The Effects of Diosgenin on Hypolipidemia and Its Underlying Mechanism: A Review

References

• Karr S . Epidemiology and management of hyperlipidemia. Am J Manag Care . 2017;23(9 Suppl):S139–S148.28978219
   PubMed Web of Science ®Google Scholar
• Benjamin EJ , Virani SS , Callaway CW , et al. Heart disease and stroke statistics-2018 update: a report from the American heart association. Circulation . 2018;137(12):e67–e492.29386200
   PubMed Web of Science ®Google Scholar
• Townsend N , Nichols M , Scarborough P , Rayner M . Cardiovascular disease in Europe–epidemiological update 2015. Eur Heart J . 2015;36(40):2696–2705. doi:10.1093/eurheartj/ehv428 26306399
   PubMed Web of Science ®Google Scholar
• Wang XG , Zhao X , Li Y , et al. Research progress of pathogenesis and treatment of hyperlipidemia. J Liaoning Univ Trad Chin Med . 2020;22(12):196–200.
   Google Scholar
• Kopin L , Lowenstein C . Dyslipidemia. Ann Intern Med . 2017;167(11):ITC81–ITC96. doi:10.7326/AITC201712050 29204622
   PubMed Web of Science ®Google Scholar
• Holven KB , Ulven SM , Bogsrud MP . Hyperlipidemia and cardiovascular disease with focus on familial hypercholesterolemia. Curr Opin Lipidol . 2017;28(5):445–447. doi:10.1097/MOL.0000000000000449 28857860
   PubMed Web of Science ®Google Scholar
• Strilchuk L , Fogacci F , Cicero AF . Safety and tolerability of injectable lipid-lowering drugs: an update of clinical data. Expert Opin Drug Saf . 2019;18(7):611–621. doi:10.1080/14740338.2019.1620730 31100030
   PubMed Web of Science ®Google Scholar
• Stroes ES , Thompson PD , Corsini A , et al. Statin-associated muscle symptoms: impact on statin therapy-European Atherosclerosis Society consensus panel statement on assessment, aetiology and management. Eur Heart J . 2015;36(17):1012–1022. doi:10.1093/eurheartj/ehv043 25694464
   PubMed Web of Science ®Google Scholar
• Mach F , Baigent C , Catapano AL , et al. 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J . 2020;41(1):111–188.31504418
   PubMed Web of Science ®Google Scholar
• Thomford NE , Senthebane DA , Rowe A , et al. Natural products for drug discovery in the 21st century: innovations for novel drug discovery. Int J Mol Sci . 2018;19(6):1578. doi:10.3390/ijms19061578
   PubMed Web of Science ®Google Scholar
• Talebi S , Bagherniya M , Atkin SL , Askari G , Orafai HM , Sahebkar A . The beneficial effects of nutraceuticals and natural products on small dense LDL levels, LDL particle number and LDL particle size: a clinical review. Lipids Health Dis . 2020;19(1):66. doi:10.1186/s12944-020-01250-6 32276631
   PubMed Web of Science ®Google Scholar
• Atanasov AG , Waltenberger B , Pferschy-Wenzig EM , et al. Discovery and resupply of pharmacologically active plant-derived natural products: a review. Biotechnol Adv . 2015;33(8):1582–1614.26281720
   PubMed Web of Science ®Google Scholar
• Rodrigues T , Reker D , Schneider P , Schneider G . Counting on natural products for drug design. Nat Chem . 2016;8(6):531–541. doi:10.1038/nchem.2479 27219696
   PubMed Web of Science ®Google Scholar
• Chen Y , Tang YM , Yu SL , et al. Advances in the pharmacological activities and mechanisms of diosgenin. Chin J Nat Med . 2015;13(8):578–587.26253490
   PubMed Web of Science ®Google Scholar
• Yuan B , Byrnes DR , Dinssa FF , Simon JE , Wu Q . Identification of polyphenols, glycoalkaloids, and saponins in Solanum scabrum berries using HPLC-UV/Vis-MS. J Food Sci . 2019;84(2):235–243. doi:10.1111/1750-3841.14424 30693503
   PubMed Web of Science ®Google Scholar
• Krol-Kogus B , Lamine KM , Migas P , Boudjeniba M , Krauze-Baranowska M . HPTLC determination of diosgenin in fenugreek seeds. Acta Pharm . 2018;68(1):97–107. doi:10.2478/acph-2018-0002 29453912
   PubMed Web of Science ®Google Scholar
• Gong J , Fang K , Dong H , Wang D , Hu M , Lu F . Effect of fenugreek on hyperglycaemia and hyperlipidemia in diabetes and prediabetes: a meta-analysis. J Ethnopharmacol . 2016;194:260–268. doi:10.1016/j.jep.2016.08.003 27496582
   PubMed Web of Science ®Google Scholar
• Wu FC , Jiang JG . Effects of diosgenin and its derivatives on atherosclerosis. Food Funct . 2019;10(11):7022–7036. doi:10.1039/C9FO00749K 31687707
   PubMed Web of Science ®Google Scholar
• Cai B , Zhang Y , Wang Z , et al. Therapeutic potential of diosgenin and its major derivatives against neurological diseases: recent advances. Oxid Med Cell Longev . 2020;2020:3153082. doi:10.1155/2020/3153082 32215172
   PubMed Web of Science ®Google Scholar
• Wu S , Zhao F , Zhao J , et al. Dioscin improves postmenopausal osteoporosis through inducing bone formation and inhibiting apoptosis in ovariectomized rats. Biosci Trends . 2019;13(5):394–401. doi:10.5582/bst.2019.01186 31611520
   PubMed Web of Science ®Google Scholar
• Li R , Liu Y , Shi J , et al. Diosgenin regulates cholesterol metabolism in hypercholesterolemic rats by inhibiting NPC1L1 and enhancing ABCG5 and ABCG8. Biochim Biophys Acta Mol Cell Biol Lipids . 2019;1864(8):1124–1133. doi:10.1016/j.bbalip.2019.04.010 31054325
   PubMed Web of Science ®Google Scholar
• Tao X , Yin L , Xu L , Peng J . Dioscin: a diverse acting natural compound with therapeutic potential in metabolic diseases, cancer, inflammation and infections. Pharmacol Res . 2018;137:259–269. doi:10.1016/j.phrs.2018.09.022 30315966
   PubMed Web of Science ®Google Scholar
• Sethi G , Shanmugam MK , Warrier S , et al. Pro-apoptotic and anti-cancer properties of diosgenin: a comprehensive and critical review. Nutrients . 2018;10(5):5. doi:10.3390/nu10050645
   Web of Science ®Google Scholar
• Cayen MN , Dvornik D . Effect of diosgenin on lipid metabolism in rats. J Lipid Res . 1979;20(2):162–174. doi:10.1016/S0022-2275(20)40628-5 438658
   PubMed Web of Science ®Google Scholar
• Liu MX , Zhang FX , Xun LY , Guan DH . Study on regulating blood lipid effects and the mechanism of diosgenin. Arch Tradit Chin Med . 2016;34(04):798–800.
   Google Scholar
• Parama D , Boruah M , Kumari Y , et al. Diosgenin, a steroidal saponin, and its analogs: effective therapies against different chronic diseases. Life Sci . 2020;260:118182.32781063
   PubMed Web of Science ®Google Scholar
• Liao AM , Jung H , Yu JW , et al. Synthesis and biological evaluation of arginyl-diosgenin conjugate as a potential bone tissue engineering agent. Chem Biol Drug Des . 2018;91(1):17–28. doi:10.1111/cbdd.13050 28643382
   PubMed Web of Science ®Google Scholar
• Chen FX , Zhao MR , Ren BZ , et al. Solubility of diosgenin in different solvents. J Chem Thermodyn . 2012;47:341–346. doi:10.1016/j.jct.2011.11.009
   Web of Science ®Google Scholar
• Chaudhary SA , Chaudhary PS , Syed BA , et al. Validation of a method for diosgenin extraction from fenugreek (Trigonella foenum-graecum L.). Acta Sci Pol Technol Aliment . 2018;17(4):377–385.30558394
   PubMed Web of Science ®Google Scholar
• Selim S , Al Jaouni S . Anticancer and apoptotic effects on cell proliferation of diosgenin isolated from Costus speciosus (Koen.) Sm. BMC Complement Altern Med . 2015;15(1):301. doi:10.1186/s12906-015-0836-8 26329920
   PubMed Web of Science ®Google Scholar
• Kim JK , Park SU . An update on the biological and pharmacological activities of diosgenin. EXCLI J . 2018;17:24–28.29383016
   PubMed Web of Science ®Google Scholar
• Li X , Wang Y , Sun J , et al. Chemotaxonomic studies of 12 Dioscorea species from China by UHPLC-QTOF-MS/MS analysis. Phytochem Anal . 2020;31(2):164–182. doi:10.1002/pca.2876 31364208
   PubMed Web of Science ®Google Scholar
• Herrera T , Navarro Del Hierro J , Fornari T , Reglero G , Martin D . Acid hydrolysis of saponin-rich extracts of quinoa, lentil, fenugreek and soybean to yield sapogenin-rich extracts and other bioactive compounds. J Sci Food Agric . 2019;99(6):3157–3167. doi:10.1002/jsfa.9531 30536393
   PubMed Web of Science ®Google Scholar
• Sahu P , Gidwani B , Dhongade HJ . Pharmacological activities of dehydroepiandrosterone: a review. Steroids . 2020;153:108507. doi:10.1016/j.steroids.2019.108507 31586606
   PubMed Web of Science ®Google Scholar
• Dong J , Lei C , Lu D , Wang Y . Direct biotransformation of dioscin into diosgenin in rhizome of Dioscorea zingiberensis by penicillium dioscin. Indian J Microbiol . 2015;55(2):200–206. doi:10.1007/s12088-014-0507-3 25805907
   PubMed Web of Science ®Google Scholar
• Sauvaire Y , Ribes G , Baccou JC , Loubatieères-Mariani MM . Implication of steroid saponins and sapogenins in the hypocholesterolemic effect of fenugreek. Lipids . 1991;26(3):191–197. doi:10.1007/BF02543970 2046485
   PubMed Web of Science ®Google Scholar
• Wang T , Choi RC , Li J , et al. Antihyperlipidemic effect of protodioscin, an active ingredient isolated from the rhizomes of Dioscorea nipponica. Planta Med . 2010;76(15):1642–1646. doi:10.1055/s-0030-1249960 20509104
   PubMed Web of Science ®Google Scholar
• Malinow MR , Elliott WH , McLaughlin P , Upson B . Effects of synthetic glycosides on steroid balance in Macaca fascicularis. J Lipid Res . 1987;28(1):1–9. doi:10.1016/S0022-2275(20)38729-0 3559397
   PubMed Web of Science ®Google Scholar
• Yamanashi Y , Takada T , Yamamoto H , Suzuki H . NPC1L1 facilitates sphingomyelin absorption and regulates diet-induced production of VLDL/LDL-associated S1P. Nutrients . 2020;12(9):2641. doi:10.3390/nu12092641
   Web of Science ®Google Scholar
• Tang W , Lin J , Ma Y , et al. Ezetimibe restores biliary cholesterol excretion in mice expressing Niemann–Pick C1-like 1 only in liver. Biochim Biophys Acta . 2011;1811(9):549–555. doi:10.1016/j.bbalip.2011.05.013 21683156
   PubMed Web of Science ®Google Scholar
• Ma HY , Zhao ZT , Wang LJ , Wang Y , Zhou QL , Wang BX . Comparative study on anti-hypercholesterolemia activity of diosgenin and total saponin of Dioscorea panthaica. J Trad Chin Med . 2002;27(7):51–54.
   Google Scholar
• Kuang SY , Li Y , Kuang WD . Effects of diosgenin on cholesterol metabolism and caveolin-1 expression in human hepatocyte L-02. Chin Pharm . 2013;24(35):3286–3288.
   Google Scholar
• Rhee EJ , Byrne CD , Sung KC . The HDL cholesterol/apolipoprotein A-I ratio: an indicator of cardiovascular disease. Curr Opin Endocrinol Diabetes Obes . 2017;24(2):148–153. doi:10.1097/MED.0000000000000315 28099205
   PubMedGoogle Scholar
• Kusano Y , Tsujihara N , Masui H , Kozai H , Takeuchi W . Consumption of Japanese yam improves lipid metabolism in high-cholesterol diet-fed rats. Nutr Sci Vitaminol (Tokyo) . 2016;62(5):350–360. doi:10.3177/jnsv.62.350
   Web of Science ®Google Scholar
• Ma W , Ding H , Gong X , et al. Methyl protodioscin increases ABCA1 expression and cholesterol efflux while inhibiting gene expressions for synthesis of cholesterol and triglycerides by suppressing SREBP transcription and microRNA 33a/b levels. Atherosclerosis . 2015;239(2):566–570. doi:10.1016/j.atherosclerosis.2015.02.034 25733328
   PubMed Web of Science ®Google Scholar
• Shen WJ , Azhar S , Kraemer FB . SR-B1: a unique multifunctional receptor for cholesterol influx and efflux. Annu Rev Physiol . 2018;80:95–116. doi:10.1146/annurev-physiol-021317-121550 29125794
   PubMed Web of Science ®Google Scholar
• Xu J , Xu Y , Xu Y , Yin L , Zhang Y . Global inactivation of carboxylesterase 1 (Ces1/Ces1g) protects against atherosclerosis in Ldlr−/− mice. Sci Rep . 2017;7(1):17845. doi:10.1038/s41598-017-18232-x 29259301
   PubMed Web of Science ®Google Scholar
• Jones H , Alpini G , Francis H . Bile acid signaling and biliary functions. Acta Pharm Sin B . 2015;5(2):123–128. doi:10.1016/j.apsb.2015.01.009 26579437
   PubMed Web of Science ®Google Scholar
• Yu L , Lu H , Yang X , et al. Diosgenin alleviates hypercholesterolemia via SRB1/CES-1/CYP7A1/FXR pathway in high-fat diet-fed rats. Toxicol Appl Pharmacol . 2021;412:115388. doi:10.1016/j.taap.2020.115388 33383043
   PubMed Web of Science ®Google Scholar
• Gesto DS , Pereira C , Cerqueira NM , Sousa SF . An atomic-level perspective of HMG-CoA-reductase: the target enzyme to treat hypercholesterolemia. Molecules . 2020;25(17):3891. doi:10.3390/molecules25173891
   Web of Science ®Google Scholar
• Fox KM , Tai M-H , Kostev K , Hatz M , Qian Y , Laufs U . Treatment patterns and low-density lipoprotein cholesterol (LDL-C) goal attainment among patients receiving high- or moderate-intensity statins. Clin Res Cardiol . 2017;107(5):380–388. doi:10.1007/s00392-017-1193-z 29273856
   PubMed Web of Science ®Google Scholar
• Hao S , Xu R , Li D , Zhu Z , Wang T , Liu K . Attenuation of streptozotocin-induced lipid profile anomalies in the heart, brain, and mRNA expression of HMG-CoA reductase by diosgenin in rats. Cell Biochem Biophys . 2015;72(3):741–749. doi:10.1007/s12013-015-0525-8 25631375
   PubMed Web of Science ®Google Scholar
• Uemura T , Goto T , Kang MS , et al. Diosgenin, the main aglycon of fenugreek, inhibits LXRalpha activity in HepG2 cells and decreases plasma and hepatic triglycerides in obese diabetic mice. J Nutr . 2011;141(1):17–23. doi:10.3945/jn.110.125591 21106928
   PubMed Web of Science ®Google Scholar
• Pan CH , Tsai CH , Liu FC , et al. Influence of different particle processing on hypocholesterolemic and antiatherogenic activities of yam (Dioscorea pseudojaponica) in cholesterol-fed rabbit model. Sci Food Agric . 2013;93(6):1278–1283. doi:10.1002/jsfa.5882
   Web of Science ®Google Scholar
• Carling D . AMPK signalling in health and disease. Curr Opin Cell Biol . 2017;45:31–37. doi:10.1016/j.ceb.2017.01.005 28232179
   PubMed Web of Science ®Google Scholar
• Cheng SL . The Action and Mechanism of Diosgenin Suppress the Nonalcoholic Fatty Liver Disease . Second Military Medical University; 2014.
   Google Scholar
• Poudel B , Lim SW , Ki HH , Nepali S , Lee YM , Kim DK . Dioscin inhibits adipogenesis through the AMPK/MAPK pathway in 3T3-L1 cells and modulates fat accumulation in obese mice. Int J Mol Med . 2014;34(5):1401–1408. doi:10.3892/ijmm.2014.1921 25189808
   PubMed Web of Science ®Google Scholar
• Ying F , Cai Y , Wong HK , et al. EP4 emerges as a novel regulator of bile acid synthesis and its activation protects against hypercholesterolemia. Biochim Biophys Acta Mol Cell Biol Lipids . 2018;1863(9):1029–1040. doi:10.1016/j.bbalip.2018.06.003 29890224
   PubMed Web of Science ®Google Scholar
• Liu S , Jing F , Yu C , Gao L , Qin Y , Zhao J . AICAR-induced activation of AMPK inhibits TSH/SREBP-2/HMGCR pathway in liver. PLoS One . 2015;10(5):e0124951. doi:10.1371/journal.pone.0124951 25933205
   PubMed Web of Science ®Google Scholar
• Patel SB , Graf GA , Temel RE . ABCG5 and ABCG8: more than a defense against xenosterols. J Lipid Res . 2018;59(7):1103–1113. doi:10.1194/jlr.R084244 29728459
   PubMed Web of Science ®Google Scholar
• Temel RE , Brown JM , Ma Y , et al. Diosgenin stimulation of fecal cholesterol excretion in mice is not NPC1L1 dependent. J Lipid Res . 2009;50(5):915–923. doi:10.1194/jlr.M800631-JLR200 19141868
   PubMed Web of Science ®Google Scholar
• Phillips MC . Is ABCA1 a lipid transfer protein? J Lipid Res . 2018. https://pubmed.ncbi.nlm.nih.gov/29305383/ references
   Web of Science ®Google Scholar
• Lv YC , Yang J , Yao F , et al. Diosgenin inhibits atherosclerosis via suppressing the MiR-19b-induced downregulation of ATP-binding cassette transporter A1. Atherosclerosis . 2015;240(1):80–89. doi:10.1016/j.atherosclerosis.2015.02.044 25765596
   PubMed Web of Science ®Google Scholar
• Gai Y , Li Y , Xu Z , Chen J . Pseudoprotodioscin inhibits SREBPs and microRNA 33a/b levels and reduces the gene expression regarding the synthesis of cholesterol and triglycerides. Fitoterapia . 2019;139:104393. doi:10.1016/j.fitote.2019.104393 31669721
   PubMed Web of Science ®Google Scholar
• Marrocco I , Altieri F , Peluso I . Measurement and clinical significance of biomarkers of oxidative stress in humans. Oxid Med Cell Longev . 2017;2017:6501046. doi:10.1155/2017/6501046 28698768
   PubMed Web of Science ®Google Scholar
• Gupta DD , Mishra S , Verma SS , et al. Evaluation of antioxidant, anti-inflammatory and anticancer activities of diosgenin enriched Paris polyphylla rhizome extract of Indian Himalayan landraces. J Ethnopharmacol . 2021;270:113842. doi:10.1016/j.jep.2021.113842 33460752
   PubMed Web of Science ®Google Scholar
• Pi WX , Feng XP , Ye LH , Cai BC . Combination of morroniside and diosgenin prevents high glucose-induced cardiomyocytes apoptosis. Molecules . 2017;22(1):163. doi:10.3390/molecules22010163
   PubMed Web of Science ®Google Scholar
• Sangeetha MK , ShriShri Mal N , Atmaja K , Sali VK , Vasanthi HR . PPAR’s and diosgenin a chemico biological insight in NIDDM. Chem Biol Interact . 2013;206(2):403–410. doi:10.1016/j.cbi.2013.08.014 24001619
   PubMed Web of Science ®Google Scholar
• Manivannan J , Balamurugan E , Silambarasan T , Raja B . Diosgenin improves vascular function by increasing aortic eNOS expression, normalize dyslipidemia and ACE activity in chronic renal failure rats. Mol Cell Biochem . 2013;384(1–2):113–120. doi:10.1007/s11010-013-1788-2 23975507
   PubMed Web of Science ®Google Scholar
• Xu T , Zheng L , Xu L , et al. Protective effects of dioscin against alcohol-induced liver injury. Arch Toxicol . 2014;88(3):739–753. doi:10.1007/s00204-013-1148-8 24146112
   PubMed Web of Science ®Google Scholar
• Son IS , Kim JH , Sohn HY , Son KH , Kim JS , Kwon CS . Antioxidative and hypolipidemic effects of diosgenin, a steroidal saponin of yam (Dioscorea spp.), on high-cholesterol fed rats. Biosci Biotechnol Biochem . 2007;71(12):3063–3071. doi:10.1271/bbb.70472 18071250
   PubMed Web of Science ®Google Scholar
• 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. Mol Nutr Food Res . 2010;54(11):1596–1608. doi:10.1002/mnfr.200900609 20540147
   PubMed Web of Science ®Google Scholar
• Koerner CM , Roberts BS , Neher SB . Endoplasmic reticulum quality control in lipoprotein metabolism. Mol Cell Endocrinol . 2019;498:110547. doi:10.1016/j.mce.2019.110547 31442546
   PubMed Web of Science ®Google Scholar
• 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. Chem Biol Interact . 2010;184(3):366–375. doi:10.1016/j.cbi.2010.02.005 20149787
   PubMed Web of Science ®Google Scholar
• Matsuo Y , Matsumoto K , Inaba N , Mimaki Y . Daisaikoto inhibits pancreatic lipase activity and decreases serum triglyceride levels in mice. Biol Pharm Bull . 2018;41(9):1485–1488. doi:10.1248/bpb.b18-00324 30175784
   PubMed Web of Science ®Google Scholar
• Kwon CS , Sohn HY , Kim SH , et al. Anti-obesity effect of Dioscorea nipponica Makino with lipase-inhibitory activity in rodents. Biosci Biotechnol Biochem . 2003;67(7):1451–1456. doi:10.1271/bbb.67.1451 12913286
   PubMed Web of Science ®Google Scholar
• Navarro Del Hierro J , Casado-Hidalgo G , Reglero G , Martin D . The hydrolysis of saponin-rich extracts from fenugreek and quinoa improves their pancreatic lipase inhibitory activity and hypocholesterolemic effect. Food Chem . 2021;338:128113. doi:10.1016/j.foodchem.2020.128113 33092009
   PubMed Web of Science ®Google Scholar
• Zhang F , Sun W , Chen J , et al. SREBP-2, a new target of metformin? Drug Des Devel Ther . 2018;12:4163–4170. doi:10.2147/DDDT.S190094
   Web of Science ®Google Scholar
• Shimano H , Sato R . SREBP-regulated lipid metabolism: convergent physiology - divergent pathophysiology. Nat Rev Endocrinol . 2017;13(12):710–730.28849786
   PubMed Web of Science ®Google Scholar
• Schulman IG . Liver X receptors link lipid metabolism and inflammation. FEBS Lett . 2017;591(19):2978. doi:10.1002/1873-3468.12702 28555747
   PubMed Web of Science ®Google Scholar
• Wang B , Tontonoz P . Liver X receptors in lipid signalling and membrane homeostasis. Nat Rev Endocrinol . 2018;14(8):452–463. doi:10.1038/s41574-018-0037-x 29904174
   PubMed Web of Science ®Google Scholar
• de la Rosa Rodriguez MA , Kersten S . Regulation of lipid droplet-associated proteins by peroxisome proliferator-activated receptors. Biochim Biophys Acta Mol Cell Biol Lipids . 2017;1862(10 Pt B):1212–1220. doi:10.1016/j.bbalip.2017.07.007 28735095
   PubMed Web of Science ®Google Scholar
• Kersten S , Stienstra R . The role and regulation of the peroxisome proliferator activated receptor alpha in human liver. Biochimie . 2017;136:75–84. doi:10.1016/j.biochi.2016.12.019 28077274
   PubMed Web of Science ®Google Scholar
• Debose-Boyd RA , Ye J . SREBPs in lipid metabolism, insulin signaling, and beyond. Trends Biochem Sci . 2018;43(5):358-368. doi: 10.1016/j.tibs.2018.01.005.
   Web of Science ®Google Scholar
• Li X , Li Y , Yang W , et al. SREBP-1c overexpression induces triglycerides accumulation through increasing lipid synthesis and decreasing lipid oxidation and VLDL assembly in bovine hepatocytes. J Steroid Biochem Mol Biol . 2014;143:174–182. doi:10.1016/j.jsbmb.2014.02.009 24565561
   PubMed Web of Science ®Google Scholar
• Hua S , Li Y , Su L , Liu X . Diosgenin ameliorates gestational diabetes through inhibition of sterol regulatory element-binding protein-1. Biomed Pharmacother . 2016;84:1460–1465. doi:10.1016/j.biopha.2016.10.049 27810341
   PubMed Web of Science ®Google Scholar
• Yao H , Tao X , Xu L , et al. Dioscin alleviates non-alcoholic fatty liver disease through adjusting lipid metabolism via SIRT1/AMPK signaling pathway. Pharmacol Res . 2018;131:51–60. doi:10.1016/j.phrs.2018.03.017 29574225
   PubMed Web of Science ®Google Scholar
• Mohammad-Sadeghipour M , Mahmoodi M , Noroozi Karimabad M , Mirzaei MR , Hajizadeh MR . Diosgenin and 4-hydroxyisoleucine from fenugreek are regulators of genes involved in lipid metabolism in the human colorectal cancer cell line SW480. Cell J . 2021;22(4):514–522.32347045
   PubMed Web of Science ®Google Scholar
• Schultz JR , Tu H , Luk A , et al. Role of LXRs in control of lipogenesis. Genes Dev . 2000;14(22):2831–2838. doi:10.1101/gad.850400 11090131
   PubMed Web of Science ®Google Scholar
• Xu HF , Luo J , Zhang XY , Li J , Bionaz M . Activation of liver X receptor promotes fatty acid synthesis in goat mammary epithelial cells via modulation of SREBP1 expression. J Dairy Sci . 2019;102(4):3544–3555. doi:10.3168/jds.2018-15538 30738675
   PubMed Web of Science ®Google Scholar
• Cheng S , Liang S , Liu Q , et al. Diosgenin prevents high-fat diet-induced rat non-alcoholic fatty liver disease through the AMPK and LXR signaling pathways. Int J Mol Med . 2018;41(2):1089–1095.29207101
   PubMed Web of Science ®Google Scholar
• Cheng HS , Tan WR , Low ZS , Marvalim C , Lee JYH , Tan NS . Exploration and development of PPAR modulators in health and disease: an update of clinical evidence. Int J Mol Sci . 2019;20(20):5055. doi:10.3390/ijms20205055
   PubMed Web of Science ®Google Scholar
• Mirza AZ , Althagafi II , Shamshad H . Role of PPAR receptor in different diseases and their ligands: physiological importance and clinical implications. Eur J Med Chem . 2019;166:502–513. doi:10.1016/j.ejmech.2019.01.067 30739829
   PubMed Web of Science ®Google Scholar
• Bougarne N , Weyers B , Desmet SJ , et al. Molecular actions of PPARα in lipid metabolism and inflammation. Endocr Rev . 2018;39(5):760–802.30020428
   PubMed Web of Science ®Google Scholar
• Janani C , Ranjitha Kumari BD . PPAR gamma gene–a review. Diabetes Metab Syndr . 2015;9(1):46–50. doi:10.1016/j.dsx.2014.09.015 25450819
   PubMed Web of Science ®Google Scholar
• Alam F , Islam MA , Mohamed M , et al. Efficacy and safety of pioglitazone monotherapy in type 2 diabetes mellitus: a systematic review and meta-analysis of randomised controlled trials. Sci Rep . 2019;9(1):5389. doi:10.1038/s41598-019-41854-2 30926892
   PubMed Web of Science ®Google Scholar
• Wang X , Liu J , Long Z , et al. Effect of diosgenin on metabolic dysfunction: role of ERbeta in the regulation of PPARgamma. Toxicol Appl Pharmacol . 2015;289(2):286–296. doi:10.1016/j.taap.2015.09.015 26408789
   PubMed Web of Science ®Google Scholar
• Zhang Y , Cui Y , Wang XL , Shang X , Xie ML . PPARα/γ agonists and antagonists differently affect hepatic lipid metabolism, oxidative stress and inflammatory cytokine production in steatohepatitic rats. Cytokine . 2015;75(1):127–135. doi:10.1016/j.cyto.2015.05.031 26194065
   PubMed Web of Science ®Google Scholar
• Nanjan MJ , Mohammed M , Prashantha Kumar BR , Chandrasekar MJN . Thiazolidinediones as antidiabetic agents: a critical review. Bioorg Chem . 2018;77:548–567. doi:10.1016/j.bioorg.2018.02.009 29475164
   PubMed Web of Science ®Google Scholar
• Gan Q , Wang J , Hu J , et al. The role of diosgenin in diabetes and diabetic complications. J Steroid Biochem Mol Biol . 2020;198:105575. doi:10.1016/j.jsbmb.2019.105575 31899316
   PubMed Web of Science ®Google Scholar
• Zhao S , Niu F , Xu CY , et al. Diosgenin prevents bone loss on retinoic acid-induced osteoporosis in rats. Ir J Med Sci . 2016;185(3):581–587. doi:10.1007/s11845-015-1309-2 26089290
   PubMed Web of Science ®Google Scholar
• Yin H , Zhang MJ , An RF , Zhou J , Huang XF . Diosgenin derivatives as potential antitumor agents: synthesis, cytotoxicity, and mechanism of action. J Nat Prod . 2020;84(3):616–29.33381964
   PubMed Web of Science ®Google Scholar
• Manda VK , Avula B , Ali Z , et al. Characterization of in vitro ADME properties of diosgenin and dioscin from Dioscorea villosa. Planta Med . 2013;79(15):1421–1428. doi:10.1055/s-0033-1336521 23970424
   PubMed Web of Science ®Google Scholar
• Liu P , Zhou JY , Chang JH , et al. Soluplus-mediated diosgenin amorphous solid dispersion with high solubility and high stability: development, characterization and oral bioavailability. Drug Des Devel Ther . 2020;14:2959–2975. doi:10.2147/DDDT.S253405
   PubMed Web of Science ®Google Scholar
• Schittny A , Huwyler J , Puchkov M . Mechanisms of increased bioavailability through amorphous solid dispersions: a review. Drug Deliv . 2020;27(1):110–127. doi:10.1080/10717544.2019.1704940 31885288
   PubMed Web of Science ®Google Scholar
• Banerjee S , Bhattacharjee P , Kar A , Mukherjee PK . LC-MS/MS analysis and network pharmacology of Trigonella foenum-graecum - a plant from Ayurveda against hyperlipidemia and hyperglycemia with combination synergy. Phytomedicine . 2019;60:152944. doi:10.1016/j.phymed.2019.152944 31178235
   PubMed Web of Science ®Google Scholar
• Ren Y , Wang Z , Wu C , et al. Ultrahigh-performance liquid chromatography with tandem mass spectrometry for the determination of 10 alkaloids in beagle plasma after the oral administration of the three Coptidis rhizoma extracts. J Ethnopharmacol . 2019;239:111896. doi:10.1016/j.jep.2019.111896 31028858
   PubMed Web of Science ®Google Scholar
• Sozen E , Yazgan B , Sahin A , Ince U , Ozer NK . High cholesterol diet-induced changes in oxysterol and scavenger receptor levels in heart tissue. Oxid Med Cell Longev . 2018;2018:8520746. doi:10.1155/2018/8520746 30008986
   PubMed Web of Science ®Google Scholar