Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, Republic of Korea.
Department of Surgery, College of Medicine, Chung-Ang University, Seoul, Republic of Korea.
Obes Facts. 2024;17(5):513-523. doi: 10.1159/000540699. Epub 2024 Aug 5.
Previous research has shown that an aqueous extract of Humulus japonicus (EH) can ameliorate hypertension, nonalcoholic fatty liver disease, and oxidative stress in adipocytes by activating the thermogenic pathway. However, the effects of an ethanol (30%) extract of EH on obesity are unknown.
Various protein expression levels in fully differentiated 3T3-L1 adipocytes were assessed by Western blotting. Lipid deposition in 3T3-L1 adipocytes was examined by oil red O staining. The MTT assay was used to evaluate adipocyte viability. Caspase 3 activity and glycerol release were determined using commercial assay kits.
In this study, we discovered that EH treatment inhibited lipogenesis and promoted lipolysis in both differentiated 3T3-L1 adipocytes and adipose tissue of mice fed a high-fat diet. EH treatment also increased phosphorylated protein kinase A (PKA) levels while reducing p38 phosphorylation. When H89, a PKA inhibitor, was used, the effects of EH on lipogenic lipid accumulation and lipolysis in 3T3-L1 adipocytes were eliminated. Treatment with luteolin 7-O-β-d-glucoside (LU), the major active compound in EH, also suppressed lipid deposition and p38 phosphorylation but enhanced lipolysis in 3T3-L1 adipocytes. These changes were abrogated by H89.
These findings indicate that EH containing LU reduces lipogenesis and stimulates lipolysis via the PKA/p38 signaling pathway, leading to an improvement in obesity in mice. Therefore, our study suggested that EH could be a promising therapeutic agent for treating obesity.
先前的研究表明，葎草（Humulus japonicus）的水提物可通过激活产热途径改善高血压、非酒精性脂肪肝和脂肪细胞中的氧化应激。然而，葎草 30%乙醇提取物对肥胖的影响尚不清楚。
通过 Western blot 检测完全分化的 3T3-L1 脂肪细胞中的各种蛋白表达水平。用油红 O 染色法检测 3T3-L1 脂肪细胞中的脂滴沉积。使用 MTT 法评估脂肪细胞活力。使用商业检测试剂盒测定 caspase 3 活性和甘油释放。
在这项研究中，我们发现 EH 处理抑制了分化的 3T3-L1 脂肪细胞和高脂肪饮食喂养的小鼠脂肪组织中的脂肪生成，并促进了脂肪分解。EH 处理还增加了磷酸化蛋白激酶 A（PKA）水平，同时减少了 p38 的磷酸化。当使用 PKA 抑制剂 H89 时，EH 对 3T3-L1 脂肪细胞中脂肪生成脂质积累和脂肪分解的作用被消除。EH 中的主要活性化合物木犀草素 7-O-β-d-葡萄糖苷（LU）的处理也抑制了脂肪沉积和 p38 磷酸化，但增强了 3T3-L1 脂肪细胞中的脂肪分解。这些变化被 H89 阻断。
这些发现表明，EH 含有 LU，通过 PKA/p38 信号通路减少脂肪生成并刺激脂肪分解，从而改善肥胖小鼠的肥胖症。因此，我们的研究表明 EH 可能是治疗肥胖症的有前途的治疗剂。
