Summary: Unsaturated pregnane derivatives containing two keto groups on side chains or ring structures.

Top Publications

  1. Cui J, Huang L, Zhao A, Lew J, Yu J, Sahoo S, 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;278:10214-20 pubmed
  2. Markham L, Spicer R, Khoury P, Wong B, Mathews K, Cripe L. Steroid therapy and cardiac function in Duchenne muscular dystrophy. Pediatr Cardiol. 2005;26:768-71 pubmed
    ..The effect appears to be sustained beyond the duration of treatment and independent of steroid type. ..
  3. Parreira S, Resende M, Zanoteli E, Carvalho M, Marie S, Reed U. Comparison of motor strength and function in patients with Duchenne muscular dystrophy with or without steroid therapy. Arq Neuropsiquiatr. 2010;68:683-8 pubmed
    ..80 point per year of age against decrease of 3.65 points on Scott's study. In patients with DMD aged five to 12 years the progression of the disease is delayed by steroids and the motor function is less reduced than muscular strength. ..
  4. Nave R, Gunawardena K, Zech K, Bethke T. Pharmacokinetic disposition of inhaled ciclesonide and its metabolite desisobutyryl-ciclesonide in healthy subjects and patients with asthma are similar. Int J Clin Pharmacol Ther. 2006;44:1-7 pubmed
  5. Shishodia S, Aggarwal B. Guggulsterone inhibits NF-kappaB and IkappaBalpha kinase activation, suppresses expression of anti-apoptotic gene products, and enhances apoptosis. J Biol Chem. 2004;279:47148-58 pubmed
    ..Overall, our results indicate that guggulsterone suppresses NF-kappaB and NF-kappaB-regulated gene products, which may explain its anti-inflammatory activities. ..
  6. Szapary P, Wolfe M, Bloedon L, Cucchiara A, DerMarderosian A, Cirigliano M, et al. Guggulipid for the treatment of hypercholesterolemia: a randomized controlled trial. JAMA. 2003;290:765-72 pubmed
    ..However, there are currently no published safety or efficacy data on the use of guggul extracts in Western populations...
  7. Houde S, Filiatrault M, Fournier A, Dubé J, D Arcy S, Bérubé D, et al. Deflazacort use in Duchenne muscular dystrophy: an 8-year follow-up. Pediatr Neurol. 2008;38:200-6 pubmed publisher
    ..Deflazacort improves cardiac function, prolongs walking, and seems to eliminate the need for spinal surgery, although vertebral fractures and stunted growth occur. The overall impact on quality of life appears positive. ..
  8. Stoeck M, Riedel R, Hochhaus G, Häfner D, Massó J, Schmidt B, et al. In vitro and in vivo anti-inflammatory activity of the new glucocorticoid ciclesonide. J Pharmacol Exp Ther. 2004;309:249-58 pubmed
    ..The in vivo data on ciclesonide highlight its effective local action and a reduced potential for side effects. ..
  9. Shishodia S, Sethi G, Ahn K, Aggarwal B. 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. 2007;74:118-30 pubmed
    ..Overall, our results indicate that guggulsterone can inhibit cell proliferation and induce apoptosis through the activation of JNK, suppression of Akt, and downregulation of antiapoptotic protein expression. ..

More Information


  1. Buhl R, Vinkler I, Magyar P, Györi Z, Rybacki C, Middle M, et al. Comparable efficacy of ciclesonide once daily versus fluticasone propionate twice daily in asthma. Pulm Pharmacol Ther. 2006;19:404-12 pubmed
    ..Ciclesonide 160 microg once daily was as effective as fluticasone propionate 88 microg twice daily in improving lung function and asthma symptoms, and in reducing rescue medication use in patients with asthma. ..
  2. An M, Cheon J, Kim S, Kim E, Kim T, Kim W. Guggulsterone induces apoptosis in colon cancer cells and inhibits tumor growth in murine colorectal cancer xenografts. Cancer Lett. 2009;279:93-100 pubmed publisher
    ..The present study suggests a potential therapeutic use for this compound in the treatment of colorectal cancer. ..
  3. Boulet L, Drollmann A, Magyar P, Timar M, Knight A, Engelstätter R, et al. Comparative efficacy of once-daily ciclesonide and budesonide in the treatment of persistent asthma. Respir Med. 2006;100:785-94 pubmed
    ..009). Frequency of adverse events was low in both groups. Ciclesonide 320 microg once daily by HFA-MDI without a spacer was at least as effective as budesonide 320 microg once daily in persistent asthma. ..
  4. Nave R, Fisher R, Zech K. In Vitro metabolism of ciclesonide in human lung and liver precision-cut tissue slices. Biopharm Drug Dispos. 2006;27:197-207 pubmed
    ..Activation and fatty acid esterification in the lung followed by rapid inactivation in the liver may explain the improved safety profile and prolonged anti-inflammatory activity of ciclesonide. ..
  5. Bonifati D, Witchel S, Ermani M, Hoffman E, Angelini C, Pegoraro E. The glucocorticoid receptor N363S polymorphism and steroid response in Duchenne dystrophy. J Neurol Neurosurg Psychiatry. 2006;77:1177-9 pubmed
    ..These data suggest that the N363S GRL polymorphism may be implicated in the long term response to glucocorticoids. ..
  6. Derendorf H, Nave R, Drollmann A, Cerasoli F, Wurst W. Relevance of pharmacokinetics and pharmacodynamics of inhaled corticosteroids to asthma. Eur Respir J. 2006;28:1042-50 pubmed
  7. Campbell C, Jacob P. Deflazacort for the treatment of Duchenne Dystrophy: a systematic review. BMC Neurol. 2003;3:7 pubmed
    ..Two trials found that DFZ causes less weight gain than prednisone. ..
  8. Leeman Neill R, Wheeler S, Singh S, Thomas S, Seethala R, Neill D, et al. Guggulsterone enhances head and neck cancer therapies via inhibition of signal transducer and activator of transcription-3. Carcinogenesis. 2009;30:1848-56 pubmed publisher
    ..Our results suggest that guggulsterone-mediated inhibition of STAT3 and HIF-1alpha provide a biologic rationale for further clinical investigation of this compound in the treatment of HNSCC. ..
  9. Nave R, Wingertzahn M, Brookman S, Kaida S, Matsunaga T. Safety, tolerability, and exposure of ciclesonide nasal spray in healthy and asymptomatic subjects with seasonal allergic rhinitis. J Clin Pharmacol. 2006;46:461-7 pubmed
    ..Ciclesonide was well tolerated and did not appear to affect serum or urine free cortisol levels. The low systemic exposure and favorable safety profile support the continued clinical development of ciclesonide nasal spray. ..
  10. Sato H, Nave R, Nonaka T, Mochizuki T, Takahama S, Kondo S. In vitro metabolism of ciclesonide in human nasal epithelial cells. Biopharm Drug Dispos. 2007;28:43-50 pubmed
    ..In conclusion, ciclesonide was rapidly converted to des-CIC by carboxylesterases and cholinesterases, and des-CIC underwent reversible fatty acid conjugation in HNEC. ..
  11. Langdon C, Adler M, Mehra S, Alexander M, Drollmann A. Once-daily ciclesonide 80 or 320 microg for 12 weeks is safe and effective in patients with persistent asthma. Respir Med. 2005;99:1275-85 pubmed
    ..Therefore, ciclesonide 80 and 320 microg administered once daily was a safe and effective maintenance treatment for patients with persistent asthma. ..
  12. Kanniess F, Richter K, Bohme S, Jörres R, Magnussen H. Effect of inhaled ciclesonide on airway responsiveness to inhaled AMP, the composition of induced sputum and exhaled nitric oxide in patients with mild asthma. Pulm Pharmacol Ther. 2001;14:141-7 pubmed
    ..These data suggest that ciclesonide is equi-effective to budesonide with regard to its potency to reduce the airway responsiveness to inhaled AMP as well as airway inflammation in patients with mild asthma. ..
  13. Nave R, Zech K, Bethke T. Lower oropharyngeal deposition of inhaled ciclesonide via hydrofluoroalkane metered-dose inhaler compared with budesonide via chlorofluorocarbon metered-dose inhaler in healthy subjects. Eur J Clin Pharmacol. 2005;61:203-8 pubmed
    ..This may explain the low frequency of oropharyngeal side effects of ciclesonide in clinical studies. ..
  14. Lee D, Fardon T, Bates C, Haggart K, McFarlane L, Lipworth B. Airway and systemic effects of hydrofluoroalkane formulations of high-dose ciclesonide and fluticasone in moderate persistent asthma. Chest. 2005;127:851-60 pubmed
    ..The present results would therefore suggest that CIC might confer a better therapeutic ratio than FP when used at higher doses. ..
  15. Ahn K, Sethi G, Sung B, Goel A, Ralhan R, Aggarwal B. Guggulsterone, a farnesoid X receptor antagonist, inhibits constitutive and inducible STAT3 activation through induction of a protein tyrosine phosphatase SHP-1. Cancer Res. 2008;68:4406-15 pubmed publisher
    ..Overall, these results suggest that GS is a novel blocker of STAT3 activation and thus may have a potential in regulation of growth and metastasis of tumor cells. ..
  16. Weinbrenner A, Hüneke D, Zschiesche M, Engel G, Timmer W, Steinijans V, et al. Circadian rhythm of serum cortisol after repeated inhalation of the new topical steroid ciclesonide. J Clin Endocrinol Metab. 2002;87:2160-3 pubmed
    ..In conclusion, inhaled ciclesonide in daily doses of 800 microg for 7 d is without clinically relevant effects on the hypothalamic-pituitary-adrenal axis independent of the time of administration. ..
  17. Xu H, Li L, Liu G. Reversal of P-glycoprotein-mediated multidrug resistance by guggulsterone in doxorubicin-resistant human myelogenous leukemia (K562/DOX) cells. Pharmazie. 2009;64:660-5 pubmed
  18. Markham L, Kinnett K, Wong B, Woodrow Benson D, Cripe L. Corticosteroid treatment retards development of ventricular dysfunction in Duchenne muscular dystrophy. Neuromuscul Disord. 2008;18:365-70 pubmed publisher
    ..16 95% CI 0.04, 0.70). We demonstrate here that steroid treatment, begun prior to ventricular dysfunction retards the anticipated development of ventricular dysfunction...
  19. Gonzalez Perez O, Luquin S, Garcia Estrada J, Ramos Remus C. Deflazacort: a glucocorticoid with few metabolic adverse effects but important immunosuppressive activity. Adv Ther. 2007;24:1052-60 pubmed
    ..Additional pharmacologic studies are needed to fully establish the immunosuppressive potency of DFZ and, consequently, to determine the appropriate ratio of bioequivalence in humans. ..
  20. Larsen B, Nielsen L, Engelstätter R, Steinijans V, Dahl R. Effect of ciclesonide on allergen challenge in subjects with bronchial asthma. Allergy. 2003;58:207-12 pubmed
    ..Cortisol excretion in 24-h urine showed no significant difference between ciclesonide and placebo. The study supports the efficacy and safety of ciclesonide. ..
  21. Biggar W, Politano L, Harris V, Passamano L, Vajsar J, Alman B, et al. Deflazacort in Duchenne muscular dystrophy: a comparison of two different protocols. Neuromuscul Disord. 2004;14:476-82 pubmed
    ..However, the protocol-T seems to be more effective and frequently is associated with asymptomatic cataracts. ..
  22. Lv N, Song M, Kim E, Park J, Kwon K, Park B. Guggulsterone, a plant sterol, inhibits NF-kappaB activation and protects pancreatic beta cells from cytokine toxicity. Mol Cell Endocrinol. 2008;289:49-59 pubmed publisher
    ..Collectively, these results suggest that guggulsterone may be used to preserve functional beta-cell mass...
  23. Kim E, Hong S, Lee H, Kim S, An M, Kim T, et al. Guggulsterone inhibits angiogenesis by blocking STAT3 and VEGF expression in colon cancer cells. Oncol Rep. 2008;20:1321-7 pubmed
  24. Samudio I, Konopleva M, Safe S, McQueen T, Andreeff M. Guggulsterones induce apoptosis and differentiation in acute myeloid leukemia: identification of isomer-specific antileukemic activities of the pregnadienedione structure. Mol Cancer Ther. 2005;4:1982-92 pubmed
  25. Lee D, Haggart K, Currie G, Bates C, Lipworth B. Effects of hydrofluoroalkane formulations of ciclesonide 400 microg once daily vs fluticasone 250 microg twice daily on methacholine hyper-responsiveness in mild-to-moderate persistent asthma. Br J Clin Pharmacol. 2004;58:26-33 pubmed
    ..Longer-term studies are indicated to evaluate their relative efficacy on asthma exacerbations. ..
  26. Xiao D, Singh S. z-Guggulsterone, a constituent of Ayurvedic medicinal plant Commiphora mukul, inhibits angiogenesis in vitro and in vivo. Mol Cancer Ther. 2008;7:171-80 pubmed publisher
    ..Together, our results provide compelling rationale for further preclinical and clinical investigation of z-guggulsterone for its efficacy against prostate cancer...
  27. Moxley R, Pandya S, Ciafaloni E, Fox D, Campbell K. Change in natural history of Duchenne muscular dystrophy with long-term corticosteroid treatment: implications for management. J Child Neurol. 2010;25:1116-29 pubmed publisher
    ..Educational, vocational, and other social counseling is now a vital part of management for Duchenne muscular dystrophy. ..
  28. Yamada T, Osawa S, Hamaya Y, Furuta T, Hishida A, Kajimura M, et al. Guggulsterone suppresses bile acid-induced and constitutive caudal-related homeobox 2 expression in gut-derived adenocarcinoma cells. Anticancer Res. 2010;30:1953-60 pubmed
    ..Guggulsterone may be used as a novel drug to target CdX2 expression in certain gut adenocarcinomas. ..
  29. Singh S, Zeng Y, Xiao D, Vogel V, Nelson J, Dhir R, et al. 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. 2005;4:1747-54 pubmed
    ..In conclusion, the present study indicates that caspase-dependent apoptosis by guggulsterone is mediated in part by Bax and Bak...
  30. Sarfaraz S, Siddiqui I, Syed D, Afaq F, Mukhtar H. Guggulsterone modulates MAPK and NF-kappaB pathways and inhibits skin tumorigenesis in SENCAR mice. Carcinogenesis. 2008;29:2011-8 pubmed publisher
    ..In summary, GUG could be useful for delaying tumor growth in humans. ..
  31. Postma D, O Byrne P, Pedersen S. Comparison of the effect of low-dose ciclesonide and fixed-dose fluticasone propionate and salmeterol combination on long-term asthma control. Chest. 2011;139:311-318 pubmed publisher; No.: NCT00163358; URL: ..
  32. Nonaka T, Nave R, McCracken N, Kawashimo A, Katsuura Y. Ciclesonide uptake and metabolism in human alveolar type II epithelial cells (A549). BMC Pharmacol. 2007;7:12 pubmed
    ..The local anti-inflammatory activity of ciclesonide in the lung may be prolonged by the slow release of active drug from the depot of fatty acid esters. ..
  33. Mazzone E, Vasco G, Sormani M, Torrente Y, Berardinelli A, Messina S, et al. Functional changes in Duchenne muscular dystrophy: a 12-month longitudinal cohort study. Neurology. 2011;77:250-6 pubmed publisher
    ..NSAA and the 6MWT had the highest correlation (r = 0.52, p < 0.001). This study provides longitudinal data of NSAA and 6MWT over a 12-month period. These data can be useful when designing a clinical trial. ..
  34. Rohatagi S, Arya V, Zech K, Nave R, Hochhaus G, Jensen B, et al. Population pharmacokinetics and pharmacodynamics of ciclesonide. J Clin Pharmacol. 2003;43:365-78 pubmed
    ..The disposition and effect of CIC-AP can be described using mixed-effect modeling. The estimated EC50 is similar to mean Cmax from an 800-micrograms dose, further suggesting CIC-AP has little effect on cortisol suppression. ..
  35. Biggar W, Harris V, Eliasoph L, Alman B. Long-term benefits of deflazacort treatment for boys with Duchenne muscular dystrophy in their second decade. Neuromuscul Disord. 2006;16:249-55 pubmed
    ..This longer-term study demonstrates that deflazacort has a very significant impact on health, quality of life and health care costs for boys with DMD and their families, and is associated with few side effects. ..
  36. Ichikawa H, Aggarwal B. 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. 2006;12:662-8 pubmed
    ..Collectively, our results indicate that guggulsterone suppresses RANKL and tumor cell-induced osteoclastogenesis by suppressing the activation of NF-kappaB. ..
  37. Alman B, Raza S, Biggar W. Steroid treatment and the development of scoliosis in males with duchenne muscular dystrophy. J Bone Joint Surg Am. 2004;86-A:519-24 pubmed
    ..At the very least, steroid treatment delays the need for spinal surgery. Therapeutic study, Level II-1 (prospective cohort study). See Instructions to Authors for a complete description of levels of evidence. ..
  38. Richter K, Kanniess F, Biberger C, Nave R, Magnussen H. Comparison of the oropharyngeal deposition of inhaled ciclesonide and fluticasone propionate in patients with asthma. J Clin Pharmacol. 2005;45:146-52 pubmed
    ..Furthermore, there is little activation of ciclesonide to its active metabolite in the oropharynx, suggesting a decreased likelihood of inhaled ciclesonide-associated oropharyngeal side effects. ..
  39. Moxley R, Ashwal S, Pandya S, Connolly A, Florence J, Mathews K, et al. Practice parameter: corticosteroid treatment of Duchenne dystrophy: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology. 2005;64:13-20 pubmed
    ..Benefits and side effects of corticosteroid therapy need to be monitored. The offer of treatment with corticosteroids should include a balanced discussion of potential risks. ..
  40. Burris T, Montrose C, Houck K, Osborne H, Bocchinfuso W, Yaden B, et al. The hypolipidemic natural product guggulsterone is a promiscuous steroid receptor ligand. Mol Pharmacol. 2005;67:948-54 pubmed
    ..These data suggest that the variety of pharmacological effects exhibited by GS may be mediated by targeting several steroid receptors. ..
  41. St Pierre S, Chakkalakal J, Kolodziejczyk S, Knudson J, Jasmin B, Megeney L. Glucocorticoid treatment alleviates dystrophic myofiber pathology by activation of the calcineurin/NF-AT pathway. FASEB J. 2004;18:1937-9 pubmed
  42. Postma D, Sevette C, Martinat Y, Schlosser N, Aumann J, Kafe H. Treatment of asthma by the inhaled corticosteroid ciclesonide given either in the morning or evening. Eur Respir J. 2001;17:1083-8 pubmed
  43. Dent G. Ciclesonide ( Byk Gulden). Curr Opin Investig Drugs. 2002;3:78-83 pubmed
    ..Deutsche Bank predicted in August 2001, that sales of the product would reach Euro70 million in 2004, rising to Euro150 million in 2005 [420814]. ..
  44. Nave R, Bethke T, van Marle S, Zech K. Pharmacokinetics of [14C]ciclesonide after oral and intravenous administration to healthy subjects. Clin Pharmacokinet. 2004;43:479-86 pubmed
    ..Drug-related metabolites are excreted mainly via the faeces, and overall recovery of administered radioactivity is virtually complete after an extended sample collection period. ..
  45. Xu H, Li L, Liu G. Protection against hydrogen peroxide-induced cytotoxicity in PC12 cells by guggulsterone. Yao Xue Xue Bao. 2008;43:1190-7 pubmed
  46. Chapman K, Patel P, D Urzo A, Alexander M, Mehra S, Oedekoven C, et al. Maintenance of asthma control by once-daily inhaled ciclesonide in adults with persistent asthma. Allergy. 2005;60:330-7 pubmed
    ..Ciclesonide (160 or 640 microg) once daily in the morning effectively maintains asthma control, does not affect cortisol levels, and has an adverse event profile comparable with placebo in adults with primarily mild to moderate asthma. ..
  47. Niphadkar P, Jagannath K, Joshi J, Awad N, Boss H, Hellbardt S, et al. Comparison of the efficacy of ciclesonide 160 microg QD and budesonide 200 microg BID in adults with persistent asthma: a phase III, randomized, double-dummy, open-label study. Clin Ther. 2005;27:1752-63 pubmed
    ..In this study, ciclesonide 160 microg QDwas as effective as budesonide 200 microg BID (400 microg total daily dose) in these adults with persistent asthma. Both treatments were well tolerated. ..
  48. Deng R. Therapeutic effects of guggul and its constituent guggulsterone: cardiovascular benefits. Cardiovasc Drug Rev. 2007;25:375-90 pubmed
    ..Such repression of NF-kappaB activation by guggulsterone has been proposed as a mechanism of the antiinflammatory effect of guggulsterone. ..
  49. Sharma B, Salunke R, Srivastava S, Majumder C, Roy P. Effects of guggulsterone isolated from Commiphora mukul in high fat diet induced diabetic rats. Food Chem Toxicol. 2009;47:2631-9 pubmed publisher
    ..However, it inhibited 3T3-L1 preadipocytes differentiation in vitro. The results presented here suggest that the guggulsterone has both hypoglycemic and hypolipidemic effect which can help to cure type II diabetes...
  50. Silversides C, Webb G, Harris V, Biggar D. Effects of deflazacort on left ventricular function in patients with Duchenne muscular dystrophy. Am J Cardiol. 2003;91:769-72 pubmed
  51. De Gottardi A, Dumonceau J, Bruttin F, Vonlaufen A, Morard I, Spahr L, et al. Expression of the bile acid receptor FXR in Barrett's esophagus and enhancement of apoptosis by guggulsterone in vitro. Mol Cancer. 2006;5:48 pubmed
    ..The induction of apoptosis by guggulsterone in a Barrett's esophagus-derived cell line suggests that FXR may contribute to the regulation of apoptosis. ..
  52. Talim B, Malaguti C, Gnudi S, Politano L, Merlini L. Vertebral compression in Duchenne muscular dystrophy following deflazacort. Neuromuscul Disord. 2002;12:294-5 pubmed
  53. Cheon J, Kim J, Kim J, Kim N, Jung H, Song I. Plant sterol guggulsterone inhibits nuclear factor-kappaB signaling in intestinal epithelial cells by blocking IkappaB kinase and ameliorates acute murine colitis. Inflamm Bowel Dis. 2006;12:1152-61 pubmed
    ..Guggulsterone blocks NF-kappaB signaling pathway by targeting IKK complex in IEC and attenuates DSS-induced acute murine colitis, which suggests that guggulsterone could be an attractive therapeutic option in the treatment of IBD. ..