Notoginsenoside R1, a metabolite from Panax notoginseng (Burkill) F.H.Chen, stimulates insulin secretion through activation of phosphatidylinositol 3-kinase (PI3K)/Akt pathway

Altaf Al-Romaiyan; Ahmad Barakat; Sulaiman K Marafie; Willias Masocha

doi:10.3389/fphar.2024.1478917

Notoginsenoside R1, a metabolite from Panax notoginseng (Burkill) F.H.Chen, stimulates insulin secretion through activation of phosphatidylinositol 3-kinase (PI3K)/Akt pathway

Front Pharmacol. 2024 Sep 27:15:1478917. doi: 10.3389/fphar.2024.1478917. eCollection 2024.

Authors

Altaf Al-Romaiyan¹, Ahmad Barakat¹, Sulaiman K Marafie², Willias Masocha¹

Affiliations

¹ Department of Pharmacology and Therapeutics, College of Pharmacy, Kuwait University, Kuwait.
² Biochemistry and Molecular Biology Department, Dasman Diabetes Institute, Kuwait.

Abstract

Background: For ages, botanical medicine has been used in the treatment of diabetes mellitus (DM). Notoginsenoside R1 (NGR1), a Panax notoginseng (Burkill) F.H.Chen metabolite, has been documented to possess antidiabetic action in vivo. However, its precise molecular mechanism of action is not clear.

Objectives: We evaluated NGR1's effects on blood glucose in vivo and then evaluated in vitro whether NGR1 has effects on insulin secretion and the probable molecular pathways involved in NGR1-induced insulin secretion.

Methods: Diabetes was induced in mice by streptozotocin. Glucose tolerance test was performed before and after NGR1 was administered intraperitoneally to diabetic animals for 4 weeks. Static and perifusion experiments were performed using isolated female BALB/c mouse islets. Preproinsulin (Ins) mRNA expression was measured using q-PCR. Protein expression of PI3K/Akt pathway was assessed using the fully automated Wes™ capillary-based protein electrophoresis.

Results: Treatment of diabetic mice with NGR1 improved their glucose intolerance. In vitro, NGR1 increased insulin secretion in a concentration-dependent manner. NGR1 initiated the secretion of insulin at 2 mM glucose and augmented glucose-stimulated insulin secretion which was sustained throughout NGR1 perifusion. NGR1-induced insulin secretion was not altered by a voltage gated calcium channel blocker or protein kinase A inhibitor. NGR1 did not significantly modulate Ins mRNA expression. However, NGR1 significantly increased the levels of phospho-Akt and phopho-p-85.

Conclusion: In conclusion, this study has shown that NGR1 ameliorates hyperglycemia in diabetic mice. NGR1 has a direct insulin secretagogue activity on mouse islets, stimulates insulin secretion at both basal and postprandial glucose concentrations, and activates PI3K/Akt pathway to induce insulin secretion. These results suggest that NGR1 may provide an alternative therapy to manage DM.

Keywords: Panax notoginseng; diabetes; insulin secretion; mouse islets; plant extract.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was funded and supported by Kuwait University, Research Grant No. PT 03/20 and Research Core Facility of the HSC grant numbers SRUL02/13 and GM01/15. The Applied biosystem 7500 Fast PCR system was supported by Oral Microbiology Specialized Research Unit Laboratory Project SRUL 01/14. The funding agencies had no involvement in the study design, in the collection, analysis, and interpretation of data, and in the writing of the report.