New insights into anti-diabetes effects and molecular mechanisms of dietary saponins

References

• Aamir, K., H. U. Khan, G. Sethi, M. A. Hossain, and A. Arya. 2020. Wnt signaling mediates TLR pathway and promote unrestrained adipogenesis and metaflammation: Therapeutic targets for obesity and type 2 diabetes. Pharmacological Research 152:104602. doi: 10.1016/j.phrs.2019.104602.
   PubMed Web of Science ®Google Scholar
• Abell, S. K., B. De Courten, J. A. Boyle, and H. J. Teede. 2015. Inflammatory and other biomarkers: Role in pathophysiology and prediction of gestational diabetes mellitus. International Journal of Molecular Sciences 16 (6):13442–73.
   PubMed Web of Science ®Google Scholar
• Achari, A. E, and S. K. Jain. 2017. Adiponectin, a therapeutic target for obesity, diabetes, and endothelial dysfunction. International Journal of Molecular Sciences 18 (6):1321. doi: 10.3390/ijms18061321.
   PubMed Web of Science ®Google Scholar
• Ahn, Y. M., S. K. Kim, J. S. Kang, and B. C. Lee. 2012. Platycodon grandiflorum modifies adipokines and the glucose uptake in high-fat diet in mice and L6 muscle cells. The Journal of Pharmacy and Pharmacology 64 (5):697–704.
   PubMed Web of Science ®Google Scholar
• Ahrén, B. 2019. DPP-4 inhibition and the path to clinical proof. Frontiers in Endocrinology 10:376. doi: 10.3389/fendo.2019.00376.
   PubMed Web of Science ®Google Scholar
• Al-Habori, M., A. Raman, M. J. Lawrence, and P. Skett. 2001. In vitro effect of fenugreek extracts on intestinal sodium-dependent glucose uptake and hepatic glycogen phosphorylase A. International Journal of Experimental Diabetes Research 2 (2):91–9. doi: 10.1155/EDR.2001.91.
   PubMedGoogle Scholar
• Ariyasu, D., H. Yoshida, and Y. Hasegawa. 2017. Endoplasmic reticulum (ER) stress and endocrine disorders. International Journal of Molecular Sciences 18 (2):382.
   PubMed Web of Science ®Google Scholar
• Asmat, U., K. Abad, and K. Ismail. 2016. Diabetes mellitus and oxidative stress—A concise review. Saudi Pharmaceutical Journal: SPJ: The Official Publication of the Saudi Pharmaceutical Society 24 (5):547–53.
   PubMed Web of Science ®Google Scholar
• Bai, L., J. Gao, F. Wei, J. Zhao, D. Wang, and J. Wei. 2018. Therapeutic potential of ginsenosides as an adjuvant treatment for diabetes. Frontiers in Pharmacology 9 (MAY):1–14. doi: 10.3389/fphar.2018.00423.
   PubMedGoogle Scholar
• Baynes, H. W. 2015. Classification, pathophysiology, diagnosis and management of diabetes mellitus. Journal of Diabetes & Metabolism 6 (5):1–9.
   Web of Science ®Google Scholar
• Behl, T., A. Gupta, A. Sehgal, S. Sharma, S. Singh, N. Sharma, C. C. Diaconu, A. Rahdar, A. Hafeez, S. Bhatia, et al. 2021. A spotlight on underlying the mechanism of AMPK in diabetes complications. Inflammation Research: Official Journal of the European Histamine Research Society 70 (9):939–57.
   PubMed Web of Science ®Google Scholar
• Bejjani, F., E. Evanno, K. Zibara, M. Piechaczyk, and I. Jariel-Encontre. 2019. The AP-1 transcriptional complex: Local switch or remote command? Biochimica et Biophysica Acta. Reviews on Cancer 1872 (1):11–23. doi: 10.1016/j.bbcan.2019.04.003.
   PubMed Web of Science ®Google Scholar
• Benchoula, K., A. Arya, I. S. Parhar, and W. E. Hwa. 2021. FoxO1 signaling as a therapeutic target for type 2 diabetes and obesity. European Journal of Pharmacology 891:173758.
   PubMed Web of Science ®Google Scholar
• Bertolio, R., F. Napoletano, M. Mano, S. Maurer-Stroh, M. Fantuz, A. Zannini, S. Bicciato, G. Sorrentino, and G. Del Sal. 2019. Sterol regulatory element binding protein 1 couples mechanical cues and lipid metabolism. Nature Communications 10 (1):1–11. doi: 10.1038/s41467-019-09152-7.
   PubMedGoogle Scholar
• Bianco, G., R. Pascale, C. F. Carbone, M. A. Acquavia, T. R. I. Cataldi, P. Schmitt-Kopplin, A. Buchicchio, D. Russo, and L. Milella. 2018. Determination of soyasaponins in Fagioli di Sarconi beans (Phaseolus vulgaris L.) by LC-ESI-FTICR-MS and evaluation of their hypoglycemic activity. Analytical and Bioanalytical Chemistry 410 (5):1561–9.
   PubMed Web of Science ®Google Scholar
• Burgos-Morón, E., Z. Abad-Jiménez, A. Martinez de Maranon, F. Iannantuoni, I. Escribano-López, S. López-Domènech, … V. M. Víctor. 2019. Relationship between oxidative stress, ER stress, and inflammation in type 2 diabetes: The battle continues. Journal of Clinical Medicine 8 (9):1385. doi: 10.3390/jcm8091385.
   PubMed Web of Science ®Google Scholar
• Burhans, M. S., D. K. Hagman, J. N. Kuzma, K. A. Schmidt, and M. Kratz. 2018. Contribution of adipose tissue inflammation to the development of type 2 diabetes mellitus. Comprehensive Physiology 9 (1):1–58.
   PubMed Web of Science ®Google Scholar
• Cai, S., J. Chen, and Y. Li. 2020. Dioscin protects against diabetic nephropathy by inhibiting renal inflammation through TLR4/NF-κB pathway in mice. Immunobiology 225 (3):151941.
   PubMed Web of Science ®Google Scholar
• Cao, Y., X. Jiang, H. Ma, Y. Wang, P. Xue, and Y. Liu. 2016. SIRT1 and insulin resistance. Journal of Diabetes and Its Complications 30 (1):178–83.
   PubMed Web of Science ®Google Scholar
• Cernea, S, and I. Raz. 2021. NAFLD in type 2 diabetes mellitus: Still many challenging questions. Diabetes/Metabolism Research and Reviews 37 (2):e3386. doi: 10.1002/dmrr.3386.
   PubMed Web of Science ®Google Scholar
• Chakraborti, C. K. 2015. Role of adiponectin and some other factors linking type 2 diabetes mellitus and obesity. World Journal of Diabetes 6 (15):1296–308. doi: 10.4239/wjd.v6.i15.1296.
   PubMed Web of Science ®Google Scholar
• Chaudhury, A., C. Duvoor, V. S. Reddy Dendi, S. Kraleti, A. Chada, R. Ravilla, A. Marco, N. S. Shekhawat, M. T. Montales, K. Kuriakose, et al. 2017. Clinical review of antidiabetic drugs: Implications for type 2 diabetes mellitus management. Frontiers in Endocrinology 8:6.
   PubMed Web of Science ®Google Scholar
• Chavez-Santoscoy, R. A., J. A. Gutierrez-Uribe, O. Granados, I. Torre-Villalvazo, S. O. Serna-Saldivar, N. Torres, B. Palacios-González, and A. R. Tovar. 2014. Flavonoids and saponins extracted from black bean (Phaseolus vulgaris L.) seed coats modulate lipid metabolism and biliary cholesterol secretion in C57BL/6 mice. The British Journal of Nutrition 112 (6):886–99.
   PubMed Web of Science ®Google Scholar
• Chen, G. Y., L. Li, F. Dai, X. J. Li, X. X. Xu, and J. G. Fan. 2015. Prevalence of and risk factors for type 2 diabetes mellitus in hyperlipidemia in China. Medical Science Monitor: International Medical Journal of Experimental and Clinical Research 21:2476.
   PubMed Web of Science ®Google Scholar
• Chen, J. C., C. B. S. Lau, J. Y. W. Chan, K. P. Fung, P. C. Leung, J. Q. Liu, L. Zhou, M. J. Xie, and M. H. Qiu. 2015. The antigluconeogenic activity of cucurbitacins from Momordica charantia. Planta Medica 81 (4):327–32.
   PubMed Web of Science ®Google Scholar
• Chen, J., S. Mangelinckx, A. Adams, Z. T. Wang, W. L. Li, and N. De Kimpe. 2015. Natural flavonoids as potential herbal medication for the treatment of diabetes mellitus and its complications. Natural Product Communications 10 (1):1934578X1501000. doi: 10.1177/1934578X1501000140.
   Web of Science ®Google Scholar
• Chen, Q, and J. X. Ma. 2017. Canonical Wnt signaling in diabetic retinopathy. Vision Research 139:47–58.
   PubMed Web of Science ®Google Scholar
• Chen, T., J. Gao, P. Xiang, Y. Chen, J. Ji, P. Xie, H. Wu, W. Xiao, Y. Wei, S. Wang, et al. 2015. Protective effect of platycodin D on liver injury in alloxan-induced diabetic mice via regulation of Treg/Th17 balance. International Immunopharmacology 26 (2):338–48.
   PubMed Web of Science ®Google Scholar
• Cheng, H. L., H. K. Huang, C. I. Chang, C. P. Tsai, and C. H. Chou. 2008. A cell-based screening identifies compounds from the stem of Momordica charantia that overcome insulin resistance and activate AMP-activated protein kinase. Journal of Agricultural and Food Chemistry 56 (16):6835–43.
   PubMed Web of Science ®Google Scholar
• Cheng, S., S. Liang, Q. Liu, Z. Deng, Y. Zhang, J. Du, Y. Zhang, S. Li, B. Cheng, and C. Ling. 2018. Diosgenin prevents high-fat diet-induced rat non-Alcoholic fatty liver disease through the AMPK and LXR signaling pathways. International Journal of Molecular Medicine 41 (2):1089–95.
   PubMed Web of Science ®Google Scholar
• Chiefari, E., B. Arcidiacono, D. Foti, and A. Brunetti. 2017. Gestational diabetes mellitus: An updated overview. Journal of Endocrinological Investigation 40 (9):899–909.
   PubMed Web of Science ®Google Scholar
• Cho, Y.-M., T. Imai, Y. Ito, S. Takami, M. Hasumura, T. Yamazaki, M. Hirose, and A. Nishikawa. 2009. A 13-week subchronic toxicity study of dietary administered saponin-rich and isoflavones-containing soybean extract in F344 rats. Food and Chemical Toxicology: An International Journal Published for the British Industrial Biological Research Association 47 (8):2150–6.
   PubMed Web of Science ®Google Scholar
• Choudhary, N., G. L. Khatik, and A. Suttee. 2021. The possible role of saponin in type-II diabetes-a review. Current Diabetes Reviews 17 (2):107–21.
   PubMed Web of Science ®Google Scholar
• Choudhury, H., M. Pandey, C. K. Hua, C. S. Mun, J. K. Jing, L. Kong, L. Y. Ern, N. A. Ashraf, S. W. Kit, T. S. Yee, et al. 2018. An update on natural compounds in the remedy of diabetes mellitus: A systematic review. Journal of Traditional and Complementary Medicine 8 (3):361–76.
   PubMedGoogle Scholar
• Cole, J. B, and J. C. Florez. 2020. Genetics of diabetes mellitus and diabetes complications. Nature Reviews. Nephrology 16 (7):377–90.
   PubMed Web of Science ®Google Scholar
• Cui, J., J. Duan, J. Chu, C. Guo, M. Xi, Y. Li, Y. Weng, G. Wei, Y. Yin, A. Wen, et al. 2020. Chikusetsu saponin IVa protects pancreatic β cell against intermittent high glucose-induced injury by activating Wnt/β-catenin/TCF7L2 pathway. Aging 12 (2):1591–609. doi: 10.18632/aging.102702.
   PubMedGoogle Scholar
• David, J. A., W. J. Rifkin, P. S. Rabbani, and D. J. Ceradini. 2017. The Nrf2/Keap1/ARE pathway and oxidative stress as a therapeutic target in type II diabetes mellitus. Journal of Diabetes Research 2017:4826724. doi: 10.1155/2017/4826724.
   PubMed Web of Science ®Google Scholar
• de Vries, M. A., A. Alipour, B. Klop, G.-J M. van de Geijn, H. W. Janssen, T. L. Njo, N. van der Meulen, A. P. Rietveld, A. H. Liem, E. M. Westerman, et al. 2015. Glucose-dependent leukocyte activation in patients with type 2 diabetes mellitus, familial combined hyperlipidemia and healthy controls. Metabolism 64 (2):213–7. doi: 10.1016/j.metabol.2014.10.011.
   PubMed Web of Science ®Google Scholar
• Demirtas, L., A. Guclu, F. M. Erdur, E. M. Akbas, A. Ozcicek, D. Onk, and K. Turkmen. 2016. Apoptosis, autophagy & endoplasmic reticulum stress in diabetes mellitus. The Indian Journal of Medical Research 144 (4):515–24. doi: 10.4103/0971-5916.200887.
   PubMedGoogle Scholar
• Deshaware, S., S. Gupta, R. S. Singhal, M. Joshi, and P. S. Variyar. 2018. Debittering of bitter gourd juice using β-cyclodextrin: Mechanism and effect on antidiabetic potential. Food Chemistry 262:78–85. doi: 10.1016/j.foodchem.2018.04.077.
   PubMed Web of Science ®Google Scholar
• Desjardins, E. M, and G. R. Steinberg. 2018. Emerging role of AMPK in brown and beige adipose tissue (BAT): Implications for obesity, insulin resistance, and type 2 diabetes. Current Diabetes Reports 18 (10):1–9. doi: 10.1007/s11892-018-1049-6.
   PubMed Web of Science ®Google Scholar
• Dhital, S., F. J. Warren, P. J. Butterworth, P. R. Ellis, and M. J. Gidley. 2017. Mechanisms of starch digestion by α-amylase—Structural basis for kinetic properties. Critical Reviews in Food Science and Nutrition 57 (5):875–92.
   PubMed Web of Science ®Google Scholar
• Dsouza, M., K. Rufina, and D. Hana. 2018. Extraction of Diosgenin from Fenugreek and evaluation of its pharmacological role in alleviating Metabolic Syndrome in vitro. Research Journal of Biotechnology 13 (12):10–7.
   Web of Science ®Google Scholar
• Duan, J., G. Wei, C. Guo, J. Cui, J. Yan, Y. Yin, Y. Guan, Y. Weng, Y. Zhu, X. Wu, et al. 2015. Aralia taibaiensis protects cardiac myocytes against high glucose-induced oxidative stress and apoptosis. The American Journal of Chinese Medicine 43 (6):1159–75.
   PubMed Web of Science ®Google Scholar
• El Barky, A. R., S. A. Hussein, A. A. Alm-Eldeen, Y. A. Hafez, and T. M. Mohamed. 2016. Anti-diabetic activity of Holothuria thomasi saponin. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie 84:1472–87.
   PubMed Web of Science ®Google Scholar
• Elekofehinti, O. O., E. O. Ariyo, M. O. Akinjiyan, O. S. Olayeriju, A. O. Lawal, I. G. Adanlawo, and J. B. T. Rocha. 2018. Potential use of bitter melon (Momordica charantia) derived compounds as antidiabetics: In silico and in vivo studies. Pathophysiology: The Official Journal of the International Society for Pathophysiology 25 (4):327–33. doi: 10.1016/j.pathophys.2018.05.003.
   PubMedGoogle Scholar
• Fang, K., H. Dong, S. Jiang, F. Li, D. Wang, D. Yang, J. Gong, W. Huang, and F. Lu. 2016. Diosgenin and 5-methoxypsoralen ameliorate insulin resistance through ERα/PI3K/akt-signaling pathways in HepG2 cells. Evidence-Based Complementary and Alternative Medicine: eCAM 2016:7493694. doi: 10.1155/2016/7493694.
   PubMed Web of Science ®Google Scholar
• Fang, L., F. Guo, L. Zhou, R. Stahl, and J. Grams. 2015. The cell size and distribution of adipocytes from subcutaneous and visceral fat is associated with type 2 diabetes mellitus in humans. Adipocyte 4 (4):273–9. doi: 10.1080/21623945.2015.1034920.
   PubMed Web of Science ®Google Scholar
• Farzaei, F., M. R. Morovati, F. Farjadmand, and M. H. Farzaei. 2017. A mechanistic review on medicinal plants used for diabetes mellitus in traditional Persian medicine. Journal of Evidence-Based Complementary & Alternative Medicine 22 (4):944–55. doi: 10.1177/2156587216686461.
   PubMedGoogle Scholar
• Feng, H., R. Su, Y. Song, C. Wang, L. Lin, J. Ma, and H. Yang. 2016. Positive correlation between enhanced expression of TLR4/MyD88/NF-κB with insulin resistance in placentae of gestational diabetes mellitus. PLoS One 11 (6):e0157185. doi: 10.1371/journal.pone.0157185.
   PubMed Web of Science ®Google Scholar
• Ferré, P., F. Phan, and F. Foufelle. 2021. SREBP-1c and lipogenesis in the liver: An update. The Biochemical Journal 478 (20):3723–39.
   PubMed Web of Science ®Google Scholar
• Fu, W., Y. Liang, Z. Xie, H. Wu, Z. Zhang, and H. Lv. 2021. Preparation and evaluation of lecithin/zein hybrid nanoparticles for the oral delivery of Panax notoginseng saponins. European Journal of Pharmaceutical Sciences: Official Journal of the European Federation for Pharmaceutical Sciences 164:105882.
   PubMed Web of Science ®Google Scholar
• Galicia-Garcia, U., A. Benito-Vicente, S. Jebari, A. Larrea-Sebal, H. Siddiqi, K. B. Uribe, H. Ostolaza, and C. Martín. 2020. Pathophysiology of type 2 diabetes mellitus. International Journal of Molecular Sciences 21 (17):6275. doi: 10.3390/ijms21176275.
   PubMed Web of Science ®Google Scholar
• Gan, Q., J. Wang, J. Hu, G. Lou, H. Xiong, C. Peng, S. Zheng, and Q. Huang. 2020. The role of diosgenin in diabetes and diabetic complications. The Journal of Steroid Biochemistry and Molecular Biology 198:105575.
   PubMed Web of Science ®Google Scholar
• Gao, Y., X. Li, Y. Huang, J. Chen, and M. Qiu. 2021. Bitter melon and diabetes mellitus. Food Reviews International 2021:1–21. doi: 10.1080/87559129.2021.1923733.
   Google Scholar
• Ghosh, S., P. More, A. Derle, A. B. Patil, P. Markad, A. Asok, N. Kumbhar, M. L. Shaikh, B. Ramanamurthy, V. S. Shinde, et al. 2014. Diosgenin from Dioscorea bulbifera: Novel hit for treatment of type II diabetes mellitus with inhibitory activity against α-amylase and α-glucosidase. PLoS One 9 (9):e106039. doi: 10.1371/journal.pone.0106039.
   PubMed Web of Science ®Google Scholar
• Gustafson, B., S. Hedjazifar, S. Gogg, A. Hammarstedt, and U. Smith. 2015. Insulin resistance and impaired adipogenesis. Trends in Endocrinology and Metabolism: TEM 26 (4):193–200. doi: 10.1016/j.tem.2015.01.006.
   PubMed Web of Science ®Google Scholar
• Guzmán, D. C., H. J. Olguín, Q. V. Corona, M. O. Herrera, N. O. Brizuela, and G. B. Mejía. 2020. Consumption of cooked common beans or saponins could reduce the risk of diabetic complications. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy 13:3481–6.
   PubMed Web of Science ®Google Scholar
• Hameed, I., S. R. Masoodi, S. A. Mir, M. Nabi, K. Ghazanfar, and B. A. Ganai. 2015. Type 2 diabetes mellitus: From a metabolic disorder to an inflammatory condition. World Journal of Diabetes 6 (4):598. doi: 10.4239/wjd.v6.i4.598.
   PubMed Web of Science ®Google Scholar
• Han, C., Q. Hui, and Y. Wang. 2008. Hypoglycaemic activity of saponin fraction extracted from Momordica charantia in PEG/salt aqueous two-phase systems. Natural Product Research 22 (13):1112–9. doi: 10.1080/14786410802079675.
   PubMed Web of Science ®Google Scholar
• Han, J., Q. Zheng, L. Fang, and X. Huang. 2021. Screening and functional evaluation of the glucose-lowering active compounds of total saponins of Baibiandou (Lablab Semen Album). Digital Chinese Medicine 4 (3):229–40.
   Google Scholar
• Hao, S., R. Xu, D. Li, Z. Zhu, T. Wang, and K. Liu. 2015. Attenuation of streptozotocin-induced lipid profile anomalies in the heart, brain, and mRNA expression of HMG-CoA reductase by diosgenin in rats. Cell Biochemistry and Biophysics 72 (3):741–9. doi: 10.1007/s12013-015-0525-8.
   PubMed Web of Science ®Google Scholar
• Hashidume, T., K. Sasaki, J. Hirata, M. Kato, Y. Yoshikawa, Y. Iwasaki, H. Arai, S. Miura, and N. Miyoshi. 2018. Effects of sanyaku and its constituent diosgenin on the fasted and postprandial hypertriacylglycerolemia in high-fat-diet-fed KK-Ay mice. Journal of Agricultural and Food Chemistry 66 (38):9968–75. doi: 10.1021/acs.jafc.8b03040.
   PubMed Web of Science ®Google Scholar
• Hazarika, R., P. Parida, B. Neog, and R. Yadav. 2012. Binding energy calculation of GSK-3 protein of human against some anti-diabetic compounds of Momordica charantia linn (Bitter melon). Bioinformation 8 (6):251–4. doi: 10.6026/97320630008251.
   PubMedGoogle Scholar
• He, M-y., G. Wang, S-s Han, Y. Jin, H. Li, X. Wu, Z-l Ma, X. cheng, X. Tang, X. Yang, et al. 2016. Nrf2 signalling and autophagy are involved in diabetes mellitus-induced defects in the development of mouse placenta. Open Biology 6 (7):160064. doi: 10.1098/rsob.160064.
   PubMed Web of Science ®Google Scholar
• He, Y., Z. Hu, A. Li, Z. Zhu, N. Yang, Z. Ying, … S. Cheng. 2019. Recent advances in biotransformation of saponins. Molecules 24 (13):2365. doi: 10.3390/molecules24132365.
   PubMed Web of Science ®Google Scholar
• Hirai, S., T. Uemura, N. Mizoguchi, J. Y. Lee, K. Taketani, Y. Nakano, S. Hoshino, N. Tsuge, T. Narukami, R. Yu, et al. 2010. Diosgenin attenuates inflammatory changes in the interaction between adipocytes and macrophages. Molecular Nutrition & Food Research 54 (6):797–804.
   PubMed Web of Science ®Google Scholar
• Ho, C., Y. C. Hsu, C. C. Lei, S. C. Mau, Y. H. Shih, and C. L. Lin. 2016. Curcumin rescues diabetic renal fibrosis by targeting superoxide-mediated Wnt signaling pathways. The American Journal of the Medical Sciences 351 (3):286–95.
   PubMed Web of Science ®Google Scholar
• Hsiao, P. C., C. C. Liaw, S. Y. Hwang, H. L. Cheng, L. J. Zhang, C. C. Shen, F. L. Hsu, and Y. H. Kuo. 2013. Antiproliferative and hypoglycemic cucurbitane-type glycosides from the fruits of Momordica charantia. Journal of Agricultural and Food Chemistry 61 (12):2979–86.
   PubMed Web of Science ®Google Scholar
• Hu, X., S. Wang, J. Xu, D. B. Wang, Y. Chen, and G. Z. Yang. 2014. Triterpenoid saponins from Stauntonia chinensis ameliorate insulin resistance via the AMP-activated protein kinase and IR/IRS-1/PI3K/Akt pathways in insulin-resistant HepG2 cells. International Journal of Molecular Sciences 15 (6):10446–58.
   PubMed Web of Science ®Google Scholar
• Hua, S., Y. Li, L. Su, and X. Liu. 2016. Diosgenin ameliorates gestational diabetes through inhibition of sterol regulatory element-binding protein-1. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie 84:1460–5.
   PubMed Web of Science ®Google Scholar
• Huang, X., G. Liu, J. Guo, and Z. Su. 2018. The PI3K/AKT pathway in obesity and type 2 diabetes. International Journal of Biological Sciences 14 (11):1483–96.
   PubMed Web of Science ®Google Scholar
• Hwang, Y. P., J. H. Choi, H. G. Kim, T. Khanal, G. Y. Song, M. S. Nam, H. S. Lee, Y. C. Chung, Y. C. Lee, and H. G. Jeong. 2013. Saponins, especially platycodin D, from Platycodon grandiflorum modulate hepatic lipogenesis in high-fat diet-fed rats and high glucose-exposed HepG2 cells. Toxicology and Applied Pharmacology 267 (2):174–83.
   PubMed Web of Science ®Google Scholar
• Hye Khan, M. A., L. Kolb, M. Skibba, M. Hartmann, R. Blöcher, E. Proschak, and J. D. Imig. 2018. A novel dual PPAR-γ agonist/sEH inhibitor treats diabetic complications in a rat model of type 2 diabetes. Diabetologia 61 (10):2235–46. doi: 10.1007/s00125-018-4685-0.
   PubMed Web of Science ®Google Scholar
• Ighodaro, O. M. 2018. Molecular pathways associated with oxidative stress in diabetes mellitus. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie 108:656–62. doi: 10.1016/j.biopha.2018.09.058.
   PubMed Web of Science ®Google Scholar
• Iskender, H., E. Dokumacioglu, T. M. Sen, I. Ince, Y. Kanbay, and S. Saral. 2017. The effect of hesperidin and quercetin on oxidative stress, NF-κB and SIRT1 levels in a STZ-induced experimental diabetes model. Biomedicine & Pharmacotherapy 90:500–8. doi: 10.1016/j.biopha.2017.03.102.
   PubMed Web of Science ®Google Scholar
• Iwamoto, K., S. Kamo, Y. Takada, A. Ieda, T. Yamashita, T. Sato, N. Zaima, and T. Moriyama. 2018. Soyasapogenols reduce cellular triglyceride levels in 3T3-L1 mouse adipocyte cells by accelerating triglyceride lipolysis. Biochemistry and Biophysics Reports 16 (May):44–9.
   PubMedGoogle Scholar
• Janani, C, and B. R. Kumari. 2015. PPAR gamma gene–a review. Diabetes & Metabolic Syndrome 9 (1):46–50.
   PubMed Web of Science ®Google Scholar
• Jeepipalli, S. P., B. Du, U. Y. Sabitaliyevich, and B. Xu. 2020. New insights into potential nutritional effects of dietary saponins in protecting against the development of obesity. Food Chemistry 318:126474.
   PubMed Web of Science ®Google Scholar
• Jiang, S., L. Xu, Y. Xu, Y. Guo, L. Wei, X. Li, and W. Song. 2020. Antidiabetic effect of Momordica charantia saponins in rats induced by high-fat diet combined with STZ. Electronic Journal of Biotechnology 43:41–7. doi: 10.1016/j.ejbt.2019.12.001.
   Web of Science ®Google Scholar
• Jo, E. K., J. K. Kim, D. M. Shin, and C. Sasakawa. 2016. Molecular mechanisms regulating NLRP3 inflammasome activation. Cellular & Molecular Immunology 13 (2):148–59. doi: 10.1038/cmi.2015.95.
   PubMed Web of Science ®Google Scholar
• Joshi, T., A. K. Singh, P. Haratipour, A. N. Sah, A. K. Pandey, R. Naseri, V. Juyal, and M. H. Farzaei. 2019. Targeting AMPK signaling pathway by natural products for treatment of diabetes mellitus and its complications. Journal of Cellular Physiology 234 (10):17212–31.
   PubMed Web of Science ®Google Scholar
• Kalailingam, P., B. Kannaian, E. Tamilmani, and R. Kaliaperumal. 2014. Efficacy of natural diosgenin on cardiovascular risk, insulin secretion, and beta cells in streptozotocin (STZ)-induced diabetic rats. Phytomedicine 21 (10):1154–61. doi: 10.1016/j.phymed.2014.04.005.
   PubMed Web of Science ®Google Scholar
• Kanchan, D. M., G. S. Somani, V. V. Peshattiwar, A. A. Kaikini, and S. Sathaye. 2016. Renoprotective effect of diosgenin in streptozotocin induced diabetic rats. Pharmacological Reports: PR 68 (2):370–7.
   PubMed Web of Science ®Google Scholar
• Kang, S., L. T. Tsai, and E. D. Rosen. 2016. Nuclear mechanisms of insulin resistance. Trends in Cell Biology 26 (5):341–51.
   PubMed Web of Science ®Google Scholar
• Keitel, V., J. Stindt, and D. Häussinger. 2019. Bile acid-activated receptors: GPBAR1 (TGR5) and other G protein-coupled receptors. Bile Acids and Their Receptors 256 19–49.
   Google Scholar
• Keller, A. C., J. Ma, A. Kavalier, K. He, A. M. B. Brillantes, and E. J. Kennelly. 2011. Saponins from the traditional medicinal plant Momordica charantia stimulate insulin secretion in vitro. Phytomedicine 19 (1):32–7. doi: 10.1016/j.phymed.2011.06.019.
   PubMed Web of Science ®Google Scholar
• Keller, A. C., K. He, A.-M. Brillantes, and E. J. Kennelly. 2021. A characterized saponin-rich fraction of Momordica charantia shows antidiabetic activity in C57BLK/6 mice fed a high fat diet. Phytomedicine Plus 1 (4):100134. doi: 10.1016/j.phyplu.2021.100134.
   Google Scholar
• Kelley, N., D. Jeltema, Y. Duan, and Y. He. 2019. The NLRP3 inflammasome: An overview of mechanisms of activation and regulation. International Journal of Molecular Sciences 20 (13):3328. doi: 10.3390/ijms20133328.
   PubMed Web of Science ®Google Scholar
• Khan, M. I., M. Z. Khan, J. H. Shin, T. S. Shin, Y. B. Lee, M. Y. Kim, and J. D. Kim. 2021. Pharmacological approaches to attenuate inflammation and obesity with natural products formulations by regulating the associated promoting molecular signaling pathways. BioMed Research International 2021:2521273. doi: 10.1155/2021/2521273.
   PubMed Web of Science ®Google Scholar
• Khateeb, S., A. Albalawi, and A. Alkhedaide. 2021. Regulatory effect of diosgenin on lipogenic genes expression in high-fat diet-induced obesity in mice. Saudi Journal of Biological Sciences 28 (1):1026–32.
   PubMed Web of Science ®Google Scholar
• Khorami, S. A. H., A. R. I. Y. O. Movahedi, K. Huzwah, and A. M. M. Sokhini. 2015. PI3K/AKT pathway in modulating glucose homeostasis and its alteration in diabetes. Annals of Medical and Biomedical Sciences 1 (2):46–55.
   Google Scholar
• Kim, D. Y., S. Y. Jung, K. Kim, and C. J. Kim. 2016. Treadmill exercise ameliorates Alzheimer disease-associated memory loss through the Wnt signaling pathway in the streptozotocin-induced diabetic rats. Journal of Exercise Rehabilitation 12 (4):276–83.
   PubMed Web of Science ®Google Scholar
• Kim, J. D., N. Chaudhary, H. J. Seo, M. Y. Kim, and T. S. Shin. 2014. Theasaponin E1 as an effective ingredient for anti-angiogenesis and anti-obesity effects. Bioscience, Biotechnology, and Biochemistry 78 (2):279–87. doi: 10.1080/09168451.2014.893183.
   PubMed Web of Science ®Google Scholar
• Kim, J. H., J. Song, and K. W. Park. 2015. The multifaceted factor peroxisome proliferator-activated receptor γ (PPARγ) in metabolism, immunity, and cancer. Archives of Pharmacal Research 38 (3):302–12.
   PubMed Web of Science ®Google Scholar
• Kiss, R., G. Pesti-Asbóth, M. M. Szarvas, L. Stündl, Z. Cziáky, C. Hegedűs, D. Kovács, A. Badale, E. Máthé, Z. Szilvássy, et al. 2019. Diosgenin and its fenugreek based biological matrix affect insulin resistance and anabolic hormones in a rat based insulin resistance model. BioMed Research International 2019:7213913. doi: 10.1155/2019/7213913.
   PubMed Web of Science ®Google Scholar
• Kjøbsted, R., A. J. T. Pedersen, J. R. Hingst, R. Sabaratnam, J. B. Birk, J. M. Kristensen, K. Højlund, and J. F. P. Wojtaszewski. 2016. Intact regulation of the AMPK signaling network in response to exercise and insulin in skeletal muscle of male patients with type 2 diabetes: Illumination of AMPK activation in recovery from exercise. Diabetes 65 (5):1219–30. doi: 10.2337/db15-1034.
   PubMed Web of Science ®Google Scholar
• Kleinert, M., C. Clemmensen, S. M. Hofmann, M. C. Moore, S. Renner, S. C. Woods, P. Huypens, J. Beckers, M. H. de Angelis, A. Schürmann, et al. 2018. Animal models of obesity and diabetes mellitus. Nature Reviews. Endocrinology 14 (3):140–62.
   PubMed Web of Science ®Google Scholar
• Koneri, R. B., S. Samaddar, and C. T. Ramaiah. 2014. Antidiabetic activity of a triterpenoid saponin isolated from Momordica cymbalaria Fenzl. Indian Journal of Experimental Biology 52 (1):46–52.
   PubMed Web of Science ®Google Scholar
• Kwon, D. Y., Y. S. Kim, S. M. Hong, and S. Park. 2009. Long-term consumption of saponins derived from Platycodi radix (22 years old) enhances hepatic insulin sensitivity and glucose-stimulated insulin secretion in 90% pancreatectomized diabetic rats fed a high-fat diet. The British Journal of Nutrition 101 (3):358–66.
   PubMed Web of Science ®Google Scholar
• Kwon, D. Y., Y. S. Kim, S. Y. Ryu, Y. H. Choi, M. R. Cha, H. J. Yang, and S. Park. 2012. Platyconic acid, a saponin from Platycodi radix, improves glucose homeostasis by enhancing insulin sensitivity in vitro and in vivo. European Journal of Nutrition 51 (5):529–40.
   PubMed Web of Science ®Google Scholar
• Labrie, F., C. Martel, A. Belanger, and G. Pelletier. 2017. Androgens in women are essentially made from DHEA in each peripheral tissue according to intracrinology. The Journal of Steroid Biochemistry and Molecular Biology 168:9–18.
   PubMed Web of Science ®Google Scholar
• Lee, H., R., Y. S. Kang, S.-I. Kim, and Y. Yoon. 2010. Platycodin D inhibits adipogenesis of 3T3-L1 cells by modulating kruppel-like factor 2 and peroxisome proliferator-activated receptor γ. Phytotherapy Research 24 (S2):S161–7. doi: 10.1002/ptr.3054.
   PubMedGoogle Scholar
• Lee, S. O., A. L. Simons, P. A. Murphy, and S. Hendrich. 2005. Soyasaponins lowered plasma cholesterol and increased fecal bile acids in female golden Syrian hamsters. Experimental Biology and Medicine 230 (7):472–8. doi: 10.1177/153537020523000705.
   Web of Science ®Google Scholar
• Lehrke, M, and N. Marx. 2017. Diabetes mellitus and heart failure. The American Journal of Cardiology 120 (1S):S37–S47. doi: 10.1016/j.amjcard.2017.05.014.
   PubMedGoogle Scholar
• Li, B., Y. Terazono, N. Hirasaki, Y. Tatemichi, E. Kinoshita, A. Obata, and T. Matsui. 2018. Inhibition of glucose transport by tomatoside A, a tomato seed steroidal saponin, through the suppression of GLUT2 expression in Caco-2 cells. Journal of Agricultural and Food Chemistry 66 (6):1428–34. doi: 10.1021/acs.jafc.7b06078.
   PubMed Web of Science ®Google Scholar
• Li, H., L. Yu, and C. Zhao. 2019. Dioscin attenuates high-fat diet-induced insulin resistance of adipose tissue through the IRS-1/PI3K/Akt signaling pathway. Molecular Medicine Reports 19 (2):1230–7.
   PubMed Web of Science ®Google Scholar
• Li, Y., T. Zhang, J. Cui, N. Jia, Y. Wu, M. Xi, and A. Wen. 2015. Chikusetsu saponin IVa regulates glucose uptake and fatty acid oxidation: Implications in antihyperglycemic and hypolipidemic effects. The Journal of Pharmacy and Pharmacology 67 (7):997–1007.
   PubMed Web of Science ®Google Scholar
• Liu, K., W. Zhao, X. Gao, F. Huang, J. Kou, and B. Liu. 2012. Diosgenin ameliorates palmitate-induced endothelial dysfunction and insulin resistance via blocking IKKβ and IRS-1 pathways. Atherosclerosis 223 (2):350–8.
   PubMed Web of Science ®Google Scholar
• Liu, L., N. Wang, Y. Ma, Y. Liu, and D. Wen. 2018. Saponins from: Boussingaultia gracilis prevent obesity and related metabolic impairments in diet-induced obese mice. Food & Function 9 (11):5660–73.
   PubMed Web of Science ®Google Scholar
• Liu, M., L. Xu, L. Yin, Y. Qi, Y. Xu, X. Han, Y. Zhao, H. Sun, J. Yao, Y. Lin, et al. 2015. Potent effects of dioscin against obesity in mice. Scientific Reports 5:7973. doi: 10.1038/srep07973.
   PubMed Web of Science ®Google Scholar
• Liu, X., K. Chen, L. Zhu, H. Liu, T. Ma, Q. Xu, and T. Xie. 2018. Soyasaponin Ab protects against oxidative stress in HepG2 cells via Nrf2/HO-1/NQO1 signaling pathways. Journal of Functional Foods 45 (March):110–7. doi: 10.1016/j.jff.2018.03.037.
   Google Scholar
• Luan, H., L. Yang, L. Liu, S. Liu, X. Zhao, H. Sui, J. Wang, and S. Wang. 2014. Effects of platycodins on liver complications of type 2 diabetes. Molecular Medicine Reports 10 (3):1597–603. doi: 10.3892/mmr.2014.2363.
   PubMed Web of Science ®Google Scholar
• Lv, X., L. Zhang, J. Sun, Z. Cai, Q. Gu, R. Zhang, and A. Shan. 2017. Interaction between peroxisome proliferator-activated receptor gamma polymorphism and obesity on type 2 diabetes in a Chinese Han population. Diabetology & Metabolic Syndrome 9 (1):1–6. doi: 10.1186/s13098-017-0205-5.
   PubMedGoogle Scholar
• Ma, C., H. Yu, Y. Xiao, and H. Wang. 2017. Momordica charantia extracts ameliorate insulin resistance by regulating the expression of SOCS-3 and JNK in type 2 diabetes mellitus rats. Pharmaceutical Biology 55 (1):2170–7. doi: 10.1080/13880209.2017.1396350.
   PubMed Web of Science ®Google Scholar
• Ma, J., P. Whittaker, A. C. Keller, E. P. Mazzola, R. S. Pawar, K. D. White, J. H. Callahan, E. J. Kennelly, A. J. Krynitsky, and J. I. Rader. 2010. Cucurbitane-type triterpenoids from Momordica charantia. Planta Medica 76 (15):1758–61.
   PubMed Web of Science ®Google Scholar
• Marín-Peñalver, J. J., I. Martín-Timón, C. Sevillano-Collantes, and F. J. del Cañizo-Gómez. 2016. Update on the treatment of type 2 diabetes mellitus. World Journal of Diabetes 7 (17):354–95.
   PubMed Web of Science ®Google Scholar
• Mayakrishnan, T., J. R. Nakkala, S. P. K. Jeepipalli, K. Raja, V. Khub Chandra, V. K. Mohan, and S. R. Sadras. 2015. Fenugreek seed extract and its phytocompounds- trigonelline and diosgenin arbitrate their hepatoprotective effects through attenuation of endoplasmic reticulum stress and oxidative stress in type 2 diabetic rats. European Food Research and Technology 240 (1):223–32. doi: 10.1007/s00217-014-2322-9.
   Web of Science ®Google Scholar
• McAnuff, M. A., F. O. Omoruyi, and H. N. Asemota. 2006. Intestinal disaccharidases and some renal enzymes in streptozotocin-induced diabetic rats fed sapogenin extract from bitter yam (Dioscorea polygonoides). Life Sciences 78 (22):2595–600.
   PubMed Web of Science ®Google Scholar
• McAnuff, M. A., F. O. Omoruyi, E. Y. S. A. Morrison, and H. N. Asemota. 2005b. Changes in some liver enzymes in streptozotocin-induced diabetic rats fed sapogenin extract from bitter yam (Dioscorea polygonoides) or commercial diosgenin. West Indian Medical Journal 54 (2):97–101. doi: 10.1590/S0043-31442005000200002.
   PubMed Web of Science ®Google Scholar
• McAnuff, M. A., F. O. Omoruyi, E. Y. S. A. Morrison, and H. N. Asemota. 2002. Plasma and liver lipid distributions in streptozotocin-induced diabetic rats fed sapogenin extract of the Jamaican bitter yam (Dioscorea polygonoides). Nutrition Research 22 (12):1427–34. doi: 10.1016/S0271-5317(02)00457-8.
   Web of Science ®Google Scholar
• McAnuff, M. A., W. W. Harding, F. O. Omoruyi, H. Jacobs, E. Y. Morrison, and H. N. Asemota. 2005a. Hypoglycemic effects of steroidal sapogenins isolated from Jamaican bitter yam, Dioscorea polygonoides. Food and Chemical Toxicology: An International Journal Published for the British Industrial Biological Research Association 43 (11):1667–72. doi: 10.1016/j.fct.2005.05.008.
   PubMed Web of Science ®Google Scholar
• McIntyre, H. D., P. Catalano, C. Zhang, G. Desoye, E. R. Mathiesen, and P. Damm. 2019. Gestational diabetes mellitus. Nature Reviews Disease Primers 5 (1):1–19. doi: 10.1038/s41572-019-0098-8.
   PubMedGoogle Scholar
• Meng, J., X. Hu, T. Zhang, P. Dong, Z. Li, C. Xue, Y. Chang, and Y. Wang. 2018. Saponin from sea cucumber exhibited more significant effects than ginsenoside on ameliorating high fat diet-induced obesity in C57BL/6 mice. MedChemComm 9 (4):725–34. doi: 10.1039/c7md00653e.
   PubMed Web of Science ®Google Scholar
• Naidu, P. B., P. Ponmurugan, M. S. Begum, K. Mohan, B. Meriga, R. Ravindarnaik, and G. Saravanan. 2015. Diosgenin reorganises hyperglycaemia and distorted tissue lipid profile in high-fat diet-streptozotocin-induced diabetic rats. Journal of the Science of Food and Agriculture 95 (15):3177–82. doi: 10.1002/jsfa.7057.
   PubMed Web of Science ®Google Scholar
• Nazaruk, J, and M. Borzym-Kluczyk. 2015. The role of triterpenes in the management of diabetes mellitus and its complications. Phytochemistry Reviews: Proceedings of the Phytochemical Society of Europe 14 (4):675–90.
   PubMed Web of Science ®Google Scholar
• Netala, V. R., S. B. Ghosh, P. Bobbu, D. Anitha, and V. Tartte. 2015. Triterpenoid saponins: A review on biosynthesis, applications and mechanism of their action. International Journal of Pharmacy and Pharmaceutical Sciences 7 (1):24–8.
   Google Scholar
• Newman, D. J, and G. M. Cragg. 2020. Natural products as sources of new drugs over the nearly four decades from 01/1981 to 09/2019. Journal of Natural Products 83 (3):770–803. doi: 10.1021/acs.jnatprod.9b01285.
   PubMed Web of Science ®Google Scholar
• Nguyen, L. T., A. C. Farcas, S. A. Socaci, M. Tofana, Z. M. Diaconeasa, O. L. Pop, and L. C. Salanta. 2020. An overview of Saponins–A bioactive group. Bulletin UASVM Food Science and Technology 77 (1):25–36.
   Web of Science ®Google Scholar
• Nhiem, N. X., Kiem, P. V. Minh, C. Van, Ban, N. K. Cuong, N. X. Tung, N. H. Ha, L. M. Ha, D. T. Tai, B. H. Quang, T. H, et al. 2010. α-Glucosidase inhibition properties of cucurbitane-type triterpene glycosides from the fruits of Momordica charantia. Chemical & Pharmaceutical Bulletin 58 (5):720–4.
   PubMed Web of Science ®Google Scholar
• Oguntibeju, O. O. 2019. Type 2 diabetes mellitus, oxidative stress and inflammation: Examining the links. International Journal of Physiology, Pathophysiology and Pharmacology 11 (3):45–63.
   PubMedGoogle Scholar
• Oishi, Y., T. Sakamoto, H. Udagawa, H. Taniguchi, K. Kobayashi-Hattori, Y. Ozawa, and T. Takita. 2007. Inhibition of increases in blood glucose and serum neutral fat by Momordica charantia saponin fraction. Bioscience, Biotechnology and Biochemistry 71 (3):735–40. doi: 10.1271/bbb.60570.
   PubMed Web of Science ®Google Scholar
• Ong, S. E., J. J. K. Koh, S.-A E. S. Toh, K. S. Chia, D. Balabanova, M. McKee, P. Perel, and H. Legido-Quigley. 2018. Assessing the influence of health systems on type 2 diabetes mellitus awareness, treatment, adherence, and control: A systematic review. PLoS One 13 (3):e0195086. doi: 10.1371/journal.pone.0195086.
   PubMed Web of Science ®Google Scholar
• Papoutsis, K., J. Zhang, M. C. Bowyer, N. Brunton, E. R. Gibney, and J. Lyng. 2021. Fruit, vegetables, and mushrooms for the preparation of extracts with α-amylase and α-glucosidase inhibition properties: A review. Food Chemistry 338:128119. doi: 10.1016/j.foodchem.2020.128119.
   PubMed Web of Science ®Google Scholar
• Pari, L., P. Monisha, and A. Mohamed Jalaludeen. 2012. Beneficial role of diosgenin on oxidative stress in aorta of streptozotocin induced diabetic rats. European Journal of Pharmacology 691 (1–3):143–50.
   PubMed Web of Science ®Google Scholar
• Pawlak, M., P. Lefebvre, and B. Staels. 2015. Molecular mechanism of PPARα action and its impact on lipid metabolism, inflammation and fibrosis in non-alcoholic fatty liver disease. Journal of Hepatology 62 (3):720–33. doi: 10.1016/j.jhep.2014.10.039.
   PubMed Web of Science ®Google Scholar
• Perera, W. H., S. R. Shivanagoudra, J. L. Pérez, D. M. Kim, Y. Sun, G. K. Jayaprakasha, and B. S. Patil. 2021. Anti-Inflammatory, antidiabetic properties and in silico modeling of cucurbitane-type triterpene glycosides from fruits of an indian cultivar of Momordica charantia L. Molecules 26 (4):1038. doi: 10.3390/molecules26041038.
   PubMed Web of Science ®Google Scholar
• Perez, J. L., G. K. Jayaprakasha, and B. S. Patil. 2019. Metabolite profiling and in vitro biological activities of two commercial bitter melon (Momordica charantia Linn.) cultivars. Food Chemistry 288:178–86.
   PubMed Web of Science ®Google Scholar
• Perez, J. L., S. R. Shivanagoudra, W. H. Perera, D. M. Kim, C. S. Wu, Y. Sun, G. K. Jayaprakasha, and B. S. Patil. 2021. Bitter melon extracts and cucurbitane-type triterpenoid glycosides antagonize lipopolysaccharide-induced inflammation via suppression of NLRP3 inflammasome. Journal of Functional Foods 86:104720. doi: 10.1016/j.jff.2021.104720.
   Web of Science ®Google Scholar
• Petersen, M. C, and G. I. Shulman. 2018. Mechanisms of insulin action and insulin resistance. Physiological Reviews 98 (4):2133–223.
   PubMed Web of Science ®Google Scholar
• Poudel, B., S. W. Lim, H. H. Ki, S. Nepali, Y. M. Lee, and D. K. Kim. 2014. Dioscin inhibits adipogenesis through the AMPK/MAPK pathway in 3T3-L1 cells and modulates fat accumulation in obese mice. International Journal of Molecular Medicine 34 (5):1401–8.
   PubMed Web of Science ®Google Scholar
• Poznyak, A., A. V. Grechko, P. Poggio, V. A. Myasoedova, V. Alfieri, and A. N. Orekhov. 2020. The diabetes mellitus–atherosclerosis connection: The role of lipid and glucose metabolism and chronic inflammation. International Journal of Molecular Sciences 21 (5):1835. doi: 10.3390/ijms21051835.
   PubMed Web of Science ®Google Scholar
• Ratan, Z. A., M. F. Haidere, Y. H. Hong, S. H. Park, J. O. Lee, J. Lee, and J. Y. Cho. 2021. Pharmacological potential of ginseng and its major component ginsenosides. Journal of Ginseng Research 45 (2):199–210.
   PubMed Web of Science ®Google Scholar
• Reichert, C. L., H. Salminen, and J. Weiss. 2019. Quillaja saponin characteristics and functional properties. Annual Review of Food Science and Technology 10:43–73.
   PubMed Web of Science ®Google Scholar
• Saarimäki-Vire, J., D. Balboa, M. A. Russell, J. Saarikettu, M. Kinnunen, S. Keskitalo, A. Malhi, C. Valensisi, C. Andrus, S. Eurola, et al. 2017. An activating STAT3 mutation causes neonatal diabetes through premature induction of pancreatic differentiation. Cell Reports 19 (2):281–94. doi: 10.1016/j.celrep.2017.03.055.
   PubMed Web of Science ®Google Scholar
• Samaddar, S., R. K. Balwanth, S. K. Sah, and K. B. Chandrasekhar. 2016. Protective effect of saponin of momordica cymbalaria fenzl on high-glucose induced neuropathy in NB-41A3 mouse neuroblastoma cells. International Journal of Pharmacy and Pharmaceutical Sciences 8 (4):229–35.
   Google Scholar
• Samuel, V. T, and G. I. Shulman. 2016. The pathogenesis of insulin resistance: Integrating signaling pathways and substrate flux. The Journal of Clinical Investigation 126 (1):12–22.
   PubMed Web of Science ®Google Scholar
• Sangeetha, M. K., N. Shrishri Mal, K. Atmaja, V. K. Sali, and H. R. Vasanthi. 2013. PPAR’s and Diosgenin a chemico biological insight in NIDDM. Chemico-Biological Interactions 206 (2):403–10. doi: 10.1016/j.cbi.2013.08.014.
   PubMed Web of Science ®Google Scholar
• Saravanan, G., P. Ponmurugan, M. A. Deepa, and B. Senthilkumar. 2014. Modulatory effects of diosgenin on attenuating the key enzymes activities of carbohydrate metabolism and glycogen content in streptozotocin-induced diabetic rats. Canadian Journal of Diabetes 38 (6):409–14. doi: 10.1016/j.jcjd.2014.02.004.
   PubMed Web of Science ®Google Scholar
• Sato, K., S. Fujita, and M. Iemitsu. 2014. Acute administration of diosgenin or dioscorea improves hyperglycemia with increases muscular steroidogenesis in STZ-induced type 1 diabetic rats. The Journal of Steroid Biochemistry and Molecular Biology 143:152–9. doi: 10.1016/j.jsbmb.2014.02.020.
   PubMed Web of Science ®Google Scholar
• Scherer, P. E. 2019. The many secret lives of adipocytes: Implications for diabetes. Diabetologia 62 (2):223–32. doi: 10.1007/s00125-018-4777-x.
   PubMed Web of Science ®Google Scholar
• Shafi, S., P. Gupta, G. L. Khatik, and J. Gupta. 2019. PPARγ: Potential therapeutic target for ailments beyond diabetes and its natural agonism. Current Drug Targets 20 (12):1281–94.
   PubMed Web of Science ®Google Scholar
• Shao, B. Z., Z. Q. Xu, B. Z. Han, D. F. Su, and C. Liu. 2015. NLRP3 inflammasome and its inhibitors: A review. Frontiers in Pharmacology 6:262.
   PubMed Web of Science ®Google Scholar
• Shao, J. W., J. L. Jiang, J. J. Zou, M. Y. Yang, F. M. Chen, Y. J. Zhang, and L. Jia. 2020. Therapeutic potential of ginsenosides on diabetes: From hypoglycemic mechanism to clinical trials. Journal of Functional Foods 64:103630. doi: 10.1016/j.jff.2019.103630.
   Web of Science ®Google Scholar
• Sharma, D., S. Verma, S. Vaidya, K. Kalia, and V. Tiwari. 2018. Recent updates on GLP-1 agonists: Current advancements & challenges. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie 108:952–62.
   PubMed Web of Science ®Google Scholar
• Shivanagoudra, S. R., W. H. Perera, J. L. Perez, G. Athrey, Y. Sun, C. S. Wu, G. K. Jayaprakasha, and B. S. Patil. 2019. In vitro and in silico elucidation of antidiabetic and anti-inflammatory activities of bioactive compounds from. Bioorganic & Medicinal Chemistry 27 (14):3097–109. doi: 10.1016/j.bmc.2019.05.035.
   PubMed Web of Science ®Google Scholar
• Shivaswamy, V., B. Boerner, and J. Larsen. 2016. Post-transplant diabetes mellitus: Causes, treatment, and impact on outcomes. Endocrine Reviews 37 (1):37–61.
   PubMed Web of Science ®Google Scholar
• Sohn, J. H., J. W. Kim, G. W. Jung, D. C. Park, S. B. Moon, H. R. Cho, S. K. Ku, and J. S. Choi. 2018. Synergic antiobesity effects of bitter melon water extract and platycodin-D in genetically obese mice. Journal of Environmental Biology 39 (5):603–11. doi: 10.22438/jeb/39/5/MRN-536.
   Web of Science ®Google Scholar
• Soma, K. K., N. M. Rendon, R. Boonstra, H. E. Albers, and G. E. Demas. 2015. DHEA effects on brain and behavior: Insights from comparative studies of aggression. The Journal of Steroid Biochemistry and Molecular Biology 145:261–72.
   PubMed Web of Science ®Google Scholar
• Son, I. S., J. H. Kim, H. Y. Sohn, K. H. Son, J. S. Kim, and C. S. Kwon. 2007. Antioxidative and hypolipidemic effects of diosgenin, a steroidal saponin of yam (Dioscorea spp.), on high-cholesterol fed rats. Bioscience. Biotechnology and Biochemistry 71 (12):3063–71. doi: 10.1271/bbb.70472.
   Google Scholar
• Sternisha, S. M, and B. G. Miller. 2019. Molecular and cellular regulation of human glucokinase. Archives of Biochemistry and Biophysics 663:199–213.
   PubMed Web of Science ®Google Scholar
• Swanson, K. V., M. Deng, and J. P. Y. Ting. 2019. The NLRP3 inflammasome: Molecular activation and regulation to therapeutics. Nature Reviews Immunology 19 (8):477–89. doi: 10.1038/s41577-019-0165-0.
   PubMed Web of Science ®Google Scholar
• Takada, I, and M. Makishima. 2020. Peroxisome proliferator-activated receptor agonists and antagonists: A patent review (2014-present). Expert Opinion on Therapeutic Patents 30 (1):1–13. doi: 10.1080/13543776.2020.1703952.
   PubMed Web of Science ®Google Scholar
• Tan, M. J., J. M. Ye, N. Turner, C. Hohnen-Behrens, C. Q. Ke, C. P. Tang, T. Chen, H. C. Weiss, E. R. Gesing, A. Rowland, et al. 2008. Antidiabetic activities of triterpenoids isolated from bitter melon associated with activation of the AMPK pathway. Chemistry & Biology 15 (3):263–73.
   PubMedGoogle Scholar
• Targher, G., K. E. Corey, C. D. Byrne, and M. Roden. 2021. The complex link between NAFLD and type 2 diabetes mellitus—mechanisms and treatments. Nature Reviews Gastroenterology & Hepatology 18 (9):599–612. doi: 10.1038/s41575-021-00448-y.
   PubMed Web of Science ®Google Scholar
• Teng, H., B. Yuan, S. Gothai, P. Arulselvan, X. Song, and L. Chen. 2018. Dietary triterpenes in the treatment of type 2 diabetes: To date. Trends in Food Science & Technology 72 (June 2017):34–44. doi: 10.1016/j.tifs.2017.11.012.
   Google Scholar
• Teoh, S. L, and S. Das. 2018. Phytochemicals and their effective role in the treatment of diabetes mellitus: A short review. Phytochemistry Reviews 17 (5):1111–28. doi: 10.1007/s11101-018-9575-z.
   Web of Science ®Google Scholar
• Thakur, M., M. F. Melzig, H. Fuchs, and A. Weng. 2011. Chemistry and pharmacology of saponins: Special focus on cytotoxic properties. Botanics: Targets and Therapy 1:19–29.
   Google Scholar
• Tharaheswari, M., N. J. Reddy, R. Kumar, K. C. Varshney, M. Kannan, and S. S. Rani. 2014. Trigonelline and diosgenin attenuate ER stress, oxidative stress-mediated damage in pancreas and enhance adipose tissue PPARγ activity in type 2 diabetic rats. Molecular and Cellular Biochemistry 396 (1-2):161–74.
   PubMed Web of Science ®Google Scholar
• Tian, J., J. L. Goldstein, and M. S. Brown. 2016. Insulin induction of SREBP-1c in rodent liver requires LXRα-C/EBPβ complex. Proceedings of the National Academy of Sciences 113 (29):8182–7. doi: 10.1073/pnas.1608987113.
   PubMed Web of Science ®Google Scholar
• Tilg, H., A. R. Moschen, and M. Roden. 2017. NAFLD and diabetes mellitus. Nature Reviews. Gastroenterology & Hepatology 14 (1):32–42. doi: 10.1038/nrgastro.2016.147.
   PubMed Web of Science ®Google Scholar
• Toulis, K. A., K. Nirantharakumar, C. Pourzitaki, A. H. Barnett, and A. A. Tahrani. 2020. Glucokinase activators for type 2 diabetes: Challenges and future developments. Drugs 80 (5):467–75.
   PubMed Web of Science ®Google Scholar
• Tsalamandris, S., A. S. Antonopoulos, E. Oikonomou, G.-A. Papamikroulis, G. Vogiatzi, S. Papaioannou, S. Deftereos, and D. Tousoulis. 2019. The role of inflammation in diabetes: Current concepts and future perspectives. European Cardiology Review 14 (1):50–9. doi: 10.15420/ecr.2018.33.1.
   PubMed Web of Science ®Google Scholar
• Uemura, T., S. Hirai, N. Mizoguchi, T. Goto, J. Y. Lee, K. Taketani, Y. Nakano, J. Shono, S. Hoshino, N. Tsuge, et al. 2010. Diosgenin present in fenugreek improves glucose metabolism by promoting adipocyte differentiation and inhibiting inflammation in adipose tissues. Molecular Nutrition & Food Research 54 (11):1596–608.
   PubMed Web of Science ®Google Scholar
• Uemura, T., T. Goto, M. S. Kang, N. Mizoguchi, S. Hirai, J. Y. Lee, Y. Nakano, J. Shono, S. Hoshino, K. Taketani, et al. 2011. Diosgenin, the main aglycon of fenugreek, inhibits lxrα activity in hepg2 cells and decreases plasma and hepatic triglycerides in obese diabetic mice1-3. The Journal of Nutrition 141 (1):17–23. doi: 10.3945/jn.110.125591.
   PubMed Web of Science ®Google Scholar
• Uruno, A., Y. Yagishita, and M. Yamamoto. 2015. The Keap1–Nrf2 system and diabetes mellitus. Archives of Biochemistry and Biophysics 566:76–84.
   PubMed Web of Science ®Google Scholar
• Vasu, S., K. Kumano, C. M. Darden, I. Rahman, M. C. Lawrence, and B. Naziruddin. 2019. MicroRNA signatures as future biomarkers for diagnosis of diabetes states. Cells 8 (12):1533. doi: 10.3390/cells8121533.
   PubMed Web of Science ®Google Scholar
• Vo, N. N. Q., E. O. Fukushima, and T. Muranaka. 2017. Structure and hemolytic activity relationships of triterpenoid saponins and sapogenins. Journal of Natural Medicines 71 (1):50–8.
   PubMed Web of Science ®Google Scholar
• Wang, P., X. Ding, H. Kim, S. M. Michalek, and P. Zhang. 2020. Structural effect on adjuvanticity of saponins. Journal of Medicinal Chemistry 63 (6):3290–7.
   PubMed Web of Science ®Google Scholar
• Wang, Q., X. Wu, F. Shi, and Y. Liu. 2019. Comparison of antidiabetic effects of saponins and polysaccharides from Momordica charantia L. in STZ-induced type 2 diabetic mice. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie 109 (May):744–50.
   PubMedGoogle Scholar
• Wang, S., L. Ding, H. Ji, Z. Xu, Q. Liu, and Y. Zheng. 2016. The role of p38 MAPK in the development of diabetic cardiomyopathy. International Journal of Molecular Sciences 17 (7):1037. doi: 10.3390/ijms17071037.
   PubMed Web of Science ®Google Scholar
• Wang, X., J. Liu, Z. Long, Q. Sun, Y. Liu, L. Wang, X. Zhang, and C. Hai. 2015. Effect of diosgenin on metabolic dysfunction: Role of ERβ in the regulation of PPARγ. Toxicology and Applied Pharmacology 289 (2):286–96.
   PubMed Web of Science ®Google Scholar
• Wang, Z, and C. Dong. 2019. Gluconeogenesis in cancer: Function and regulation of PEPCK, FBPase, and G6Pase. Trends in Cancer 5 (1):30–45.
   PubMed Web of Science ®Google Scholar
• Weng, Y., L. Yu, J. Cui, Y. R. Zhu, C. Guo, G. Wei, J. L. Duan, Y. Yin, Y. Guan, Y. H. Wang, et al. 2014. Antihyperglycemic, hypolipidemic and antioxidant activities of total saponins extracted from Aralia taibaiensis in experimental type 2 diabetic rats. Journal of Ethnopharmacology 152 (3):553–60. doi: 10.1016/j.jep.2014.02.001.
   PubMed Web of Science ®Google Scholar
• Xi, M., C. Hai, H. Tang, M. Chen, K. Fang, and X. Liang. 2008. Antioxidant and antiglycation properties of total saponins extracted from traditional Chinese medicine used to treat diabetes mellitus. Phytotherapy Research 22 (2):228–37. doi: 10.1002/ptr.2297.
   PubMed Web of Science ®Google Scholar
• Xie, Q., X. Gu, J. Chen, M. Liu, F. Xiong, X. Wu, Y. Zhang, F. Chen, H. Chen, M. Li, et al. 2018. Soyasaponins reduce inflammation and improve serum lipid profiles and glucose homeostasis in high fat diet‐induced obese mice. Molecular Nutrition & Food Research 62 (19):1800205. doi: 10.1002/mnfr.201800205.
   Web of Science ®Google Scholar
• Xu, J., S. Wang, T. Feng, Y. Chen, and G. Yang. 2018. Hypoglycemic and hypolipidemic effects of total saponins from Stauntonia chinensis in diabetic db/db mice. Journal of Cellular and Molecular Medicine 22 (12):6026–38.
   PubMed Web of Science ®Google Scholar
• Xu, L. N., L. H. Yin, Y. Jin, Y. Qi, X. Han, Y. W. Xu, K. X. Liu, Y. Y. Zhao, and J. Y. Peng. 2020. Effect and possible mechanisms of dioscin on ameliorating metabolic glycolipid metabolic disorder in type-2-diabetes. Phytomedicine: International Journal of Phytotherapy and Phytopharmacology 67 (April):153139.
   PubMedGoogle Scholar
• Xu, L., Y. Li, L. Yin, Y. Qi, H. Sun, P. Sun, M. Xu, Z. Tang, and J. Peng. 2018. miR-125a-5p ameliorates hepatic glycolipid metabolism disorder in type 2 diabetes mellitus through targeting of STAT3. Theranostics 8 (20):5593–609.
   PubMed Web of Science ®Google Scholar
• Xu, L., Y. Li, Y. Dai, and J. Peng. 2018. Natural products for the treatment of type 2 diabetes mellitus: Pharmacology and mechanisms. Pharmacological Research 130:451–65.
   PubMed Web of Science ®Google Scholar
• Yang, H, and L. Yang. 2016. Targeting cAMP/PKA pathway for glycemic control and type 2 diabetes therapy. Journal of Molecular Endocrinology 57 (2):R93–R108.
   PubMed Web of Science ®Google Scholar
• Yang, Y., H. Wang, M. Kouadir, H. Song, and F. Shi. 2019. Recent advances in the mechanisms of NLRP3 inflammasome activation and its inhibitors. Cell Death & Disease 10 (2):1–11.
   Web of Science ®Google Scholar
• Yao, H., X. Tao, L. Xu, Y. Qi, L. Yin, X. Han, Y. Xu, L. Zheng, and J. Peng. 2018. Dioscin alleviates non-alcoholic fatty liver disease through adjusting lipid metabolism via SIRT1/AMPK signaling pathway. Pharmacological Research 131 (March):51–60.
   PubMedGoogle Scholar
• Yao, L., J. Wan, H. Li, J. Ding, Y. Wang, X. Wang, and M. Li. 2015. Resveratrol relieves gestational diabetes mellitus in mice through activating AMPK. Reproductive Biology and Endocrinology 13 (1):1–7. doi: 10.1186/s12958-015-0114-0.
   PubMedGoogle Scholar
• Yaribeygi, H., F. R. Farrokhi, A. E. Butler, and A. Sahebkar. 2019. Insulin resistance: Review of the underlying molecular mechanisms. Journal of Cellular Physiology 234 (6):8152–61.
   PubMed Web of Science ®Google Scholar
• Yu, F., L. Bing, Y. Xie, and W. Yu. 2018. Dioscin promotes proliferation of pancreatic beta cells via Wnt/β-catenin signaling pathways. Clinical Laboratory 64 (05/2018):785–91. doi: 10.7754/Clin.Lab.2018.171136.
   PubMedGoogle Scholar
• Yu, H., L. Zheng, L. Xu, L. Yin, Y. Lin, H. Li, K. Liu, and J. Peng. 2015. Potent effects of the total saponins from Dioscorea nipponica Makino against streptozotocin-induced type 2 diabetes mellitus in rats. Phytotherapy Research: PTR 29 (2):228–40.
   PubMed Web of Science ®Google Scholar
• Yue, J., J. Xu, J. Cao, X. Zhang, and Y. Zhao. 2017. Cucurbitane triterpenoids from Momordica charantia L. and their inhibitory activity against α-glucosidase, α-amylase and protein tyrosine phosphatase 1B (PTP1B). Journal of Functional Foods 37:624–31. doi: 10.1016/j.jff.2017.07.041.
   Web of Science ®Google Scholar
• Zaccardi, F., D. R. Webb, T. Yates, and M. J. Davies. 2016. Pathophysiology of type 1 and type 2 diabetes mellitus: A 90-year perspective. Postgraduate Medical Journal 92 (1084):63–9.
   PubMed Web of Science ®Google Scholar
• Zeeshan, H. M. A., G. H. Lee, H. R. Kim, and H. J. Chae. 2016. Endoplasmic reticulum stress and associated ROS. International Journal of Molecular Sciences 17 (3):327.
   PubMed Web of Science ®Google Scholar
• Zha, L., J. Chen, S. Sun, L. Mao, X. Chu, H. Deng, J. Cai, X. Li, Z. Liu, and W. Cao. 2014. Soyasaponins can blunt inflammation by inhibiting the reactive oxygen species-mediated activation of PI3K/Akt/NF-kB pathway. PLoS One 9 (9):e107655–9. doi: 10.1371/journal.pone.0107655.
   PubMed Web of Science ®Google Scholar
• Zhang, H., J. Xu, M. Wang, X. Xia, R. Dai, and Y. Zhao. 2020. Steroidal saponins and sapogenins from fenugreek and their inhibitory activity against α-glucosidase. Steroids 161 (June):108690.
   PubMedGoogle Scholar
• Zheng, Y., J. Tian, W. Yang, S. Chen, D. Liu, H. Fang, H. Zhang, and X. Ye. 2020. Inhibition mechanism of ferulic acid against α-amylase and α-glucosidase. Food Chemistry 317:126346.
   PubMed Web of Science ®Google Scholar
• Zhou, P., W. Xie, S. He, Y. Sun, X. Meng, G. Sun, and X. Sun. 2019. Ginsenoside Rb1 as an Anti-Diabetic Agent and Its Underlying Mechanism Analysis. Cells 8 (3):204. doi: 10.3390/cells8030204.
   PubMed Web of Science ®Google Scholar
• Zhou, X., W. Zhang, X. Liu, W. Zhang, and Y. Li. 2015. Interrelationship between diabetes and periodontitis: Role of hyperlipidemia. Archives of Oral Biology 60 (4):667–74.
   PubMed Web of Science ®Google Scholar
• Zhou, Y., H. R. El-Seedi, and B. Xu. 2021. Insights into health promoting effects and myochemical profiles of pine mushroom Tricholoma matsutake. Critical Reviews in Food Science and Nutrition 2021:1–26.
   Google Scholar
• Zhu, Y.-X., H.-Q. Hu, M.-L. Zuo, L. Mao, G.-L. Song, T.-M. Li, L.-C. Dong, Z.-B. Yang, and M. S. Ali Sheikh. 2021. Effect of oxymatrine on liver gluconeogenesis is associated with the regulation of PEPCK and G6Pase expression and AKT phosphorylation. Biomedical Reports 15 (1):1–10. doi: 10.3892/br.2021.1432.
   Web of Science ®Google Scholar