Type 2 diabetes mellitus (T2DM) is a chronic disease characterized by hyperglycemia that can lead to long-term complications including heart diseases, stroke, retinopathy, and renal failure. Treatment strategies include stimulating glucose uptake and controlling blood glucose level. Bofutsushosan (BOF) and Daisaikoto (DAI) are two herb-based kampo medicines that have been demonstrated to improve metabolism-associated disorders including obesity, hyperlipidemia, and nonalcoholic fatty liver. Given their bioactivities against metabolic syndromes, we explored in this study the effect of BOF and DAI extracts on glucose absorption and used them as source to identify phytochemical stimulator of glucose absorption. Glucose uptake and mechanistic studies were evaluated in differentiated C2C12 skeletal muscle cells, and HPLC analysis was used to determine the molecular bioactive constituents. Our results indicated that the ethanolic extracts of BOF and DAI (BOFEE and DAIEE, respectively) enhanced the glucose uptake ratio in the differentiated C2C12 cells, and further analysis identified the flavone baicalin as a major constituent capable of efficiently stimulating glucose absorption. Mechanistic studies revealed that the effect from baicalin involved the activation of IRS-1 and GLUT-4, and implicated the AMPK, PI3K/Akt, and MAPK/ERK signaling cascades. Due to its potency, we suggest that baicalin merit further evaluation as a potential candidate anti-hyperglycemic agent for the treatment and management of T2DM.

中文翻译：

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从 Bofutsushosan 和 Daisaikoto 中鉴定黄芩苷作为葡萄糖摄取的有效诱导剂和胰岛素信号相关通路的调节剂

2 型糖尿病 (T2DM) 是一种以高血糖为特征的慢性疾病，可导致长期并发症，包括心脏病、中风、视网膜病变和肾功能衰竭。治疗策略包括刺激葡萄糖摄取和控制血糖水平。Bofutsushosan (BOF) 和 Daisaikoto (DAI) 是两种以草药为基础的汉方药物，已被证明可改善代谢相关疾病，包括肥胖、高脂血症和非酒精性脂肪肝。鉴于它们对代谢综合征的生物活性，我们在本研究中探讨了 BOF 和 DAI 提取物对葡萄糖吸收的影响，并将它们用作鉴定葡萄糖吸收的植物化学刺激物的来源。在分化的 C2C12 骨骼肌细胞中评估葡萄糖摄取和机制研究，高效液相色谱分析用于确定分子生物活性成分。我们的结果表明，BOF 和 DAI（分别为 BOFEE 和 DAIEE）的乙醇提取物提高了分化的 C2C12 细胞的葡萄糖摄取率，进一步分析确定黄芩苷是能够有效刺激葡萄糖吸收的主要成分。机制研究表明，黄芩苷的作用涉及 IRS-1 和 GLUT-4 的激活，并涉及 AMPK、PI3K/Akt 和 MAPK/ERK 信号级联。由于其效力，我们建议黄芩苷作为治疗和管理 T2DM 的潜在候选抗高血糖剂值得进一步评估。分别）增强分化的C2C12细胞中的葡萄糖摄取率，进一步分析确定黄芩苷是能够有效刺激葡萄糖吸收的主要成分。机制研究表明，黄芩苷的作用涉及 IRS-1 和 GLUT-4 的激活，并涉及 AMPK、PI3K/Akt 和 MAPK/ERK 信号级联。由于其效力，我们建议黄芩苷作为治疗和管理 T2DM 的潜在候选抗高血糖剂值得进一步评估。分别）增强分化的C2C12细胞中的葡萄糖摄取率，进一步分析确定黄芩苷是能够有效刺激葡萄糖吸收的主要成分。机制研究表明，黄芩苷的作用涉及 IRS-1 和 GLUT-4 的激活，并涉及 AMPK、PI3K/Akt 和 MAPK/ERK 信号级联。由于其效力，我们建议黄芩苷作为治疗和管理 T2DM 的潜在候选抗高血糖剂值得进一步评估。PI3K/Akt 和 MAPK/ERK 信号级联。由于其效力，我们建议黄芩苷作为治疗和管理 T2DM 的潜在候选抗高血糖剂值得进一步评估。PI3K/Akt 和 MAPK/ERK 信号级联。由于其效力，我们建议黄芩苷作为治疗和管理 T2DM 的潜在候选抗高血糖剂值得进一步评估。