代谢功能障碍相关脂肪性肝病（MASLD）是2023年国际共识确立的慢性肝病，以肝细胞脂肪变性（>5%）伴代谢危险因素为特征，核心发病机制为胰岛素抵抗与脂质代谢失衡驱动的“代谢-炎症”恶性循环，目前缺乏特效药物。黄酮类中药单体为含2-苯基色原酮骨架的天然活性成分，按母核结构分为黄酮醇、异黄酮、黄酮、黄烷酮及查耳酮等亚类，其C3位羟基、C环饱和度等核心结构特征决定了对MASLD关键信号通路的选择性调控能力。结合近5年文献报道，系统综述不同亚类黄酮单体的差异化调控作用：黄酮醇类（如槲皮素）可多靶点干预腺苷酸激活蛋白激酶（AMPK）、Toll样受体（TLR）、磷脂酰肌醇3-激酶（PI3K）/蛋白激酶B(Akt)/哺乳动物雷帕霉素靶蛋白（m TOR）及核因子-κB(NF-κB)等多条通路；异黄酮类（如葛根素）侧重调节PI3K/Akt/mTOR与NF-κB，并可通过核受体机制协同抗炎；黄酮类（如木犀草素）凭借高平面性结构高效抑制关键激酶与炎症通路；黄烷酮类（如柚皮苷）则以非平面构象特色性激活AMPK并抑制MAPK；查耳酮类（如三叶苷）主要靶向抑制NF-κB/NOD样受体家族含热蛋白结构域蛋白3(NLRP3)-消皮素D(GSDMD)炎症焦亡轴。这些通路相互交织，其中AMPK与TLR分别作为能量与炎症感知的上游枢纽，PI3K/Akt/mTOR、NF-κB及MAPK则构成下游代谢与炎症执行网络。当前研究存在结构-机制阐释的同质化局限，未来需整合多组学技术深入解析构效关系，并发展靶向递送系统，以推动黄酮类单体向MASLD临床治疗转化提供理论依据。

Metabolic dysfunction-associated steatotic liver disease(MASLD) is a chronic liver disease established by international consensus in 2023, characterized by hepatic steatosis(> 5%) accompanied by cardiometabolic risk factors. Its core pathogenesis involves the “metabolism-inflammation” vicious cycle driven by insulin resistance and lipid metabolism disorders, and there is currently a lack of widely approved specific drugs. Flavonoid monomers from traditional Chinese medicine are natural bioactive components with a 2-phenylchromone skeleton, which can be classified into subclasses such as flavonols, isoflavones, flavones, flavanones, and chalcones based on their parent nucleus structures. Their core structural features(e.g., C3 hydroxyl group, C-ring saturation, and B-ring attachment position) directly determine their selective regulatory capacity on key signaling pathways of MASLD. Based on relevant literature published in the past five years, this review systematically summarizes the differential regulatory effects of flavonoid monomers from different subclasses: Flavonols(e.g., quercetin) exert multi-targeted intervention on multiple pathways including AMPK, PI3K/Akt/mTOR, and NF-κB; isoflavones(e.g., puerarin) mainly regulate PI3K/Akt/mTOR and NF-κB pathways, and may synergistically exert anti-inflammatory effects through nuclear receptor mechanisms; Flavones(e.g., luteolin) efficiently inhibit key kinases and inflammatory pathways by virtue of their high planarity; Flavanones(e.g., naringin) characteristically activate AMPK and inhibit MAPK with their non-planar conformation; chalcones(e.g., trilobatin) primarily target and inhibit the NF-κB/NLRP3-GSDMD inflammatory pyroptosis axis. These pathways are interconnected: AMPK and TLR serve as upstream hubs for energy and inflammation sensing, respectively, while PI3K/Akt/mTOR, NF-κB, and MAPK constitute the downstream execution network for metabolism and inflammation. Current studies have limitations such as homogenization in the interpretation of structuremechanism relationships. In the future, it is necessary to integrate multi-omics technologies to deeply analyze the structure-activity relationship and develop targeted delivery systems, so as to provide a theoretical basis for promoting the clinical transformation of flavonoid monomers in the treatment of MASLD.

R285.5

吉林省卫生健康科技能力提升项目(2024A084); 吉林省卫生健康科技能力提升计划项目(20252Y-YA005)