Yan Tingting, Yan Nana, Wang Ping, Xia Yangliu, Hao Haiping, Wang Guangji, Gonzalez Frank J
Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
State Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China.
Acta Pharm Sin B. 2020 Jan;10(1):3-18. doi: 10.1016/j.apsb.2019.11.017. Epub 2019 Dec 10.
Few medications are available for meeting the increasing disease burden of nonalcoholic fatty liver disease (NAFLD) and its progressive stage, nonalcoholic steatohepatitis (NASH). Traditional herbal medicines (THM) have been used for centuries to treat indigenous people with various symptoms but without clarified modern-defined disease types and mechanisms. In modern times, NAFLD was defined as a common chronic disease leading to more studies to understand NAFLD/NASH pathology and progression. THM have garnered increased attention for providing therapeutic candidates for treating NAFLD. In this review, a new model called "multiple organs-multiple hits" is proposed to explain mechanisms of NASH progression. Against this proposed model, the effects and mechanisms of the frequently-studied THM-yielded single anti-NAFLD drug candidates and multiple herb medicines are reviewed, among which silymarin and berberine are already under U.S. FDA-sanctioned phase 4 clinical studies. Furthermore, experimental designs for anti-NAFLD drug discovery from THM in treating NAFLD are discussed. The opportunities and challenges of reverse pharmacology and reverse pharmacokinetic concepts-guided strategies for THM modernization and its global recognition to treat NAFLD are highlighted. Increasing mechanistic evidence is being generated to support the beneficial role of THM in treating NAFLD and anti-NAFLD drug discovery.
用于应对非酒精性脂肪性肝病（NAFLD）及其进展期非酒精性脂肪性肝炎（NASH）日益增加的疾病负担的药物寥寥无几。传统草药（THM）已被使用了几个世纪，用于治疗有各种症状的原住民，但没有明确现代定义的疾病类型和机制。在现代，NAFLD被定义为一种常见的慢性疾病，这引发了更多旨在了解NAFLD/NASH病理和进展的研究。传统草药因能为治疗NAFLD提供治疗候选药物而受到越来越多的关注。在本综述中，提出了一种名为“多器官-多重打击”的新模型来解释NASH进展的机制。针对这一提出的模型，综述了经常研究的传统草药产生的单一抗NAFLD候选药物和多种草药的作用及机制，其中水飞蓟素和黄连素已处于美国食品药品监督管理局（FDA）批准的4期临床研究阶段。此外，还讨论了从传统草药中发现抗NAFLD药物用于治疗NAFLD的实验设计。强调了反向药理学和反向药代动力学概念指导的策略在传统草药现代化及其治疗NAFLD的全球认可方面的机遇和挑战。越来越多的机制证据支持传统草药在治疗NAFLD和抗NAFLD药物发现中的有益作用。
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