel disease. Biochem Pharmacol. 2009 Nov 1;78(9):1214-23. Epub 2009 Jun 23.

26. Lv N, Song MY, Kim EK, Park JW, Kwon KB, Park BH.Guggulsterone, a plant sterol, inhibits NF-kappaB activation and protects pancreatic beta cells from cytokine toxicity. Mol Cell Endocrinol. 2008 Jul 16;289(1-2):49-59.

27. Singh BB, Mishra LC, Vinjamury SP, Aquilina N, Singh VJ and Shepard N: The effectiveness of Commiphora mukul for osteoarthritis of the knee: an outcomes study. Altern Ther Health Med 9: 74-79, 2003.

28. Dalvi SS, Nayak VK, Pohujani SM, Desai NK, Kshirsagar NA and Gupta KC: Effect of guggulipid on bioavailability of diltiazem and propranolol. J Assoc Physicians India 42: 454-455, 1994.

29. Kaul S and Kapoor NK: Cardiac sarcolemma enzymes and liver microsomal cytochrome P450 in isoproterenol-treated rats. Indian J Med Res 90: 62-68,

30. Szapary P.O. et al. Guggulipid for the treatment of hypercholesterolemia: a randomized controlled trial. JAMA. 290(6):765-72, 2003. PMID 12915429.

31. Sahni, S; Hepfinger, CA; Sauer, KA (2005). “Guggulipid Use in Hyperlipidemia”. Am J Health-Syst Pharm. 62 (16): 1690–1692. doi:10.2146/ajhp040580. PMID 16085931.

32. Satyavati GV. Gum guggul (Commiphora mukul)–the success story of an ancient insight leading to a modern discovery. Indian J Med Res.1988;87:327-335.PubMed

33. Dev S. Ethnotherapeutics and modern drug development: the potential of Ayurveda. Curr Sci.1997;73:909-928.

34. Nityanand S, Kapoor NK. Cholesterol lowering activity of the various fractions of guggul. Indian J Exp Biol.1973;11:395-398.PubMed

35. Urizar NL, Liverman AB, Dodds DT. et al. A natural product that lowers cholesterol as an antagonist ligand for the FXR. Science.2002;296:1703-1706.PubMed

36. 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;278:10214-10220.PubMed

37. Wu J, Xia C, Meier J, Li S, Hu X, Lala DS. The hypolipidemic natural product guggulsterone acts as an antagonist of the bile acid receptor. Mol Endocrinol.2002;16:1590-1597.PubMed

38. Agarwal RC, Singh SP, Saran RK. et al. Clinical trial of gugulipid–a new hypolipidemic agent of plant origin in primary hyperlipidemia. Indian J Med Res.1986;84:626-634.PubMed

39. Gopal K, Saran RK, Nityanand S. et al. Clinical trial of ethyl acetate extract of gum gugulu (gugulipid) in primary hyperlipidemia. J Assoc Physicians India.1986;34:249-251.PubMed

40. Nityanand S, Srivastava JS, Asthana OP. Clinical trials with gugulipid: a new hypolipidaemic agent. J Assoc Physicians India.1989;37:323-328.PubMed

41. Singh RB, Niaz MA, Ghosh S. Hypolipidemic and antioxidant effects of Commiphora mukul as an adjunct to dietary therapy in patients with hypercholesterolemia. Cardiovasc Drugs Ther.1994;8:659-664.PubMed

42. Ghorai M, Mandal SC, Pal M, Pal SP, Saha BP. A comparative study on hypocholesterolaemic effect of allicin, whole germinated seeds of bengal gram and guggulipid of gum gugglu. Phytother Res.2000;14:200-202.PubMed

43. Kuppurajan K, Rajagopalan SS, Rao TK, Sitaraman R. Effect of guggulu (Commiphora mukul–Engl.) on serum lipids in obese, hypercholesterolemic and hyperlipemic cases. J Assoc Physicians India.1978;26:367-373.PubMed

44. Verma SK, Bordia A. Effect of Commiphora mukul (gum guggulu) in patients of hyperlipidemia with special reference to HDL-cholesterol. Indian J Med Res.1988;87:356-360.PubMed

45. Malhotra SC, Ahuja MM. Comparative hypolipidaemic effectiveness of gum guggulu (Commiphora mukul) fraction ‘A’, ethyl-P-chlorophenoxyisobutyrate and Ciba-13437-Su. Indian J Med Res.1971;59:1621-1632.PubMed

46. Malhotra SC, Ahuja MM, Sundaram KR. Long-term clinical studies on the hypolipidaemic effect of Commiphora mukul (Guggulu) and clofibrate. Indian J Med Res.1977;65:390-395.

47. Nagarajan M, Waszkuc TW, Sun J. Simultaneous determination of E- and Z-guggulsterones in dietary supplements containing Commiphora mukul extract (guggulipid) by liquid chromatography. J AOAC Int.2001;84:24-28.PubMed

48. Das Gupta R. A new hypolipidaemic agent (gugulipid). J Assoc Physicians India.1990;38:186.PubMed18.Das Gupta R. Gugulipid: pro-lipaemic effect. J Assoc Physicians India.1990;38:598.PubMed

49. Tripathi YB, Malhotra OP, Tripathi SN. Thyroid stimulating action of Z-guggulsterone obtained from Commiphora mukul. Planta Med.1984;1:78-80.PubMed

50. Panda S, Kar A. Gugulu (Commiphora mukul) induces triiodothyronine production: possible involvement of lipid peroxidation. Life Sci.1999;65:PL137-PL141.PubMed

51. Russell DW. Nuclear orphan receptors control cholesterol catabolism. Cell.1999;97:539-542.PubMed

52. Sinal CJ, Tohkin M, Miyata M, Ward JM, Lambert G, Gonzalez FJ. Targeted disruption of the nuclear receptor FXR/BAR impairs bile acid and lipid homeostasis. Cell.2000;102:731-744.PubMed

53. Chawla A, Saez E, Evans RM. “Don’t know much bile-ology.” Cell.2000;103:1-4.PubMed

54. De Smet PA. Herbal remedies. N Engl J Med.2002;347:2046-2056.PubMed

55. Goldman P. Herbal medicines today and the roots of modern pharmacology. Ann Intern Med.2001;135(8 pt 1):594-600.PubMed

56. Arora RB, Taneja V, Sharma RC, Gupta SK. Anti-inflammatory studies on a crystalline steroid isolated from Commiphora mukul. Indian J Med Res.1972;60:929-931.PubMed

57. -Duwiejua M, Zeitlin IJ, Waterman PG, Chapman J, Mhango GJ, Provan GJ. Anti-inflammatory activity of resins from some species of the plant family Burseraceae. Planta Med.1993;59:12-16.PubMed JAMA®