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Bioactivity-based molecular networking-guided identification of methyl rosmarinate from Orthosiphon aristatus as a PTP1B inhibitor that improves insulin sensitivity in diabetic mice

文献类型：期刊论文

作者Xie, Bojun2; Zhu, Dafu3,4; Li, Linxuan2; Lou, Ruohan2; Wang, Rui2; Min, Jingli2; Ye, Yang3,4; Ma, Xiaojun1; Lin, Ligen2,5
刊名PHYTOMEDICINE
出版日期2025-11-25
卷号148页码:14
关键词Type 2 diabetes Bioactivity-based molecular networking Protein tyrosine phosphatase 1B Orthosiphon aristatus Methyl rosmarinate Insulin sensitivity
ISSN号0944-7113
DOI10.1016/j.phymed.2025.157444
英文摘要Background and purpose: Type 2 diabetes (T2D) is a popular chronic metabolic disorder with high morbidity and mortality. Protein tyrosine phosphatase 1B (PTP1B) acts as a negative regulator of insulin action, considering as a promising anti-T2D target. The stems and leaves of Orthosiphon aristatus have been widely utilized for treating hyperglycemia. However, the anti-hyperglycemic principles and underlying mechanism remain unclear. Our study aims to identify potential PTP1B inhibitors from O. aristatus and explore the underlying mechanisms. Methods: The bioactivity-based molecular networking (BMN) was conducted to discover and targeted isolate methyl rosmarinate (MR) from O. aristatus as a PTP1B inhibitor. C2C12 myotubes and high-fat diet-fed plus streptozotocin-injection induced T2D mice were utilized to evaluate the insulin sensitizing effect of MR. Results: MR acted as a reversible inhibitor of PTP1B, with competitive inhibition as its dominant mode and an IC50 value of 24.70 +/- 0.60 mu M. CETSA and DARTS experiments confirmed that MR directly binds to PTP1B in C2C12 myotubes. In C2C12 myotubes, MR (6.25, 12.5 and 25 mu M) promoted insulin-stimulated glucose uptake, and enhanced glycogen synthesis. Furthermore, MR (6.25, 25 mg/kg/d) enhanced insulin sensitivity, improved lipid profile, and rescued skeletal muscle damage in T2D mice. Conclusions: The BMN strategy was utilized for the quick identification of MR as a PTP1B inhibitor from O. aristatus. MR improves insulin sensitivity in skeletal muscle of T2D mice by binding to and inhibiting PTP1B activity, which could serve as a promising candidate for treating T2D.
WOS关键词TYROSINE-PHOSPHATASE 1B ; SKELETAL-MUSCLE ; RESISTANCE ; STAMINEUS ; GLUCOSE ; METABOLISM ; DISCOVERY ; EXTRACT ; PROFILE ; ACID
资助项目National Natural Science Foundation of China[82073715] ; National Natural Science Foundation of China[82270927] ; National Key R&D Program of China[2023YFC2508300] ; Science and Technology Development Fund, Macao SAR[FDCT 005/2023/SKL] ; Open Project of State Key Laboratory of Phytochemistry and Natural Medicines[P2025-KF05]
WOS研究方向Plant Sciences ; Pharmacology & Pharmacy ; Integrative & Complementary Medicine
语种英语
WOS记录号WOS:001607586900002
出版者ELSEVIER GMBH
源URL[http://119.78.100.183/handle/2S10ELR8/319773]  
专题国家级研究中心_原创新药研究全国重点实验室
通讯作者Ma, Xiaojun; Lin, Ligen
作者单位1.Zhengzhou Univ, Affiliated Hosp 1, Dept Endocrinol & Metab, Zhengzhou 450001, Peoples R China
2.Univ Macau, Inst Chinese Med Sci, State Key Lab Mech & Qual Chinese Med, Macau 999078, Peoples R China
3.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
4.Chinese Acad Sci, Shanghai Inst Mat Med, Nat Prod Chem Dept, Shanghai 201203, Peoples R China
5.Univ Macau, Fac Hlth Sci, Dept Pharmaceut Sci, Macau 999078, Peoples R China
推荐引用方式
GB/T 7714		 Xie, Bojun,Zhu, Dafu,Li, Linxuan,et al. Bioactivity-based molecular networking-guided identification of methyl rosmarinate from Orthosiphon aristatus as a PTP1B inhibitor that improves insulin sensitivity in diabetic mice[J]. PHYTOMEDICINE,2025,148:14.
APA Xie, Bojun.,Zhu, Dafu.,Li, Linxuan.,Lou, Ruohan.,Wang, Rui.,...&Lin, Ligen.(2025).Bioactivity-based molecular networking-guided identification of methyl rosmarinate from Orthosiphon aristatus as a PTP1B inhibitor that improves insulin sensitivity in diabetic mice.PHYTOMEDICINE,148,14.
MLA Xie, Bojun,et al."Bioactivity-based molecular networking-guided identification of methyl rosmarinate from Orthosiphon aristatus as a PTP1B inhibitor that improves insulin sensitivity in diabetic mice".PHYTOMEDICINE 148(2025):14.

入库方式： OAI收割

来源：上海药物研究所

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