Zhang Jing-Bei, Jin Hong-Liu, Feng Xiao-Ying, Feng Sen-Ling, Zhu Wen-Ting, Nan Hong-Mei, Yuan Zhong-Wen
Collage of Chinese Medicine, Changchun University of Chinese Medicine, Jilin, China.
Department of Pharmacy, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Front Pharmacol. 2022 Aug 19;13:984611. doi: 10.3389/fphar.2022.984611. eCollection 2022.
To explore the active components and epigenetic regulation mechanism underlying the anti-inflammatory effects of and herb-pair (LFP) in carbon tetrachloride (CCl)-induced rat liver fibrosis. The main active ingredients and disease-related gene targets of LFP were determined using TCMSP and UniProt, and liver fibrosis disease targets were screened in the GeneCards database. A network was constructed with Cytoscape 3.8.0 and the STRING database, and potential protein functions were analyzed using bioinformatics analysis. Based on these analyses, we determined the main active ingredients of LFP and evaluated their effects in a CCl-induced rat liver fibrosis model. Serum biochemical indices were measured using commercial kits, hepatocyte tissue damage and collagen deposition were evaluated by histopathological studies, and myofibroblast activation and inflammation were detected by reverse transcription-polymerase chain reaction (RT-PCR) and western blotting. High-performance liquid chromatography-mass spectrometry was performed to determine the levels of homocysteine, reduced glutathione, and oxidized glutathione, which are involved in inflammation and oxidative stress. The main active components of LFP were quercetin, kaempferol, and luteolin, and its main targets were α-smooth muscle actin, cyclooxygenase-2, formyl-peptide receptor-2, prostaglandin-endoperoxide synthase 1, nuclear receptor coactivator-2, interleukinβ, tumor necrosis factor α, CXC motif chemokine ligand 14, and transforming growth factor β1. A combination of quercetin, kaempferol, and luteolin alleviated the symptoms of liver fibrosis. The results of this study support the role of LFP in the treatment of liver fibrosis, and reveal that LFP reduces collagen formation, inflammation, and oxidative stress. This study suggests a potential mechanism of action of LFP in the treatment of liver fibrosis.
探讨茵陈蒿汤（LFP）对四氯化碳（CCl）诱导的大鼠肝纤维化抗炎作用的活性成分及表观遗传调控机制。利用中药系统药理学数据库与分析平台（TCMSP）和通用蛋白质数据库（UniProt）确定LFP的主要活性成分和疾病相关基因靶点，并在基因卡片数据库（GeneCards）中筛选肝纤维化疾病靶点。使用Cytoscape 3.8.0软件和STRING数据库构建网络，并通过生物信息学分析潜在的蛋白质功能。基于这些分析，我们确定了LFP的主要活性成分，并在CCl诱导的大鼠肝纤维化模型中评估了它们的作用。使用商业试剂盒检测血清生化指标，通过组织病理学研究评估肝细胞组织损伤和胶原沉积，并通过逆转录-聚合酶链反应（RT-PCR）和蛋白质免疫印迹法检测肌成纤维细胞活化和炎症。采用高效液相色谱-质谱联用技术测定参与炎症和氧化应激的同型半胱氨酸、还原型谷胱甘肽和氧化型谷胱甘肽的水平。LFP的主要活性成分是槲皮素、山奈酚和木犀草素，其主要靶点是α-平滑肌肌动蛋白、环氧化酶-2、甲酰肽受体-2、前列腺素内过氧化物合酶1、核受体辅激活因子-2、白细胞介素β、肿瘤坏死因子α、CXC基序趋化因子配体14和转化生长因子β1。槲皮素、山奈酚和木犀草素的组合减轻了肝纤维化症状。本研究结果支持LFP在肝纤维化治疗中的作用，并揭示LFP可减少胶原形成、炎症和氧化应激。本研究提示了LFP治疗肝纤维化的潜在作用机制。
