Fangjifuling Ameliorates Lipopolysaccharide-Induced Renal Injury via Inhibition of Inflammatory and Apoptotic Response in Mice

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.

RIPK3 mediates renal tubular epithelial cell apoptosis in endotoxin‑induced acute kidney injury

“…Previous studies have shown that LPS could directly lead to renal tubular cell injury and AKI by binding to TLR4 (6,27–29). Consistent with previous studies (6,9–11), the present study found that LPS induced renal tubular epithelial cell apoptosis in vitro and in vivo . However, the mechanisms of LPS-induced tubular epithelial cell apoptosis are not completely understood.…”

“…LPS not only triggers a large number of inflammatory cytokines, but can also directly induce renal tubular epithelial cell injury through the activation of Toll-like receptor 4 (TLR4). Tubular epithelial cell apoptosis is one of the characteristic changes that occurs in LPS-induced AKI (1,4,7,8), and accumulating evidence has demonstrated that tubular epithelial cell apoptosis has an important role in LPS-induced AKI (6,9–11). Inhibiting tubular epithelial cell apoptosis could be an effective strategy to prevent or treat LPS-induced AKI.…”

Antioxidative, Antiapoptotic, and Anti-Inflammatory Effects of Apamin in a Murine Model of Lipopolysaccharide-Induced Acute Kidney Injury

“…In addition, several substances have been reported to exert therapeutic effects in a cecal ligation and puncture (CLP) mouse model primarily through inhibiting tubular cell apoptosis [27,28]. Tubular cell apoptosis was also observed in LPS-injected rodents [29,30], where the administration of a pan-caspase inhibitor was shown to ameliorate LPS-induced AKI [31]. In our study, LPS treatment increased the amounts of lipid peroxidation products and reversed a reduction in GSH/GSSG ratio in the kidneys.…”

Oridonin Attenuates Lipopolysaccharide‐Induced ROS Accumulation and Inflammation in HK‐2 Cells

“…erefore, the inhibition of inflammation and oxidative stress may serve as a good strategy for the treatment of CKD. Su et al reported the renal protective effect of Fangjifuling against LPS-induced inflammatory and apoptotic responses in vitro and in vivo [29]. Similar protective effects were reported for berberine against chronic renal failure mediated via tumor necrosis factor receptor associated factor 5-(TRAF5-) induced activation of the NF-κB signaling pathway in mouse podocytes [30].…”