Skip to main content
SpringerLink
Log in

Guggulsterone and Its Role in Chronic Diseases

  • Chapter
  • First Online:
Drug Discovery from Mother Nature

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 929))

Abstract

Guggulsterone is a plant sterol derived from gum resin of Commiphora wightii. The gum resin from guggul plants has been used for thousand years in Ayurveda to treat various disorders, including internal tumors, obesity, liver disorders, malignant sores and ulcers, urinary complaints, intestinal worms, leucoderma, sinuses, edema, and sudden paralytic seizures. Guggulsterone has been identified a bioactive components of this gum resin. This plant steroid has been reported to work as an antagonist of certain nuclear receptors, especially farnesoid X receptor, which regulates bile acids and cholesterol metabolism. Guggulsterone also mediates gene expression through the regulation of transcription factors, including nuclear factor-kappa B and signal transducer and activator of transcription 3, which plays important roles in the development of inflammation and tumorigenesis. Guggulsterone has been shown to downregulate the expression of proteins involved in anti-apoptotic, cell survival, cell proliferation, angiogenic, metastatic, and chemoresistant activities in tumor cells. This review aimed to clarify the cell signal pathways targeted by guggulsterone and the bioactivities of guggulsterone in animal models and humans.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Aggarwal BB (2004) Nuclear factor-kappaB: the enemy within. Cancer Cell 6(3):203–208

    Article  CAS  PubMed  Google Scholar 

  2. Aggarwal BB, Kunnumakkara AB, Harikumar KB, Gupta SR, Tharakan ST, Koca C, Dey S, Sung B (2009) Signal transducer and activator of transcription-3, inflammation, and cancer: how intimate is the relationship? Ann N Y Acad Sci 1171:59–76

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Ahn DW, Seo JK, Lee SH, Hwang JH, Lee JK, Ryu JK, Kim YT, Yoon YB (2012) Enhanced antitumor effect of combination therapy with gemcitabine and guggulsterone in pancreatic cancer. Pancreas 41(7):1048–1057

    Article  CAS  PubMed  Google Scholar 

  4. Ahn KS, Sethi G, Sung B, Goel A, Ralhan R, Aggarwal BB (2008) Guggulsterone, a farnesoid X receptor antagonist, inhibits constitutive and inducible STAT3 activation through induction of a protein tyrosine phosphatase SHP-1. Cancer Res 68(11):4406–4415

    Article  CAS  PubMed  Google Scholar 

  5. Almazari I, Park JM, Park SA, Suh JY, Na HK, Cha YN, Surh YJ (2012) Guggulsterone induces heme oxygenase-1 expression through activation of Nrf2 in human mammary epithelial cells: PTEN as a putative target. Carcinogenesis 33(2):368–376

    Article  CAS  PubMed  Google Scholar 

  6. An MJ, Cheon JH, Kim SW, Kim ES, Kim TI, Kim WH (2009) Guggulsterone induces apoptosis in colon cancer cells and inhibits tumor growth in murine colorectal cancer xenografts. Cancer Lett 279(1):93–100

    Article  CAS  PubMed  Google Scholar 

  7. Baldwa VS, Bhasin V, Ranka PC, Mathur KM (1981) Effects of Commiphora mukul (Guggul) in experimentally induced hyperlipemia and atherosclerosis. J Assoc Phys India 29(1):13–17

    CAS  Google Scholar 

  8. Burris TP, Montrose C, Houck KA, Osborne HE, Bocchinfuso WP, Yaden BC, Cheng CC, Zink RW, Barr RJ, Hepler CD, Krishnan V, Bullock HA, Burris LL, Galvin RJ, Bramlett K, Stayrook KR (2005) The hypolipidemic natural product guggulsterone is a promiscuous steroid receptor ligand. Mol Pharmacol 67(3):948–954

    Article  CAS  PubMed  Google Scholar 

  9. Capello A, Moons LM, Van De Winkel A, Siersema PD, Van Dekken H, Kuipers EJ, Kusters JG (2008) Bile acid-stimulated expression of the farnesoid X receptor enhances the immune response in Barrett esophagus. Am J Gastroenterol 103(6):1510–1516

    Article  CAS  PubMed  Google Scholar 

  10. Chander R, Rizvi F, Khanna AK, Pratap R (2003) Cardioprotective activity of synthetic guggulsterone (E and Z-isomers) in isoproterenol induced myocardial ischemia in rats: a comparative study. Indian J Clin Biochem 18(2):71–79

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Chang KO, George DW (2007) Bile acids promote the expression of hepatitis C virus in replicon-harboring cells. J Virol 81(18):9633–9640

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Chen KG, Sikic BI (2012) Molecular pathways: regulation and therapeutic implications of multidrug resistance. Clin Cancer Res 18(7):1863–1869

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Cheon JH, Kim JS, Kim JM, Kim N, Jung HC, Song IS (2006) Plant sterol guggulsterone inhibits nuclear factor-kappaB signaling in intestinal epithelial cells by blocking IkappaB kinase and ameliorates acute murine colitis. Inflamm Bowel Dis 12(12):1152–1161

    Article  PubMed  Google Scholar 

  14. Choudhuri R, Degraff W, Gamson J, Mitchell JB, Cook JA (2011) Guggulsterone-mediated enhancement of radiosensitivity in human tumor cell lines. Front Oncol 1:19

    Article  PubMed  PubMed Central  Google Scholar 

  15. Clevers H (2006) Wnt/beta-catenin signaling in development and disease. Cell 127(3):469–480

    Article  CAS  PubMed  Google Scholar 

  16. Cornick CL, Strongitharm BH, Sassano G, Rawlins C, Mayes AE, Joseph AN, O’dowd J, Stocker C, Wargent E, Cawthorne MA, Brown AL, Arch JR (2009) Identification of a novel agonist of peroxisome proliferator-activated receptors alpha and gamma that may contribute to the anti-diabetic activity of guggulipid in Lep(ob)/Lep(ob) mice. J Nutr Biochem 20(10):806–815

    Google Scholar 

  17. Cui J, Huang L, Zhao A, Lew JL, Yu J, Sahoo S, Meinke PT, Royo I, Pelaez F, Wright SD (2003) 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(12):10214–10220

    Article  CAS  PubMed  Google Scholar 

  18. De Gottardi A, Dumonceau JM, Bruttin F, Vonlaufen A, Morard I, Spahr L, Rubbia-Brandt L, Frossard JL, Dinjens WN, Rabinovitch PS, Hadengue A (2006) Expression of the bile acid receptor FXR in Barrett’s esophagus and enhancement of apoptosis by guggulsterone in vitro. Mol Cancer 5:48

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Deng R (2007) Therapeutic effects of guggul and its constituent guggulsterone: cardiovascular benefits. Cardiovasc Drug Rev 25(4):375–390

    CAS  PubMed  Google Scholar 

  20. Dhillon AS, Hagan S, Rath O, Kolch W (2007) MAP kinase signalling pathways in cancer. Oncogene 26(22):3279–3290

    Article  CAS  PubMed  Google Scholar 

  21. Ding X, Staudinger JL (2005) The ratio of constitutive androstane receptor to pregnane X receptor determines the activity of guggulsterone against the Cyp2b10 promoter. J Pharmacol Exp Ther 314(1):120–127

    Article  CAS  PubMed  Google Scholar 

  22. Dixit D, Ghildiyal R, Anto NP, Ghosh S, Sharma V, Sen E (2013) Guggulsterone sensitizes glioblastoma cells to Sonic hedgehog inhibitor SANT-1 induced apoptosis in a Ras/NFkappaB dependent manner. Cancer Lett 336(2):347–358

    Article  CAS  PubMed  Google Scholar 

  23. Dixit VP, Joshi S, Sinha R, Bharvava SK, Varma M (1980) Hypolipidemic activity of guggal resin (Commiphora mukul) and garlic (Alium sativum linn.) in dogs (Canis familiaris) and monkeys (Presbytis entellus entellus Dufresne). Biochem Exp Biol 16(4):421–424

    CAS  PubMed  Google Scholar 

  24. Dufer M, Horth K, Wagner R, Schittenhelm B, Prowald S, Wagner TF, Oberwinkler J, Lukowski R, Gonzalez FJ, Krippeit-Drews P, Drews G (2012) Bile acids acutely stimulate insulin secretion of mouse beta-cells via farnesoid X receptor activation and K(ATP) channel inhibition. Diabetes 61(6):1479–1489

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Gao Y, Zeng Y, Tian J, Islam MS, Jiang G, Xiao D (2014) Guggulsterone inhibits prostate cancer growth via inactivation of Akt regulated by ATP citrate lyase signaling. Oncotarget

    Google Scholar 

  26. Gebhard C, Stampfli SF, Gebhard CE, Akhmedov A, Breitenstein A, Camici GG, Holy EW, Luscher TF, Tanner FC (2009) Guggulsterone, an anti-inflammatory phytosterol, inhibits tissue factor and arterial thrombosis. Basic Res Cardiol 104(3):285–294

    Article  CAS  PubMed  Google Scholar 

  27. Ghorai M, Mandal SC, Pal M, Pal SP, Saha BP (2000) A comparative study on hypocholesterolaemic effect of allicin, whole germinated seeds of bengal gram and guggulipid of gum gugglu. Phytother Res 14(3):200–202

    Article  CAS  PubMed  Google Scholar 

  28. Gonzalez R, Garitaonandia I, Abramihina T, Wambua GK, Ostrowska A, Brock M, Noskov A, Boscolo FS, Craw JS, Laurent LC, Snyder EY, Semechkin RA (2013) Deriving dopaminergic neurons for clinical use. A practical approach. Sci Rep 3:1463

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Gopal K, Saran RK, Nityanand S, Gupta PP, Hasan M, Das SK, Sinha N, Agarwal SS (1986) Clinical trial of ethyl acetate extract of gum gugulu (gugulipid) in primary hyperlipidemia. J Assoc Physicians India 34(4):249–251

    CAS  PubMed  Google Scholar 

  30. Guan B, Li H, Yang Z, Hoque A, Xu X (2013) Inhibition of farnesoid X receptor controls esophageal cancer cell growth in vitro and in nude mouse xenografts. Cancer 119(7):1321–1329

    Article  CAS  PubMed  Google Scholar 

  31. Ichikawa H, Aggarwal BB (2006) Guggulsterone inhibits osteoclastogenesis induced by receptor activator of nuclear factor-kappaB ligand and by tumor cells by suppressing nuclear factor-kappaB activation. Clin Cancer Res 12(2):662–668

    Article  CAS  PubMed  Google Scholar 

  32. Id Boufker H, Lagneaux L, Fayyad-Kazan H, Badran B, Najar M, Wiedig M, Ghanem G, Laurent G, Body JJ, Journe F (2011) Role of farnesoid X receptor (FXR) in the process of differentiation of bone marrow stromal cells into osteoblasts. Bone 49(6):1219–1231

    Article  PubMed  CAS  Google Scholar 

  33. Janakiram NB, Rao CV (2012) iNOS-selective inhibitors for cancer prevention: promise and progress. Future Med Chem 4(17):2193–2204

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Jiang G, Xiao X, Zeng Y, Nagabhushanam K, Majeed M, Xiao D (2013) Targeting beta-catenin signaling to induce apoptosis in human breast cancer cells by z-guggulsterone and Gugulipid extract of Ayurvedic medicine plant Commiphora mukul. BMC Complement Altern Med 13:203

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Kalariya NM, Shoeb M, Reddy AB, Zhang M, Van Kuijk FJ, Ramana KV (2010) Prevention of endotoxin-induced uveitis in rats by plant sterol guggulsterone. Invest Ophthalmol Vis Sci 51(10):5105–5113

    Article  PubMed  PubMed Central  Google Scholar 

  36. Kang SJ, Kim JM, Koh SJ, Kim SH, Im JP, Jung HC, Kim JS (2013) The guggulsterone derivative GG-52 inhibits NF-kappaB signaling in bone marrow-derived dendritic cells and attenuates colitis in IL-10 knockout mice. Life Sci 92(22):1064–1071

    Article  CAS  PubMed  Google Scholar 

  37. Kaul S, Kapoor NK (1989) Cardiac sarcolemma enzymes and liver microsomal cytochrome P450 in isoproterenol treated rats. Indian J Med Res 90:62–68

    CAS  PubMed  Google Scholar 

  38. Khan MK, Ansari IA, Khan MS (2013) Dietary phytochemicals as potent chemotherapeutic agents against breast cancer: inhibition of NF-kappaB pathway via molecular interactions in rel homology domain of its precursor protein p105. Pharmacogn Mag 9(33):51–57

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Khanna DS, Agarwal OP, Gupta SK, Arora RB (1969) A biochemical approach to anti-atherosclerotic action of Commiphora-mukul: an Indian indigenous drug in Indian domestic pigs (Sus scrofa). Indian J Med Res 57(5):900–906

    CAS  PubMed  Google Scholar 

  40. Kim BH, Yoon JH, Yang JI, Myung SJ, Lee JH, Jung EU, Yu SJ, Kim YJ, Lee HS, Kim CY (2013) Guggulsterone attenuates activation and survival of hepatic stellate cell by inhibiting nuclear factor kappa B activation and inducing apoptosis. J Gastroenterol Hepatol 28(12):1859–1868

    Article  CAS  PubMed  Google Scholar 

  41. Kim DG, Bae GS, Choi SB, Jo IJ, Shin JY, Lee SK, Kim MJ, Kim MJ, Jeong HW, Choi CM, Seo SH, Choo GC, Seo SW, Song HJ, Park SJ (2015) Guggulsterone attenuates cerulein-induced acute pancreatitis via inhibition of ERK and JNK activation. Int Immunopharmacol 26(1):194–202

    Article  CAS  PubMed  Google Scholar 

  42. Kim DG, Bae GS, Jo IJ, Choi SB, Kim MJ, Jeong JH, Kang DG, Lee HS, Song HJ, Park SJ (2015) Guggulsterone attenuated lipopolysaccharide-induced inflammatory responses in mouse inner medullary collecting duct-3 cells. Inflammation 39:87–95

    Article  CAS  Google Scholar 

  43. Kim ES, Hong SY, Lee HK, Kim SW, An MJ, Kim TI, Lee KR, Kim WH, Cheon JH (2008) Guggulsterone inhibits angiogenesis by blocking STAT3 and VEGF expression in colon cancer cells. Oncol Rep 20(6):1321–1327

    CAS  PubMed  Google Scholar 

  44. Kim JM, Kang HW, Cha MY, Yoo D, Kim N, Kim IK, Ku J, Kim S, Ma SH, Jung HC, Song IS, Kim JS (2010) Novel guggulsterone derivative GG-52 inhibits NF-kappaB signaling in intestinal epithelial cells and attenuates acute murine colitis. Lab Invest 90(7):1004–1015

    Article  CAS  PubMed  Google Scholar 

  45. Koo JH, Rhee KS, Koh HW, Jang HY, Park BH, Park JW (2012) Guggulsterone inhibits melanogenesis in B16 murine melanoma cells by downregulating tyrosinase expression. Int J Mol Med 30(4):974–978

    CAS  PubMed  Google Scholar 

  46. Krishnamurthy K, Wang G, Rokhfeld D, Bieberich E (2008) Deoxycholate promotes survival of breast cancer cells by reducing the level of pro-apoptotic ceramide. Breast Cancer Res 10(6):R106

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  47. Kuppurajan K, Rajagopalan SS et al (1973) Effect of guggul (Commiphora mukul) on serum lipids in obese subjects. J Res India Med 8:8

    Google Scholar 

  48. Lata S, Saxena KK, Bhasin V, Saxena RS, Kumar A, Srivastava VK (1991) Beneficial effects of Allium sativum, Allium cepa and Commiphora mukul on experimental hyperlipidemia and atherosclerosis—a comparative evaluation. J Postgrad Med 37(3):132–135

    CAS  PubMed  Google Scholar 

  49. Lee JY, Lee KT, Lee JK, Lee KH, Jang KT, Heo JS, Choi SH, Kim Y, Rhee JC (2011) Farnesoid X receptor, overexpressed in pancreatic cancer with lymph node metastasis promotes cell migration and invasion. Br J Cancer 104(6):1027–1037

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Lee YR, Lee JH, Noh EM, Kim EK, Song MY, Jung WS, Park SJ, Kim JS, Park JW, Kwon KB, Park BH (2008) Guggulsterone blocks IL-1beta-mediated inflammatory responses by suppressing NF-kappaB activation in fibroblast-like synoviocytes. Life Sci 82(23–24):1203–1209

    Article  CAS  PubMed  Google Scholar 

  51. Leeman-Neill RJ, Wheeler SE, Singh SV, Thomas SM, Seethala RR, Neill DB, Panahandeh MC, Hahm ER, Joyce SC, Sen M, Cai Q, Freilino ML, Li C, Johnson DE, Grandis JR (2009) Guggulsterone enhances head and neck cancer therapies via inhibition of signal transducer and activator of transcription-3. Carcinogenesis 30(11):1848–1856

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Li C, Zang Y, Sen M, Leeman-Neill RJ, Man DS, Grandis JR, Johnson DE (2009) Bortezomib up-regulates activated signal transducer and activator of transcription-3 and synergizes with inhibitors of signal transducer and activator of transcription-3 to promote head and neck squamous cell carcinoma cell death. Mol Cancer Ther 8(8):2211–2220

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Luo J, Manning BD, Cantley LC (2003) Targeting the PI3K-Akt pathway in human cancer: rationale and promise. Cancer Cell 4(4):257–262

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  55. Macha MA, Matta A, Chauhan S, Siu KM, Ralhan R (2010) 14-3-3 zeta is a molecular target in guggulsterone induced apoptosis in head and neck cancer cells. BMC Cancer 10:655

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Macha MA, Matta A, Chauhan SS, Siu KW, Ralhan R (2011) Guggulsterone (GS) inhibits smokeless tobacco and nicotine-induced NF-kappaB and STAT3 pathways in head and neck cancer cells. Carcinogenesis 32(3):368–380

    Article  CAS  PubMed  Google Scholar 

  57. Macha MA, Rachagani S, Gupta S, Pai P, Ponnusamy MP, Batra SK, Jain M (2013) Guggulsterone decreases proliferation and metastatic behavior of pancreatic cancer cells by modulating JAK/STAT and Src/FAK signaling. Cancer Lett 341(2):166–177

    Article  CAS  PubMed  Google Scholar 

  58. Makishima M, Okamoto AY, Repa JJ, Tu H, Learned RM, Luk A, Hull MV, Lustig KD, Mangelsdorf DJ, Shan B (1999) Identification of a nuclear receptor for bile acids. Science 284(5418):1362–1365

    Article  CAS  PubMed  Google Scholar 

  59. Malhotra SC, Ahuja MM (1971) Comparative hypolipidaemic effectiveness of gum guggulu (Commiphora mukul) fraction ‘A’, ethyl-P-chlorophenoxyisobutyrate and Ciba-13437-Su. Indian J Med Res 59(10):1621–1632

    CAS  PubMed  Google Scholar 

  60. Mencarelli A, Renga B, Palladino G, Distrutti E, Fiorucci S (2009) The plant sterol guggulsterone attenuates inflammation and immune dysfunction in murine models of inflammatory bowel disease. Biochem Pharmacol 78(9):1214–1223

    Article  CAS  PubMed  Google Scholar 

  61. Meselhy MR (2003) Inhibition of LPS-induced NO production by the oleogum resin of Commiphora wightii and its constituents. Phytochemistry 62(2):213–218

    Article  CAS  PubMed  Google Scholar 

  62. Meyer U, Costantino G, Macchiarulo A, Pellicciari R (2005) Is antagonism of E/Z-guggulsterone at the farnesoid X receptor mediated by a noncanonical binding site? A molecular modeling study. J Med Chem 48(22):6948–6955

    Article  CAS  PubMed  Google Scholar 

  63. Moon DO, Park SY, Choi YH, Ahn JS, Kim GY (2011) Guggulsterone sensitizes hepatoma cells to TRAIL-induced apoptosis through the induction of CHOP-dependent DR5: involvement of ROS-dependent ER-stress. Biochem Pharmacol 82(11):1641–1650

    Article  CAS  PubMed  Google Scholar 

  64. Moon Y, Choi SM, Chang S, Park B, Lee S, Lee MO, Choi HS, Park H (2015) Chenodeoxycholic acid reduces hypoxia inducible factor-1alpha protein and its target genes. PLoS ONE 10(6):e0130911

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  65. Nabekura T, Yamaki T, Ueno K, Kitagawa S (2008) Effects of plant sterols on human multidrug transporters ABCB1 and ABCC1. Biochem Biophys Res Commun 369(2):363–368

    Article  CAS  PubMed  Google Scholar 

  66. Noh EM, Chung EY, Youn HJ, Jung SH, Hur H, Lee YR, Kim JS (2013) Cis-guggulsterone inhibits the IKK/NF-kappaB pathway, whereas trans-guggulsterone inhibits MAPK/AP-1 in MCF7 breast cancer cells: guggulsterone regulates MMP9 expression in an isomer-specific manner. Int J Mol Med 31(2):393–399

    CAS  PubMed  Google Scholar 

  67. Nohr LA, Rasmussen LB, Straand J (2009) Resin from the mukul myrrh tree, guggul, can it be used for treating hypercholesterolemia? A randomized, controlled study. Complement Ther Med 17(1):16–22

    Article  PubMed  Google Scholar 

  68. Ojha S, Bhatia J, Arora S, Golechha M, Kumari S, Arya DS (2011) Cardioprotective effects of Commiphora mukul against isoprenaline-induced cardiotoxicity: a biochemical and histopathological evaluation. J Environ Biol 32(6):731–738

    CAS  PubMed  Google Scholar 

  69. Owsley E, Chiang JY (2003) Guggulsterone antagonizes farnesoid X receptor induction of bile salt export pump but activates pregnane X receptor to inhibit cholesterol 7alpha-hydroxylase gene. Biochem Biophys Res Commun 304(1):191–195

    Article  CAS  PubMed  Google Scholar 

  70. Pal P, Kanaujiya JK, Lochab S, Tripathi SB, Sanyal S, Behre G, Trivedi AK (2013) Proteomic analysis of rosiglitazone and guggulsterone treated 3T3-L1 preadipocytes. Mol Cell Biochem 376(1–2):81–93

    Article  CAS  PubMed  Google Scholar 

  71. Parks DJ, Blanchard SG, Bledsoe RK, Chandra G, Consler TG, Kliewer SA, Stimmel JB, Willson TM, Zavacki AM, Moore DD, Lehmann JM (1999) Bile acids: natural ligands for an orphan nuclear receptor. Science 284(5418):1365–1368

    Article  CAS  PubMed  Google Scholar 

  72. Pu J, Yuan A, Shan P, Gao E, Wang X, Wang Y, Lau WB, Koch W, Ma XL, He B (2013) Cardiomyocyte-expressed farnesoid-X-receptor is a novel apoptosis mediator and contributes to myocardial ischaemia/reperfusion injury. Eur Heart J 34(24):1834–1845

    Article  CAS  PubMed  Google Scholar 

  73. Qin P, Borges-Marcucci LA, Evans MJ, Harnish DC (2005) Bile acid signaling through FXR induces intracellular adhesion molecule-1 expression in mouse liver and human hepatocytes. Am J Physiol Gastrointest Liver Physiol 289(2):G267–G273

    Article  CAS  PubMed  Google Scholar 

  74. Rizzo G, Disante M, Mencarelli A, Renga B, Gioiello A, Pellicciari R, Fiorucci S (2006) The farnesoid X receptor promotes adipocyte differentiation and regulates adipose cell function in vivo. Mol Pharmacol 70(4):1164–1173

    Article  CAS  PubMed  Google Scholar 

  75. Sarfaraz S, Siddiqui IA, Syed DN, Afaq F, Mukhtar H (2008) Guggulsterone modulates MAPK and NF-kappaB pathways and inhibits skin tumorigenesis in SENCAR mice. Carcinogenesis 29(10):2011–2018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  77. Satyavati GV, Dwarakanath C, Tripathi SN (1969) Experimental studies on the hypocholesterolemic effect of Commiphora mukul Engl. (Guggul). Indian J Med Res 57(10):1950–1962

    CAS  PubMed  Google Scholar 

  78. Saxena G, Singh SP, Pal R, Singh S, Pratap R, Nath C (2007) Gugulipid, an extract of Commiphora whighitii with lipid-lowering properties, has protective effects against streptozotocin-induced memory deficits in mice. Pharmacol Biochem Behav 86(4):797–805

    Article  CAS  PubMed  Google Scholar 

  79. Scholtes C, Diaz O, Icard V, Kaul A, Bartenschlager R, Lotteau V, Andre P (2008) Enhancement of genotype 1 hepatitis C virus replication by bile acids through FXR. J Hepatol 48(2):192–199

    Article  CAS  PubMed  Google Scholar 

  80. Sharma B, Salunke R, Srivastava S, Majumder C, Roy P (2009) Effects of guggulsterone isolated from Commiphora mukul in high fat diet induced diabetic rats. Food Chem Toxicol 47(10):2631–2639

    Article  CAS  PubMed  Google Scholar 

  81. Sharma JN, Sharma JN (1977) 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 27(7):1455–1457

    CAS  PubMed  Google Scholar 

  82. Shishodia S, Aggarwal BB (2004) Guggulsterone inhibits NF-kappaB and IkappaBalpha kinase activation, suppresses expression of anti-apoptotic gene products, and enhances apoptosis. J Biol Chem 279(45):47148–47158

    Article  CAS  PubMed  Google Scholar 

  83. Shishodia S, Azu N, Rosenzweig JA, Jackson DA (2015) Guggulsterone for chemoprevention of cancer. Curr Pharm Des 22:294–306

    Article  CAS  Google Scholar 

  84. Shishodia S, Harikumar KB, Dass S, Ramawat KG, Aggarwal BB (2008) The guggul for chronic diseases: ancient medicine, modern targets. Anticancer Res 28(6a):3647–3664

    CAS  PubMed  Google Scholar 

  85. Shishodia S, Sethi G, Ahn KS, Aggarwal BB (2007) Guggulsterone inhibits tumor cell proliferation, induces S-phase arrest, and promotes apoptosis through activation of c-Jun N-terminal kinase, suppression of Akt pathway, and downregulation of antiapoptotic gene products. Biochem Pharmacol 74(1):118–130

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Silva J, Dasgupta S, Wang G, Krishnamurthy K, Ritter E, Bieberich E (2006) Lipids isolated from bone induce the migration of human breast cancer cells. J Lipid Res 47(4):724–733

    Article  CAS  PubMed  Google Scholar 

  87. Sinal CJ, Tohkin M, Miyata M, Ward JM, Lambert G, Gonzalez FJ (2000) Targeted disruption of the nuclear receptor FXR/BAR impairs bile acid and lipid homeostasis. Cell 102(6):731–744

    Article  CAS  PubMed  Google Scholar 

  88. Singh BB, Mishra LC, Vinjamury SP, Aquilina N, Singh VJ, Shepard N (2003) The effectiveness of Commiphora mukul for osteoarthritis of the knee: an outcomes study. Altern Ther Health Med 9(3):74–79

    PubMed  Google Scholar 

  89. Singh SV, Choi S, Zeng Y, Hahm ER, Xiao D (2007) Guggulsterone-induced apoptosis in human prostate cancer cells is caused by reactive oxygen intermediate dependent activation of c-Jun NH2-terminal kinase. Cancer Res 67(15):7439–7449

    Article  CAS  PubMed  Google Scholar 

  90. Singh SV, Zeng Y, Xiao D, Vogel VG, Nelson JB, Dhir R, Tripathi YB (2005) Caspase-dependent apoptosis induction by guggulsterone, a constituent of Ayurvedic medicinal plant Commiphora mukul, in PC-3 human prostate cancer cells is mediated by Bax and Bak. Mol Cancer Ther 4(11):1747–1754

    Article  CAS  PubMed  Google Scholar 

  91. Singh V, Kaul S, Chander R, Kapoor NK (1990) Stimulation of low density lipoprotein receptor activity in liver membrane of guggulsterone treated rats. Pharmacol Res 22(1):37–44

    Article  CAS  PubMed  Google Scholar 

  92. Szapary PO, Wolfe ML, Bloedon LT, Cucchiara AJ, Dermarderosian AH, Cirigliano MD, Rader DJ (2003) Guggulipid for the treatment of hypercholesterolemia: a randomized controlled trial. JAMA 290(6):765–772

    Article  CAS  PubMed  Google Scholar 

  93. Thappa DM, Dogra J (1994) Nodulocystic acne: oral gugulipid versus tetracycline. J Dermatol 21(10):729–731

    Article  CAS  PubMed  Google Scholar 

  94. Tripathi YB, Malhotra OP, Tripathi SN (1984) Thyroid stimulating action of Z-guggulsterone obtained from Commiphora mukul. Planta Med 50(1):78–80

    Article  CAS  Google Scholar 

  95. Tripathi YB, Tripathi P, Malhotra OP, Tripathi SN (1988) Thyroid stimulatory action of (Z)-guggulsterone: mechanism of action. Planta Med 54(4):271–277

    Article  CAS  PubMed  Google Scholar 

  96. Ulbricht C, Basch E, Szapary P, Hammerness P, Axentsev S, Boon H, Kroll D, Garraway L, Vora M, Woods J, Natural Standard Research C (2005) Guggul for hyperlipidemia: a review by the Natural Standard Research Collaboration. Complement Ther Med 13(4):279–290

    Google Scholar 

  97. Urizar NL, Liverman AB, Dodds DT, Silva FV, Ordentlich P, Yan Y, Gonzalez FJ, Heyman RA, Mangelsdorf DJ, Moore DD (2002) A natural product that lowers cholesterol as an antagonist ligand for FXR. Science 296(5573):1703–1706

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  99. Wang H, Chen J, Hollister K, Sowers LC, Forman BM (1999) Endogenous bile acids are ligands for the nuclear receptor FXR/BAR. Mol Cell 3(5):543–553

    Article  CAS  PubMed  Google Scholar 

  100. Wang WC, Uen YH, Chang ML, Cheah KP, Li JS, Yu WY, Lee KC, Choy CS, Hu CM (2012) Protective effect of guggulsterone against cardiomyocyte injury induced by doxorubicin in vitro. BMC Complement Altern Med 12:138

    Article  PubMed  PubMed Central  Google Scholar 

  101. Xiao D, Singh SV (2008) Z-guggulsterone, a constituent of Ayurvedic medicinal plant Commiphora mukul, inhibits angiogenesis in vitro and in vivo. Mol Cancer Ther 7(1):171–180

    Article  CAS  PubMed  Google Scholar 

  102. Xiao D, Zeng Y, Prakash L, Badmaev V, Majeed M, Singh SV (2011) Reactive oxygen species-dependent apoptosis by gugulipid extract of ayurvedic medicine plant Commiphora mukul in human prostate cancer cells is regulated by c-Jun N-terminal kinase. Mol Pharmacol 79(3):499–507

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Xu HB, Li L, Liu GQ (2011) Reversal of multidrug resistance by guggulsterone in drug-resistant MCF-7 cell lines. Chemotherapy 57(1):62–70

    Article  CAS  PubMed  Google Scholar 

  104. Xu HB, Shen ZL, Fu J, Xu LZ (2014) Reversal of doxorubicin resistance by guggulsterone of Commiphora mukul in vivo. Phytomedicine 21(11):1221–1229

    Article  CAS  PubMed  Google Scholar 

  105. Xu HB, Xu LZ, Li L, Fu J, Mao XP (2012) Reversion of P-glycoprotein-mediated multidrug resistance by guggulsterone in multidrug-resistant human cancer cell lines. Eur J Pharmacol 694(1–3):39–44

    Article  CAS  PubMed  Google Scholar 

  106. Xu HB, Xu LZ, Mao XP, Fu J (2014) Guggulsterone of Commiphora mukul resin reverses drug resistance in imatinib-resistant leukemic cells by inhibiting cyclooxygenase-2 and P-glycoprotein. Phytomedicine 21(7):1004–1009

    Article  CAS  PubMed  Google Scholar 

  107. Xu Y, Watanabe T, Tanigawa T, Machida H, Okazaki H, Yamagami H, Watanabe K, Tominaga K, Fujiwara Y, Oshitani N, Arakawa T (2010) Bile acids induce cdx2 expression through the farnesoid x receptor in gastric epithelial cells. J Clin Biochem Nutr 46(1):81–86

    Article  CAS  PubMed  Google Scholar 

  108. Yamada T, Osawa S, Hamaya Y, Furuta T, Hishida A, Kajimura M, Ikuma M (2010) Guggulsterone suppresses bile acid-induced and constitutive caudal-related homeobox 2 expression in gut-derived adenocarcinoma cells. Anticancer Res 30(6):1953–1960

    CAS  PubMed  Google Scholar 

  109. Yamada T, Osawa S, Ikuma M, Kajimura M, Sugimoto M, Furuta T, Iwaizumi M, Sugimoto K (2014) Guggulsterone, a plant-derived inhibitor of NF-TB, suppresses CDX2 and COX-2 expression and reduces the viability of esophageal adenocarcinoma cells. Digestion 90(3):208–217

    Article  CAS  PubMed  Google Scholar 

  110. Yang JY, Della-Fera MA, Baile CA (2008) Guggulsterone inhibits adipocyte differentiation and induces apoptosis in 3T3-L1 cells. Obesity (Silver Spring) 16(1):16–22

    Article  CAS  Google Scholar 

  111. Yang L, Broderick D, Jiang Y, Hsu V, Maier CS (2014) Conformational dynamics of human FXR-LBD ligand interactions studied by hydrogen/deuterium exchange mass spectrometry: insights into the antagonism of the hypolipidemic agent Z-guggulsterone. Biochim Biophys Acta 1844(9):1684–1693

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Yang MH, Lee KT, Yang S, Lee JK, Lee KH, Moon IH, Rhee JC (2012) Guggulsterone enhances antitumor activity of gemcitabine in gallbladder cancer cells through suppression of NF-kappaB. J Cancer Res Clin Oncol 138(10):1743–1751

    Article  CAS  PubMed  Google Scholar 

  113. Zhang Y, Kast-Woelbern HR, Edwards PA (2003) Natural structural variants of the nuclear receptor farnesoid X receptor affect transcriptional activation. J Biol Chem 278(1):104–110

    Article  CAS  PubMed  Google Scholar 

  114. Zhang Y, Lee FY, Barrera G, Lee H, Vales C, Gonzalez FJ, Willson TM, Edwards PA (2006) Activation of the nuclear receptor FXR improves hyperglycemia and hyperlipidemia in diabetic mice. Proc Natl Acad Sci U S A 103(4):1006–1011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Zhao C, Wang X, Cong Y, Deng Y, Xu Y, Chen A, Yin Y (2014) Effects of bile acids and the bile acid receptor FXR agonist on the respiratory rhythm in the in vitro brainstem medulla slice of neonatal Sprague-Dawley rats. PLoS ONE 9(11):e112212

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Gastroenterology, Iwata City Hospital, 512-3, Okubo, Iwata, 438-8550, Japan

    Takanori Yamada

  2. First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, 431-3192, Japan

    Ken Sugimoto

Authors
  1. Takanori Yamada
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ken Sugimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Takanori Yamada .

Editor information

Editors and Affiliations

  1. Banaras Hindu University, Varanasi, Uttar Pradesh, India

    Subash Chandra Gupta

  2. MD Anderson Cancer Center, University of Texas, Houston, Texas, USA

    Sahdeo Prasad

  3. Inflammation Research Institute, San Diego, California, USA

    Bharat B. Aggarwal

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Yamada, T., Sugimoto, K. (2016). Guggulsterone and Its Role in Chronic Diseases. In: Gupta, S., Prasad, S., Aggarwal, B. (eds) Drug Discovery from Mother Nature. Advances in Experimental Medicine and Biology, vol 929. Springer, Cham. https://doi.org/10.1007/978-3-319-41342-6_15

Download citation

Publish with us

Policies and ethics

Search

Navigation