Liu Pai Chinese Medical Center, The Seventh Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, China.
School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China.
Pharm Biol. 2022 Dec;60(1):1819-1838. doi: 10.1080/13880209.2022.2106250.
Shen-Shi-Jiang-Zhuo formula (SSJZF) exhibits a definite curative effect in the clinical treatment of non-alcoholic fatty liver disease (NAFLD).
To explore the therapeutic effect and mechanism of SSJZF on NAFLD.
Sprague Dawley rats were randomly divided into control, NAFLD, positive drug (12 mg/kg/day), SSJZF high-dose (200 mg/kg/day), SSJZF middle-dose (100 mg/kg/day), and SSJZF low-dose (50 mg/kg/day) groups. After daily intragastric administration of NAFLD rats for 8 weeks, lipid metabolism and hepatic fibrosis were evaluated by biochemical indices and histopathology. Then we uncovered the main active compounds and mechanism of SSJZF against NAFLD by integrating RNA-sequencing and network pharmacology, and PI3K/AKT pathway activity was verified by western blot.
High dose SSJZF had the best inhibitory effect on hepatic lipid accumulation and fibrosis in rats with NAFLD, which significantly down-regulated otal triglycerides (58%), cholesterol (62%), aspartate aminotransferase (57%), alanine aminotransferase (41%) andγ-glutamyl transpeptidase (36%), as well as the expression of ACC (5.3-fold), FAS (12.1-fold), SREBP1C (2.3-fold), and CD36 (4.4-fold), and significantly reduced collagen deposition (67%). Then we identified 23 compounds of SSJZF that acted on 25 key therapeutic targets of NAFLD by integrating RNA-sequencing and network pharmacology. Finally, we also confirmed that high dose SSJZF increased p-PI3K/PI3K (1.6-fold) and p-AKT/AKT (1.6-fold) in NAFLD rats.
We found for first time that SSJZF improved NAFLD in rats by activating the PI3K/Akt pathway. These findings provide scientific support for SSJZF in the clinical treatment of NAFLD and contribute to the development of new NAFLD drugs.
参术降脂方（SSJZF）在非酒精性脂肪性肝病（NAFLD）的临床治疗中具有明确疗效。
探讨 SSJZF 对 NAFLD 的治疗作用及机制。
将 Sprague Dawley 大鼠随机分为对照组、NAFLD 组、阳性药物（12mg/kg/天）组、SSJZF 高剂量（200mg/kg/天）组、SSJZF 中剂量（100mg/kg/天）组和 SSJZF 低剂量（50mg/kg/天）组。NAFLD 大鼠每日灌胃给药 8 周后，通过生化指标和组织病理学评估脂质代谢和肝纤维化。然后，我们通过整合 RNA 测序和网络药理学揭示 SSJZF 治疗 NAFLD 的主要活性化合物和机制，并通过 Western blot 验证 PI3K/AKT 通路活性。
高剂量 SSJZF 对 NAFLD 大鼠肝内脂质蓄积和纤维化的抑制作用最佳，显著下调总甘油三酯（58%）、胆固醇（62%）、天冬氨酸转氨酶（57%）、丙氨酸转氨酶（41%）和γ-谷氨酰转肽酶（36%），以及 ACC（5.3 倍）、FAS（12.1 倍）、SREBP1C（2.3 倍）和 CD36（4.4 倍）的表达，显著减少胶原沉积（67%）。然后，我们通过整合 RNA 测序和网络药理学鉴定出 23 种 SSJZF 化合物，这些化合物作用于 25 个 NAFLD 的关键治疗靶点。最后，我们还证实高剂量 SSJZF 增加了 NAFLD 大鼠中的 p-PI3K/PI3K（1.6 倍）和 p-AKT/AKT（1.6 倍）。
我们首次发现 SSJZF 通过激活 PI3K/Akt 通路改善了 NAFLD 大鼠的病情。这些发现为 SSJZF 在 NAFLD 的临床治疗提供了科学依据，并为开发新的 NAFLD 药物做出了贡献。
