Buyang Huanwu Decoction protects against STZ-induced diabetic nephropathy by inhibiting TGF-β/Smad3 signaling-mediated renal fibrosis and inflammation

Abstract Background Buyang Huanwu Decoction (BHD) is a classical Chinese Medicine formula empirically used for diabetic nephropathy (DN). However, its therapeutic efficacies and the underlying mechanisms remain obscure. In our study, we aim to evaluate the renoprotective effect of BHD on a streptozo...

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Autores principales:	Weifeng Wu, Yifan Wang, Haidi Li, Haiyong Chen, Jiangang Shen
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Buyang Huanwu Decoction Calycosin-7-Glucoside Diabetic nephropathy Fibrosis Inflammation TGF-β1 Other systems of medicine RZ201-999
Acceso en línea:	https://doaj.org/article/96429ac7c2704f5fa87b95abdd68e852
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spelling	oai:doaj.org-article:96429ac7c2704f5fa87b95abdd68e8522021-11-21T12:06:45ZBuyang Huanwu Decoction protects against STZ-induced diabetic nephropathy by inhibiting TGF-β/Smad3 signaling-mediated renal fibrosis and inflammation10.1186/s13020-021-00531-11749-8546https://doaj.org/article/96429ac7c2704f5fa87b95abdd68e8522021-11-01T00:00:00Zhttps://doi.org/10.1186/s13020-021-00531-1https://doaj.org/toc/1749-8546Abstract Background Buyang Huanwu Decoction (BHD) is a classical Chinese Medicine formula empirically used for diabetic nephropathy (DN). However, its therapeutic efficacies and the underlying mechanisms remain obscure. In our study, we aim to evaluate the renoprotective effect of BHD on a streptozotocin (STZ)-induced diabetic nephropathy mouse model and explore the potential underlying mechanism in mouse mesangial cells (MCs) treated with high glucose in vitro, followed by screening the active compounds in BHD. Methods Mice were received 50 mg/kg streptozotocin (STZ) or citrate buffer intraperitoneally for 5 consecutive days. BHD was intragastrically administrated for 12 weeks starting from week 4 after the diabetes induction. The quality control and quantitative analysis of BHD were studied by high-performance liquid chromatography (HPLC). Renal function was evaluated by urinary albumin excretion (UAE) using ELISA. The mesangial matrix expansion and renal fibrosis were measured using periodic acid-schiff (PAS) staining and Masson Trichrome staining. Mouse mesangial cells (MCs) were employed to study molecular mechanisms. Results We found that the impaired renal function in diabetic nephropathy was significantly restored by BHD, as indicated by the decreased UAE without affecting the blood glucose level. Consistently, BHD markedly alleviated STZ-induced diabetic glomerulosclerosis and tubulointerstitial injury as shown by PAS staining, accompanied by a reduction of renal inflammation and fibrosis. Mechanistically, BHD inhibited the activation of TGF-β1/Smad3 and NF-κB signaling in diabetic nephropathy while suppressing Arkadia expression and restoring renal Smad7. We further found that calycosin-7-glucoside (CG) was one of the active compounds from BHD, which significantly suppressed high glucose-induced inflammation and fibrosis by inhibiting TGF-β1/Smad3 and NF-κB signaling pathways in mesangial cells. Conclusion BHD could attenuate renal fibrosis and inflammation in STZ-induced diabetic kidneys via inhibiting TGF-β1/Smad3 and NF-κB signaling while suppressing the Arkadia and restoring renal Smad7. CG could be one of the active compounds in BHD to suppress renal inflammation and fibrosis in diabetic nephropathy.Weifeng WuYifan WangHaidi LiHaiyong ChenJiangang ShenBMCarticleBuyang Huanwu DecoctionCalycosin-7-GlucosideDiabetic nephropathyFibrosisInflammationTGF-β1Other systems of medicineRZ201-999ENChinese Medicine, Vol 16, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Buyang Huanwu Decoction Calycosin-7-Glucoside Diabetic nephropathy Fibrosis Inflammation TGF-β1 Other systems of medicine RZ201-999
spellingShingle	Buyang Huanwu Decoction Calycosin-7-Glucoside Diabetic nephropathy Fibrosis Inflammation TGF-β1 Other systems of medicine RZ201-999 Weifeng Wu Yifan Wang Haidi Li Haiyong Chen Jiangang Shen Buyang Huanwu Decoction protects against STZ-induced diabetic nephropathy by inhibiting TGF-β/Smad3 signaling-mediated renal fibrosis and inflammation
description	Abstract Background Buyang Huanwu Decoction (BHD) is a classical Chinese Medicine formula empirically used for diabetic nephropathy (DN). However, its therapeutic efficacies and the underlying mechanisms remain obscure. In our study, we aim to evaluate the renoprotective effect of BHD on a streptozotocin (STZ)-induced diabetic nephropathy mouse model and explore the potential underlying mechanism in mouse mesangial cells (MCs) treated with high glucose in vitro, followed by screening the active compounds in BHD. Methods Mice were received 50 mg/kg streptozotocin (STZ) or citrate buffer intraperitoneally for 5 consecutive days. BHD was intragastrically administrated for 12 weeks starting from week 4 after the diabetes induction. The quality control and quantitative analysis of BHD were studied by high-performance liquid chromatography (HPLC). Renal function was evaluated by urinary albumin excretion (UAE) using ELISA. The mesangial matrix expansion and renal fibrosis were measured using periodic acid-schiff (PAS) staining and Masson Trichrome staining. Mouse mesangial cells (MCs) were employed to study molecular mechanisms. Results We found that the impaired renal function in diabetic nephropathy was significantly restored by BHD, as indicated by the decreased UAE without affecting the blood glucose level. Consistently, BHD markedly alleviated STZ-induced diabetic glomerulosclerosis and tubulointerstitial injury as shown by PAS staining, accompanied by a reduction of renal inflammation and fibrosis. Mechanistically, BHD inhibited the activation of TGF-β1/Smad3 and NF-κB signaling in diabetic nephropathy while suppressing Arkadia expression and restoring renal Smad7. We further found that calycosin-7-glucoside (CG) was one of the active compounds from BHD, which significantly suppressed high glucose-induced inflammation and fibrosis by inhibiting TGF-β1/Smad3 and NF-κB signaling pathways in mesangial cells. Conclusion BHD could attenuate renal fibrosis and inflammation in STZ-induced diabetic kidneys via inhibiting TGF-β1/Smad3 and NF-κB signaling while suppressing the Arkadia and restoring renal Smad7. CG could be one of the active compounds in BHD to suppress renal inflammation and fibrosis in diabetic nephropathy.
format	article
author	Weifeng Wu Yifan Wang Haidi Li Haiyong Chen Jiangang Shen
author_facet	Weifeng Wu Yifan Wang Haidi Li Haiyong Chen Jiangang Shen
author_sort	Weifeng Wu
title	Buyang Huanwu Decoction protects against STZ-induced diabetic nephropathy by inhibiting TGF-β/Smad3 signaling-mediated renal fibrosis and inflammation
title_short	Buyang Huanwu Decoction protects against STZ-induced diabetic nephropathy by inhibiting TGF-β/Smad3 signaling-mediated renal fibrosis and inflammation
title_full	Buyang Huanwu Decoction protects against STZ-induced diabetic nephropathy by inhibiting TGF-β/Smad3 signaling-mediated renal fibrosis and inflammation
title_fullStr	Buyang Huanwu Decoction protects against STZ-induced diabetic nephropathy by inhibiting TGF-β/Smad3 signaling-mediated renal fibrosis and inflammation
title_full_unstemmed	Buyang Huanwu Decoction protects against STZ-induced diabetic nephropathy by inhibiting TGF-β/Smad3 signaling-mediated renal fibrosis and inflammation
title_sort	buyang huanwu decoction protects against stz-induced diabetic nephropathy by inhibiting tgf-β/smad3 signaling-mediated renal fibrosis and inflammation
publisher	BMC
publishDate	2021
url	https://doaj.org/article/96429ac7c2704f5fa87b95abdd68e852
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Buyang Huanwu Decoction protects against STZ-induced diabetic nephropathy by inhibiting TGF-β/Smad3 signaling-mediated renal fibrosis and inflammation

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