Protective effects and regulatory mechanisms of Shen-shuai-yi recipe on renal fibrosis in unilateral ureteral obstruction-induced mice
Ping-lan Lin,
Tao-tao Weng,
Lian-xiang Duan,
Lin-zhang Zhang,
Xia Wei,
Sheng-lan Qi,
Jia-wen You,
Yu Cao,
Guang-bo Ge,
Wei Liu,
Xiao-li He,
Jing Hu
Affiliations
Ping-lan Lin
Department of Nephropathy, The Seventh People's Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China; Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Department of Pharmacy, Institute of Kidney Disease, Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
Tao-tao Weng
Department of Nephropathy, The Seventh People's Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China; Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Department of Pharmacy, Institute of Kidney Disease, Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
Lian-xiang Duan
Department of Nephropathy, The Seventh People's Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Lin-zhang Zhang
Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Department of Pharmacy, Institute of Kidney Disease, Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
Xia Wei
Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Department of Pharmacy, Institute of Kidney Disease, Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
Sheng-lan Qi
Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Department of Pharmacy, Institute of Kidney Disease, Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
Jia-wen You
Department of Endocrinology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Yu Cao
Department of Nephropathy, The Seventh People's Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Guang-bo Ge
Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Wei Liu
Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Department of Pharmacy, Institute of Kidney Disease, Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China; Corresponding author.
Xiao-li He
Department of Endocrinology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China; Corresponding author.
Jing Hu
Department of Nephropathy, The Seventh People's Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China; Corresponding author.
Renal fibrosis (RF) is a common pathological feature of chronic kidney disease (CKD), which remains a major public health problem. As now, there is still lack of chemical or biological drugs to reverse RF. Shen-shuai-yi Recipe (SSYR) is a classical Chinese herbal formula for the treatment of CKD. However, the effects and mechanisms of SSYR in treating RF are still not clear. In this study, the active constituents SSYR for treating RF were explored by UHPLC-Q-Orbitrap HRMS. Bioinformatics analyses were employed to analyze the key pharmacological targets and the core active constituents of SSYR in the treatment of RF. In experimental validation, vehicle or SSYR at doses of 2.12 g/kg/d and 4.25 g/kg/d were given by orally to unilateral ureteric obstruction (UUO) mice. 13 days after treatment, we detected the severity of renal fibrosis, extracellular collagen deposition and pre-fibrotic signaling pathways. Bioinformatics analysis suggested that signal transducer and activator of transcription 3 (STAT3) was the core target and lenticin, luteolin-7-O-rutinoside, hesperidin, kaempferol-3-O-rutinoside, and 3,5,6,7,8,3′,4′-heptamethoxyflavone were the key constituents in SSYR for treating RF. SSYR significantly reduced the expressions of fibronectin (FN), α-smooth muscle actin (α-SMA), collagen-I and alleviated renal interstitial collagen deposition in UUO kidneys. In mechanism, SSYR potently blocked the phosphorylation of STAT3 and Smad3 and suppressed the expression of connective tissue growth factor (CTGF). Collectively, SSYR can ameliorate RF via inhibiting the phosphorylation of STAT3 and its downstream and reducing the collagen deposition, suggesting that SSYR can be developed as a novel medicine for treating RF.
