2,3,5,4'-四羟基二苯乙烯-2-O-β-D-葡萄糖苷通过激活糖尿病前期大鼠的 PI3K/Akt 和 Erk 通路诱导肝自噬。
2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside induces autophagy of liver by activating PI3K/Akt and Erk pathway in prediabetic rats.
机构信息
Laboratory of Chinese Herbal Pharmacology, Oncology Center, Renmin Hospital; Hubei Key Laboratory of Wudang Local Chinese Medicine Research; Biomedical Research Institute, Hubei University of Medicine, 39 Middle Chaoyang Road, Shiyan, 442000, Hubei Province, China.
Department of Traditional Chinese Medicine, Taihe Hospital, Hubei University of Medicine, 32 South Renmin Road, Shiyan, 442000, Hubei Province, China.
出版信息
BMC Complement Med Ther. 2020 Jun 8;20(1):177. doi: 10.1186/s12906-020-02949-w.
BACKGROUND
2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside (TSG) is an active compound derived from Polygonum multiflorum Thunb., a Chinese Taoist herbal medicine, which exerts lipid lowering, anti-cancer, anti-aging, anti-inflammatory and hepatoprotective effects. However, its role in protecting hepatocytes under pre-diabetic condition remains unclear.
METHODS
In this study, we developed prediabetic SD rats by feeding high-fat and high-sugar diet. The body weight, blood lipid, blood glucose, and fasting insulin (FINS) and insulin resistance index (HOMA-IR) were detected and calculated to assess the potential risk of prediabetes. HE and Oil Red O staining was used, and blood level of biochemical index was detected to observe the liver injury. The autophagic cell death-associated signaling proteins, and the potential signaling factors p-Akt/Akt and p-Erk/Erk were detected using western blot to explore the potential effects of TSG on pre-diabetic liver and the underlying mechanisms.
RESULTS
The results showed that the body weight in TSG-treated group was significantly decreased vs. the model group. The blood glucose, the level of FINS and HOMA-IR, TC and TG were decreased in TSG-treated group as well. Furthermore, TSG treatment significantly ameliorated lipid droplet accumulation, enhanced liver anti-oxidative response which may be associated with an increased activity of SOD and GSH-Px, and a decrease of LDLC and MDA. The autophagic cell death-associated proteins, p-AMPK, ATG12, LC3 II, and Beclin 1 were up-regulated in the TSG-treated group, while the upstream signaling pathway, PI3K/Akt and Erk, were activated.
CONCLUSIONS
TSG induced liver autophagic cell death to protect liver from prediabetic injury by activating PI3K/Akt and Erk.
背景
2,3,5,4'-四羟基二苯乙烯-2-O-β-D-葡萄糖苷（TSG）是一种源自中国道家草药何首乌的活性化合物，具有降血脂、抗癌、抗衰老、抗炎和保肝作用。然而，其在糖尿病前期状态下保护肝细胞的作用尚不清楚。
方法
本研究通过给予高脂高糖饮食构建糖尿病前期 SD 大鼠模型。检测并计算体重、血脂、血糖、空腹胰岛素（FINS）和胰岛素抵抗指数（HOMA-IR），以评估糖尿病前期的潜在风险。采用 HE 和油红 O 染色观察肝脏损伤，检测血液生化指标水平。采用 Western blot 检测自噬细胞死亡相关信号蛋白及潜在信号因子 p-Akt/Akt 和 p-Erk/Erk，探讨 TSG 对糖尿病前期肝脏的潜在作用及其潜在机制。
结果
结果显示，与模型组相比，TSG 治疗组大鼠体重明显减轻。TSG 治疗组血糖、FINS 和 HOMA-IR 水平、TC 和 TG 水平均降低。此外，TSG 治疗显著改善了脂滴堆积，增强了肝脏抗氧化反应，可能与 SOD 和 GSH-Px 活性增加以及 LDLC 和 MDA 降低有关。自噬细胞死亡相关蛋白 p-AMPK、ATG12、LC3 II 和 Beclin 1 在 TSG 治疗组上调，而上游信号通路 PI3K/Akt 和 Erk 被激活。
结论
TSG 通过激活 PI3K/Akt 和 Erk 诱导肝自噬细胞死亡，从而保护肝脏免受糖尿病前期损伤。
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