Ph.D. Program for the Clinical Drug Discovery from Herbal Medicine, College of Pharmacy, Taipei Medical University, Taipei 110, Taiwan.
Division of Chinese Medicinal Chemistry, National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei 112, Taiwan.
Int J Mol Sci. 2022 Apr 6;23(7):4052. doi: 10.3390/ijms23074052.
Phytochemicals that interrupt adipocyte lifecycle can provide anti-obesity effects. 1,2,3,4,6-penta-O-galloyl-d-glucose (PGG) is a tannin with two isomers that occurs widely in plants and exhibits various pharmacological activities. The aim of the investigation is to comprehensively examine effects of PGG isomer(s) on adipocyte lifecycle and diet-induced obesity. Human mesenchymal stem cells (hMSC), 3T3-L1 fibroblasts, and H4IIE hepatoma cells were used to determine the effects of PGG isomers on cell viability and adipogenesis. Mice with diet-induced obesity were generated from male C57/BL6 mice fed with a 45% high fat diet. Oral administration of β-PGG (0.1 and 5 mg/kg) lasted for 14 weeks. Viability was reduced by repeated PGG treatment in hMSC, preadipocytes, and cells under differentiation. PGG mainly induces apoptosis, and this effect is independent of its insulin mimetic action. In vivo, administration of β-PGG attenuated shortening of the colon, hyperlipidaemia, fat cells and islet hypertrophy in DIO mice. Hepatic steatosis and related gene expression were improved along with glucose intolerance. Increased serum adiponectin, leptin, and glucagon-like peptide-1 levels were also observed. In conclusion, repeated PGG treatment interrupts the adipocyte lifecycle. PGG administration reduces adiposity and fatty liver development in DIO mice, and therefore, PGG could aid in clinical management of obesity.
植物化学物质可以打断脂肪细胞的生命周期，从而产生抗肥胖的效果。1,2,3,4,6-五没食子酰葡萄糖（PGG）是一种广泛存在于植物中的单宁，有两种异构体，具有多种药理活性。本研究旨在全面研究 PGG 异构体对脂肪细胞生命周期和饮食诱导肥胖的影响。使用人骨髓间充质干细胞（hMSC）、3T3-L1 成纤维细胞和 H4IIE 肝癌细胞来确定 PGG 异构体对细胞活力和脂肪生成的影响。用 45%高脂肪饮食喂养雄性 C57/BL6 小鼠，生成饮食诱导肥胖的小鼠。β-PGG（0.1 和 5mg/kg）口服给药持续 14 周。PGG 重复处理会降低 hMSC、前脂肪细胞和分化中的细胞的活力。PGG 主要诱导细胞凋亡，这种作用与其胰岛素模拟作用无关。在体内，β-PGG 的给药可减轻 DIO 小鼠结肠缩短、高脂血症、脂肪细胞和胰岛肥大。肝脂肪变性和相关基因表达得到改善，同时伴有葡萄糖不耐受。还观察到血清脂联素、瘦素和胰高血糖素样肽-1 水平升高。总之，重复的 PGG 处理会打断脂肪细胞的生命周期。PGG 给药可减少 DIO 小鼠的肥胖和脂肪肝的发生，因此，PGG 可能有助于肥胖的临床管理。
