Abstract：
Oxyberberine (OBB), a main gut-mediated metabolite of Phellodendron chinense Cortex (PC), exhibits prominent protective property against acute liver injury (ALI). Heme oxygenase-1 (HO-1) is a vital molecule in attenuating acute and chronic liver injury for its prominent anti-oxidative injury and anti-inflammation properties. The present study was performed to investigate the hepatoprotective role of OBB through HO-1 signaling pathway in lipopolysaccharide/D-galactosamine (LPS/D-GalN) induced ALI. Our results indicated that PC treatment improved survival rate and its metabolite OBB evidently improved histopathological deteriorations and liver function. Additionally, OBB dramatically ameliorated hepatic oxidative stress and inflammation. Besides, OBB exerted remarkable HO-1 agonistic activity, even be comparable to hemin (a HO-1 inducer), as evidenced by increased HO-1 level, carbon monoxide and bilirubin activities, which are the markers of erythrocyte metabolism. Moreover, OBB modulated the parameters of inflammation and oxidative stress through HO-1 dependent pathway. Beyond this, OBB also notably suppressed the translocation of p65, enhanced antioxidation defense genes expressions, promoted the degradation of Kelch-like ECH-associated protein 1 (Keap1) and the nuclear translocation of nuclear factor-erythroid-2-related factor 2 (Nrf2). In conclusion, OBB could be the principle active metabolite substance of PC and exert excellent hepatoprotective effects via inducing HO-1 through coactivation of erythrocyte metabolism and Nrf2/HO-1 pathway.
摘要：
氧连素(OBB),黄柏（PC）的主要肠道介导的代谢产物，对急性肝损伤（ALI）具有突出的保护特性。血红素加氧酶-1（HO-1）是减轻急性和慢性肝损伤的重要分子，具有显着的抗氧化损伤和抗炎特性。本研究旨在研究OBB通过HO-1信号通路在脂多糖/D-半乳糖胺（LPS/D-GalN）诱导的ALI中的保护作用。我们的结果表明，PC治疗提高了生存率，其代谢产物OBB明显改善了组织病理学恶化和肝功能。此外,OBB显著改善肝脏氧化应激和炎症。此外,OBB发挥显著的HO-1激动活性，甚至与血红素（HO-1诱导剂）相当，HO-1水平升高证明了这一点，一氧化碳和胆红素活性，是红细胞代谢的标志.此外，OBB通过HO-1依赖性途径调节炎症和氧化应激参数。除此之外,OBB还显著抑制了p65的易位，增强了抗氧化防御基因的表达，促进Kelch样ECH相关蛋白1（Keap1）的降解和核因子-红细胞相关因子2（Nrf2）的核易位。总之,OBB可能是PC的主要活性代谢产物，通过诱导红细胞代谢和Nrf2/HO-1途径共同激活HO-1，发挥良好的肝保护作用。
