Guggulsterone (GS) is a bioactive compound primarily extracted from the oleo-gum resin of plants in the Commiphora and Boswellia genera. Modern pharmacological studies have demonstrated that GS possesses a broad spectrum of biological activities, with notable therapeutic potential in inflammatory disorders, neurodegenerative conditions, diabetes mellitus, and various cancers. In this review, we systematically analyzed relevant literature published up to 2024 from the CNKI, Web of Science, ScienceDirect, and PubMed databases to summarize the current understanding of GS’s pharmacological effects, toxicity profile, and pharmacokinetic properties. The findings indicate that GS exerts potent antioxidant, anti-inflammatory, anticancer, antiviral, antidepressant, lipid-lowering, and cardiovascular protective effects, primarily through modulation of key signaling pathways such as the Janus kinase (JAK)-signal transducer and activator of transcription 3 (STAT3), nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1), Nrf2/Keap1, nuclear factor kappa-B (NF-κB), AMPK, phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt), and mitogen-activated protein kinase (MAPK)/activator protein-1 (AP-1). Additionally, GS may help overcome limitations associated with conventional chemotherapy by modulating drug resistance via regulation of p-glycoprotein activity. Following hepatic metabolism mediated by cytochrome P450 enzymes, GS does not appear to cause significant adverse effects. This review provides a comprehensive synthesis of the sources, pharmacological actions, safety, pharmacokinetics, and potential applications of GS. Future research should focus on structural modification of GS, development of novel formulations, and exploration of synergistic combinations with other therapeutic agents to broaden its clinical utility.
Funding
This work was supported by the National Natural Science Foundation of China (Nos. 81873232 and 82074026), and the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine (No. ZYYCXTD-D-202209).
Supporting information
Supporting information for this work can be obtained by contacting the corresponding authors via E-mail.
Declaration of competing interest
The authors declare no competing financial interest.
| [1] |
Yamada T, Sugimoto K. Guggulsterone and its role in chronic diseases. Adv Exp Med Biol. 2016; 929:329-361. https://doi.org/10.1007/978-3-319-41342-6_15.
|
| [2] |
Li SG, Yang GC, Zhao N, et al. Chemical constituents from Myrrha and their antitumor activities. Chin Tradit Herb Drugs. 2017; 48(5):853-858. https://doi.org/10.7501/j.issn.0253-2670.2017.05.002.
|
| [3] |
Han L, Sun JY, Zhou L, et al. Advances on chemistry and pharmacological research of Myrrh. Asia Pac Tradit Med. 2015; 11(3):38-42. https://doi.org/10.11954/ytctyy.201503015.
|
| [4] |
Huang C, Wang J, Lu X, et al. Z-guggulsterone negatively controls microglia-mediated neuroinflammation via blocking IκBα-NF-κB signals. Neurosci Lett. 2016; 619:34-42. https://doi.org/10.1016/j.neulet.2016.02.021.
|
| [5] |
Khera R, Mehan S, Bhalla S, et al. Guggulsterone mediated JAK/STAT and PPAR-γ modulation prevents neurobehavioral and neurochemical abnormalities in propionic acid-induced experimental model of autism. Molecules. 2022; 27(3):889. https://doi.org/10.3390/molecules27030889.
|
| [6] |
Kunnumakkara AB, Banik K, Bordoloi D, et al. Googling the guggul (Commiphora and Boswellia) for prevention of chronic diseases. Front Pharmacol. 2018; 9:686. https://doi.org/10.3389/fphar.2018.00686.
|
| [7] |
Sairkar PK, Sharma A, Shukla NP. Estimation of guggulsterone E and Z in the guggul-based commercial formulations using high-performance thin-layer chromatography. J Pharm Bioallied Sci. 2017; 9(1):1-7. https://doi.org/10.4103/0975-7406.206225.
|
| [8] |
Hung T, Stuppner H, Ellmerer-Müller EP, et al. Steroids and terpenoids from the gum resin of Ailanthus grandis. Phytochemistry. 1995; 39(6):1403-1409. https://doi.org/10.1016/0031-9422(95)00113-L.
|
| [9] |
Deng R. Therapeutic effects of guggul and its constituent guggulsterone: cardiovascular benefits. Cardiovasc Drug Rev. 2007; 25(4):375-390. https://doi.org/10.1111/j.1527-3466.2007.00023.x.
|
| [10] |
Kulhari A, Sheorayan A, Chaudhury A, et al. Quantitative determination of guggulsterone in existing natural populations of Commiphora wightii (Arn.) Bhandari for identification of germplasm having higher guggulsterone content. Physiol Mol Biol Plants. 2015; 21(1):71-81. https://doi.org/10.1007/s12298-014-0271-1.
|
| [11] |
Mathur M, Ramawat KG. Guggulsterone production in cell suspension cultures of the guggul tree, Commiphora wightii, grown in shake-flasks and bioreactors. Biotechnol Lett. 2007; 29(6):979-982. https://doi.org/10.1007/s10529-007-9342-5.
|
| [12] |
Benn WR, Dodson RM. The synthesis and stereochemistry of isomeric 16-hydroxy-17(20)-pregnenes. J Org Chem. 1964; 29(5):1142-1148. https://doi.org/10.1021/jo01028a035.
|
| [13] |
Han J, Chin J, Kang H, et al. A regioselective synthesis of E-guggulsterone. Molecules. 2011; 16:4165-4171. https://doi.org/10.3390/molecules16054165.
|
| [14] |
Gioiello A, Sardella R, Rosatelli E, et al. Novel stereoselective synthesis and chromatographic evaluation of E-guggulsterone. Steroids. 2012; 77(3):250-254. https://doi.org/10.1016/j.steroids.2011.11.012.
|
| [15] |
Athawale PR, Zade VM, Rama KG, et al. Tuning of α-silyl carbocation reactivity into enone transposition: application to the synthesis of peribysin D, E-volkendousin, and E-guggulsterone. Org Lett. 2021; 23(17):6642-6647. https://doi.org/10.1021/acs.orglett.1c02173.
|
| [16] |
Bhat AA, Prabhu KS, Kuttikrishnan S, et al. Potential therapeutic targets of guggulsterone in cancer. Nutr Metab (Lond). 2017; 14:23. https://doi.org/10.1186/s12986-017-0180-8.
|
| [17] |
Shi JJ, Jia XL, Li M, et al. Guggulsterone induces apoptosis of human hepatocellular carcinoma cells through intrinsic mitochondrial pathway. World J Gastroenterol. 2015; 21(47):13277-13287. https://doi.org/10.3748/wjg.v21.i47.13277.
|
| [18] |
You W, Chen B, Liu X, et al. Farnesoid X receptor, a novel proto-oncogene in non-small cell lung cancer, promotes tumor growth via directly transactivating CCND1. Sci Rep. 2017; 7(1):591. https://doi.org/10.1038/s41598-017-00698-4.
|
| [19] |
You W, Li L, Sun D, et al. Farnesoid X receptor constructs an immunosuppressive microenvironment and sensitizes FXR(high)PD-L1(low) NSCLC to anti-PD-1 immunotherapy. Cancer Immunol Res. 2019; 7(6):990-1000. https://doi.org/10.1158/2326-6066.CIR-17-0672.
|
| [20] |
Tian H, Gui Y, Wei Y, et al. Z-guggulsterone induces PD-L1 upregulation partly mediated by FXR, Akt and Erk1/2 signaling pathways in non-small cell lung cancer. Int Immunopharmacol. 2021; 93:107395. https://doi.org/10.1016/j.intimp.2021.107395.
|
| [21] |
Alharbi B, Alharethi SH, Al-Soud WA, et al. Exploring the potential of phytochemicals as inhibitors of 3'-phosphoadenosine 5'-phosphosulfate synthase 1 targeting cancer therapy. J Biomol Struct Dyn. 2024; 42(6):3193-3203. https://doi.org/10.1080/07391102.2023.2212810.
|
| [22] |
Jin X, Shang B, Wang J, et al. Farnesoid X receptor promotes non-small cell lung cancer metastasis by activating JAK2/STAT3 signaling via transactivation of IL-6ST and IL-6 genes. Cell Death Dis. 2024; 15(2):148. https://doi.org/10.1038/s41419-024-06495-y.
|
| [23] |
Dovedi SJ, Adlard AL, Lipowska-Bhalla G, et al. Acquired resistance to fractionated radiotherapy can be overcome by concurrent PD-L1 blockade. Cancer Res. 2014; 74(19):5458-5468. https://doi.org/10.1158/0008-5472.CAN-14-1258.
|
| [24] |
Peng J, Hamanishi J, Matsumura N, et al. Chemotherapy induces programmed cell death-ligand 1 overexpression via the nuclear factor-κB to foster an immunosuppressive tumor microenvironment in ovarian cancer. Cancer Res. 2015; 75(23):5034-5045. https://doi.org/10.1158/0008-5472.CAN-14-3098.
|
| [25] |
Rekoske BT, Smith HA, Olson BM, et al. PD-1 or PD-L1 blockade restores antitumor efficacy following SSX2 epitope-modified DNA vaccine immunization. Cancer Immunol Res. 2015; 3(8):946-955. https://doi.org/10.1158/2326-6066.CIR-14-0206.
|
| [26] |
Loi S, Dushyanthen S, Beavis PA, et al. RAS/MAPK activation is associated with reduced tumor-infiltrating lymphocytes in triple-negative breast cancer: therapeutic cooperation between MEK and PD-1/PD-L1 immune checkpoint inhibitors. Clin Cancer Res. 2016; 22(6):1499-1509. https://doi.org/10.1158/1078-0432.CCR-15-1125.
|
| [27] |
Noh EM, Chung EY, Youn HJ, et al. Cis-guggulsterone inhibits the IKK/NF-κB pathway, whereas trans-guggulsterone inhibits MAPK/AP-1 in MCF-7 breast cancer cells: guggulsterone regulates MMP-9 expression in an isomer-specific manner. Int J Mol Med. 2013; 31(2):393-399. https://doi.org/10.3892/ijmm.2012.1214.
|
| [28] |
Jiang G, Xiao X, Zeng Y, et al. Targeting β-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. 2013; 13:203. https://doi.org/10.1186/1472-6882-13-203.
|
| [29] |
Mirza S, Sharma G, Parshad R, et al. Expression of DNA methyltransferases in breast cancer patients and to analyze the effect of natural compounds on DNA methyltransferases and associated proteins. J Breast Cancer. 2013; 16(1):23-31. https://doi.org/10.4048/jbc.2013.16.1.23.
|
| [30] |
Wu Y, Zhou T, Qian D, et al. Z-guggulsterone induces cell cycle arrest and apoptosis by targeting the p53/CCNB1/PLK1 pathway in triple-negative breast cancer. ACS Omega. 2023; 8(2):2780-2792. https://doi.org/10.1021/acsomega.2c07480.
|
| [31] |
Gupta N, Mohan CD, Shanmugam MK, et al. CXCR4 expression is elevated in TNBC patient derived samples and Z-guggulsterone abrogates tumor progression by targeting CXCL12/CXCR4 signaling axis in preclinical breast cancer model. Environ Res. 2023; 232:116335. https://doi.org/10.1016/j.envres.2023.116335.
|
| [32] |
Absil L, Journé F, Larsimont D, et al. Farnesoid X receptor as marker of osteotropism of breast cancers through its role in the osteomimetism of tumor cells. BMC Cancer. 2020; 20(1):640. https://doi.org/10.1186/s12885-020-07106-7.
|
| [33] |
Moon DO, Park SY, Choi YH, et al. Guggulsterone sensitizes hepatoma cells to TRAIL-induced apoptosis through the induction of CHOP-dependent DR5: involvement of ROS-dependent ER-stress. Biochem Pharmacol. 2011; 82(11):1641-1650. https://doi.org/10.1016/j.bcp.2011.08.019.
|
| [34] |
Gupta M, Ghufran SM, Kausar T, et al. Z-guggulsterone is a potential lead molecule of Dawa-ul-Kurkum against hepatocellular carcinoma. Molecules. 2022; 27(16):5104. https://doi.org/10.3390/molecules27165104.
|
| [35] |
Takahashi Y, Kitadai Y, Bucana CD, et al. Expression of vascular endothelial growth factor and its receptor, KDR, correlates with vascularity, metastasis, and proliferation of human colon cancer. Cancer Res. 1995; 55(18):3964-3968.
|
| [36] |
Kim ES, Hong SY, Lee HK, et al. Guggulsterone inhibits angiogenesis by blocking STAT3 and VEGF expression in colon cancer cells. Oncol Rep. 2008; 20(6):1321-1327. https://doi.org/10.3892/OR_00000147.
|
| [37] |
An MJ, Cheon JH, Kim SW, et al. Guggulsterone induces apoptosis in colon cancer cells and inhibits tumor growth in murine colorectal cancer xenografts. Cancer Lett. 2009; 279(1):93-100. https://doi.org/10.1016/j.canlet.2009.01.026.
|
| [38] |
Leo R, Therachiyil L, Siveen SK, et al. Protein expression profiling identifies key proteins and pathways involved in growth inhibitory effects exerted by guggulsterone in human colorectal cancer cells. Cancers (Basel). 2019; 11(10):1478. https://doi.org/10.3390/cancers11101478.
|
| [39] |
Leeman-Neill RJ, Wheeler SE, Singh SV, et al. Guggulsterone enhances head and neck cancer therapies via inhibition of signal transducer and activator of transcription-3. Carcinogenesis. 2009; 30(11):1848-1856. https://doi.org/10.1093/carcin/bgp211.
|
| [40] |
Macha MA, Matta A, Chauhan SS, et al. Guggulsterone targets smokeless tobacco induced PI3K/Akt pathway in head and neck cancer cells. PLoS One. 2011; 6(2):e14728. https://doi.org/10.1371/journal.pone.0014728.
|
| [41] |
Macha MA, Matta A, Chauhan S, et al. 14-3-3 Zeta is a molecular target in guggulsterone induced apoptosis in head and neck cancer cells. BMC Cancer. 2010; 10:655. https://doi.org/10.1186/1471-2407-10-655.
|
| [42] |
Macha MA, Matta A, Chauhan SS, et al. Guggulsterone (GS) inhibits smokeless tobacco and nicotine-induced NF-κB and STAT3 pathways in head and neck cancer cells. Carcinogenesis. 2011; 32(3):368-380. https://doi.org/10.1093/carcin/bgq278.
|
| [43] |
Leeman-Neill RJ, Seethala RR, Singh SV, et al. Inhibition of EGFR-STAT3 signaling with erlotinib prevents carcinogenesis in a chemically-induced mouse model of oral squamous cell carcinoma. Cancer Prev Res (Phila). 2011; 4(2):230-237. https://doi.org/10.1158/1940-6207.CAPR-10-0249.
|
| [44] |
Mollazadeh S, Sahebkar A, Hadizadeh F, et al. Structural and functional aspects of P-glycoprotein and its inhibitors. Life Sci. 2018; 214:118-123. https://doi.org/10.1016/j.lfs.2018.10.048.
|
| [45] |
Xu HB, Li L, Liu GQ. Reversal of P-glycoprotein-mediated multidrug resistance by guggulsterone in doxorubicin-resistant human myelogenous leukemia (K562/DOX) cells. Pharmazie. 2009; 64(10):660-665.
|
| [46] |
Xu HB, Xu LZ, Li L, et al. Reversion of P-glycoprotein-mediated multidrug resistance by guggulsterone in multidrug-resistant human cancer cell lines. Eur J Pharmacol. 2012; 694(1-3):39-44. https://doi.org/10.1016/j.ejphar.2012.06.046.
|
| [47] |
Xu HB, Xu LZ, Mao XP, et al. Guggulsterone of Commiphora mukul resin reverses drug resistance in imatinib-resistant leukemic cells by inhibiting cyclooxygenase-2 and P-glycoprotein. Phytomedicine. 2014; 21(7):1004-1009. https://doi.org/10.1016/j.phymed.2014.02.014.
|
| [48] |
Xu HB, Tang ZQ, Wang J, et al. Z-Guggulsterone regulates MDR1 expression mainly through the pregnane X receptor-dependent manner in human brain microvessel endothelial cells. Eur J Pharmacol. 2020; 874:173023. https://doi.org/10.1016/j.ejphar.2020.173023.
|
| [49] |
Shishodia S, Sethi G, Ahn KS, et al. 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(1):118-130. https://doi.org/10.1016/j.bcp.2007.03.026.
|
| [50] |
Che X, Park KC, Park SJ, et al. Protective effects of guggulsterone against colitis are associated with the suppression of TREM-1 and modulation of macrophages. Am J Physiol Gastrointest Liver Physiol. 2018; 315(1):G128-G139. https://doi.org/10.1152/ajpgi.00027.2018.
|
| [51] |
Kim DG, Bae GS, Choi SB, et al. Guggulsterone attenuates cerulein-induced acute pancreatitis via inhibition of ERK and JNK activation. Int Immunopharmacol. 2015; 26(1):194-202. https://doi.org/10.1016/j.intimp.2015.03.030.
|
| [52] |
Kim N, Park JM, Lee SH, et al. Effect of combinatory treatment with resveratrol and guggulsterone on mild acute pancreatitis in mice. Pancreas. 2017; 46(3):366-371. https://doi.org/10.1097/MPA.0000000000000763.
|
| [53] |
Shishodia S, Aggarwal BB. Guggulsterone inhibits NF-κB and IκBα kinase activation, suppresses expression of anti-apoptotic gene products, and enhances apoptosis. J Biol Chem. 2004; 279(45):47148-47158. https://doi.org/10.1074/jbc.M408093200.
|
| [54] |
Zhang L, Lin W, Cai Y, et al. Farnesoid X receptor activation is required for the anti-inflammatory and anti-oxidative stress effects of Alisol B 23-acetate in carbon tetrachloride-induced liver fibrosis in mice. Int Immunopharmacol. 2023;123:-110768. https://doi.org/10.1016/j.intimp.2023.110768.
|
| [55] |
Lobo V, Patil A, Phatak A, et al. Free radicals, antioxidants and functional foods: impact on human health. Phcog Rev. 2010; 4(8):118-126. https://doi.org/10.4103/0973-7847.70902.
|
| [56] |
Sabarathinam S, Ganamurali N. Targeting 7-ketocholesterol-induced oxidative stress and inflammation: guggulsterone as a novel vascular protectant. J Steroid Biochem Mol Biol. 2025; 254:106846. https://doi.org/10.1016/j.jsbmb.2025.106846.
|
| [57] |
Almazari I, Park JM, Park SA, et al. Guggulsterone induces heme oxygenase-1 expression through activation of Nrf2 in human mammary epithelial cells: PTEN as a putative target. Carcinogenesis. 2012; 33(2):368-376. https://doi.org/10.1093/carcin/bgr259.
|
| [58] |
Xu Y, Guan J, Xu J, et al. Z-Guggulsterone attenuates glucocorticoid-induced osteoporosis through activation of Nrf2/HO-1 signaling. Life Sci. 2019; 224:58-66. https://doi.org/10.1016/j.lfs.2019.03.051.
|
| [59] |
Liu T, Wang W, Liu M, et al. Z-Guggulsterone alleviated oxidative stress and inflammation through inhibiting the TXNIP/NLRP3 axis in ischemic stroke. Int Immunopharmacol. 2020;89(Pt B):107094. https://doi.org/10.1016/j.intimp.2020.107094.
|
| [60] |
Saxena G, Singh SP, Pal R, et al. Gugulipid, an extract of Commiphora whighitii with lipid-lowering properties, has protective effects against streptozotocin-induced memory deficits in mice. Pharmacol Biochem Behav. 2007; 86(4):797-805. https://doi.org/10.1016/j.pbb.2007.03.010.
|
| [61] |
Kweon B, Kim DU, Oh JY, et al. Guggulsterone protects against lipopolysaccharide-induced inflammation and lethal endotoxemia via heme oxygenase-1. Int Immunopharmacol. 2023;124(Pt B):111073. https://doi.org/10.1016/j.intimp.2023.111073.
|
| [62] |
Satyavati GV, Dwarakanath C, Tripathi SN. Experimental studies on the hypocholesterolemic effect of Commiphora mukul Engl. (Guggul). Indian J Med Res. 2013; 137(2):403.
|
| [63] |
Urizar NL, Liverman AB, Dodds DT, et al. A natural product that lowers cholesterol as an antagonist ligand for FXR. Science. 2002; 296(5573):1703-1706. https://doi.org/10.1126/science.1072891.
|
| [64] |
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. https://doi.org/10.1210/mend.16.7.0894.
|
| [65] |
Yang JY, Della-Fera MA, Baile CA. Guggulsterone inhibits adipocyte differentiation and induces apoptosis in 3T3-L1 cells. Obesity (Silver Spring). 2008; 16(1):16-22. https://doi.org/10.1038/oby.2007.24.
|
| [66] |
Miller CN, Samuels JS, Azhar Y, et al. Guggulsterone activates adipocyte beiging through direct effects on 3T3-L1 adipocytes and indirect effects mediated through RAW264.7 macrophages. Medicines (Basel). 2019; 6(1):22. https://doi.org/10.3390/medicines6010022.
|
| [67] |
Rayalam S, Della-Fera MA, Ambati S, et al. Enhanced effects of guggulsterone plus 1,25(OH)2D3 on 3T3-L1 adipocytes. Biochem Biophys Res Commun. 2007; 364(3):450-456. https://doi.org/10.1016/j.bbrc.2007.10.051.
|
| [68] |
Rayalam S, Yang JY, Della-Fera MA, et al. Anti-obesity effects of xanthohumol plus guggulsterone in 3T3-L 1 adipocytes. J Med Food. 2009; 12(4):846-853. https://doi.org/10.1089/jmf.2008.0158.
|
| [69] |
Yang JY, Della-Fera MA, Rayalam S, et al. Enhanced pro-apoptotic and anti-adipogenic effects of genistein plus guggulsterone in 3T3-L 1 adipocytes. Biofactors. 2007; 30(3):159-169. https://doi.org/10.1002/biof.5520300303.
|
| [70] |
Wang X, Greilberger J, Ledinski G, et al. The hypolipidemic natural product Commiphora mukul and its component guggulsterone inhibit oxidative modification of LDL. Atherosclerosis. 2004; 172(2):239-246. https://doi.org/10.1016/j.atherosclerosis.2003.10.008.
|
| [71] |
Sharma B, Salunke R, Srivastava S, et al. Effects of guggulsterone isolated from Commiphora mukul in high fat diet induced diabetic rats. Food Chem Toxicol. 2009; 47(10):2631-2639. https://doi.org/10.1016/j.fct.2009.07.021.
|
| [72] |
Bouslama L, Kouidhi B, Alqurashi YM, et al. Virucidal effect of guggulsterone isolated from Commiphora gileadensis. Planta Med. 2019; 85(16):1225-1232. https://doi.org/10.1055/a-1014-3303.
|
| [73] |
Chen WC, Wei CK, Hossen M, et al. (E)-Guggulsterone inhibits dengue virus replication by upregulating antiviral interferon responses through the induction of heme oxygenase-1 expression. Viruses. 2021; 13(4):712. https://doi.org/10.3390/v13040712.
|
| [74] |
Vidhya VR, Ramu A, Chinnappan J, et al. Interleukin-10 as Covid-19 biomarker targeting KSK and its analogues: integrated network pharmacology. PLoS One. 2023; 18(3):e0282263. https://doi.org/10.1371/journal.pone.0282263.
|
| [75] |
Brevini T, Maes M, Webb GJ, et al. FXR inhibition may protect from SARS-CoV-2 infection by reducing ACE2. Nature. 2023; 615(7950):134-142. https://doi.org/10.1038/s41586-022-05594-0.
|
| [76] |
Liu T, Liu M, Zhang T, et al. Z-Guggulsterone attenuates astrocytes-mediated neuroinflammation after ischemia by inhibiting toll-like receptor 4 pathway. J Neurochem. 2018; 147(6):803-815. https://doi.org/10.1111/jnc.14583.
|
| [77] |
Liu T, Bai M, Liu M, et al. Novel synergistic mechanism of 11-keto-β-boswellic acid and Z-guggulsterone on ischemic stroke revealed by single-cell transcriptomics. Pharmacol Res. 2023; 193:106803. https://doi.org/10.1016/j.phrs.2023.106803.
|
| [78] |
Liu J, Lin Y, Yang Y, et al. Z-Guggulsterone attenuates cognitive defects and decreases neuroinflammation in APPswe/PS1dE9 mice through inhibiting the TLR4 signaling pathway. Biochem Pharmacol. 2022; 202:115149. https://doi.org/10.1016/j.bcp.2022.115149.
|
| [79] |
Dang SJ, Wei WB, Li RL, et al. Z-Guggulsterone relieves neuropathic pain by inhibiting the expression of astrocytes and proinflammatory cytokines in the spinal dorsal horn. J Pain Res. 2022; 15:1315-1324. https://doi.org/10.2147/JPR.S360126.
|
| [80] |
Nicolas CS, Amici M, Bortolotto ZA, et al. The role of JAK-STAT signaling within the CNS. Jakstat. 2013; 2(1):e22925. https://doi.org/10.4161/jkst.22925.
|
| [81] |
Kumar N, Sharma N, Khera R, et al. Guggulsterone ameliorates ethidium bromide-induced experimental model of multiple sclerosis via restoration of behavioral, molecular, neurochemical and morphological alterations in rat brain. Metab Brain Dis. 2021; 36(5):911-925. https://doi.org/10.1007/s11011-021-00691-x.
|
| [82] |
Muthian G, Bright JJ. Quercetin, a flavonoid phytoestrogen, ameliorates experimental allergic encephalomyelitis by blocking IL-12 signaling through JAK-STAT pathway in T lymphocyte. J Clin Immunol. 2004; 24(5):542-552. https://doi.org/10.1023/B:JOCI.0000040925.55682.a5.
|
| [83] |
Kumar S, Mehan S, Khan Z, et al. Guggulsterone selectively modulates STAT-3, mTOR, and PPAR-γ signaling in a methylmercury-exposed experimental neurotoxicity: evidence from CSF, blood plasma, and brain samples. Mol Neurobiol. 2024; 61(8):5161-5193. https://doi.org/10.1007/s12035-023-03902-x.
|
| [84] |
Chen Z, Huang C, Ding W. Z-Guggulsterone improves the scopolamine-induced memory impairments through enhancement of the BDNF signal in C57BL/6J mice. Neurochem Res. 2016; 41(12):3322-3332. https://doi.org/10.1007/s11064-016-2064-0.
|
| [85] |
Liu FG, Hu WF, Wang JL, et al. Z-Guggulsterone produces antidepressant-like effects in mice through activation of the BDNF signaling pathway. Int J Neuropsychopharmacol. 2017; 20(6):485-497. https://doi.org/10.1093/ijnp/pyx009.
|
| [86] |
Kaul S, Kapoor NK. Cardiac sarcolemma enzymes & liver microsomal cytochrome P450 in isoproterenol treated rats. Indian J Med Res. 1989; 90:62-68.
|
| [87] |
Chander R, Rizvi F, Khanna AK, et al. Cardioprotective activity of synthetic guggulsterone (E and Z-isomers) in isoproterenol induced myocardial ischemia in rats: a comparative study. Indian J Clin Biochem. 2003; 18(2):71-79. https://doi.org/10.1007/BF02867370.
|
| [88] |
Pu J, Yuan A, Shan P, et al. Cardiomyocyte-expressed farnesoid-X-receptor is a novel apoptosis mediator and contributes to myocardial ischaemia/reperfusion injury. Eur Heart J. 2013; 34(24):1834-1845. https://doi.org/10.1093/eurheartj/ehs011.
|
| [89] |
Wang WC, Uen YH, Chang ML, et al. Protective effect of guggulsterone against cardiomyocyte injury induced by doxorubicin in vitro. BMC Complement Altern Med. 2012; 12:138. https://doi.org/10.1186/1472-6882-12-138.
|
| [90] |
Liu M, Wang W, Wang J, et al. Z-Guggulsterone alleviates renal fibrosis by mitigating G2/M cycle arrest through Klotho/p53 signaling. Chem Biol Interact. 2022; 354:109846. https://doi.org/10.1016/j.cbi.2022.109846.
|
| [91] |
Kim BH, Yoon JH, Yang JI, et al. Guggulsterone attenuates activation and survival of hepatic stellate cell by inhibiting nuclear factor kappa B activation and inducing apoptosis. J Gastroenterol Hepatol. 2013; 28(12):1859-1868. https://doi.org/10.1111/jgh.12314.
|
| [92] |
Barthe L, Woodley J, Houin G. Gastrointestinal absorption of drugs: methods and studies. Fundam Clin Pharmacol. 1999; 13(2):154-168. https://doi.org/10.1111/j.1472-8206.1999.tb00334.x.
|
| [93] |
Verma N, Singh SK, Gupta RC. Pharmacokinetics of guggulsterone after intravenous and oral administration in rats. J Pharm Pharmacol. 1999; 5(5):349-354. https://doi.org/10.1211/146080899128734956.
|
| [94] |
Bhatta RS, Kumar D, Chhonker YS, et al. Simultaneous estimation of E- and Z-isomers of guggulsterone in rabbit plasma using liquid chromatography tandem mass spectrometry and its application to pharmacokinetic study. Biomed Chromatogr. 2011; 25(9):1054-1060. https://doi.org/10.1002/bmc.1574.
|
| [95] |
Chhonker YS, Chandasana H, Mukkavilli R, et al. Assessment of in vitro metabolic stability, plasma protein binding, and pharmacokinetics of E- and Z-guggulsterone in rat. Drug Test Anal. 2016; 8(9):966-975. https://doi.org/10.1002/dta.1885.
|
| [96] |
Chhonker YS, Chandasana H, Bala V, et al. In-vitro metabolism, CYP profiling and metabolite identification of E- and Z-guggulsterone, a potent hypolipidmic agent. J Pharm Biomed Anal. 2018; 160:202-211. https://doi.org/10.1016/j.jpba.2018.06.047.
|
| [97] |
Balhara A, Ladumor M, Singh DK, et al. In vitro evaluation of reactive nature of E- and Z-guggulsterones and their metabolites in human liver microsomes using UHPLC-Orbitrap mass spectrometer. J Pharm Biomed Anal. 2020; 186:113275. https://doi.org/10.1016/j.jpba.2020.113275.
|
| [98] |
Kölönte A, Guillot B, Raison-Peyron N. Allergic contact dermatitis to guggul extract contained in an anticellulite gel-cream. Contact Dermatitis. 2006; 54(4):226-227. https://doi.org/10.1111/j.0105-1873.2006.0775m.x.
|
| [99] |
Szapary PO, Wolfe ML, Bloedon LT, et al. Guggulipid for the treatment of hypercholesterolemia: a randomized controlled trial. JAMA. 2003; 290(6):765-772. https://doi.org/10.1001/jama.290.6.765.
|
| [100] |
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.
|
| [101] |
Balkrishna A, Sinha S, Bhattacharya K, et al. Twenty-eight days of repeated dose sub-acute toxicological evaluation of polyherbal Ayurvedic medicine BPGrit in Sprague-Dawley rats. J Appl Toxicol. 2024; 44(9):1372-1387. https://doi.org/10.1002/jat.4625.
|
| [102] |
Kim JM, Kang HW, Cha MY, et al. Novel guggulsterone derivative GG-52 inhibits NF-κB signaling in intestinal epithelial cells and attenuates acute murine colitis. Lab Invest. 2010; 90(7):1004-1015. https://doi.org/10.1038/labinvest.2010.54.
|
| [103] |
Kang SJ, Kim JM, Koh SJ, et al. The guggulsterone derivative GG-52 inhibits NF-κB signaling in bone marrow-derived dendritic cells and attenuates colitis in IL-10 knockout mice. Life Sci. 2013; 92(22):1064-1071. https://doi.org/10.1016/j.lfs.2013.04.003.
|
| [104] |
Lee D, Kim T, Kim KH, et al. Evaluation of guggulsterone derivatives as novel kidney cell protective agents against cisplatin-induced nephrotoxicity. Bioorg Med Chem Lett. 2017; 27(14):3156-3161. https://doi.org/10.1016/j.bmcl.2017.05.033.
|
| [105] |
Kohyama A, Kim MJ, Yokoyama R, et al. Structure-activity relationship and mechanistic study on guggulsterone derivatives; discovery of new anti-pancreatic cancer candidate. Bioorg Med Chem. 2022; 54:116563. https://doi.org/10.1016/j.bmc.2021.116563.
|
| [106] |
Kohyama A, Yokoyama R, Dibwe DF, et al. Synthesis of guggulsterone derivatives as potential anti-austerity agents against PANC-1 human pancreatic cancer cells. Bioorg Med Chem Lett. 2020; 30(7):126964. https://doi.org/10.1016/j.bmcl.2020.126964.
|
PDF
(3892KB)
