Zhonghao Su1, Ping Yu2, Lanyue Sheng1, Jin Ye1, Zhenxia Qin1. 1. School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China. 2. Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Abstract
BACKGROUND/AIMS: Acute kidney injury (AKI) is a frequent and serious complication of sepsis; however, there is no effective treatment for it. FangJiFuling (FF) decoction is widely used to treat acute glomerulonephritis and nephritic syndrome in the clinical setting. METHODS: On the basis of its anti-inflammatory properties, the renoprotective effect of FF on a mouse model of lipopolysaccharide (LPS)-induced AKI was investigated. Major compounds were identified in FF with high-performance liquid chromatography. A bioinformatics analysis tool was used to predict target genes. Quantitative real-time PCR and western blot analyses were performed to validate the targets. Furthermore, the expression of a target gene was silenced by small interfering RNA-mediated knockdown in vitro. RESULTS: Bioinformatics analysis indicated that inflammation, apoptosis, and cell junction were closely related to the renoprotective effects of FF. Validation was confirmed by an in vivo test. A reduction of inflammatory cell infiltration and inflammatory cytokine mRNA expression (iNOS, NF-κB, MCP-1, and TNF-α) following the administration of FF (50 mg/kg) was observed in LPS-treated renal tissue. In addition, FF treatment suppressed mitochondrial-mediated apoptosis by regulating the Bax/Bcl-2 ratio in LPS-induced renal injury. Silencing Cx43, a cell-to-cell junction protein, was found to enhance the protective effect of FF against LPS-induced renal injury. CONCLUSION: Our study suggests that FF exhibits a renoprotective effect against LPS-induced inflammatory and apoptotic responses. In addition, Cx43 might be involved in these processes. These findings indicate the potential role of FF as a natural renoprotective product.
BACKGROUND/AIMS: Acute kidney injury (AKI) is a frequent and serious complication of sepsis; however, there is no effective treatment for it. FangJiFuling (FF) decoction is widely used to treat acute glomerulonephritis and nephritic syndrome in the clinical setting. METHODS: On the basis of its anti-inflammatory properties, the renoprotective effect of FF on a mouse model of lipopolysaccharide (LPS)-induced AKI was investigated. Major compounds were identified in FF with high-performance liquid chromatography. A bioinformatics analysis tool was used to predict target genes. Quantitative real-time PCR and western blot analyses were performed to validate the targets. Furthermore, the expression of a target gene was silenced by small interfering RNA-mediated knockdown in vitro. RESULTS: Bioinformatics analysis indicated that inflammation, apoptosis, and cell junction were closely related to the renoprotective effects of FF. Validation was confirmed by an in vivo test. A reduction of inflammatory cell infiltration and inflammatory cytokine mRNA expression (iNOS, NF-κB, MCP-1, and TNF-α) following the administration of FF (50 mg/kg) was observed in LPS-treated renal tissue. In addition, FF treatment suppressed mitochondrial-mediated apoptosis by regulating the Bax/Bcl-2 ratio in LPS-induced renal injury. Silencing Cx43, a cell-to-cell junction protein, was found to enhance the protective effect of FF against LPS-induced renal injury. CONCLUSION: Our study suggests that FF exhibits a renoprotective effect against LPS-induced inflammatory and apoptotic responses. In addition, Cx43 might be involved in these processes. These findings indicate the potential role of FF as a natural renoprotective product.