Advances in the pharmacological activities and mechanisms of diosgenin

CHEN Yan; TANG You-Mei; YU Su-Lan; HAN Yu-Wei; KOU Jun-Ping; LIU Bao-Lin; YU Bo-Yang

Volume 13 Issue 8

Aug. 2015

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Article Navigation > Chinese Journal of Natural Medicines > 2015 > 13(8): 578-587

Citation:

Advances in the pharmacological activities and mechanisms of diosgenin

Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing 211198, China

Corresponding author: KOU Jun-Ping
Received Date: 06-Feb.-2015

Fund Project: This work was supported by National Natural Science Foundation of China (No. 81274131), the Priority Academic Program Development of Jiangsu Higher Education Institutions, and 2011 Program for Excellent Scientific and Technological Innovation Team of Jiangsu Higher Education.

Abstract

Diosgenin, a well-known steroid sapogenin derived from plants, has been used as a starting material for production of steroidal hormones. The present review will summarize published literature concerning pharmacological potential of diosgenin, and the underlying mechanisms of actions. Diosgenin has shown a vast range of pharmacological activities in preclinical studies. It exhibits anticancer, cardiovascular protective, anti-diabetes, neuroprotective, immunomodulatory, estrogenic, and skin protective effects, mainly by inducing apoptosis, suppressing malignant transformation, decreasing oxidative stress, preventing inflammatory events, promoting cellular differentiation/proliferation, and regulating T-cell immune response, etc. It interferes with cell death pathways and their regulators to induce apoptosis. Diosgenin antagonizes tumor metastasis by modulating epithelial-mesenchymal transition and actin cytoskeleton to change cellular motility, suppressing degradation of matrix barrier, and inhibiting angiogenesis. Additionally, diosgenin improves antioxidant status and inhibits lipid peroxidation. Its anti-inflammatory activity is through inhibiting production of pro-inflammatory cytokines, enzymes and adhesion molecules. Furthermore, diosgenin drives cellular growth/differentiation through the estrogen receptor (ER) cascade and transcriptional factor PPAR. In summary, these mechanistic studies provide a basis for further development of this compound for pharmacotherapy of various diseases.
- Diosgenin,
- Steroid sapogenin,
- Pharmacological activities,
- Multiple targets

References

[1]	Butler MS. Natural products to drugs:natural product derived compounds in clinical trials[J]. Nat Prod Rep, 2005, 22(2):162-195.
[2]	Gurib-Fakim A. Medicinal plants:traditions of yesterday and drugs of tomorrow[J]. Mol Aspects Med, 2006, 27(1):1-93.
[3]	Man S, Gao W, Zhang Y, et al. Chemical study and medical application of saponins as anti-cancer agents[J]. Fitoterapia, 2010, 81(7):703-714.
[4]	Shi J, Arunasalam K, Yeung D, et al. Saponins from edible legumes:chemistry, processing, and health benefits[J]. J Med Food, 2004, 7(1):67-78.
[5]	Djerassi C, Rosenkranz G, Pataki J, et al. Steroids, XXVII. Synthesis of allopregnane-3beta, 11beta, 17alpha-, 20beta, 21-pentol from cortisone and diosgenin[J]. J Biol Chem, 1952, 194(1):115-118.
[6]	Raju J, Mehta R. Cancer chemopreventive and therapeutic effects of diosgenin, a food saponin[J]. Nutr Cancer, 2008, 61(1):27-35.
[7]	Yue L, Chen L, Kou JP, et al. Recent advances of diosgenin in its pharmacological activities and mechanism[J]. Chin J Clin Pharmacol Ther, 2010, 15(2):233-237.
[8]	Corbiere C, Liagre B, Bianchi A, et al. Different contribution of apoptosis to the antiproliferative effects of diosgenin and other plant steroids, hecogenin and tigogenin, on human 1547 osteosarcoma cells[J]. Int J Oncol, 2003, 22(4):899-906.
[9]	Corbiere C, Liagre B, Terro F, et al. Induction of antiproliferative effect by diosgenin through activation of p53, release of apoptosis-inducing factor (AIF) and modulation of caspase-3 activity in different human cancer cells[J]. Cell Res, 2004, 14(3):188-196
[10]	Wang WC, Liu SF, Chang WT, et al. The effects of diosgenin in the regulation of renal proximal tubular fibrosis[J]. Exp Cell Res, 2014, 323(2):255-262.
[11]	Chen PS, Shih YW, Huang HC, et al. Diosgenin, a steroidal saponin, inhibits migration and invasion of human prostate cancer PC-3 cells by reducing matrix metalloproteinases expression[J]. PLos One, 2011, 6(5):e20164.
[12]	He Z, Chen H, Li G, et al. Diosgenin inhibits the migration of human breast cancer MDA-MB-231 cells by suppressing Vav2 activity[J]. Phytomedicine, 2014, 21(6):871-876.
[13]	Mao ZJ, Tang QJ, Zhang CA, et al. Anti-proliferation and anti-invasion effects of diosgenin on gastric cancer BGC-823 cells with HIF-1 shRNAs[J]. Int J Mol Sci, 2012, 13(5):6521-6533.
[14]	Evan GI, Vousden KH. Proliferation, cell cycle and apoptosis in cancer[J]. Nature, 2001, 411(6835):342-348.
[15]	Shishodia S, Aggarwal BB. Diosgenin inhibits osteoclastogenesis, invasion, and proliferation through the downregulation of Akt, IB kinase activation and NF-B-regulated gene expression[J]. Oncogene, 2005, 25(10):1463-1473.
[16]	Chiang CT, Way TD, Tsai SJ, et al. Diosgenin, a naturally occurring steroid, suppresses fatty acid synthase expression in HER2-overexpressing breast cancer cells through modulating Akt, mTOR and JNK phosphorylation[J]. Febs Lett, 2007, 581(30):5735-5742.
[17]	Cailleteau C, Liagre B, Beneytout JL. A proteomic approach to the identification of molecular targets in subsequent apoptosis of HEL cells after diosgenin-induced megakaryocytic differentiation[J]. J Cell Biochem, 2009, 107(4):785-796.
[18]	Raju J, Patlolla JM, Swamy MV, et al. Diosgenin, a steroid saponin of Trigonella foenum graecum (Fenugreek), inhibits azoxymethane-induced aberrant crypt foci formation in F344 rats and induces apoptosis in HT-29 human colon cancer cells[J]. Cancer Epidemiol Biomarkers Prev, 2004, 13(8):1392-1398.
[19]	Mohammad RY, Somayyeh G, Gholamreza H, et al. Diosgenin inhibits hTERT gene expression in the A549 lung cancer cell line[J]. Asian Pac J Cancer Prev, 2013, 14(11):6945-6948.
[20]	Bian D, Li Z, Ma H, et al. Effects of diosgenin on cell proliferation induced by IGF-1 in primary human thyrocytes[J]. Arch Pharm Res, 2011, 34(6):997-1005.
[21]	Mu S, Tian X, Ruan Y, et al. Diosgenin induces apoptosis in IGF-1-stimulated human thyrocytes through two caspasedependent pathways[J]. Biochem Biophys Res Commun, 2012, 418(2):347-352.
[22]	Cai H, Wang Z, Zhang H, et al. Diosgenin relieves goiter via the inhibition of thyrocyte proliferation in a mouse model of Graves' disease[J]. Acta Pharmacol Sini, 2014, 35(1):65-73.
[23]	Mani SA, Guo W, Liao MJ, et al. The epithelial-mesenchymal transition generates cells with properties of stem cells[J]. Cell, 2008, 133(4):704-715.
[24]	Zhou X, Zhang H, Han X. Role of epithelial to mesenchymal transition proteins in gynecological cancers:pathological and therapeutic perspectives[J]. Tumor Biology, 2014, 35(10):9523-9530.
[25]	Chang HY, Kao MC, Way TD, et al. Diosgenin suppresses hepatocyte growth factor (HGF)-induced epithelialmesenchymal transition by down-regulation of Mdm2 and Vimentin[J]. J Agric Food Chem, 2011, 59(10):5357-5363.
[26]	Gialeli C, Theocharis AD, Karamanos NK. Roles of matrix metalloproteinases in cancer progression and their pharmacological targeting[J]. FEBS J, 2011, 278(1):16-27.
[27]	Wang W, Goswami S, Sahai E, et al. Tumor cells caught in the act of invading:their strategy for enhanced cell motility[J]. Trends Cell Biol, 2005, 15(3):138-145.
[28]	Le Clainche C, Carlier MF. Regulation of actin assembly associated with protrusion and adhesion in cell migration[J]. Physiol Rev, 2008, 88(2):489-513.
[29]	Rathinam R, Berrier A, Alahari SK. Role of Rho GTPases and their regulators in cancer progression[J]. Front Biosci, 2011, 16(1):2561-2571.
[30]	Lin M, van Golen KL. Rho-regulatory proteins in breast cancer cell motility and invasion[J]. Breast Cancer Res Treat, 2004, 84(1):49-60.
[31]	Mihalache A, Rogoveanu I. Angiogenesis factors involved in the pathogenesis of colorectal cancer[J]. Curr Health Sci J, 2014, 40(1):5-11.
[32]	Shimizu T, Tolcher AW, Papadopoulos KP, et al. The clinical effect of the dual-targeting strategy involving PI3K/AKT/mTOR and RAS/MEK/ERK pathways in patients with advanced cancer[J]. Clin Cancer Res, 2012, 18(8):2316-2325.
[33]	Das S, Dey KK, Dey G, et al. Antineoplastic and apoptotic potential of traditional medicines thymoquinone and diosgenin in squamous cell carcinoma[J]. PLos One, 2012, 7(10):e46641
[34]	Srinivasan S, Koduru S, Kumar R, et al. Diosgenin targets Akt-mediated prosurvival signaling in human breast cancer cells[J]. Int J Cancer, 2009, 125(4):961-967.
[35]	Kim DS, Jeon BK, Lee YE, et al. Diosgenin induces apoptosis in HepG2 cells through generation of reactive oxygen species and mitochondrial pathway[J]. Evid Based Complement Alternat Med, 2012, 2012:981675.
[36]	Liagre B, Bertrand J, Leger DY, et al. Diosgenin, a plant steroid, induces apoptosis in COX-2 deficient K562 cells with activation of the p38 MAP kinase signalling and inhibition of NF-B binding[J]. Int J Mol Med, 2005, 16(6):1095-1101.
[37]	Bertrand J, Liagre B, Bgaud-Grimaud G, et al. Study of diosgenin-induced apoptosis kinetics in K562 cells by sedimentation field flow fractionation[J]. J Chromatogr B, 2008, 869(1):75-83.
[38]	Yadav VR, Prasad S, Sung B, et al. Targeting inflammatory pathways by triterpenoids for prevention and treatment of cancer[J]. Toxins, 2010, 2(10):2428-2466.
[39]	Shishodia S, Aggarwal BB. Diosgenin inhibits osteoclastogenesis, invasion, and proliferation through the downregulation of Akt, IB kinase activation and NF-B-regulated gene expression[J]. Oncogene, 2006, 25(10):1463-1473.
[40]	Li F, Fernandez PP, Rajendran P, et al. Diosgenin, a steroidal saponin, inhibits STAT3 signaling pathway leading to suppression of proliferation and chemosensitization of human hepatocellular carcinoma cells[J]. Cancer Lett, 2010, 292(2):197-207.
[41]	Khan Z, Khan N, Tiwari RP, et al. Biology of Cox-2:an application in cancer therapeutics[J]. Curr Drug Targets, 2011, 12(7):1082-1093.
[42]	Hsu AL, Ching TT, Wang DS, et al. The cyclooxygenase-2 inhibitor celecoxib induces apoptosis by blocking Akt activation in human prostate cancer cells independently of Bcl-2[J]. J Biol Chem, 2000, 275(15):11397-11403.
[43]	Cailleteau C, Liagre B, Battu S, et al. Increased cyclooxygenase-2 and thromboxane synthase expression is implicated in diosgenin-induced megakaryocytic differentiation in human erythroleukemia cells[J]. Anal Biochem, 2008, 380(1):26-34.
[44]	Lepage C, Liagre B, Cook-Moreau J, et al. Cyclooxygenase-2 and 5-lipoxygenase pathways in diosgenin-induced apoptosis in HT-29 and HCT-116 colon cancer cells[J]. Int J Oncol, 2010, 36(5):1183-1191.
[45]	Lepage C, Lger DY, Bertrand J, et al. Diosgenin induces death receptor-5 through activation of p38 pathway and promotes TRAIL-induced apoptosis in colon cancer cells[J]. Cancer Lett, 2011, 301(2):193-202.
[46]	Miyoshi N, Nagasawa T, Mabuchi R, et al. Chemoprevention of azoxymethane/dextran sodium sulfate-induced mouse colon carcinogenesis by freeze-dried Yam Sanyaku and its constituent diosgenin[J]. Cancer Prev Res, 2011, 4(6):924-934.
[47]	Knudson AG. Two genetic hits (more or less) to cancer[J]. Nat Rev Cancer, 2001, 1(2):157-162.
[48]	Menendez JA, Lupu R. Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis[J]. Nat Rev Cancer, 2007,7(10):763-777.
[49]	Baron A, Migita T, Tang D, et al. Fatty acid synthase:a metabolic oncogene in prostate cancer[J]. J Cell Biochem, 2004, 91(1):47-53.
[50]	Lee BH, Taylor MG, Robinet P, et al. Dysregulation of cholesterol homeostasis in human prostate cancer through loss of ABCA1[J]. Cancer Res, 2013, 73(3):1211-1218.
[51]	Guruswamy S, Rao CV. Multi-target approaches in colon cancer chemoprevention based on systems biology of tumor cell-signaling[J]. Gene Regul Syst Biol, 2008, 2:163-176.
[52]	DeBose-Boyd RA. Feedback regulation of cholesterol synthesis:sterol-accelerated ubiquitination and degradation of HMG CoA reductase[J]. Cell Res, 2008, 18(6):609-621.
[53]	Raju J, Bird RP. Diosgenin, a naturally occurring furostanol saponin suppresses 3-hydroxy-3-methylglutaryl CoA reductase expression and induces apoptosis in HCT-116 human colon carcinoma cells[J]. Cancer Lett, 2007, 255(2):194-204.
[54]	Ebrahimi H, Badalzadeh R, Mohammadi M, et al. Diosgenin attenuates inflammatory response induced by myocardial reperfusion injury:role of mitochondrial ATP-sensitive potassium channels[J]. J Physiol Biochem, 2014, 70(2):435-432.
[55]	Salimeh A, Mohammadi M, Rashidi B. Preconditioning with diosgenin and treadmill exercise preserves the cardiac toxicity of isoproterenol in rats[J]. J Physiol Biochem, 2013, 69(2):255-265.
[56]	Jayachandran KS, Vasanthi HR, Rajamanickam GV. Antilipoperoxidative and membrane stabilizing effect of diosgenin, in experimentally induced myocardial infarction[J]. Mol Cell Biochem, 2009, 327(1-2):203-210.
[57]	Gutirrez E, Flammer AJ, Lerman LO, et al. Endothelial dysfunction over the course of coronary artery disease[J]. Eur Heart J, 2013, 34(41):3175-3181.
[58]	McVeigh GE, Brennan GM, Johnston GD, et al. Impaired endothelium-dependent and independent vasodilation in patients with type 2(non-insulin-dependent) diabetes mellitus[J]. Diabetologia, 1992, 35(8):771-776.
[59]	Manivannan J, Balamurugan E, Silambarasan T, et al. Diosgenin improves vascular function by increasing aortic eNOS expression, normalize dyslipidemia and ACE activity in chronic renal failure rats[J]. Mol Cell Biochem, 2013, 384(1-2):113-120.
[60]	Liu K, Zhao W, Gao X, et al. Diosgenin ameliorates palmitate-induced endothelial dysfunction and insulin resistance via blocking IKK and IRS-1 pathways[J]. Atherosclerosis, 2012, 223(2):350-358.
[61]	Dias KL, Correia NA, Pereira KK, et al. Mechanisms involved in the vasodilator effect induced by diosgenin in rat superior mesenteric artery[J]. Eur J Pharmacol, 2007, 574(2):172-178.
[62]	Gong G, Qin Y, Huang W, et al. Protective effects of diosgenin in the hyperlipidemic rat model and in human vascular endothelial cells against hydrogen peroxide-induced apoptosis[J]. Chem-Biol Interact, 2010, 184(3):366-375.
[63]	Au AL, Kwok CC, Lee AT, et al. Activation of iberiotoxin-sensitive, Ca2+ activated K+ channels of porcine isolated left anterior descending coronary artery by diosgenin[J]. Eur J Pharmacol, 2004, 502(1):123-133.
[64]	Esfandiarei M, Lam JT, Yazdi SA, et al. Diosgenin modulates vascular smooth muscle cell function by regulating cell viability, migration, and calcium homeostasis[J]. J Pharmacol Exp Ther, 2011, 336(3):925-939.
[65]	Mayer K, Merfels M, Muhly-Reinholz M, et al. -3 Fatty acids suppress monocyte adhesion to human endothelial cells:role of endothelial PAF generation[J]. Am J Physiol-Heart C, 2002, 283(2):H811-H818.
[66]	Liu YC, Zou XB, Chai YF, et al. Macrophage polarization in inflammatory diseases[J]. Int J Biol Sci, 2014, 10(5):520-529.
[67]	Carlos TM, Schwartz BR, Kovach NL, et al. Vascular cell adhesion molecule-1 mediates lymphocyte adherence to cytokine-activated cultured human endothelial cells[J]. Blood, 1990, 76(5):965-970.
[68]	Ling S, Nheu L, A Komesaroff P. Cell adhesion molecules as pharmaceutical target in atherosclerosis[J]. Mini-Rev Med Chem, 2012, 12(2):175-183.
[69]	Choi KW, Park HJ, Jung DH, et al. Inhibition of TNF--induced adhesion molecule expression by diosgenin in mouse vascular smooth muscle cells via down regulation of the MAPK, Akt and NF-B signaling pathways[J]. Vasc Pharmacol, 2010, 53(5):273-280.
[70]	Song JX, Ma L, Kou JP, et al. Diosgenin reduces leukocytes adhesion and migration linked with inhibition of intercellular adhesion molecule-1 expression and NF-B p65 activation in endothelial cells[J]. Chin J Nat Med, 2012, 10(2):142-149.
[71]	Drozdowska J. Tissue factor in endothelial cells--its structure and function according to the current literature[J]. Postepy Biochem, 2011, 58(3):273-280.
[72]	berg M, Siegbahn A. Tissue factor non-coagulant signaling-molecular mechanisms and biological consequences with a focus on cell migration and apoptosis[J]. J Thromb Haemost, 2013, 11(5):817-825.
[73]	Yang HP, Yue L, Jiang WW, et al. Diosgenin inhibits tumor necrosis factor-induced tissue factor activity and expression in THP-1 cells via down-regulation of the NF-B, Akt, and MAPK signaling pathways[J]. Chin J Nat Med, 2013, 11(6):608-615.
[74]	Gong G, Qin Y, Huang W. Anti-thrombosis effect of diosgenin extract from Dioscorea zingiberensis CH Wright in vitro and in vivo[J]. Phytomedicine, 2011, 18(6):458-463.
[75]	Yan MX, Li YQ, Meng M, et al. Long-term high-fat diet induces pancreatic injuries via pancreatic microcirculatory disturbances and oxidative stress in rats with hyperlipidemia[J]. Biochem Biophys Res Commun, 2006, 347(1):192-199.
[76]	Scheuer H, Gwinner W, Hohbach J, et al. Oxidant stress in hyperlipidemia-induced renal damage[J]. Am J Physiol-Renal, 2000, 278(1):F63-F74.
[77]	Frohnert BI, Bernlohr DA. Protein carbonylation, mitochondrial dysfunction, and insulin resistance[J]. Adv Nutr, 2013, 4(2):157-163.
[78]	Argani H, Ghorbani A, Rashtchizade N, et al. Effect of lovastatin on lipid peroxidation and total antioxidant concentrations in hemodialysis patients[J]. Lipids Health Dis, 2004, 3:6.
[79]	Kregel KC, Zhang HJ. An integrated view of oxidative stress in aging:basic mechanisms, functional effects, and pathological considerations[J]. Am J Physiol-Reg I, 2007, 292(1):R18-R36.
[80]	Czak L, Szabolcs A, Vajda , et al. Hyperlipidemia induced by a cholesterol-rich diet aggravates necrotizing pancreatitis in rats[J]. Eur J Pharmacol, 2007, 572(1):74-81.
[81]	Son IS, Kim JH, Sohn HY, et al. Antioxidative and hypolipidemic effects of diosgenin, a steroidal saponin of yam (Dioscorea spp.), on high-cholesterol fed rats[J]. Biosci Biotech Biochem, 2007, 71(12):3063-3071.
[82]	Manivannan J, Barathkumar TR, Sivasubramanian J, et al. Diosgenin attenuates vascular calcification in chronic renal failure rats[J]. Mol Cell Biochem, 2013, 378(1-2):9-18.
[83]	Esser N, Legrand-Poels S, Piette J, et al. Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes[J]. Diabetes Res Clin Pract, 2014, 105(2):141-150.
[84]	Uemura T, Goto T, Kang MS, et al. Diosgenin, the main aglycon of fenugreek, inhibits LXR activity in HepG2 cells and decreases plasma and hepatic triglycerides in obese diabetic mice[J]. J Nutr, 2011, 141(1):17-23.
[85]	Sangeetha MK, ShriShri Mal N, Atmaja K, et al. PPAR's and diosgenin a chemico biological insight in NIDDM[J]. Chem-Biol Interact, 2013, 206(2):403-410.
[86]	Pari L, Monisha P, Mohamed Jalaludeen A. Beneficial role of diosgenin on oxidative stress in aorta of streptozotocin induced diabetic rats[J]. Eur J Pharmacol, 2012, 691(1):143-150.
[87]	Uemura T, Hirai S, Mizoguchi N, et al. Diosgenin present in fenugreek improves glucose metabolism by promoting adipocyte differentiation and inhibiting inflammation in adipose tissues[J]. Mol Nutr Food Res, 2010, 54(11):1596-1608.
[88]	Hirai S, Uemura T, Mizoguchi N, et al. Diosgenin attenuates inflammatory changes in the interaction between adipocytes and macrophages[J]. Mol Nutr Food Res, 2010, 54(6):797-804.
[89]	Xiao L, Guo D, Hu C, et al. Diosgenin promotes oligodendrocyte progenitor cell differentiation through estrogen receptor mediated ERK1/2 activation to accelerate remyelination[J]. Glia, 2012, 60(7):1037-1052.
[90]	Girach A, Vignati L. Diabetic microvascular complications-can the presence of one predict the development of another[J]. J Diabetes Complicat, 2006, 20(4):228-237.
[91]	Cheng HT, Dauch JR, Hayes JM, et al. Nerve growth factor mediates mechanical allodynia in a mouse model of type 2 diabetes[J]. J Neuropath Exp Neur, 2009, 68(11):1229-1243.
[92]	Kang TH, Moon E, Hong BN, et al. Diosgenin from Dioscorea nipponica ameliorates diabetic neuropathy by inducing nerve growth factor[J]. Biol Pharm Bull, 2011, 34(9):1493-1498.
[93]	Kondeva-Burdina M, Lopez MU, Mitcheva M, et al. In vitro effect of diosgenin, isolated from Asparagus officinalis, in a dopamine model of oxidative stress in isolated rat synaptosomes[J]. Toxicol Lett, 2007, 172(s7):S68.
[94]	Chiu CS, Chiu YJ, Wu LY, et al. Diosgenin ameliorates cognition deficit and attenuates oxidative damage in senescent mice induced by D-galactose[J]. Am J Chin Med, 2011, 39(3):551-563.
[95]	Tohda C, Lee YA, Goto Y, et al. Diosgenin-induced cognitive enhancement in normal mice is mediated by 1, 25D3-MARRS[J]. Sci Rep, 2013, 3:3395.
[96]	Wang YJ, Liu YC, Chang HD, et al. Diosgenin, a plant-derived sapogenin, stimulates Ca2+ -activated K+ current in human cortical HCN-1A neuronal cells[J]. Planta Med, 2006, 72(5):430-436.
[97]	Huang CH, Liu DZ, Jan TR. Diosgenin, a plant-derived sapogenin, enhances regulatory T-cell immunity in the intestine of mice with food allergy[J]. J Nat Prod, 2010, 73(6):1033-1037.
[98]	Huang CH, Ku CY, Jan TR. Diosgenin attenuates allergen-induced intestinal inflammation and IgE production in a murine model of food allergy[J]. Planta Med, 2009, 75(12):1300-1305.
[99]	Jan TR, Wey SP, Kuan CC, et al. Diosgenin, a steroidal sapogenin, enhances antigen-specific IgG2a and interferon- expression in ovalbumin-sensitized BALB/c mice[J]. Planta Med, 2007, 73(5):421-426.
[100]	Ku CM, Lin JY. Anti-inflammatory effects of 27 selected terpenoid compounds tested through modulating Th1/Th2 cytokine secretion profiles using murine primary splenocytes[J]. Food Chem, 2013, 141(2):1104-1113.
[101]	Gao M, Chen L, Yu H, et al. Diosgenin down-regulates NF-B p65/p50 and p38MAPK pathways and attenuates acute lung injury induced by lipopolysaccharide in mice[J]. Int Immunopharmacol, 2013, 15(2):240-245.
[102]	Jung DH, Park HJ, Byun HE, et al. Diosgenin inhibits macrophage-derived inflammatory mediators through downregulation of CK2, JNK, NF-B and AP-1 activation[J]. Int Immunopharmacol, 2010, 10(9):1047-1054.
[103]	He Z, Tian Y, Zhang X, et al. Anti-tumour and immunomodulating activities of diosgenin, a naturally occurring steroidal saponin[J]. Nat Prod Res, 2012, 26(23):2243-2246.
[104]	Conner P. Breast response to menopausal hormone therapy-aspects on proliferation, apoptosis and mammographic density[J]. Ann Med, 2007, 39(1):28-41.
[105]	Komesaroff PA, Black CV, Cable V, et al. Effects of wild yam extract on menopausal symptoms, lipids and sex hormones in healthy menopausal women[J]. Climacteric, 2001, 4(2):144-150.
[106]	Accatino L, Pizarro M, Sols N, et al. Effects of diosgenin, a plant-derived steroid, on bile secretion and hepatocellular cholestasis induced by estrogens in the rat[J]. Hepatology, 1998, 28(1):129-140.
[107]	Rao AR, Kale RK. Diosgenin-a growth stimulator of mammary gland of ovariectomized mouse[J]. Indian J Exp Biol, 1992, 30(5):367-370.
[108]	Chiang SS, Chang SP, Pan TM. Osteoprotective effect of monascus-fermented dioscorea in ovariectomized rat model of postmenopausal osteoporosis[J]. J Agric Food Chem, 2011, 59(17):9150-9157.
[109]	Higdon K, Scott A, Tucci M, et al. The use of estrogen, DHEA, and diosgenin in a sustained delivery setting as a novel treatment approach for osteoporosis in the ovariectomized adult rat model[J]. Biomed Sci Instrum, 2001, 37:281-286.
[110]	Yen ML, Su JL, Chien CL, et al. Diosgenin induces hypoxia-inducible factor-1 activation and angiogenesis through estrogen receptor-related phosphatidylinositol 3-kinase/Akt and p38 mitogen-activated protein kinase pathways in osteoblasts[J]. Mol Pharmacol, 2005, 68(4):1061-1073.
[111]	Medigović I, Ristić N, Živanović J, et al. Diosgenin does not express estrogenic activity:a uterotrophic assay[J]. Can J Physiol Pharm, 2014, 92(4):292-298.
[112]	Hsu KH, Chang CC, Tsai HD, et al. Effects of yam and diosgenin on calpain systems in skeletal muscle of ovariectomized rats[J]. Taiwan J Obstet Gynecol, 2008, 47(2):180-186.
[113]	Tada Y, Kanda N, Haratake A, et al. Novel effects of diosgenin on skin aging[J]. Steroids, 2009, 74(6):504-511.
[114]	Lee J, Jung K, Kim YS, et al. Diosgenin inhibits melanogenesis through the activation of phosphatidylinositol-3-kinase pathway (PI3K) signaling[J]. Life Sci, 2007, 81(3):249-254.
[115]	Zheng L, Zhou Y, Zhang JY, et al. Two new steroidal saponins from the rhizomes of Dioscorea zingiberensis[J]. Chin J Nat Med, 2014, 12(2):142-147.
[116]	Noguchi E, Fujiwara Y, Matsushita S, et al. Metabolism of tomato steroidal glycosides in humans[J]. Chem Pharm Bull, 2006, 54(9):1312-1314.

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Advances in the pharmacological activities and mechanisms of diosgenin

Corresponding author: KOU Jun-Ping;

1. Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing 211198, China

Received Date: 2015-02-06

Fund Project: This work was supported by National Natural Science Foundation of China (No. 81274131), the Priority Academic Program Development of Jiangsu Higher Education Institutions, and 2011 Program for Excellent Scientific and Technological Innovation Team of Jiangsu Higher Education.

Abstract: Diosgenin, a well-known steroid sapogenin derived from plants, has been used as a starting material for production of steroidal hormones. The present review will summarize published literature concerning pharmacological potential of diosgenin, and the underlying mechanisms of actions. Diosgenin has shown a vast range of pharmacological activities in preclinical studies. It exhibits anticancer, cardiovascular protective, anti-diabetes, neuroprotective, immunomodulatory, estrogenic, and skin protective effects, mainly by inducing apoptosis, suppressing malignant transformation, decreasing oxidative stress, preventing inflammatory events, promoting cellular differentiation/proliferation, and regulating T-cell immune response, etc. It interferes with cell death pathways and their regulators to induce apoptosis. Diosgenin antagonizes tumor metastasis by modulating epithelial-mesenchymal transition and actin cytoskeleton to change cellular motility, suppressing degradation of matrix barrier, and inhibiting angiogenesis. Additionally, diosgenin improves antioxidant status and inhibits lipid peroxidation. Its anti-inflammatory activity is through inhibiting production of pro-inflammatory cytokines, enzymes and adhesion molecules. Furthermore, diosgenin drives cellular growth/differentiation through the estrogen receptor (ER) cascade and transcriptional factor PPAR. In summary, these mechanistic studies provide a basis for further development of this compound for pharmacotherapy of various diseases.

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Reference (116)

[1]	Butler MS. Natural products to drugs:natural product derived compounds in clinical trials[J]. Nat Prod Rep, 2005, 22(2):162-195.
[2]	Gurib-Fakim A. Medicinal plants:traditions of yesterday and drugs of tomorrow[J]. Mol Aspects Med, 2006, 27(1):1-93.
[3]	Man S, Gao W, Zhang Y, et al. Chemical study and medical application of saponins as anti-cancer agents[J]. Fitoterapia, 2010, 81(7):703-714.
[4]	Shi J, Arunasalam K, Yeung D, et al. Saponins from edible legumes:chemistry, processing, and health benefits[J]. J Med Food, 2004, 7(1):67-78.
[5]	Djerassi C, Rosenkranz G, Pataki J, et al. Steroids, XXVII. Synthesis of allopregnane-3beta, 11beta, 17alpha-, 20beta, 21-pentol from cortisone and diosgenin[J]. J Biol Chem, 1952, 194(1):115-118.
[6]	Raju J, Mehta R. Cancer chemopreventive and therapeutic effects of diosgenin, a food saponin[J]. Nutr Cancer, 2008, 61(1):27-35.
[7]	Yue L, Chen L, Kou JP, et al. Recent advances of diosgenin in its pharmacological activities and mechanism[J]. Chin J Clin Pharmacol Ther, 2010, 15(2):233-237.
[8]	Corbiere C, Liagre B, Bianchi A, et al. Different contribution of apoptosis to the antiproliferative effects of diosgenin and other plant steroids, hecogenin and tigogenin, on human 1547 osteosarcoma cells[J]. Int J Oncol, 2003, 22(4):899-906.
[9]	Corbiere C, Liagre B, Terro F, et al. Induction of antiproliferative effect by diosgenin through activation of p53, release of apoptosis-inducing factor (AIF) and modulation of caspase-3 activity in different human cancer cells[J]. Cell Res, 2004, 14(3):188-196
[10]	Wang WC, Liu SF, Chang WT, et al. The effects of diosgenin in the regulation of renal proximal tubular fibrosis[J]. Exp Cell Res, 2014, 323(2):255-262.
[11]	Chen PS, Shih YW, Huang HC, et al. Diosgenin, a steroidal saponin, inhibits migration and invasion of human prostate cancer PC-3 cells by reducing matrix metalloproteinases expression[J]. PLos One, 2011, 6(5):e20164.
[12]	He Z, Chen H, Li G, et al. Diosgenin inhibits the migration of human breast cancer MDA-MB-231 cells by suppressing Vav2 activity[J]. Phytomedicine, 2014, 21(6):871-876.
[13]	Mao ZJ, Tang QJ, Zhang CA, et al. Anti-proliferation and anti-invasion effects of diosgenin on gastric cancer BGC-823 cells with HIF-1 shRNAs[J]. Int J Mol Sci, 2012, 13(5):6521-6533.
[14]	Evan GI, Vousden KH. Proliferation, cell cycle and apoptosis in cancer[J]. Nature, 2001, 411(6835):342-348.
[15]	Shishodia S, Aggarwal BB. Diosgenin inhibits osteoclastogenesis, invasion, and proliferation through the downregulation of Akt, IB kinase activation and NF-B-regulated gene expression[J]. Oncogene, 2005, 25(10):1463-1473.
[16]	Chiang CT, Way TD, Tsai SJ, et al. Diosgenin, a naturally occurring steroid, suppresses fatty acid synthase expression in HER2-overexpressing breast cancer cells through modulating Akt, mTOR and JNK phosphorylation[J]. Febs Lett, 2007, 581(30):5735-5742.
[17]	Cailleteau C, Liagre B, Beneytout JL. A proteomic approach to the identification of molecular targets in subsequent apoptosis of HEL cells after diosgenin-induced megakaryocytic differentiation[J]. J Cell Biochem, 2009, 107(4):785-796.
[18]	Raju J, Patlolla JM, Swamy MV, et al. Diosgenin, a steroid saponin of Trigonella foenum graecum (Fenugreek), inhibits azoxymethane-induced aberrant crypt foci formation in F344 rats and induces apoptosis in HT-29 human colon cancer cells[J]. Cancer Epidemiol Biomarkers Prev, 2004, 13(8):1392-1398.
[19]	Mohammad RY, Somayyeh G, Gholamreza H, et al. Diosgenin inhibits hTERT gene expression in the A549 lung cancer cell line[J]. Asian Pac J Cancer Prev, 2013, 14(11):6945-6948.
[20]	Bian D, Li Z, Ma H, et al. Effects of diosgenin on cell proliferation induced by IGF-1 in primary human thyrocytes[J]. Arch Pharm Res, 2011, 34(6):997-1005.
[21]	Mu S, Tian X, Ruan Y, et al. Diosgenin induces apoptosis in IGF-1-stimulated human thyrocytes through two caspasedependent pathways[J]. Biochem Biophys Res Commun, 2012, 418(2):347-352.
[22]	Cai H, Wang Z, Zhang H, et al. Diosgenin relieves goiter via the inhibition of thyrocyte proliferation in a mouse model of Graves' disease[J]. Acta Pharmacol Sini, 2014, 35(1):65-73.
[23]	Mani SA, Guo W, Liao MJ, et al. The epithelial-mesenchymal transition generates cells with properties of stem cells[J]. Cell, 2008, 133(4):704-715.
[24]	Zhou X, Zhang H, Han X. Role of epithelial to mesenchymal transition proteins in gynecological cancers:pathological and therapeutic perspectives[J]. Tumor Biology, 2014, 35(10):9523-9530.
[25]	Chang HY, Kao MC, Way TD, et al. Diosgenin suppresses hepatocyte growth factor (HGF)-induced epithelialmesenchymal transition by down-regulation of Mdm2 and Vimentin[J]. J Agric Food Chem, 2011, 59(10):5357-5363.
[26]	Gialeli C, Theocharis AD, Karamanos NK. Roles of matrix metalloproteinases in cancer progression and their pharmacological targeting[J]. FEBS J, 2011, 278(1):16-27.
[27]	Wang W, Goswami S, Sahai E, et al. Tumor cells caught in the act of invading:their strategy for enhanced cell motility[J]. Trends Cell Biol, 2005, 15(3):138-145.
[28]	Le Clainche C, Carlier MF. Regulation of actin assembly associated with protrusion and adhesion in cell migration[J]. Physiol Rev, 2008, 88(2):489-513.
[29]	Rathinam R, Berrier A, Alahari SK. Role of Rho GTPases and their regulators in cancer progression[J]. Front Biosci, 2011, 16(1):2561-2571.
[30]	Lin M, van Golen KL. Rho-regulatory proteins in breast cancer cell motility and invasion[J]. Breast Cancer Res Treat, 2004, 84(1):49-60.
[31]	Mihalache A, Rogoveanu I. Angiogenesis factors involved in the pathogenesis of colorectal cancer[J]. Curr Health Sci J, 2014, 40(1):5-11.
[32]	Shimizu T, Tolcher AW, Papadopoulos KP, et al. The clinical effect of the dual-targeting strategy involving PI3K/AKT/mTOR and RAS/MEK/ERK pathways in patients with advanced cancer[J]. Clin Cancer Res, 2012, 18(8):2316-2325.
[33]	Das S, Dey KK, Dey G, et al. Antineoplastic and apoptotic potential of traditional medicines thymoquinone and diosgenin in squamous cell carcinoma[J]. PLos One, 2012, 7(10):e46641
[34]	Srinivasan S, Koduru S, Kumar R, et al. Diosgenin targets Akt-mediated prosurvival signaling in human breast cancer cells[J]. Int J Cancer, 2009, 125(4):961-967.
[35]	Kim DS, Jeon BK, Lee YE, et al. Diosgenin induces apoptosis in HepG2 cells through generation of reactive oxygen species and mitochondrial pathway[J]. Evid Based Complement Alternat Med, 2012, 2012:981675.
[36]	Liagre B, Bertrand J, Leger DY, et al. Diosgenin, a plant steroid, induces apoptosis in COX-2 deficient K562 cells with activation of the p38 MAP kinase signalling and inhibition of NF-B binding[J]. Int J Mol Med, 2005, 16(6):1095-1101.
[37]	Bertrand J, Liagre B, Bgaud-Grimaud G, et al. Study of diosgenin-induced apoptosis kinetics in K562 cells by sedimentation field flow fractionation[J]. J Chromatogr B, 2008, 869(1):75-83.
[38]	Yadav VR, Prasad S, Sung B, et al. Targeting inflammatory pathways by triterpenoids for prevention and treatment of cancer[J]. Toxins, 2010, 2(10):2428-2466.
[39]	Shishodia S, Aggarwal BB. Diosgenin inhibits osteoclastogenesis, invasion, and proliferation through the downregulation of Akt, IB kinase activation and NF-B-regulated gene expression[J]. Oncogene, 2006, 25(10):1463-1473.
[40]	Li F, Fernandez PP, Rajendran P, et al. Diosgenin, a steroidal saponin, inhibits STAT3 signaling pathway leading to suppression of proliferation and chemosensitization of human hepatocellular carcinoma cells[J]. Cancer Lett, 2010, 292(2):197-207.
[41]	Khan Z, Khan N, Tiwari RP, et al. Biology of Cox-2:an application in cancer therapeutics[J]. Curr Drug Targets, 2011, 12(7):1082-1093.
[42]	Hsu AL, Ching TT, Wang DS, et al. The cyclooxygenase-2 inhibitor celecoxib induces apoptosis by blocking Akt activation in human prostate cancer cells independently of Bcl-2[J]. J Biol Chem, 2000, 275(15):11397-11403.
[43]	Cailleteau C, Liagre B, Battu S, et al. Increased cyclooxygenase-2 and thromboxane synthase expression is implicated in diosgenin-induced megakaryocytic differentiation in human erythroleukemia cells[J]. Anal Biochem, 2008, 380(1):26-34.
[44]	Lepage C, Liagre B, Cook-Moreau J, et al. Cyclooxygenase-2 and 5-lipoxygenase pathways in diosgenin-induced apoptosis in HT-29 and HCT-116 colon cancer cells[J]. Int J Oncol, 2010, 36(5):1183-1191.
[45]	Lepage C, Lger DY, Bertrand J, et al. Diosgenin induces death receptor-5 through activation of p38 pathway and promotes TRAIL-induced apoptosis in colon cancer cells[J]. Cancer Lett, 2011, 301(2):193-202.
[46]	Miyoshi N, Nagasawa T, Mabuchi R, et al. Chemoprevention of azoxymethane/dextran sodium sulfate-induced mouse colon carcinogenesis by freeze-dried Yam Sanyaku and its constituent diosgenin[J]. Cancer Prev Res, 2011, 4(6):924-934.
[47]	Knudson AG. Two genetic hits (more or less) to cancer[J]. Nat Rev Cancer, 2001, 1(2):157-162.
[48]	Menendez JA, Lupu R. Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis[J]. Nat Rev Cancer, 2007,7(10):763-777.
[49]	Baron A, Migita T, Tang D, et al. Fatty acid synthase:a metabolic oncogene in prostate cancer[J]. J Cell Biochem, 2004, 91(1):47-53.
[50]	Lee BH, Taylor MG, Robinet P, et al. Dysregulation of cholesterol homeostasis in human prostate cancer through loss of ABCA1[J]. Cancer Res, 2013, 73(3):1211-1218.
[51]	Guruswamy S, Rao CV. Multi-target approaches in colon cancer chemoprevention based on systems biology of tumor cell-signaling[J]. Gene Regul Syst Biol, 2008, 2:163-176.
[52]	DeBose-Boyd RA. Feedback regulation of cholesterol synthesis:sterol-accelerated ubiquitination and degradation of HMG CoA reductase[J]. Cell Res, 2008, 18(6):609-621.
[53]	Raju J, Bird RP. Diosgenin, a naturally occurring furostanol saponin suppresses 3-hydroxy-3-methylglutaryl CoA reductase expression and induces apoptosis in HCT-116 human colon carcinoma cells[J]. Cancer Lett, 2007, 255(2):194-204.
[54]	Ebrahimi H, Badalzadeh R, Mohammadi M, et al. Diosgenin attenuates inflammatory response induced by myocardial reperfusion injury:role of mitochondrial ATP-sensitive potassium channels[J]. J Physiol Biochem, 2014, 70(2):435-432.
[55]	Salimeh A, Mohammadi M, Rashidi B. Preconditioning with diosgenin and treadmill exercise preserves the cardiac toxicity of isoproterenol in rats[J]. J Physiol Biochem, 2013, 69(2):255-265.
[56]	Jayachandran KS, Vasanthi HR, Rajamanickam GV. Antilipoperoxidative and membrane stabilizing effect of diosgenin, in experimentally induced myocardial infarction[J]. Mol Cell Biochem, 2009, 327(1-2):203-210.
[57]	Gutirrez E, Flammer AJ, Lerman LO, et al. Endothelial dysfunction over the course of coronary artery disease[J]. Eur Heart J, 2013, 34(41):3175-3181.
[58]	McVeigh GE, Brennan GM, Johnston GD, et al. Impaired endothelium-dependent and independent vasodilation in patients with type 2(non-insulin-dependent) diabetes mellitus[J]. Diabetologia, 1992, 35(8):771-776.
[59]	Manivannan J, Balamurugan E, Silambarasan T, et al. Diosgenin improves vascular function by increasing aortic eNOS expression, normalize dyslipidemia and ACE activity in chronic renal failure rats[J]. Mol Cell Biochem, 2013, 384(1-2):113-120.
[60]	Liu K, Zhao W, Gao X, et al. Diosgenin ameliorates palmitate-induced endothelial dysfunction and insulin resistance via blocking IKK and IRS-1 pathways[J]. Atherosclerosis, 2012, 223(2):350-358.
[61]	Dias KL, Correia NA, Pereira KK, et al. Mechanisms involved in the vasodilator effect induced by diosgenin in rat superior mesenteric artery[J]. Eur J Pharmacol, 2007, 574(2):172-178.
[62]	Gong G, Qin Y, Huang W, et al. Protective effects of diosgenin in the hyperlipidemic rat model and in human vascular endothelial cells against hydrogen peroxide-induced apoptosis[J]. Chem-Biol Interact, 2010, 184(3):366-375.
[63]	Au AL, Kwok CC, Lee AT, et al. Activation of iberiotoxin-sensitive, Ca2+ activated K+ channels of porcine isolated left anterior descending coronary artery by diosgenin[J]. Eur J Pharmacol, 2004, 502(1):123-133.
[64]	Esfandiarei M, Lam JT, Yazdi SA, et al. Diosgenin modulates vascular smooth muscle cell function by regulating cell viability, migration, and calcium homeostasis[J]. J Pharmacol Exp Ther, 2011, 336(3):925-939.
[65]	Mayer K, Merfels M, Muhly-Reinholz M, et al. -3 Fatty acids suppress monocyte adhesion to human endothelial cells:role of endothelial PAF generation[J]. Am J Physiol-Heart C, 2002, 283(2):H811-H818.
[66]	Liu YC, Zou XB, Chai YF, et al. Macrophage polarization in inflammatory diseases[J]. Int J Biol Sci, 2014, 10(5):520-529.
[67]	Carlos TM, Schwartz BR, Kovach NL, et al. Vascular cell adhesion molecule-1 mediates lymphocyte adherence to cytokine-activated cultured human endothelial cells[J]. Blood, 1990, 76(5):965-970.
[68]	Ling S, Nheu L, A Komesaroff P. Cell adhesion molecules as pharmaceutical target in atherosclerosis[J]. Mini-Rev Med Chem, 2012, 12(2):175-183.
[69]	Choi KW, Park HJ, Jung DH, et al. Inhibition of TNF--induced adhesion molecule expression by diosgenin in mouse vascular smooth muscle cells via down regulation of the MAPK, Akt and NF-B signaling pathways[J]. Vasc Pharmacol, 2010, 53(5):273-280.
[70]	Song JX, Ma L, Kou JP, et al. Diosgenin reduces leukocytes adhesion and migration linked with inhibition of intercellular adhesion molecule-1 expression and NF-B p65 activation in endothelial cells[J]. Chin J Nat Med, 2012, 10(2):142-149.
[71]	Drozdowska J. Tissue factor in endothelial cells--its structure and function according to the current literature[J]. Postepy Biochem, 2011, 58(3):273-280.
[72]	berg M, Siegbahn A. Tissue factor non-coagulant signaling-molecular mechanisms and biological consequences with a focus on cell migration and apoptosis[J]. J Thromb Haemost, 2013, 11(5):817-825.
[73]	Yang HP, Yue L, Jiang WW, et al. Diosgenin inhibits tumor necrosis factor-induced tissue factor activity and expression in THP-1 cells via down-regulation of the NF-B, Akt, and MAPK signaling pathways[J]. Chin J Nat Med, 2013, 11(6):608-615.
[74]	Gong G, Qin Y, Huang W. Anti-thrombosis effect of diosgenin extract from Dioscorea zingiberensis CH Wright in vitro and in vivo[J]. Phytomedicine, 2011, 18(6):458-463.
[75]	Yan MX, Li YQ, Meng M, et al. Long-term high-fat diet induces pancreatic injuries via pancreatic microcirculatory disturbances and oxidative stress in rats with hyperlipidemia[J]. Biochem Biophys Res Commun, 2006, 347(1):192-199.
[76]	Scheuer H, Gwinner W, Hohbach J, et al. Oxidant stress in hyperlipidemia-induced renal damage[J]. Am J Physiol-Renal, 2000, 278(1):F63-F74.
[77]	Frohnert BI, Bernlohr DA. Protein carbonylation, mitochondrial dysfunction, and insulin resistance[J]. Adv Nutr, 2013, 4(2):157-163.
[78]	Argani H, Ghorbani A, Rashtchizade N, et al. Effect of lovastatin on lipid peroxidation and total antioxidant concentrations in hemodialysis patients[J]. Lipids Health Dis, 2004, 3:6.
[79]	Kregel KC, Zhang HJ. An integrated view of oxidative stress in aging:basic mechanisms, functional effects, and pathological considerations[J]. Am J Physiol-Reg I, 2007, 292(1):R18-R36.
[80]	Czak L, Szabolcs A, Vajda , et al. Hyperlipidemia induced by a cholesterol-rich diet aggravates necrotizing pancreatitis in rats[J]. Eur J Pharmacol, 2007, 572(1):74-81.
[81]	Son IS, Kim JH, Sohn HY, et al. Antioxidative and hypolipidemic effects of diosgenin, a steroidal saponin of yam (Dioscorea spp.), on high-cholesterol fed rats[J]. Biosci Biotech Biochem, 2007, 71(12):3063-3071.
[82]	Manivannan J, Barathkumar TR, Sivasubramanian J, et al. Diosgenin attenuates vascular calcification in chronic renal failure rats[J]. Mol Cell Biochem, 2013, 378(1-2):9-18.
[83]	Esser N, Legrand-Poels S, Piette J, et al. Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes[J]. Diabetes Res Clin Pract, 2014, 105(2):141-150.
[84]	Uemura T, Goto T, Kang MS, et al. Diosgenin, the main aglycon of fenugreek, inhibits LXR activity in HepG2 cells and decreases plasma and hepatic triglycerides in obese diabetic mice[J]. J Nutr, 2011, 141(1):17-23.
[85]	Sangeetha MK, ShriShri Mal N, Atmaja K, et al. PPAR's and diosgenin a chemico biological insight in NIDDM[J]. Chem-Biol Interact, 2013, 206(2):403-410.
[86]	Pari L, Monisha P, Mohamed Jalaludeen A. Beneficial role of diosgenin on oxidative stress in aorta of streptozotocin induced diabetic rats[J]. Eur J Pharmacol, 2012, 691(1):143-150.
[87]	Uemura T, Hirai S, Mizoguchi N, et al. Diosgenin present in fenugreek improves glucose metabolism by promoting adipocyte differentiation and inhibiting inflammation in adipose tissues[J]. Mol Nutr Food Res, 2010, 54(11):1596-1608.
[88]	Hirai S, Uemura T, Mizoguchi N, et al. Diosgenin attenuates inflammatory changes in the interaction between adipocytes and macrophages[J]. Mol Nutr Food Res, 2010, 54(6):797-804.
[89]	Xiao L, Guo D, Hu C, et al. Diosgenin promotes oligodendrocyte progenitor cell differentiation through estrogen receptor mediated ERK1/2 activation to accelerate remyelination[J]. Glia, 2012, 60(7):1037-1052.
[90]	Girach A, Vignati L. Diabetic microvascular complications-can the presence of one predict the development of another[J]. J Diabetes Complicat, 2006, 20(4):228-237.
[91]	Cheng HT, Dauch JR, Hayes JM, et al. Nerve growth factor mediates mechanical allodynia in a mouse model of type 2 diabetes[J]. J Neuropath Exp Neur, 2009, 68(11):1229-1243.
[92]	Kang TH, Moon E, Hong BN, et al. Diosgenin from Dioscorea nipponica ameliorates diabetic neuropathy by inducing nerve growth factor[J]. Biol Pharm Bull, 2011, 34(9):1493-1498.
[93]	Kondeva-Burdina M, Lopez MU, Mitcheva M, et al. In vitro effect of diosgenin, isolated from Asparagus officinalis, in a dopamine model of oxidative stress in isolated rat synaptosomes[J]. Toxicol Lett, 2007, 172(s7):S68.
[94]	Chiu CS, Chiu YJ, Wu LY, et al. Diosgenin ameliorates cognition deficit and attenuates oxidative damage in senescent mice induced by D-galactose[J]. Am J Chin Med, 2011, 39(3):551-563.
[95]	Tohda C, Lee YA, Goto Y, et al. Diosgenin-induced cognitive enhancement in normal mice is mediated by 1, 25D3-MARRS[J]. Sci Rep, 2013, 3:3395.
[96]	Wang YJ, Liu YC, Chang HD, et al. Diosgenin, a plant-derived sapogenin, stimulates Ca2+ -activated K+ current in human cortical HCN-1A neuronal cells[J]. Planta Med, 2006, 72(5):430-436.
[97]	Huang CH, Liu DZ, Jan TR. Diosgenin, a plant-derived sapogenin, enhances regulatory T-cell immunity in the intestine of mice with food allergy[J]. J Nat Prod, 2010, 73(6):1033-1037.
[98]	Huang CH, Ku CY, Jan TR. Diosgenin attenuates allergen-induced intestinal inflammation and IgE production in a murine model of food allergy[J]. Planta Med, 2009, 75(12):1300-1305.
[99]	Jan TR, Wey SP, Kuan CC, et al. Diosgenin, a steroidal sapogenin, enhances antigen-specific IgG2a and interferon- expression in ovalbumin-sensitized BALB/c mice[J]. Planta Med, 2007, 73(5):421-426.
[100]	Ku CM, Lin JY. Anti-inflammatory effects of 27 selected terpenoid compounds tested through modulating Th1/Th2 cytokine secretion profiles using murine primary splenocytes[J]. Food Chem, 2013, 141(2):1104-1113.
[101]	Gao M, Chen L, Yu H, et al. Diosgenin down-regulates NF-B p65/p50 and p38MAPK pathways and attenuates acute lung injury induced by lipopolysaccharide in mice[J]. Int Immunopharmacol, 2013, 15(2):240-245.
[102]	Jung DH, Park HJ, Byun HE, et al. Diosgenin inhibits macrophage-derived inflammatory mediators through downregulation of CK2, JNK, NF-B and AP-1 activation[J]. Int Immunopharmacol, 2010, 10(9):1047-1054.
[103]	He Z, Tian Y, Zhang X, et al. Anti-tumour and immunomodulating activities of diosgenin, a naturally occurring steroidal saponin[J]. Nat Prod Res, 2012, 26(23):2243-2246.
[104]	Conner P. Breast response to menopausal hormone therapy-aspects on proliferation, apoptosis and mammographic density[J]. Ann Med, 2007, 39(1):28-41.
[105]	Komesaroff PA, Black CV, Cable V, et al. Effects of wild yam extract on menopausal symptoms, lipids and sex hormones in healthy menopausal women[J]. Climacteric, 2001, 4(2):144-150.
[106]	Accatino L, Pizarro M, Sols N, et al. Effects of diosgenin, a plant-derived steroid, on bile secretion and hepatocellular cholestasis induced by estrogens in the rat[J]. Hepatology, 1998, 28(1):129-140.
[107]	Rao AR, Kale RK. Diosgenin-a growth stimulator of mammary gland of ovariectomized mouse[J]. Indian J Exp Biol, 1992, 30(5):367-370.
[108]	Chiang SS, Chang SP, Pan TM. Osteoprotective effect of monascus-fermented dioscorea in ovariectomized rat model of postmenopausal osteoporosis[J]. J Agric Food Chem, 2011, 59(17):9150-9157.
[109]	Higdon K, Scott A, Tucci M, et al. The use of estrogen, DHEA, and diosgenin in a sustained delivery setting as a novel treatment approach for osteoporosis in the ovariectomized adult rat model[J]. Biomed Sci Instrum, 2001, 37:281-286.
[110]	Yen ML, Su JL, Chien CL, et al. Diosgenin induces hypoxia-inducible factor-1 activation and angiogenesis through estrogen receptor-related phosphatidylinositol 3-kinase/Akt and p38 mitogen-activated protein kinase pathways in osteoblasts[J]. Mol Pharmacol, 2005, 68(4):1061-1073.
[111]	Medigović I, Ristić N, Živanović J, et al. Diosgenin does not express estrogenic activity:a uterotrophic assay[J]. Can J Physiol Pharm, 2014, 92(4):292-298.
[112]	Hsu KH, Chang CC, Tsai HD, et al. Effects of yam and diosgenin on calpain systems in skeletal muscle of ovariectomized rats[J]. Taiwan J Obstet Gynecol, 2008, 47(2):180-186.
[113]	Tada Y, Kanda N, Haratake A, et al. Novel effects of diosgenin on skin aging[J]. Steroids, 2009, 74(6):504-511.
[114]	Lee J, Jung K, Kim YS, et al. Diosgenin inhibits melanogenesis through the activation of phosphatidylinositol-3-kinase pathway (PI3K) signaling[J]. Life Sci, 2007, 81(3):249-254.
[115]	Zheng L, Zhou Y, Zhang JY, et al. Two new steroidal saponins from the rhizomes of Dioscorea zingiberensis[J]. Chin J Nat Med, 2014, 12(2):142-147.
[116]	Noguchi E, Fujiwara Y, Matsushita S, et al. Metabolism of tomato steroidal glycosides in humans[J]. Chem Pharm Bull, 2006, 54(9):1312-1314.

Advances in the pharmacological activities and mechanisms of diosgenin

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