Yang Zhen, Wang Lin
Department of Hepatobiliary Surgery, Xi-Jing Hospital, The Fourth Military Medical University, Xi'an, China.
Front Pharmacol. 2023 Mar 30;14:1152042. doi: 10.3389/fphar.2023.1152042. eCollection 2023.
Non-alcoholic fatty liver disease (NAFLD) has been identified as the most common chronic liver disease worldwide, with a growing incidence. NAFLD is considered the hepatic manifestation of a metabolic syndrome that emerges from multiple factors (e.g., oxidative stress, metabolic disorders, endoplasmic reticulum stress, cell death, and inflammation). Non-alcoholic steatohepatitis (NASH), an advanced form of NAFLD, has been reported to be a leading cause of cirrhosis and hepatic carcinoma, and it is progressing rapidly. Since there is no approved pharmacotherapy for NASH, a considerable number of therapeutic targets have emerged with the deepening of the research on NASH pathogenesis. In this study, the therapeutic potential and properties of regulating metabolism, the gut microbiome, antioxidant, microRNA, inhibiting apoptosis, targeting ferroptosis, and stem cell-based therapy in NASH are reviewed and evaluated. Since the single-drug treatment of NASH is affected by individual heterogeneous responses and side effects, it is imperative to precisely carry out targeted therapy with low toxicity. Lastly, targeted therapeutic agent delivery based on exosomes is proposed in this study, such that drugs with different mechanisms can be incorporated to generate high-efficiency and low-toxicity individualized medicine.
非酒精性脂肪性肝病(NAFLD)已被确认为全球最常见的慢性肝病,且发病率不断上升。NAFLD被认为是一种由多种因素(如氧化应激、代谢紊乱、内质网应激、细胞死亡和炎症)引发的代谢综合征的肝脏表现。据报道,非酒精性脂肪性肝炎(NASH)作为NAFLD的一种晚期形式,是肝硬化和肝癌的主要病因,且其发病率正在迅速上升。由于目前尚无获批用于治疗NASH的药物疗法,随着对NASH发病机制研究的深入,出现了相当数量的治疗靶点。在本研究中,对调节代谢、肠道微生物群、抗氧化剂、微小RNA、抑制细胞凋亡、靶向铁死亡以及基于干细胞的疗法在NASH中的治疗潜力和特性进行了综述和评估。由于NASH的单一药物治疗受到个体异质性反应和副作用的影响,因此必须精确地进行低毒性的靶向治疗。最后,本研究提出了基于外泌体的靶向治疗药物递送方法,以便能够纳入不同作用机制的药物,从而生成高效低毒的个体化药物。