School of Bioengineering, Dalian University of Technology, Dalian, Liaoning, 116024, China.
School of Bioengineering, Dalian University of Technology, Dalian, Liaoning, 116024, China.
Phytomedicine. 2023 Dec;121:155106. doi: 10.1016/j.phymed.2023.155106. Epub 2023 Sep 23.
Prediabetes, a stage characterized by chronic inflammation, obesity and insulin resistance. Morin and 1-deoxynojirimycin (DNJ) are natural flavonoids and alkaloids extracted from Morus nigra L., exhibiting anti-hyperglycemic efficacy. However, the benefits of DNJ are shadowed by the adverse events, and the mechanism of morin in anti-diabetes remains under investigation.
In this study, the combinational efficacy and mechanisms of DNJ and morin in ameliorating insulin resistance and pre-diabetes were investigated.
The mice model with prediabetes and Alpha mouse liver-12 (AML-12) cell model with insulin resistance were established. The anti-prediabetic efficacy of the drug combination was determined via analyzing the blood glucose, lipid profiles and inflammatory factors. The application of network pharmacology provided guidance for the research mechanism.
In our study, the intervention of morin ameliorated the insulin resistance via activating the Peroxisome proliferator-activated receptor γ (PPARγ). However, PPARγ activation leaded to the lipid accumulation in prediabetic mice. The combination of 5 mg/kg dose of DNJ and 25 mg/kg morin effectively hindered the progression of T2DM by 87.56%, which was achieved via inhibition of Suppressors of cytokine signaling 3 (SOCS3) and promotion of PPARγ as well as SOCS2 expression. Furthermore, this treatment exhibited notable capabilities in combating dyslipidemia and adipogenesis, achieved by suppressing the Cluster of differentiation 36/ Sterol-regulatory element binding proteins-1/ Fatty acid synthetase (CD36/Serbp1/Fas) signaling.
This research confirmed that the drug combination of DNJ and morin in ameliorating insulin resistance and lipid accumulation, and revealed the potential mechanisms. In summary, the combination of DNJ and morin is an underlying alternative pharmaceutical composition in T2DM prevention.
糖尿病前期是一个以慢性炎症、肥胖和胰岛素抵抗为特征的阶段。密蒙花苷和 1-脱氧野尻霉素（DNJ）是从桑科植物密蒙花中提取的天然类黄酮和生物碱，具有降血糖作用。然而，DNJ 的益处被其不良反应所掩盖，密蒙花在抗糖尿病方面的机制仍在研究中。
本研究旨在探讨 DNJ 和密蒙花联合改善胰岛素抵抗和糖尿病前期的疗效及机制。
建立糖尿病前期小鼠模型和胰岛素抵抗的 Alpha 小鼠肝-12（AML-12）细胞模型，分析药物组合对血糖、血脂谱和炎症因子的影响，确定其抗糖尿病疗效。网络药理学的应用为研究机制提供了指导。
本研究表明，密蒙花通过激活过氧化物酶体增殖物激活受体 γ（PPARγ）改善胰岛素抵抗，但 PPARγ 激活导致糖尿病前期小鼠脂质堆积。DNJ（5mg/kg）和密蒙花（25mg/kg）联合应用可有效抑制 SOCS3 表达，促进 PPARγ 和 SOCS2 表达，抑制 Suppressors of cytokine signaling 3（SOCS3），阻止 T2DM 进展，抑制率达 87.56%。此外，该治疗方案还能显著改善血脂异常和脂肪生成，抑制 CD36/Serbp1/Fas 信号通路。
本研究证实了 DNJ 和密蒙花联合改善胰岛素抵抗和脂质堆积的作用，并揭示了其潜在机制。总之，DNJ 和密蒙花的联合用药可能是预防 T2DM 的一种潜在药物组合。
