State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 611137, China; School of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 611137, China.
School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 611137, China.
J Ethnopharmacol. 2024 Nov 15;334:118577. doi: 10.1016/j.jep.2024.118577. Epub 2024 Jul 15.
Gynostemma pentaphyllum (Thunb.) Makino (G. pentaphyllum) is an oriental herb documented to treat many diseases, including obesity, hyperlipidemia, metabolic syndromes and aging. However, the anti-obesity mechanism of G. pentaphyllum remains poorly understood.
To reveal the anti-obesity mechanism of G. pentaphyllum Extract (GPE) in High-Fat Diet (HFD)-induced obese mice through untargeted metabolomics, Real-Time Quantitative PCR (RT-qPCR), and immunohistochemical experiments. Additionally, to tentatively identify the active constituents through LC-MS/MS and molecular docking approaches.
GPE was prepared using ethanol reflux and purified by HP-20 macroporous resins. The components of GPE were identified by Liquid Chromatography- Mass Spectrometry (LC-MS) system. Forty-two C57BL/6 J mice were randomly and evenly divided into six groups, with seven mice in each group: the control group, obese model group, Beinaglutide group (positive control), and GPE low, medium, and high-dose groups (50 mg/kg, 100 mg/kg, and 200 mg/kg of 80% ethanol extract). Body weight, liver weight, blood glucose, blood lipids, and liver histopathological changes were assessed. Untargeted metabolomics was employed to characterize metabolic changes in obese mice after GPE treatment. The expression of genes related to differential metabolites was verified using Real-Time Quantitative PCR (RT-qPCR) and immunohistochemical experiments. The constituents with anti-obesity effects from GPE were tentatively identified through molecular docking approaches.
A total of 17 compounds were identified in GPE. GPE significantly lowered body weight, total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in obese mice and reduced liver weight and hepatic steatosis. Serum metabolomics identified 20 potential biomarkers associated with GPE treatment in obese mice, primarily related to tryptophan metabolism. GPE treatment downregulated the expression of Slc6a19 and Tph1 and upregulated Ucp1 expression. Molecular docking illustrated that compounds such as 20(R)-ginsenoside Rg3, Araliasaponin I, Damulin B, Gypenoside L, Oleifolioside B, and Tricin7-neohesperidoside identified in GPE exhibited favorable interaction with Tph1.
The extract of G. pentaphyllum can inhibit the absorption of tryptophan and its conversion to 5-HT through the Slc6a19/Tph1 pathway, upregulating the expression of Ucp1, thereby promoting thermogenesis in brown adipose tissue, facilitating weight loss, and mitigating symptoms of fatty liver. Triterpenoids such as Araliasaponin I, identified in GPE, could be the potential inhibitor of Tph1 and responsible for the anti-obesity activities.
绞股蓝（Thunb.）Makino（G. pentaphyllum）是一种东方草药，据记载可治疗多种疾病，包括肥胖、高血脂、代谢综合征和衰老。然而，绞股蓝的减肥机制仍知之甚少。
通过非靶向代谢组学、实时定量 PCR（RT-qPCR）和免疫组织化学实验，揭示绞股蓝提取物（GPE）在高脂饮食（HFD）诱导的肥胖小鼠中的减肥机制。此外，通过 LC-MS/MS 和分子对接方法，初步鉴定活性成分。
采用乙醇回流法制备 GPE，并用 HP-20 大孔树脂进行纯化。采用液相色谱-质谱（LC-MS）系统鉴定 GPE 的成分。将 42 只 C57BL/6J 小鼠随机均分为六组，每组 7 只：对照组、肥胖模型组、贝那鲁肽组（阳性对照）和 GPE 低、中、高剂量组（50mg/kg、100mg/kg 和 200mg/kg 的 80%乙醇提取物）。评估体重、肝重、血糖、血脂和肝组织病理学变化。采用非靶向代谢组学方法描述 GPE 治疗肥胖小鼠后的代谢变化。通过实时定量 PCR（RT-qPCR）和免疫组织化学实验验证与差异代谢物相关的基因表达。通过分子对接方法，初步鉴定 GPE 中具有减肥作用的成分。
GPE 中鉴定出 17 种化合物。GPE 可显著降低肥胖小鼠的体重、总胆固醇（TC）和低密度脂蛋白胆固醇（LDL-C），并降低肝重和肝脂肪变性。血清代谢组学鉴定出 20 种与 GPE 治疗肥胖小鼠相关的潜在生物标志物，主要与色氨酸代谢有关。GPE 处理下调 Slc6a19 和 Tph1 的表达，上调 Ucp1 的表达。分子对接表明，GPE 中鉴定出的 20（R）-人参皂苷 Rg3、竹节参皂苷 I、达木林 B、绞股蓝皂苷 L、橄榄叶苷 B 和三萜 7-新橙皮苷等化合物与 Tph1 表现出良好的相互作用。
绞股蓝提取物可通过 Slc6a19/Tph1 途径抑制色氨酸的吸收及其向 5-HT 的转化，上调 Ucp1 的表达，从而促进棕色脂肪组织的产热，促进体重减轻，并减轻脂肪肝的症状。GPE 中鉴定出的三萜类化合物，如竹节参皂苷 I，可能是 Tph1 的潜在抑制剂，负责其减肥活性。
