Physalin B ameliorates nonalcoholic steatohepatitis by stimulating autophagy and NRF2 activation mediated improvement in oxidative stress

The Cape Gooseberry Constituent Physalin B Ameliorates Nonalcoholic Steatohepatitis and Attenuates Liver Fibrosis

“…In two very recent studies, the laboratory of Ling-yi Kong (Jiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University Nanjing, China) published the beneficial effects of Physalin B in models of experimental non-alcoholic steatohepatitis (NASH) [5] and hepatic fibrosis [6]. In two very recent studies, the laboratory of Ling-yi Kong (Jiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University Nanjing, China) published the beneficial effects of Physalin B in models of experimental non-alcoholic steatohepatitis (NASH) [5] and hepatic fibrosis [6].…”

“…In the first paper, the authors performed experiments in methionine-choline deficient diet (MCD)-induced NASH mice and in cultured human fetal hepatocyte line L02 [5]. The authors showed that orally administered Physalin B significantly ameliorated hepatic injury during MCD, as assessed by lowered transaminase activities, decreased hepatic lipid accumulation, and attenuated ROS formation.…”

“…The authors further demonstrated that the reduction in GLI1 acetylation hindered complex formation between the Lamina-associated polypeptide 2α (LAP2α) and the histone deacetylase 1 (HDAC1), which normally promotes GLI1 deacetylation. In the first paper, the authors performed experiments in methionine-choline deficient diet (MCD)-induced NASH mice and in cultured human fetal hepatocyte line L02 [5]. The authors showed that orally administered Physalin B significantly ameliorated hepatic injury during MCD, as assessed by lowered transaminase activities, decreased hepatic lipid accumulation, and attenuated ROS formation.…”

Commentary on: Physalin B attenuates liver fibrosis via suppressing LAP2α-HDAC1 mediated deacetylation of GLI1 and hepatic stellate cell activation

“…The finding that PB treatment mitigated liver fibrosis viainhibiting the interaction between LAP2α and HDAC1 that provokes increased acetylation and nuclear translocation of GLI1 is novel. In a related study, the same authors have recently shown that PB ameliorates experimental non-alcoholic steatohepatitis (NASH) in mice by stimulating autophagy and p62-Keap1-Nrf2 anti-oxidative signaling, suggesting that this drug has also some general anti-inflammatory and hepatoprotective activities (Zhang et al, 2021). In line, in a more previous report PB was considered to inhibit NO production by lipopolysaccharide-or interferon-γ-activated macrophages and to protect mice against a lethal lipopolysaccharide challenge (Soares et al, 2003).…”

Physalin B attenuates liver fibrosis via suppressing LAP2α‐HDAC1 mediated deacetylation of glioma‐associated oncogene 1 and hepatic stellate cell activation

“…The finding that physalin B treatment mitigated liver fibrosis via inhibiting the interaction between LAP2α and HDAC1, which provoke increased acetylation and nuclear translocation of GLI1 is novel. In a related study, the same authors have recently shown that physalin B ameliorates experimental non‐alcoholic steatohepatitis in mice by stimulating autophagy and p62‐Keap1‐Nrf2 anti‐oxidative signalling, suggesting that this drug has also some general anti‐inflammatory and hepatoprotective activities (Zhang et al, 2021). In line with a previous report, physalin B was shown to inhibit nitric oxide production by lipopolysaccharide (LPS) or interferon‐γ‐activated macrophages, and to protect mice against a lethal LPS challenge.…”