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Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry

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ISSN (Print): 1871-5230
ISSN (Online): 1875-614X

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Review Article

Diosgenin: Mechanistic Insights on its Anti-inflammatory Effects

Author(s): Somayyeh Karami-Mohajeri, Reza Mohammadinejad, Milad Ashrafizadeh, Neda Mohamadi, Mohammad Mohajeri and Fariba Sharififar*

Volume 21, Issue 1, 2022

Published on: 27 April, 2022

Page: [2 - 9] Pages: 8

DOI: 10.2174/1871523021666220328121721

Price: $65

Abstract

Diosgenin (DG), a well-known steroid saponin, has shown anti-inflammatory effects. This review was aimed to discuss all published literature concerning the anti-inflammatory effects of diosgenin. Based on the modulatory impact of DG on the NF-κB pathway, its supplementation is associated with downregulation of the NF-κB pathway and TGF-β, resulting in inhibition of inflammation. It appears that upstream modulators of NF-κB signaling pathways such as Tlrs and downstream mediators include iNOS and COX-2, leading to the inhibition of the inflammatory response and development of pathological conditions. Due to the low toxicity of the herbal compounds, the risk of the side effects of DG use for the management of inflammatory disorders such as asthma, rheumatism, rhinitis, and arthritis is lower than that of synthetic glucocorticoids. It has been shown that regulation of NF-κB and oxidative stress signaling pathways by DG is beneficial against cardiotoxicity induced by chemotherapeutic agents such as doxorubicin.

Keywords: Phytosterol, diosgenin, inflammation, oxidative stress, NF-κB, cyclooxygenase.

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[1]
Ashley, N.T.; Weil, Z.M.; Nelson, R. J. Inflammation: Mechanisms, costs, and natural variation. Annu. Rev. Ecol. Evol. Syst., 2012, 43(1), 385-406.
[http://dx.doi.org/10.1146/annurev-ecolsys-040212-092530]
[2]
Straub, R.H.; Schradin, C. Chronic inflammatory systemic diseases: An evolutionary trade-off between acutely beneficial but chronically harmful programs. Evol. Med. Public Health, 2016, 2016(1), 37-51.
[http://dx.doi.org/10.1093/emph/eow001] [PMID: 26817483]
[3]
Maroon, J.C.; Bost, J.W.; Maroon, A. Natural anti-inflammatory agents for pain relief. Surg. Neurol. Int., 2010, 1, 80.
[http://dx.doi.org/10.4103/2152-7806.73804] [PMID: 21206541]
[4]
Güçlü-Ustündağ, O.; Mazza, G. Saponins: properties, applications and processing. Crit. Rev. Food Sci. Nutr., 2007, 47(3), 231-258.
[http://dx.doi.org/10.1080/10408390600698197] [PMID: 17453922]
[5]
Foresta, P.; Ghirardi, O.; Gabetta, B.; Cristoni, A. Triterpene saponins having anti-inflammatory, mucolytic and antiedemic activities, process for the preparation thereof and pharmaceutical compositions containing them. EP0251197A3, 1987.
[6]
Aburdeineh, S.G.; Aburdeineh, H.G. inventors. Fenugreek seed extract to lower blood cholesterol. US Patent 8337915, 2005.
[7]
Ayadev, R.; Chinthalapally, V.R. Diosgenin, a steroid saponin constituent of yams and fenugreek: Emerging evidence for applications in medicine. Bioact. Comp. Phytomed., 2012, 125, 143.
[8]
Mohamadi, N.; Pournamdari, M.; Sharififar, F.; Ansari, M. Simultaneous spectrophotometric determination of trigonelline, diosgenin and nicotinic acid in dosage forms prepared from fenugreek seed extract. Iran. J. Pharm. Res., 2020, 19(2), 153.
[9]
Mohamadi, N.; Sharififar, F.; Pournamdari, M.; Ansari, M. A review on biosynthesis, analytical techniques, and pharmacological activities of Trigonelline as a plant alkaloid. J. Diet. Suppl., 2018, 15(2), 207-222.
[http://dx.doi.org/10.1080/19390211.2017.1329244] [PMID: 28816550]
[10]
Sharififar, F.; Khazaeli, P.; Alli, N. In vivo evaluation of anti-inflammatory activity of topical preparations from Fenugreek (Trigonella foenum-graecum L.) seeds in a cream base. Indian J. Pharm. Sci., 2009, 5(3), 157-162.
[11]
Pournamdari, M.; Mandegary, A.; Sharififar, F.; Zarei, G.; Zareshahi, R.; Asadi, A.; Mehdipour, M. Anti-inflammatory subfractions sepa-rated from acidified chloroform fraction of fenugreek seeds (Trigonella foenum-graecum L.). J. Diet. Suppl., 2018, 15(1), 98-107.
[http://dx.doi.org/10.1080/19390211.2017.1326431] [PMID: 28558255]
[12]
Prioult, G.; Nagler-Anderson, C. Mucosal immunity and allergic responses: Lack of regulation and/or lack of microbial stimulation? Immunol. Rev., 2005, 206(1), 204-218.
[http://dx.doi.org/10.1111/j.0105-2896.2005.00277.x] [PMID: 16048551]
[13]
van Driel, I.R.; Ang, D.K. Role of regulatory T cells in gastrointestinal inflammatory disease. J. Gastroenterol. Hepatol., 2008, 23(2), 171-177.
[http://dx.doi.org/10.1111/j.1440-1746.2007.05278.x] [PMID: 18289352]
[14]
Zhang, L.L.; Chen, X.; Zheng, P.Y.; Luo, Y.; Lu, G.F.; Liu, Z.Q.; Huang, H.; Yang, P.C. Oral Bifidobacterium modulates intestinal immune inflammation in mice with food allergy. J. Gastroenterol. Hepatol., 2010, 25(5), 928-934.
[http://dx.doi.org/10.1111/j.1440-1746.2009.06193.x] [PMID: 20546446]
[15]
Venigalla, R.K.C.; Guttikonda, P.J.; Eckstein, V.; Ho, A.D.; Sertel, S.; Lorenz, H-M.; Tretter, T. Identification of a human Th1-like IFNγ-secreting Treg subtype deriving from effector T cells. J. Autoimmun., 2012, 39(4), 377-387.
[http://dx.doi.org/10.1016/j.jaut.2012.06.004] [PMID: 22824211]
[16]
Verma, N.D.; Hall, B.M.; Plain, K.M.; Robinson, C.M.; Boyd, R.; Tran, G.T.; Wang, C.; Bishop, G.A.; Hodgkinson, S.J. Interleukin-12 (IL-12p70) promotes induction of highly potent Th1-like CD4+ CD25+ T regulatory cells that inhibit allograft rejection in unmodified recipi-ents. Front. Immunol., 2014, 5, 190.
[http://dx.doi.org/10.3389/fimmu.2014.00190] [PMID: 24847323]
[17]
Liu, W.; Zhu, M.; Yu, Z.; Yin, D.; Lu, F.; Pu, Y.; Zhao, C.; He, C.; Cao, L. Therapeutic effects of diosgenin in experimental autoimmune encephalomyelitis. J. Neuroimmunol., 2017, 313, 152-160.
[http://dx.doi.org/10.1016/j.jneuroim.2017.10.018] [PMID: 29132838]
[18]
Miyoshi, N.; Nagasawa, T.; Mabuchi, R.; Yasui, Y.; Wakabayashi, K.; Tanaka, T.; Ohshima, H. Chemoprevention of azoxyme-thane/dextran sodium sulfate-induced mouse colon carcinogenesis by freeze-dried yam sanyaku and its constituent diosgenin. Cancer Prev. Res. (Phila.), 2011, 4(6), 924-934.
[http://dx.doi.org/10.1158/1940-6207.CAPR-10-0279] [PMID: 21367960]
[19]
Huang, C-H.; Wang, C-C.; Lin, Y-C.; Hori, M.; Jan, T-R. Oral administration with diosgenin enhances the induction of intestinal T helper 1-like regulatory T cells in a murine model of food allergy. Int. Immunopharmacol., 2017, 42, 59-66.
[http://dx.doi.org/10.1016/j.intimp.2016.11.021] [PMID: 27886644]
[20]
Huang, C-H.; Liu, D-Z.; Jan, T-R. Diosgenin, a plant-derived sapogenin, enhances regulatory T-cell immunity in the intestine of mice with food allergy. J. Nat. Prod., 2010, 73(6), 1033-1037.
[http://dx.doi.org/10.1021/np900690z] [PMID: 20465230]
[21]
Choi, K.W.; Park, H.J.; Jung, D.H.; Kim, T.W.; Park, Y.M.; Kim, B.O.; Sohn, E.H.; Moon, E.Y.; Um, S.H.; Rhee, D.K.; Pyo, S. Inhibition of TNF-α-induced adhesion molecule expression by diosgenin in mouse vascular smooth muscle cells via downregulation of the MAPK, Akt and NF-κB signaling pathways. Vascul. Pharmacol., 2010, 53(5-6), 273-280.
[http://dx.doi.org/10.1016/j.vph.2010.09.007] [PMID: 20932938]
[22]
Wu, S.; Xu, H.; Peng, J.; Wang, C.; Jin, Y.; Liu, K.; Sun, H.; Qin, J. Potent anti-inflammatory effect of dioscin mediated by suppression of TNF-α-induced VCAM-1, ICAM-1and EL expression via the NF-κB pathway. Biochimie, 2015, 110, 62-72.
[http://dx.doi.org/10.1016/j.biochi.2014.12.022] [PMID: 25577996]
[23]
Yang, R.; Chen, W.; Lu, Y.; Li, Y.; Du, H.; Gao, S. Dioscin relieves endotoxemia induced acute neuro-inflammation and protect neurogen-esis via improving 5-HT metabolism. J. Sci. Rep., 2017, 7(1), 1-13.
[http://dx.doi.org/10.1038/srep40035] [PMID: 28127051]
[24]
Ebrahimi, H.; Badalzadeh, R.; Mohammadi, M.; Yousefi, B. Diosgenin attenuates inflammatory response induced by myocardial reperfu-sion injury: Role of mitochondrial ATP-sensitive potassium channels. J. Physiol. Biochem., 2014, 70(2), 425-432.
[http://dx.doi.org/10.1007/s13105-014-0320-9] [PMID: 24535716]
[25]
Wang, H.W.; Liu, H.J.; Cao, H.; Qiao, Z.Y.; Xu, Y.W. Diosgenin protects rats from myocardial inflammatory injury induced by ischemia-reperfusion. Med. Sci. Monit., 2018, 24, 246-253.
[http://dx.doi.org/10.12659/MSM.907745] [PMID: 29329279]
[26]
Zhang, X.; Xue, X.; Xian, L.; Guo, Z.; Ito, Y.; Sun, W. Potential neuroprotection of protodioscin against cerebral ischemia-reperfusion injury in rats through intervening inflammation and apoptosis. Steroids, 2016, 113, 52-63.
[http://dx.doi.org/10.1016/j.steroids.2016.06.008] [PMID: 27343977]
[27]
Junchao, Y.; Zhen, W.; Yuan, W.; Liying, X.; Libin, J.; Yuanhong, Z.; Wei, Z.; Ruilin, C.; Lu, Z. Anti- trachea inflammatory effects of diosgenin from Dioscorea nipponica through interactions with glucocorticoid receptor α. J. Int. Med. Res., 2017, 45(1), 101-113.
[http://dx.doi.org/10.1177/0300060516676724] [PMID: 27913746]
[28]
Kiasalari, Z.; Rahmani, T.; Mahmoudi, N.; Baluchnejadmojarad, T.; Roghani, M. Diosgenin ameliorates development of neuropathic pain in diabetic rats: Involvement of oxidative stress and inflammation. Biomed. Pharmacother., 2017, 86, 654-661.
[http://dx.doi.org/10.1016/j.biopha.2016.12.068] [PMID: 28033582]
[29]
Khosravi, Z.; Sedaghat, R.; Baluchnejadmojarad, T.; Roghani, M. Diosgenin ameliorates testicular damage in streptozotocin-diabetic rats through attenuation of apoptosis, oxidative stress, and inflammation. Int. Immunopharmacol., 2019, 70, 37-46.
[http://dx.doi.org/10.1016/j.intimp.2019.01.047] [PMID: 30785089]
[30]
Chen, Y.; Gao, F.; Jiang, R.; Liu, H.; Hou, J.; Yi, Y.; Kang, L.; Liu, X.; Li, Y.; Yang, M. Down-regulation of AQP4 expression via p38 MAPK signaling in temozolomide-induced glioma cells growth inhibition and invasion impairment. J. Cell. Biochem., 2017, 118(12), 4905-4913.
[http://dx.doi.org/10.1002/jcb.26176] [PMID: 28569417]
[31]
Kim, J.E.; Go, J.; Koh, E.K.; Song, S.H.; Sung, J.E.; Lee, H.A.; Kim, D.S.; Son, H.J.; Lee, H.S.; Lee, C.Y.; Hong, J.T.; Hwang, D.Y. Dios-genin effectively suppresses skin inflammation induced by phthalic anhydride in IL-4/Luc/CNS-1 transgenic mice. Biosci. Biotechnol. Biochem., 2016, 80(5), 891-901.
[http://dx.doi.org/10.1080/09168451.2015.1135040] [PMID: 26998565]
[32]
Wang, S.; Wang, F.; Yang, H.; Li, R.; Guo, H.; Hu, L. Diosgenin glucoside provides neuroprotection by regulating microglial M1 polariza-tion. Int. Immunopharmacol., 2017, 50, 22-29.
[http://dx.doi.org/10.1016/j.intimp.2017.06.008] [PMID: 28623715]
[33]
Liu, K.; Zhao, W.; Gao, X.; Huang, F.; Kou, J.; Liu, B. Diosgenin ameliorates palmitate-induced endothelial dysfunction and insulin re-sistance via blocking IKKβ and IRS-1 pathways. Atherosclerosis, 2012, 223(2), 350-358.
[http://dx.doi.org/10.1016/j.atherosclerosis.2012.06.012] [PMID: 22766331]
[34]
Ku, C.M.; Lin, J.Y. Anti-inflammatory effects of 27 selected terpenoid compounds tested through modulating Th1/Th2 cytokine secretion profiles using murine primary splenocytes. Food Chem., 2013, 141(2), 1104-1113.
[http://dx.doi.org/10.1016/j.foodchem.2013.04.044] [PMID: 23790892]
[35]
Huang, C.H.; Ku, C.Y.; Jan, T.R. Diosgenin attenuates allergen-induced intestinal inflammation and IgE production in a murine model of food allergy. Planta Med., 2009, 75(12), 1300-1305.
[http://dx.doi.org/10.1055/s-0029-1185578] [PMID: 19343624]
[36]
Moalic, S.; Liagre, B.; Corbière, C.; Bianchi, A.; Dauça, M.; Bordji, K.; Beneytout, J.L. A plant steroid, diosgenin, induces apoptosis, cell cycle arrest and COX activity in osteosarcoma cells. FEBS Lett., 2001, 506(3), 225-230.
[http://dx.doi.org/10.1016/S0014-5793(01)02924-6] [PMID: 11602250]
[37]
Wang, L.; Ma, T.; Zheng, Y.; Lv, S.; Li, Y.; Liu, S. Diosgenin inhibits IL-1β-induced expression of inflammatory mediators in human osteoarthritis chondrocytes. Int. J. Clin. Exp. Pathol., 2015, 8(5), 4830-4836.
[PMID: 26191174]
[38]
Tao, X.; Wan, X.; Xu, Y.; Xu, L.; Qi, Y.; Yin, L.; Han, X.; Lin, Y.; Peng, J. Dioscin attenuates hepatic ischemia-reperfusion injury in rats through inhibition of oxidative-nitrative stress, inflammation and apoptosis. Transplantation, 2014, 98(6), 604-611.
[http://dx.doi.org/10.1097/TP.0000000000000262] [PMID: 25083618]
[39]
Shishodia, S.; Aggarwal, B.B. Diosgenin inhibits osteoclastogenesis, invasion, and proliferation through the downregulation of Akt, I kap-pa B kinase activation and NF-kappa B-regulated gene expression. Oncogene, 2006, 25(10), 1463-1473.
[http://dx.doi.org/10.1038/sj.onc.1209194] [PMID: 16331273]
[40]
Hirai, S.; Uemura, T.; Mizoguchi, N.; Lee, J.Y.; Taketani, K.; Nakano, Y.; Hoshino, S.; Tsuge, N.; Narukami, T.; Yu, R.; Takahashi, N.; Kawada, T. Diosgenin attenuates inflammatory changes in the interaction between adipocytes and macrophages. Mol. Nutr. Food Res., 2010, 54(6), 797-804.
[http://dx.doi.org/10.1002/mnfr.200900208] [PMID: 19998383]
[41]
Binesh, A.; Devaraj, S.N.; Halagowder, D. Atherogenic diet induced lipid accumulation induced NFkappaB level in heart, liver and brain of Wistar rat and diosgenin as an anti-inflammatory agent. Life sciences, 2018, 196, 28-37.
[42]
Cai, B.; Seong, K.J.; Bae, S.W.; Chun, C.; Kim, W.J.; Jung, J.Y. A synthetic diosgenin primary amine derivative attenuates LPS-stimulated inflammation via inhibition of NF-κB and JNK MAPK signaling in microglial BV2 cells. Int. Immunopharmacol., 2018, 61, 204-214.
[http://dx.doi.org/10.1016/j.intimp.2018.05.021] [PMID: 29890414]
[43]
Zheng, L.; Yin, L.; Xu, L.; Qi, Y.; Li, H.; Xu, Y.; Han, X.; Liu, K.; Peng, J. Protective effect of dioscin against thioacetamide-induced acute liver injury via FXR/AMPK signaling pathway in vivo. Biomed. Pharmacother., 2018, 97, 481-488.
[http://dx.doi.org/10.1016/j.biopha.2017.10.153] [PMID: 29091898]
[44]
Lin, Y.; Jia, R.; Liu, Y.; Gao, Y.; Zeng, X.; Kou, J.; Yu, B. Diosgenin inhibits superoxide generation in FMLP-activated mouse neutrophils via multiple pathways. Free Radic. Res., 2014, 48(12), 1485-1493.
[http://dx.doi.org/10.3109/10715762.2014.966705] [PMID: 25246240]
[45]
Yang, B.; Xu, B.; Zhao, H.; Wang, Y.B.; Zhang, J.; Li, C.W.; Wu, Q.; Cao, Y.K.; Li, Y.; Cao, F. Dioscin protects against coronary heart disease by reducing oxidative stress and inflammation via Sirt1/Nrf2 and p38 MAPK pathways. Mol. Med. Rep., 2018, 18(1), 973-980.
[http://dx.doi.org/10.3892/mmr.2018.9024] [PMID: 29845299]
[46]
Jung, D-H.; Park, H-J.; Byun, H-E.; Park, Y-M.; Kim, T-W.; Kim, B-O.; Um, S.H.; Pyo, S. Diosgenin inhibits macrophage-derived inflam-matory mediators through downregulation of CK2, JNK, NF-kappaB and AP-1 activation. Int. Immunopharmacol., 2010, 10(9), 1047-1054.
[http://dx.doi.org/10.1016/j.intimp.2010.06.004] [PMID: 20601188]
[47]
Li, C.; Lu, Y.; Du, S.; Li, S.; Zhang, Y.; Liu, F.; Chen, Y.; Weng, D.; Chen, J. Dioscin exerts protective effects against crystalline silica-induced pulmonary fibrosis in mice. Theranostics, 2017, 7(17), 4255-4275.
[http://dx.doi.org/10.7150/thno.20270] [PMID: 29158824]
[48]
Zhu, S.; Tang, S.; Su, F. Dioscin inhibits ischemic stroke induced inflammation through inhibition of the TLR4/MyD88/NF κB signaling pathway in a rat model. Mol. Med. Rep., 2018, 17(1), 660-666.
[PMID: 29115455]
[49]
Wu, Y.; Ye, F.; Lu, Y.; Yong, H.; Yin, R.; Chen, B.; Yong, Y. Diosgenin glucoside protects against myocardial injury in diabetic mice by inhibiting RIP140 signaling. Am. J. Transl. Res., 2018, 10(11), 3742-3749.
[PMID: 30662624]
[50]
Chen, Y.; Xu, X.; Zhang, Y. Diosgenin regulates adipokine expression in perivascular adipose tissue and ameliorates endothelial dysfunction via regulation of AMPK. J. Steroid. Biochem. Mol. Biol., 2016, 155(Pt A), 155-165.
[http://dx.doi.org/10.1016/j.jsbmb.2015.07.005]
[51]
Kornblit, B.; Munthe-Fog, L.; Madsen, H.O.; Strøm, J.; Vindeløv, L.; Garred, P. Association of HMGB1 polymorphisms with outcome in patients with systemic inflammatory response syndrome. Crit. Care, 2008, 12(3), R83.
[http://dx.doi.org/10.1186/cc6935] [PMID: 18577209]
[52]
Lei, C.; Jiao, Y.; He, B.; Wang, G.; Wang, Q.; Wang, J. RIP140 down-regulation alleviates acute lung injury via the inhibition of LPS-induced PPARγ promoter methylation. Pulm. Pharmacol. Ther., 2016, 37, 57-64.
[http://dx.doi.org/10.1016/j.pupt.2016.02.001] [PMID: 26921464]
[53]
Lee, J.; Jung, K.; Kim, Y.S.; Park, D. Diosgenin inhibits melanogenesis through the activation of phosphatidylinositol-3-kinase pathway (PI3K) signaling. Life Sciences, 2007, 81(3), 249-254.
[54]
Mortezaee, K.; Salehi, E.; Mirtavoos-Mahyari, H.; Motevaseli, E.; Najafi, M.; Farhood, B.; Rosengren, R.J.; Sahebkar, A. Mechanisms of apoptosis modulation by curcumin: Implications for cancer therapy. J. Cell. Physiol., 2019, 234(8), 12537-12550.
[http://dx.doi.org/10.1002/jcp.28122] [PMID: 30623450]
[55]
Mortezaee, K.; Najafi, M.; Farhood, B. Modulation of apoptosis by melatonin for improving cancer treatment efficiency: An updated re-view. Life Sci., 2019, 228, 228-241.
[56]
Fardid, R.; Salajegheh, A.; Mosleh-Shirazi, M.A.; Sharifzadeh, S.; Okhovat, M.A.; Najafi, M.; Rezaeyan, A.; Abaszadeh, A. Melatonin ameliorates the production of COX-2, iNOS, and the formation of 8-OHdG in non-targeted lung tissue after pelvic irradiation. Cell J., 2017, 19(2), 324-331.
[PMID: 28670525]
[57]
Selim, S.; Al Jaouni, S. Anti-inflammatory, antioxidant and antiangiogenic activities of diosgenin isolated from traditional medicinal plant, Costus speciosus (Koen ex.Retz.). Sm. Nat. Prod. Res., 2016, 30(16), 1830-1833.
[http://dx.doi.org/10.1080/14786419.2015.1065493] [PMID: 26222585]
[58]
Wang, X.; Campos, C.R.; Peart, J.C.; Smith, L.K.; Boni, J.L.; Cannon, R.E.; Miller, D.S. Nrf2 upregulates ATP binding cassette transporter expression and activity at the blood-brain and blood-spinal cord barriers. J. Neurosci., 2014, 34(25), 8585-8593.
[http://dx.doi.org/10.1523/JNEUROSCI.2935-13.2014] [PMID: 24948812]
[59]
Zhang, W.; Yin, L.; Tao, X.; Xu, L.; Zheng, L.; Han, X.; Xu, Y.; Wang, C.; Peng, J. Dioscin alleviates dimethylnitrosamine-induced acute liver injury through regulating apoptosis, oxidative stress and inflammation. Environ. Toxicol. Pharmacol., 2016, 45, 193-201.
[http://dx.doi.org/10.1016/j.etap.2016.06.002] [PMID: 27317992]
[60]
Qiao, Y.; Xu, L.; Tao, X.; Yin, L.; Qi, Y.; Xu, Y.; Han, X.; Tang, Z.; Ma, X.; Liu, K.; Peng, J. Protective effects of dioscin against fructose-induced renal damage via adjusting Sirt3-mediated oxidative stress, fibrosis, lipid metabolism and inflammation. Toxicol. Lett., 2018, 284, 37-45.
[http://dx.doi.org/10.1016/j.toxlet.2017.11.031] [PMID: 29197622]
[61]
Kanchan, D.M.; Somani, G.S.; Peshattiwar, V.V.; Kaikini, A.A.; Sathaye, S. Renoprotective effect of diosgenin in streptozotocin induced diabetic rats. Pharmacol. Rep., 2016, 68(2), 370-377.
[http://dx.doi.org/10.1016/j.pharep.2015.10.011] [PMID: 26922541]
[62]
Jagtap, A.G.; Shirke, S.S.; Phadke, A.S. Effect of polyherbal formulation on experimental models of inflammatory bowel diseases. J. Ethnopharmacol., 2004, 90(2-3), 195-204.
[http://dx.doi.org/10.1016/j.jep.2003.09.042] [PMID: 15013181]
[63]
Farkhondeh, T.; Samarghandian, S.; Roshanravan, B. Impact of chrysin on the molecular mechanisms underlying diabetic complications. J. Cell. Physiol., 2019, 234(10), 17144-17158.
[http://dx.doi.org/10.1002/jcp.28488] [PMID: 30916403]
[64]
Zeferino-Díaz, R.; Olivera-Castillo, L.; Dávalos, A.; Grant, G.; Kantún-Moreno, N.; Rodriguez-Canul, R.; Bernès, S.; Sandoval-Ramírez, J.; Fernández-Herrera, M.A. 22-Oxocholestane oximes as potential anti-inflammatory drug candidates. Eur. J. Med. Chem., 2019, 168, 78-86.
[http://dx.doi.org/10.1016/j.ejmech.2019.02.035] [PMID: 30798054]
[65]
Baba, H.; Kohno, T.; Moore, K.A.; Woolf, C.J. Direct activation of rat spinal dorsal horn neurons by prostaglandin E2. J. Neurosci., 2001, 21(5), 1750-1756.
[http://dx.doi.org/10.1523/JNEUROSCI.21-05-01750.2001] [PMID: 11222664]
[66]
Alba, E.; Llombart, A.; Ribelles, N.; Ramos, M.; Fernández, R.; Mayordomo, J.I.; Tusquets, I.; Gil, M.; Barnadas, A.; Carabante, F.; Ruiz, M.; Vera, R.; Palomero, I.; Soriano, V.; González, J.; Colomer, R. Serum endostatin and bFGF as predictive factors in advanced breast cancer patients treated with letrozole. Clin. Transl. Oncol., 2006, 8(3), 193-199.
[http://dx.doi.org/10.1007/s12094-006-0010-3] [PMID: 16648119]
[67]
Lee, B-K.; Kim, C-J.; Shin, M-S.; Cho, Y.S. Diosgenin improves functional recovery from sciatic crushed nerve injury in rats. J. Exerc. Rehabil., 2018, 14(4), 566-572.
[http://dx.doi.org/10.12965/jer.1836340.170] [PMID: 30276175]
[68]
Ahmed, L.A.; Obaid, A.A.; Zaki, H.F.; Agha, A.M. Role of oxidative stress, inflammation, nitric oxide and transforming growth factor-beta in the protective effect of diosgenin in monocrotaline-induced pulmonary hypertension in rats. Eur. J. Pharmacol., 2014, 740, 379-387.
[http://dx.doi.org/10.1016/j.ejphar.2014.07.026] [PMID: 25062790]
[69]
Fung, E.; Tang, S.M.; Canner, J.P.; Morishige, K.; Arboleda-Velasquez, J.F.; Cardoso, A.A.; Carlesso, N.; Aster, J.C.; Aikawa, M. Delta-like 4 induces notch signaling in macrophages: Implications for inflammation. Circulation, 2007, 115(23), 2948-2956.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.106.675462] [PMID: 17533181]
[70]
Nakano, T.; Fukuda, D.; Koga, J.; Aikawa, M. Delta-like ligand 4-Notch signaling in macrophage activation. Arterioscler. Thromb. Vasc. Biol., 2016, 36(10), 2038-2047.
[http://dx.doi.org/10.1161/ATVBAHA.116.306926] [PMID: 27562914]
[71]
Geling, A.; Steiner, H.; Willem, M.; Bally-Cuif, L.; Haass, C. A gamma-secretase inhibitor blocks Notch signaling in vivo and causes a severe neurogenic phenotype in Zebrafish. EMBO Rep., 2002, 3(7), 688-694.
[http://dx.doi.org/10.1093/embo-reports/kvf124] [PMID: 12101103]
[72]
Andersson, E.R.; Sandberg, R.; Lendahl, U. Notch signaling: Simplicity in design, versatility in function. Development, 2011, 138(17), 3593-3612.
[http://dx.doi.org/10.1242/dev.063610] [PMID: 21828089]
[73]
Binesh, A.; Devaraj, S.N.; Devaraj, H. Inhibition of nuclear translocation of notch intracellular domain (NICD) by diosgenin prevented atherosclerotic disease progression. Biochimie, 2018, 148, 63-71.
[http://dx.doi.org/10.1016/j.biochi.2018.02.011] [PMID: 29481959]
[74]
Xiao, L.; Guo, D.; Hu, C.; Shen, W.; Shan, L.; Li, C.; Liu, X.; Yang, W.; Zhang, W.; He, C. Diosgenin promotes oligodendrocyte progenitor cell differentiation through estrogen receptor-mediated ERK1/2 activation to accelerate remyelination. J. Glia, 2012, 60(7), 1037-1052.
[http://dx.doi.org/10.1002/glia.22333] [PMID: 22461009]
[75]
Chen, Y.; Tang, Y.M.; Yu, S.L.; Han, Y.W.; Kou, J.P.; Liu, B.L.; Yu, B.Y. Advances in the pharmacological activities and mechanisms of diosgenin. Chin. J. Nat. Med., 2015, 13(8), 578-587.
[http://dx.doi.org/10.1016/S1875-5364(15)30053-4] [PMID: 26253490]
[76]
Cai, B.; Seong, K-J.; Bae, S-W.; Kook, M.S.; Chun, C.; Lee, J.H. Water-soluble arginyl–diosgenin analog attenuates hippocampal neurogen-esis impairment through blocking microglial activation underlying NF-κB and JNK MAPK signaling in adult mice challenged by LPS. Mol. Neurobiol., 2019, 56(9), 6218-6238.
[http://dx.doi.org/10.1007/s12035-019-1496-3]
[77]
Gao, M.; Chen, L.; Yu, H.; Sun, Q.; Kou, J.; Yu, B. Diosgenin down-regulates NF-κB p65/p50 and p38MAPK pathways and attenuates acute lung injury induced by lipopolysaccharide in mice. Int. Immunopharmacol., 2013, 15(2), 240-245.
[http://dx.doi.org/10.1016/j.intimp.2012.11.019] [PMID: 23246979]
[78]
Zhao, W.X.; Wang, P.F.; Song, H.G.; Sun, N. Diosgenin attenuates neuropathic pain in a rat model of chronic constriction injury. Mol. Med. Rep., 2017, 16(2), 1559-1564.
[http://dx.doi.org/10.3892/mmr.2017.6723] [PMID: 29067449]
[79]
Kumar, D.; Kirshenbaum, L.A.; Li, T.; Danelisen, I.; Singal, P.K. Apoptosis in adriamycin cardiomyopathy and its modulation by probucol. Antioxid. Redox Signal., 2001, 3(1), 135-145.
[http://dx.doi.org/10.1089/152308601750100641] [PMID: 11291592]
[80]
Hadi, N.; Yousif, N.G.; Al-amran, F.G.; Huntei, N.K.; Mohammad, B.I.; Ali, S.J. Vitamin E and telmisartan attenuates doxorubicin induced cardiac injury in rat through down regulation of inflammatory response. BMC Cardiovasc. Disord., 2012, 12(1), 63.
[http://dx.doi.org/10.1186/1471-2261-12-63] [PMID: 22867422]
[81]
Lin, M.C.; Yin, M.C. Preventive effects of ellagic acid against doxorubicin-induced cardio-toxicity in mice. Cardiovasc. Toxicol., 2013, 13(3), 185-193.
[http://dx.doi.org/10.1007/s12012-013-9197-z] [PMID: 23322372]
[82]
Zhang, X.; Xue, X.; Zhao, J.; Qian, C.; Guo, Z.; Ito, Y.; Sun, W. Diosgenin attenuates the brain injury induced by transient focal cerebral ischemia-reperfusion in rats. Steroids, 2016, 113, 103-112.
[http://dx.doi.org/10.1016/j.steroids.2016.07.006] [PMID: 27425638]
[83]
Yang, H.P.; Yue, L.; Jiang, W.W.; Liu, Q.; Kou, J.P.; Yu, B.Y. Diosgenin inhibits tumor necrosis factor-induced tissue factor activity and expression in THP-1 cells via down-regulation of the NF-κB, Akt, and MAPK signaling pathways. Chin. J. Nat. Med., 2013, 11(6), 608-615.
[http://dx.doi.org/10.1016/S1875-5364(13)60070-9] [PMID: 24345501]
[84]
Li, B.; Xu, P.; Wu, S.; Jiang, Z.; Huang, Z.; Li, Q.; Chen, D. Diosgenin attenuates lipopolysaccharide-induced Parkinson’s disease by in-hibiting the TLR/NF-κB pathway. J. Alzheimers Dis., 2018, 64(3), 943-955.
[http://dx.doi.org/10.3233/JAD-180330] [PMID: 29966203]
[85]
Mohamadi, N.; Sharififar, F.; Ansari, M.; Pournamdari, M.; Rezaei, M.; Hassanabadi, N. Pharmacokinetic profile of diosgenin and trigonelline following intravenous and oral administration of fenugreek seed extract and pure compound in rabbit. J. Asian Nat. Prod. Res., 2021, 23(5), 466-477.
[PMID: 32447972]
[86]
Ghobadi, A.; Shirazi, A.; Najafi, M.; Kahkesh, M.H.; Rezapoor, S. Melatonin ameliorates radiation-induced oxidative stress at targeted and nontargeted lung tissue. J. Med. Phys., 2017, 42(4), 241-244.
[http://dx.doi.org/10.4103/jmp.JMP_60_17] [PMID: 29296038]
[87]
Okawara, M.; Tokudome, Y.; Todo, H.; Sugibayashi, K.; Hashimoto, F. Enhancement of diosgenin distribution in the skin by cyclodextrin complexation following oral administration. Biol. Pharm. Bull., 2013, 36(1), 36-40.
[http://dx.doi.org/10.1248/bpb.b12-00467] [PMID: 23302635]

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