Phytomedicine : international journal of phytotherapy and phytopharmacology · 2026
Fupenzic acid ameliorates radiation-induced liver fibrosis by regulating RBMS1 to inhibit the cGAS-STING pathway and restore mitochondrial function.
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Guo Xin, Liu Yu-Han, Huang Bao-Nian, Tai Yi, Liu Xue-Kun, Du Rui, Jin Xue-Jun
Аннотация
BACKGROUND: Liver fibrosis, a progressive pathological condition, may culminate in cirrhosis and liver failure, with chronic inflammation and oxidative stress being key drivers. Fupenzic acid (FA), a natural triterpenoid derived from Rubus idaeus L., exhibits notable antioxidant and anti-inflammatory effects in various biological contexts.
OBJECTIVE: This study sought to explore FA's therapeutic potential and underlying mechanism in mitigating radiotherapy (RT)-induced liver fibrosis.
METHODS: A mouse model of hepatic fibrosis was induced through RT, with FA administered concurrently to evaluate its effects. LX-2 cells were activated with TGF-β1 to mimic fibrotic activation. The molecular mechanism was further explored using cellular thermal shift assay (CETSA) and Rbms1 overexpression experiments.
RESULTS: FA treatment significantly alleviated RT-induced liver dysfunction, histological damage, and collagen deposition in mice. It also reduced serum levels of fibrotic markers and downregulated the expression of fibrosis-related genes (Col4, Fn1, Timp1) as well as proteins. Mechanistically, FA inhibited oxidative stress and inflammation. Moreover, FA preserved mitochondrial homeostasis by enhancing PINK1/Parkin-mediated mitophagy. Importantly, FA directly bound to and downregulated the RNA-binding protein RBMS1, thereby inhibiting downstream cGAS-STING signaling pathway both in vivo and in vitro. Overexpression of RBMS1 attenuated anti-fibrotic, anti-inflammatory, and pro-mitophagic effects of FA.
CONCLUSION: Our research demonstrated that FA ameliorated RT-induced liver fibrosis by directly targeting RBMS1, thereby suppressing cGAS-STING pathway, mitigating inflammation as well as oxidative stress, and improving mitochondrial function. Therefore, FA emerges as a promising therapeutic candidate for preventing and treating hepatic fibrosis.
OBJECTIVE: This study sought to explore FA's therapeutic potential and underlying mechanism in mitigating radiotherapy (RT)-induced liver fibrosis.
METHODS: A mouse model of hepatic fibrosis was induced through RT, with FA administered concurrently to evaluate its effects. LX-2 cells were activated with TGF-β1 to mimic fibrotic activation. The molecular mechanism was further explored using cellular thermal shift assay (CETSA) and Rbms1 overexpression experiments.
RESULTS: FA treatment significantly alleviated RT-induced liver dysfunction, histological damage, and collagen deposition in mice. It also reduced serum levels of fibrotic markers and downregulated the expression of fibrosis-related genes (Col4, Fn1, Timp1) as well as proteins. Mechanistically, FA inhibited oxidative stress and inflammation. Moreover, FA preserved mitochondrial homeostasis by enhancing PINK1/Parkin-mediated mitophagy. Importantly, FA directly bound to and downregulated the RNA-binding protein RBMS1, thereby inhibiting downstream cGAS-STING signaling pathway both in vivo and in vitro. Overexpression of RBMS1 attenuated anti-fibrotic, anti-inflammatory, and pro-mitophagic effects of FA.
CONCLUSION: Our research demonstrated that FA ameliorated RT-induced liver fibrosis by directly targeting RBMS1, thereby suppressing cGAS-STING pathway, mitigating inflammation as well as oxidative stress, and improving mitochondrial function. Therefore, FA emerges as a promising therapeutic candidate for preventing and treating hepatic fibrosis.