Institute of Biomedical Research, School of Life Sciences, Shandong University of Technology, Zibo, Shandong 255000, China.
Institute of Biomedical Research, School of Life Sciences, Shandong University of Technology, Zibo, Shandong 255000, China.
Phytomedicine. 2021 Jul 15;88:153498. doi: 10.1016/j.phymed.2021.153498. Epub 2021 Feb 12.
The incidence of nonalcoholic fatty liver disease (NAFLD), especially nonalcoholic steatohepatitis (NASH), has significantly increased in recent years and has become an important public health issue. However, no U.S. Food and Drug Administration (FDA)-approved first-line drug is currently available for the treatment of NAFLD and NASH; therefore, research on new drugs is currently a hot topic. Oroxylum indicum (Linn.) Kurz is extensively distributed in South China and South Asia and has many biological activities. However, its effects on NAFLD or even NASH and the corresponding mechanisms are still not clear.
To investigate the effect and mechanism of O. indicum seed extract (OISE) on preventing anti-inflammatory action in the progression from simple nonalcoholic fatty liver (NAFL) to NASH.
A network pharmacology method to construct ingredient-target networks and the protein-protein interaction (PPI) network of OISE in NASH were constructed for topological analyses and hub-target screening. Enrichment analyses were performed to identify the critical biological processes and signaling pathways. Simultaneously, in vitro and in vivo experiments investigated the effect and mechanism of OISE, baicalein, and chrysin on inflammation by biochemical indicator detection, luciferase reporters, pathological staining, and immunoblotting in oleic acid-stimulated HepG2 cells or in high-fat diet-fed rats.
The network pharmacology showed that OISE prevented the development and progression of NAFL into NASH through various pathways and targets and that the nuclear factor NF-κB (NF-κB) pathway regulated by baicalein and chrysin played an important role in the treatment of NASH. In in vitro experiments, we further showed that OISE and its ingredients, namely, baicalein and chrysin, all improved the inflammatory status in oleic acid-stimulated HepG2 cells, inhibited the nuclear transcriptional activities of NF-κB, increased the IκB level, and decreased the phosphorylation level of NF-κB. Furthermore, in a high-fat diet-induced NASH model in rats, we also showed that OISE prevented the development and progression of NASH by inhibiting the nuclear transcriptional activity of NF-κB.
OISE suppressed inflammatory responses and prevented the development and progression of NAFL into NASH through inhibition of the nuclear transcriptional activity of NF-κB. OISE may be used to treat NAFLD through many functions, including an increase in insulin sensitivity, a decrease in lipid accumulation in the liver, suppression of inflammation, and clearance of free radicals.
近年来，非酒精性脂肪性肝病（NAFLD）的发病率，尤其是非酒精性脂肪性肝炎（NASH），显著增加，已成为重要的公共卫生问题。然而，目前尚无美国食品和药物管理局（FDA）批准的一线药物用于治疗 NAFLD 和 NASH；因此，新药研究目前是一个热点。黄粱木（Linn.） Kurz 广泛分布于华南和南亚，具有多种生物学活性。然而，其对 NAFLD 甚至 NASH 的作用及其相应机制尚不清楚。
研究黄粱木种仁提取物（OISE）在预防从单纯非酒精性脂肪肝（NAFL）进展为 NASH 过程中的抗炎作用及机制。
构建 OISE 治疗 NASH 的网络药理学方法，构建 OISE 治疗 NASH 的成分-靶点网络和蛋白质-蛋白质相互作用（PPI）网络，并进行拓扑分析和枢纽靶点筛选。进行富集分析以确定关键的生物学过程和信号通路。同时，通过生化指标检测、荧光素酶报告基因、病理染色和免疫印迹法，在油酸刺激的 HepG2 细胞或高脂饮食喂养的大鼠中，研究 OISE、白杨素和白杨黄素对炎症的作用和机制。
网络药理学表明，OISE 通过多种途径和靶点预防 NAFL 向 NASH 的发展和进展，白杨素和白杨黄素调节的核因子 NF-κB（NF-κB）通路在 NASH 的治疗中发挥重要作用。在体外实验中，我们进一步表明，OISE 及其成分白杨素和白杨黄素均改善了油酸刺激的 HepG2 细胞中的炎症状态，抑制了 NF-κB 的核转录活性，增加了 IκB 水平，并降低了 NF-κB 的磷酸化水平。此外，在高脂饮食诱导的大鼠 NASH 模型中，我们还表明 OISE 通过抑制 NF-κB 的核转录活性来预防 NASH 的发生和进展。
OISE 通过抑制 NF-κB 的核转录活性抑制炎症反应，预防 NAFL 向 NASH 的发展和进展。OISE 可能通过增加胰岛素敏感性、减少肝脏脂质积累、抑制炎症和清除自由基等多种功能用于治疗 NAFLD。
