Liu Jie, Shi Yun, Peng Daiyin, Wang Lei, Yu Nianjun, Wang Guokai, Chen Weidong
School of Pharmacy, Anhui University of Chinese Medicine, Hefei, China.
Anhui Province Key Laboratory of Chinese Medicinal Formula, Hefei, China.
Front Cardiovasc Med. 2022 Apr 22;9:842980. doi: 10.3389/fcvm.2022.842980. eCollection 2022.
Non-alcoholic fatty liver disease (NAFLD) is rapidly prevalent due to its strong association with increased metabolic syndrome such as cardio- and cerebrovascular disorders and diabetes. Few drugs can meet the growing disease burden of NAFLD. Bge. (Danshen) have been used for over 2,000 years in clinical trials to treat NAFLD and metabolic syndrome disease without clarified defined mechanisms. Metabolic targets restored metabolic homeostasis in patients with NAFLD and improved steatosis by reducing the delivery of metabolic substrates to liver as a promising way. Here we systematic review evidence showing that Danshen against NAFLD through diverse and crossing mechanisms based on metabolic targets. A synopsis of the phytochemistry and pharmacokinetic of Danshen and the mechanisms of metabolic targets regulating the progression of NAFLD is initially provided, followed by the pharmacological activity of Danshen in the management NAFLD. And then, the possible mechanisms of Danshen in the management of NAFLD based on metabolic targets are elucidated. Specifically, the metabolic targets c-Jun N-terminal kinases (JNK), sterol regulatory element-binding protein-1c (SREBP-1c), nuclear translocation carbohydrate response element-binding protein (ChREBP) related with lipid metabolism pathway, and peroxisome proliferator-activated receptors (PPARs), cytochrome P450 (CYP) and the others associated with pleiotropic metabolism will be discussed. Finally, providing a critical assessment of the preclinic and clinic model and the molecular mechanism in NAFLD.
非酒精性脂肪性肝病(NAFLD)由于与心血管疾病和糖尿病等代谢综合征增加密切相关,正在迅速流行。很少有药物能够应对NAFLD日益增加的疾病负担。丹参已在临床试验中使用了2000多年来治疗NAFLD和代谢综合征疾病,但机制尚不明确。代谢靶点通过减少代谢底物向肝脏的输送来恢复NAFLD患者的代谢稳态并改善脂肪变性,这是一种很有前景的方法。在这里,我们系统地综述了证据,表明丹参基于代谢靶点通过多种交叉机制对抗NAFLD。首先介绍了丹参的植物化学、药代动力学以及代谢靶点调节NAFLD进展的机制,随后阐述了丹参在治疗NAFLD中的药理活性。然后,阐明了丹参基于代谢靶点治疗NAFLD的可能机制。具体而言,将讨论与脂质代谢途径相关的代谢靶点c-Jun氨基末端激酶(JNK)、固醇调节元件结合蛋白-1c(SREBP-1c)、核转位碳水化合物反应元件结合蛋白(ChREBP),以及与多效性代谢相关的过氧化物酶体增殖物激活受体(PPARs)、细胞色素P450(CYP)等。最后,对NAFLD的临床前和临床模型以及分子机制进行批判性评估。