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.

中文翻译：

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发现用于治疗非酒精性脂肪肝的草药。

很少有药物可用于满足非酒精性脂肪肝疾病（NAFLD）及其进展期非酒精性脂肪性肝炎（NASH）不断增加的疾病负担。传统草药（THM）已被用于治疗具有多种症状但未明确现代定义的疾病类型和机制的土著人民。在现代，NAFLD被定义为一种常见的慢性疾病，导致人们需要开展更多的研究来了解NAFLD / NASH的病理学和进展。THM为提供治疗NAFLD的候选药物而引起了越来越多的关注。在这篇综述中，提出了一种称为“多器官多击中”的新模型来解释NASH进展的机制。针对这种提议的模型，综述了经常研究的THM产生的单一抗NAFLD候选药物和多种草药的作用和机理，其中水飞蓟素和小ber碱已在美国FDA批准的第4期临床研究中。此外，讨论了从THM中发现抗NAFLD药物治疗NAFLD的实验设计。重点介绍了逆向药理学和逆向药代动力学概念指导的THM现代化策略及其在治疗NAFLD方面的全球认可度所带来的机遇和挑战。越来越多的机械证据支持THM在治疗NAFLD和抗NAFLD药物发现中的有益作用。讨论了THM在治疗NAFLD中发现抗NAFLD药物的实验设计。重点介绍了逆向药理学和逆向药代动力学概念指导的THM现代化策略及其在治疗NAFLD方面的全球认可度所带来的机遇和挑战。越来越多的机械证据支持THM在治疗NAFLD和抗NAFLD药物发现中的有益作用。讨论了THM在治疗NAFLD中发现抗NAFLD药物的实验设计。重点介绍了逆向药理学和逆向药代动力学概念指导的THM现代化策略及其在治疗NAFLD方面的全球认可度所带来的机遇和挑战。越来越多的机械证据支持THM在治疗NAFLD和抗NAFLD药物发现中的有益作用。