Breviscapine alleviates NASH by inhibiting TGF‐β‐activated kinase 1‐dependent signaling

Abstract

Background and Aims: NAFLD is a key component of metabolic syndrome, ranging from nonalcoholic fatty liver to NASH, and is now becoming the leading cause of cirrhosis and HCC worldwide. However, due to the complex and unclear pathophysiological mechanism, there are no specific approved agents for treating NASH. Breviscapine, a natural flavonoid prescription drug isolated from the traditional Chinese herb Erigeron breviscapus, exhibits a wide range of pharmacological properties, including effects on metabolism.However, the anti-NASH efficacy and mechanisms of breviscapine have not yet been characterized. Approach and Results:We evaluated the effects of breviscapine on the development of hepatic steatosis, inflammation, and fibrosis in vivo and in vitro under metabolic stress. Breviscapine treatment significantly reduced lipid accumulation, inflammatory cell infiltration, liver injury, and fibrosis in mice fed a high-fat diet, a high-fat/high-cholesterol diet, or a methionineand choline-deficient diet. In addition, breviscapine attenuated lipid accumulation, inflammation, and lipotoxicity in hepatocytes undergoing metabolic stress. RNA-sequencing and multiomics analyses further indicated that the

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“…Undoubtedly, treating hepatic inflammation is a valuable method to treat NASH. The research of Lan et al further confirmed the feasibility of drugs targeting inflammation in treating NASH [ 30 ].…”

Traditional Chinese medicine: An important source for discovering candidate agents against hepatic fibrosis

“…A mouse model of NASH was established by feeding a high-fat/high-cholesterol diet, for 16 weeks, and breviscapine (15 and 30 mg/kg) was administered daily by oral gavage after 8 weeks of treatment, significantly reduced lipid accumulation, inflammatory cell infiltration, liver injury, and fibrosis in mice. Further RNA-sequencing and multiomics analyses indicated that breviscapine inhibited TGF-β-activated kinase 1 (TAK1) -dependent signaling to alleviate NASH ( Lan et al, 2022 ). Moreover, in vitro and in vivo results of the experiment showed that gastrodin (25, 50, 100, 200 μg/ml; 10, 20, 50 mg/kg) activated the AMPK/Nrf2 pathway, ameliorated hepatic oxidative stress/proinflammatory response and significantly improved metabolic disorders in NAFLD ( Qu et al, 2016 ).…”

Frontier progress of the combination of modern medicine and traditional Chinese medicine in the treatment of hepatocellular carcinoma

“…Bufalin regulated tumor immune microenvironments by Nuclear Factor kappa B (NF-κB) and activates anti-tumor T cell immune response [ 30 ]. Breviscapine alleviated nonalcoholic steatohepatitis and liver fibrosis by inhibiting TGF-β-activated kinase 1 and toll-like receptor 4 (TLR4) / NF-κB signaling pathway to protect the liver and prevent the further development of liver disease to HCC [ 31 , 32 ]. Astragaloside IV inhibited macrophage M2 polarization, invasion and proliferation of hepatocellular cells by regulating TLR4 / NF-κB / signal transducer and activator of transcription 3 (STAT3) signaling pathway [ 33 ].…”