Laboratory of Veterinary Pharmacokinetics and Pharmacodynamics, College of Veterinary Medicine, Kyungpook National University, Daegu 41566, the Republic of Korea; Bacterial Disease Division, Animal and Plant Quarantine Agency, 177 Hyeksin 8-ro, Gimcheon-si, Gyeongsangbuk-do 39660, the Republic of Korea; Cardiovascular Research Institute, Kyungpook National University School of Medicine, Gukchabosang-ro 680, Jung-Gu, Daegu 41944, the Republic of Korea.
Laboratory of Veterinary Pharmacokinetics and Pharmacodynamics, College of Veterinary Medicine, Kyungpook National University, Daegu 41566, the Republic of Korea.
Biomed Pharmacother. 2022 Oct;154:113629. doi: 10.1016/j.biopha.2022.113629. Epub 2022 Sep 1.
Pyrus ussuriensis Maxim (Korean pear) has been used for hundreds of years as a traditional herbal medicine due to its strong phytochemical profile and pharmacological efficacy. In this study, we evaluated the anti-obesity potential of Pyrus ussuriensis Maxim extracts (PUE) and investigated the underlying mechanisms using a combination of in vitro, in vivo, and microbiota regulation approaches. In an adipogenesis assay, the fermented (F)PUE and non-fermented (NF)PUE significantly reduced the differentiation of 3T3-L1 preadipocyte in a dose-dependent manner with an IC of 85.33 and 96.67 µg/mL, respectively. In a high-fat diet (HFD)-induced obese rat model (n = 8 animals/group), oral administration of FPUE additionally reduced the total body weight gain significantly. No difference in food intake was observed, however, between the control-chow diet, FPUE, and NFPUE-treated HFD rats. Adipose tissue mass and systemic insulin resistance were markedly reduced in FPUE-treated HFD rats, in a dose-dependent manner. Treatment with FPUE also greatly improved obesity-related biomarkers, including total cholesterol, leptin, active ghrelin, Total GIP, adiponectin, and proinflammatory cytokines. Moreover, FPUE significantly suppressed HFD-induced adipogenic genes expression, while increasing fatty acid oxidation-related genes expression. Additionally, FPUE treatment attenuated the HFD-induced Firmicutes proportion within the intestinal microbiota by regulating key metabolic pathways, thus enhancing microbial population diversity (e.g., increasing Bacteroides, Bifidobacterium, Prevotella, Eubacterium, and Clostridium). Together, these results reveal a strong anti-obesity potential of FPUE through adipogenesis, lipid metabolism, weight reduction, and microbiota regulation, raising the possibility of developing FPUE as a novel therapeutic agent to control obesity and obesity-associated metabolic disorders.
沙梨（Pyrus ussuriensis Maxim）作为一种传统草药，因其具有丰富的植物化学成分和显著的药理功效，已被使用了数百年。本研究采用体外、体内和微生物组调节相结合的方法，评估了沙梨提取物（Pyrus ussuriensis Maxim extracts，PUE）的抗肥胖潜力，并探讨了其作用机制。在脂肪生成测定中，发酵（F）PUE 和非发酵（NF）PUE 均能显著抑制 3T3-L1 前脂肪细胞的分化，其 IC 分别为 85.33 和 96.67 µg/mL，呈剂量依赖性。在高脂饮食（HFD）诱导的肥胖大鼠模型中（n = 8 只/组），FPUE 口服给药还能显著降低总体重增加。然而，在对照饲料、FPUE 和 NF-PUE 处理的 HFD 大鼠中，未观察到食物摄入量的差异。FPUE 处理还能显著降低 HFD 大鼠的脂肪组织质量和全身胰岛素抵抗，呈剂量依赖性。FPUE 处理还极大地改善了与肥胖相关的生物标志物，包括总胆固醇、瘦素、活性胃饥饿素、总 GIP、脂联素和促炎细胞因子。此外，FPUE 显著抑制了 HFD 诱导的脂肪生成基因表达，同时增加了脂肪酸氧化相关基因的表达。此外，FPUE 通过调节关键代谢途径，抑制了肠道微生物群中厚壁菌门的比例，从而提高了微生物种群的多样性（例如，增加了拟杆菌属、双歧杆菌属、普雷沃氏菌属、真杆菌属和梭菌属）。总之，这些结果表明 FPUE 通过脂肪生成、脂质代谢、体重减轻和微生物组调节，具有很强的抗肥胖潜力，为开发 FPUE 作为控制肥胖和肥胖相关代谢紊乱的新型治疗药物提供了可能。
