Edmond H. Fischer Signal Transduction Laboratory, Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, China.
Int J Mol Sci. 2024 Mar 25;25(7):3654. doi: 10.3390/ijms25073654.
Type 2 diabetes mellitus (T2DM) is marked by persistent hyperglycemia, insulin resistance, and pancreatic β-cell dysfunction, imposing substantial health burdens and elevating the risk of systemic complications and cardiovascular diseases. While the pathogenesis of diabetes remains elusive, a cyclical relationship between insulin resistance and inflammation is acknowledged, wherein inflammation exacerbates insulin resistance, perpetuating a deleterious cycle. Consequently, anti-inflammatory interventions offer a therapeutic avenue for T2DM management. In this study, a herb called Baikal skullcap, renowned for its repertoire of bioactive compounds with anti-inflammatory potential, is posited as a promising source for novel T2DM therapeutic strategies. Our study probed the anti-diabetic properties of compounds from Baikal skullcap via network pharmacology, molecular docking, and cellular assays, concentrating on their dual modulatory effects on diabetes through Protein Tyrosine Phosphatase 1B (PTP1B) enzyme inhibition and anti-inflammatory actions. We identified the major compounds in Baikal skullcap using liquid chromatography-mass spectrometry (LC-MS), highlighting six flavonoids, including the well-studied baicalein, as potent inhibitors of PTP1B. Furthermore, cellular experiments revealed that baicalin and baicalein exhibited enhanced anti-inflammatory responses compared to the active constituents of licorice, a known anti-inflammatory agent in TCM. Our findings confirmed that baicalin and baicalein mitigate diabetes via two distinct pathways: PTP1B inhibition and anti-inflammatory effects. Additionally, we have identified six flavonoid molecules with substantial potential for drug development, thereby augmenting the T2DM pharmacotherapeutic arsenal and promoting the integration of herb-derived treatments into modern pharmacology.
2 型糖尿病（T2DM）的特征是持续的高血糖、胰岛素抵抗和胰岛β细胞功能障碍，给健康带来了巨大负担，并增加了全身并发症和心血管疾病的风险。尽管糖尿病的发病机制仍不清楚，但人们已经认识到胰岛素抵抗和炎症之间存在循环关系，即炎症加剧胰岛素抵抗，从而使恶性循环持续存在。因此，抗炎干预为 T2DM 治疗提供了一种治疗途径。在这项研究中，一种名为黄芩的草药因其具有抗炎潜力的生物活性化合物而备受关注，被认为是一种有前途的新型 T2DM 治疗策略的来源。我们通过网络药理学、分子对接和细胞测定研究了黄芩化合物的抗糖尿病特性，重点研究了它们通过抑制蛋白酪氨酸磷酸酶 1B（PTP1B）和抗炎作用对糖尿病的双重调节作用。我们使用液相色谱-质谱（LC-MS）鉴定了黄芩中的主要化合物，其中六种黄酮类化合物，包括研究得较多的黄芩素，是 PTP1B 的有效抑制剂。此外，细胞实验表明，黄芩苷和黄芩素与甘草（TCM 中的一种已知抗炎剂）的活性成分相比，具有更强的抗炎反应。我们的研究结果证实，黄芩苷和黄芩素通过两种不同的途径缓解糖尿病：PTP1B 抑制和抗炎作用。此外，我们还鉴定了六种具有很大药物开发潜力的黄酮类分子，从而增强了 T2DM 药物治疗的武器库，并促进了草药治疗方法与现代药理学的整合。
