薯蓣皂苷元对代谢系统疾病治疗作用及机制研究
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摘要
薯蓣皂苷元是一种从豆科和薯蓣科植物中提取的天然存在的甾体皂苷元,具有抗肿瘤、抗炎、抗氧化等多种显著的药理作用,对于免疫系统、心血管系统、消化系统、沁尿系统、肿瘤等疾病治疗有明显优势。有关薯蓣皂苷元的作用及机制越来越引人关注,该文就薯蓣皂苷元治疗糖尿病周围神经病变、痛风、Graves眼病等疾病治疗机制进行研究、总结与综述,将有助于提高薯蓣皂苷元的临床应用及新药研发。为薯蓣皂苷元研究和进一步开发提供参考。
Diosgenin is a naturally occurring steroidal saponin extracted from Leguminosae and Dioscorea. It has many remarkable pharmacological effects against tumor,anti-inflammatory and antioxidation,for immune system,cardiovascular system and digestion system,urinary system,tumor and other diseases have obvious advantages. The role and mechanism of diosgenin has attracted more and more attention. This paper summarized and summarized the research on the therapeutic mechanism of diosgenin in the treatment of diabetic peripheral neuropathy,gout,graves ophthalmopathy and other diseases,which will help to improve diosgenin's clinical application and new drug development. To provide reference for the research and further development of diosgenin.
Diosgenin is a naturally occurring steroidal saponin extracted from Leguminosae and Dioscorea. It has many remarkable pharmacological effects against tumor,anti-inflammatory and antioxidation,for immune system,cardiovascular system and digestion system,urinary system,tumor and other diseases have obvious advantages. The role and mechanism of diosgenin has attracted more and more attention. This paper summarized and summarized the research on the therapeutic mechanism of diosgenin in the treatment of diabetic peripheral neuropathy,gout,graves ophthalmopathy and other diseases,which will help to improve diosgenin's clinical application and new drug development. To provide reference for the research and further development of diosgenin.
引文
[1]He Z,Tian Y,Zhang X,etal.Anti-tumour and immunomodulating activities of diosgenin,a naturally occurring steroidal saponin[J]. Natural product research,2012,26(23):2243-2246.
[2]Dong J,Lei C,Lu D,et al. Direct Biotransformation of Dioscin into Diosgenin in Rhizome of Dioscorea zingiberensis by Penicillium dioscin[J]. Indian Journal of Microbiology,2015,55(2):200-206.
[3]Al Jasem Y,Khan M,Taha A,et al. ChemInform Abstract:PreparationofSteroidalHormoneswithanEmphasison Transformations of Phytosterols and Cholesterol[J]. Cheminform,2015,46(2):796-830.
[4]Jesus M,Martins A P,Gallardo E,et al. Diosgenin:Recent Highlights on Pharmacology and Analytical Methodology[J].Journal of Analytical Methods in Chemistry,2016,2016(4):1-16.
[5]Sangeetha M K,Vallabi D E,Sali V K,et al. Sub-acute Toxicity Profile of a Modified Resveratrol Supplement[J]. Food&Chemical Toxicology,2013,59(8):492-500.
[6]Uemura T. Diosgenin present in fenugreek improves glucose metabolism by promoting adipocyte differentiation and inhibiting inflammation in adipose tissues[J]. Molecular Nutrition&Food Research,2010,54(11):1596-1608.
[7]Kanchan D M,Somani G S,Peshattiwar V V,et al. Renoprotective effect of diosgenin in streptozotocin induced diabetic rats[J].Pharmacological Reports,2016,68(2):370-377.
[8]Shanmugasundarapandian J K,Rachel V A H,Narasimman G.Steroidal Saponin Diosgenin fromDioscorea bulbiferaProtects Cardiac Cells from Hypoxia-reoxygenation Injury Through Modulation of Pro-survival and Pro-death Molecules[J].Pharmacognosy Magazine,2016,12(45):14.
[9]Badalzadeh R,Yousefi B,Tajaddini A,et al. Diosgenin-induced protection against myocardial ischaemia-reperfusion injury is mediated by mitochondrial KATP channels in a rat model[J].Perfusion,2015,30(7):565.
[10]Badalzadeh R,Yavari R,Chalabiani D. Mitochondrial ATPsensitive K+channels mediate the antioxidative influence of diosgenin on myocardial reperfusion injury in rat hearts[J].General Physiology&Biophysics,2015,34(3):323-329.
[11]Wang S,Wang F,Yang H,et al. Diosgenin glucoside provides neuroprotection by regulating microglial M1 polarization.[J].International Immunopharmacology,2017,50:22.
[12]Lin Y,Jia R,Liu Y,et al. Diosgenin inhibits superoxide generation in FMLP-activated mouse neutrophils via multiple pathways[J]. Free Radical Research,2014,48(12):1485-1493.
[13]Raju J,Patlolla J M R,Swamy M V,et al. Diosgenin,a Steroid Saponin of Trigonella foenum graecum(Fenugreek),Inhibits Azoxymethane-Induced Aberrant Crypt Foci Formation in F344Rats and Induces Apoptosis in HT-29 Human Colon Cancer Cells[J]. Cancer Epidemiol Biomarkers Prev,2004,13(8):1392-1398.
[14]CHEN,TANG,You-Mei,et al. Advances in the pharmacological activities and mechanisms of diosgenin[J]. Chinese Journal of Natural Medicines,2015,13(8):578-587.
[15]Selim S,Jaouni S A. Anticancer and apoptotic effects on cell proliferation of diosgenin isolated from Costus speciosus(Koen.)Sm[J]. BMC Complementary and Alternative Medicine,2015,15(1):301.
[16]Kiasalari Z,Rahmani T,Mahmoudi N,et al. Diosgenin ameliorates development of neuropathic pain in diabetic rats:Involvement of oxidative stress and inflammation[J].Biomedicine&Pharmacotherapy,2017,86:654-661.
[17]Kang TH,Moon E,Hong BN,et al. Diosgenin from Dioscorea nipponica ameliorates diabetic neuropathy by inducing nerve growth factor[J].Biological&pharmaceutical bulletin,2011,34(9):1493-1498.
[18]Ahmed L A,Obaid A A,Zaki H F,et al. Role of oxidative stress,inflammation,nitric oxide and transforming growth factor-beta in the protective effect of diosgenin in monocrotalineinduced pulmonary hypertension in rats[J]. European Journal of Pharmacology,2014,740:379-387.
[19]P. Kalailingam,B. Kannaian,E. Tamilmani,et al. Efficacy of natural diosgenin on cardiovascular risk,insulin secretion,and beta cells in streptozotocin(STZ)-induced diabetic rats[J].Phytomedicine,2014,21(10):1154-1161.
[20]T Uemura,S Hirai,N Mizoguchi,et al. Diosgenin present in fenugreek improves glucose metabolism by promoting adipocyte differentiation and inhibiting inflammation in adipose tissues[J].Mol Nutr Food Res,2010,54(11):1596-1608.
[21]F Roghani-Dehkordi,M Roghani,T Baluchnejadmojarad.Diosgenin mitigates streptozotocin diabetes-induced vascular dysfunction of the rat aorta:the involved mechanisms[J]. J Cardiovasc Pharmacol,2015,66(6):584-592.
[22]J Manivannan,E Balamurugan,T Silambarasan. Diosgenin improvesvascularfunctionbyincreasingaorticeNOS expression,normalize dyslipidemia and ACE activity in chronic renal failure rats[J].Mol Cell Biochem,2013,384(1-2):113-120.
[23]YP Zhang,CY Song,Y Yuan,et al. Diabetic neuropathic pain development in type 2 diabetic mouse model and the prophylactic and therapeutic effects of coenzyme Q10[J]. Neurobiol Dis,2013,58:169-178.
[24]Rees F,Hui M,Doherty M. Optimizing current treatment of gout[J].Nat Rev Rheumatol,2014,10(5):271-283.
[25]Becker MA,Ruoff GE. What do I need to know about gout[J]. J Fam Pract,2010,59(6 Suppl):S1-8.
[26]Pope RM,Tschopp J. The role of interleukin-1 and the inflammasome in gout[J].Arthritis Rheum,2007,56(10):3183-3188.
[27]周琦,张宁,卢芳,等.穿山龙总皂苷对痛风性关节炎大鼠关节炎滑膜IL-1β及其信号转导通路的影响[J].中药药理与临床,2013(6):52-57.
[28]罗心静,莫选荣,周玲玲.TNF-α诱导类风湿关节炎滑膜细胞NF-κB信号通路活化的探讨[J].免疫学杂志,2012,28(4):321-332.
[29]姚芳芳,张锐,付瑞娟,等.同等剂量棚皮素、芹菜素对高尿酸血症大鼠的影响及其机制研究[J].现代预防医学,2012,39(6):1365-1367.
[30]周琦,张翀,于栋华,等.穿山龙总皂苷对高尿酸血症的降尿酸及细胞抗炎作用研究[J].中华中医药杂志,2013(5):1444-1448.
[31]Lipkowitz MS. Regulation of uric acid excretion by the kidney[J].Curr Rheumatol Rep,2012,14:179-188.
[32]Bobulescu IA,Moe OW. Renal transport of uric acid:evolving concepts and uncertainties[J].Adv. Chronic Kidney D,2012,19:358-371.
[33]Bhatnagar V,Richard EL,Wu W,et al. Analysis of ABCG2and other urate transporters in uric acid homeostasis in chronic kidney disease:potential role of remote sensing and signaling[J].Clin. Kidney J,2016,9:444-453.
[34]Zhang Y,Jin L,Liu J,et al. Effect and mechanism of dioscin from Dioscorea spongiosa on uric acid excretion in animal model of hyperuricemia[J].J Ethnopharmacol,2018,214:29-36.
[35]Cai H,Wang Z,Zhang HQ,et al. Diosgenin relieves goiter via the inhibition of thyrocyte proliferation in a mouse model of Graves'disease[J].Acta pharmacologica Sinica,2014,35:65-73.
[36]Ren M,Zhong X,Ma CY,et al. Insulin-like growth factor-1promotes cell cycle progression via upregulation of cyclin D1expression through the phosphatidylinositol 3-kinase/nuclear factor-kappaB signaling pathway in FRTL thyroid cells[J].Acta Pharmacol Sin,2009,30:113-119.
[37]HaddadJJ,Abdel-KarimNE.NF-kappaBcellularand molecular regulatory mechanisms and pathways:therapeutic pattern or pseudoregulation?[J].Cell Immunol,2011,271:5-14.
[38]Salminen A,Kaarniranta K. Insulin/IGF-1 paradox of aging:regulation via AKT/IKK/NF-kappaB signaling[J].Cell Signal,2010,22:573-577.
[39]Kuo SH,Chou CH,Cheng AL,et al. Expression of BCL10 in cervical cancer has a role in the regulation of cell growth through the activation of NF-kappaB-dependent cyclin D1 signaling[J].Gynecol Oncol,2012,126:245-251.
[40]Stacey DW. Cyclin D1 serves as a cell cycle regulatory switch in actively proliferating cells[J].Curr Opin Cell Biol,2003,15:158-163.
[41]Travali S,Ku DH,Rizzo MG,et al. Structure of the human gene for the proliferating cell nuclear antigen[J].J Biol Chem,1989,264:7466-7472.
[42]BianD,LiZ,MaH,etal.Effectsofdiosgeninoncell proliferation induced by IGF-1 in primary human thyrocytes[J].Archives of pharmacal research,2011,34(6):997-1005.
[43]唐春颖,冷锦红.穿山龙薯蓣皂苷对痛性糖尿病周围神经病变大鼠电压门控Ca2+通道基因表达的影响[J].辽宁中医药大学学报,2018,20(3):25-27.
[44]冷锦红,侯丽,邓丽,等.穿山龙提取物薯蓣皂苷对痛性糖尿病周围神经病变大鼠钠通道基因表达的影响[J].中华中医药学刊,2018,36(10):2372-2374.
[2]Dong J,Lei C,Lu D,et al. Direct Biotransformation of Dioscin into Diosgenin in Rhizome of Dioscorea zingiberensis by Penicillium dioscin[J]. Indian Journal of Microbiology,2015,55(2):200-206.
[3]Al Jasem Y,Khan M,Taha A,et al. ChemInform Abstract:PreparationofSteroidalHormoneswithanEmphasison Transformations of Phytosterols and Cholesterol[J]. Cheminform,2015,46(2):796-830.
[4]Jesus M,Martins A P,Gallardo E,et al. Diosgenin:Recent Highlights on Pharmacology and Analytical Methodology[J].Journal of Analytical Methods in Chemistry,2016,2016(4):1-16.
[5]Sangeetha M K,Vallabi D E,Sali V K,et al. Sub-acute Toxicity Profile of a Modified Resveratrol Supplement[J]. Food&Chemical Toxicology,2013,59(8):492-500.
[6]Uemura T. Diosgenin present in fenugreek improves glucose metabolism by promoting adipocyte differentiation and inhibiting inflammation in adipose tissues[J]. Molecular Nutrition&Food Research,2010,54(11):1596-1608.
[7]Kanchan D M,Somani G S,Peshattiwar V V,et al. Renoprotective effect of diosgenin in streptozotocin induced diabetic rats[J].Pharmacological Reports,2016,68(2):370-377.
[8]Shanmugasundarapandian J K,Rachel V A H,Narasimman G.Steroidal Saponin Diosgenin fromDioscorea bulbiferaProtects Cardiac Cells from Hypoxia-reoxygenation Injury Through Modulation of Pro-survival and Pro-death Molecules[J].Pharmacognosy Magazine,2016,12(45):14.
[9]Badalzadeh R,Yousefi B,Tajaddini A,et al. Diosgenin-induced protection against myocardial ischaemia-reperfusion injury is mediated by mitochondrial KATP channels in a rat model[J].Perfusion,2015,30(7):565.
[10]Badalzadeh R,Yavari R,Chalabiani D. Mitochondrial ATPsensitive K+channels mediate the antioxidative influence of diosgenin on myocardial reperfusion injury in rat hearts[J].General Physiology&Biophysics,2015,34(3):323-329.
[11]Wang S,Wang F,Yang H,et al. Diosgenin glucoside provides neuroprotection by regulating microglial M1 polarization.[J].International Immunopharmacology,2017,50:22.
[12]Lin Y,Jia R,Liu Y,et al. Diosgenin inhibits superoxide generation in FMLP-activated mouse neutrophils via multiple pathways[J]. Free Radical Research,2014,48(12):1485-1493.
[13]Raju J,Patlolla J M R,Swamy M V,et al. Diosgenin,a Steroid Saponin of Trigonella foenum graecum(Fenugreek),Inhibits Azoxymethane-Induced Aberrant Crypt Foci Formation in F344Rats and Induces Apoptosis in HT-29 Human Colon Cancer Cells[J]. Cancer Epidemiol Biomarkers Prev,2004,13(8):1392-1398.
[14]CHEN,TANG,You-Mei,et al. Advances in the pharmacological activities and mechanisms of diosgenin[J]. Chinese Journal of Natural Medicines,2015,13(8):578-587.
[15]Selim S,Jaouni S A. Anticancer and apoptotic effects on cell proliferation of diosgenin isolated from Costus speciosus(Koen.)Sm[J]. BMC Complementary and Alternative Medicine,2015,15(1):301.
[16]Kiasalari Z,Rahmani T,Mahmoudi N,et al. Diosgenin ameliorates development of neuropathic pain in diabetic rats:Involvement of oxidative stress and inflammation[J].Biomedicine&Pharmacotherapy,2017,86:654-661.
[17]Kang TH,Moon E,Hong BN,et al. Diosgenin from Dioscorea nipponica ameliorates diabetic neuropathy by inducing nerve growth factor[J].Biological&pharmaceutical bulletin,2011,34(9):1493-1498.
[18]Ahmed L A,Obaid A A,Zaki H F,et al. Role of oxidative stress,inflammation,nitric oxide and transforming growth factor-beta in the protective effect of diosgenin in monocrotalineinduced pulmonary hypertension in rats[J]. European Journal of Pharmacology,2014,740:379-387.
[19]P. Kalailingam,B. Kannaian,E. Tamilmani,et al. Efficacy of natural diosgenin on cardiovascular risk,insulin secretion,and beta cells in streptozotocin(STZ)-induced diabetic rats[J].Phytomedicine,2014,21(10):1154-1161.
[20]T Uemura,S Hirai,N Mizoguchi,et al. Diosgenin present in fenugreek improves glucose metabolism by promoting adipocyte differentiation and inhibiting inflammation in adipose tissues[J].Mol Nutr Food Res,2010,54(11):1596-1608.
[21]F Roghani-Dehkordi,M Roghani,T Baluchnejadmojarad.Diosgenin mitigates streptozotocin diabetes-induced vascular dysfunction of the rat aorta:the involved mechanisms[J]. J Cardiovasc Pharmacol,2015,66(6):584-592.
[22]J Manivannan,E Balamurugan,T Silambarasan. Diosgenin improvesvascularfunctionbyincreasingaorticeNOS expression,normalize dyslipidemia and ACE activity in chronic renal failure rats[J].Mol Cell Biochem,2013,384(1-2):113-120.
[23]YP Zhang,CY Song,Y Yuan,et al. Diabetic neuropathic pain development in type 2 diabetic mouse model and the prophylactic and therapeutic effects of coenzyme Q10[J]. Neurobiol Dis,2013,58:169-178.
[24]Rees F,Hui M,Doherty M. Optimizing current treatment of gout[J].Nat Rev Rheumatol,2014,10(5):271-283.
[25]Becker MA,Ruoff GE. What do I need to know about gout[J]. J Fam Pract,2010,59(6 Suppl):S1-8.
[26]Pope RM,Tschopp J. The role of interleukin-1 and the inflammasome in gout[J].Arthritis Rheum,2007,56(10):3183-3188.
[27]周琦,张宁,卢芳,等.穿山龙总皂苷对痛风性关节炎大鼠关节炎滑膜IL-1β及其信号转导通路的影响[J].中药药理与临床,2013(6):52-57.
[28]罗心静,莫选荣,周玲玲.TNF-α诱导类风湿关节炎滑膜细胞NF-κB信号通路活化的探讨[J].免疫学杂志,2012,28(4):321-332.
[29]姚芳芳,张锐,付瑞娟,等.同等剂量棚皮素、芹菜素对高尿酸血症大鼠的影响及其机制研究[J].现代预防医学,2012,39(6):1365-1367.
[30]周琦,张翀,于栋华,等.穿山龙总皂苷对高尿酸血症的降尿酸及细胞抗炎作用研究[J].中华中医药杂志,2013(5):1444-1448.
[31]Lipkowitz MS. Regulation of uric acid excretion by the kidney[J].Curr Rheumatol Rep,2012,14:179-188.
[32]Bobulescu IA,Moe OW. Renal transport of uric acid:evolving concepts and uncertainties[J].Adv. Chronic Kidney D,2012,19:358-371.
[33]Bhatnagar V,Richard EL,Wu W,et al. Analysis of ABCG2and other urate transporters in uric acid homeostasis in chronic kidney disease:potential role of remote sensing and signaling[J].Clin. Kidney J,2016,9:444-453.
[34]Zhang Y,Jin L,Liu J,et al. Effect and mechanism of dioscin from Dioscorea spongiosa on uric acid excretion in animal model of hyperuricemia[J].J Ethnopharmacol,2018,214:29-36.
[35]Cai H,Wang Z,Zhang HQ,et al. Diosgenin relieves goiter via the inhibition of thyrocyte proliferation in a mouse model of Graves'disease[J].Acta pharmacologica Sinica,2014,35:65-73.
[36]Ren M,Zhong X,Ma CY,et al. Insulin-like growth factor-1promotes cell cycle progression via upregulation of cyclin D1expression through the phosphatidylinositol 3-kinase/nuclear factor-kappaB signaling pathway in FRTL thyroid cells[J].Acta Pharmacol Sin,2009,30:113-119.
[37]HaddadJJ,Abdel-KarimNE.NF-kappaBcellularand molecular regulatory mechanisms and pathways:therapeutic pattern or pseudoregulation?[J].Cell Immunol,2011,271:5-14.
[38]Salminen A,Kaarniranta K. Insulin/IGF-1 paradox of aging:regulation via AKT/IKK/NF-kappaB signaling[J].Cell Signal,2010,22:573-577.
[39]Kuo SH,Chou CH,Cheng AL,et al. Expression of BCL10 in cervical cancer has a role in the regulation of cell growth through the activation of NF-kappaB-dependent cyclin D1 signaling[J].Gynecol Oncol,2012,126:245-251.
[40]Stacey DW. Cyclin D1 serves as a cell cycle regulatory switch in actively proliferating cells[J].Curr Opin Cell Biol,2003,15:158-163.
[41]Travali S,Ku DH,Rizzo MG,et al. Structure of the human gene for the proliferating cell nuclear antigen[J].J Biol Chem,1989,264:7466-7472.
[42]BianD,LiZ,MaH,etal.Effectsofdiosgeninoncell proliferation induced by IGF-1 in primary human thyrocytes[J].Archives of pharmacal research,2011,34(6):997-1005.
[43]唐春颖,冷锦红.穿山龙薯蓣皂苷对痛性糖尿病周围神经病变大鼠电压门控Ca2+通道基因表达的影响[J].辽宁中医药大学学报,2018,20(3):25-27.
[44]冷锦红,侯丽,邓丽,等.穿山龙提取物薯蓣皂苷对痛性糖尿病周围神经病变大鼠钠通道基因表达的影响[J].中华中医药学刊,2018,36(10):2372-2374.