Investigation of cellular mechanisms underlying insulin-releasing or glucose-lowering effects of extracts of selected plants used in traditional medicinal practice for the management of diabetes

Type 2 diabetes is a condition which affects millions of people globally and is one of the leading causes of death. Despite the increasing prevalence of the diseases, there are significant challenges associated with the management of the diseases. These include side effects associated with available drugs, shortage of diabetic medications in places where the disease is rising faster, and concerns regarding affordability of drugs where they are available. These challenges motivate research focused on the identification of new agents with better therapeutic efficacy. Specifically, this study focuses on the investigation of anti-diabetic effects of selected African plants, Jatropha tanjorensis (J. tanjorensis), Calotropis procera (C. procera) and Pterocarpus mildbraedii (P. mildbraedii), typically consumed as food. Extracts of various parts of the plants were collected in 2019 from Adamawa and Nasarawa States of Nigeria through local herbalists. Selected plants materials were extracted using a Soxhlet extraction and water or ethanol or methanol as the solvent. Qualitative and quantitative analysis of phytochemical constituents of selected plant extracts were conducted prior to the assessment of the insulin releasing effects, cytotoxicity as well as effects of plant extracts on cell viability, oxidative stress, and protein glycation. Subsequently, the involvement of the ATP-dependent pathway in the actions of selected plants was investigated. For P. mildbraedii, in vivo effects of the extract in animals with diet-induced obesity-diabetes were investigated. Results obtained confirmed presence of key phytochemicals including alkaloids, tannins, anthraquinones, saponins, cardiac glycosides and phlobatannins within aqueous C. Procera seed extracts and a majority of these phytochemicals found within the other C. procera extracts. Aqueous J. tanjorensis leaf extracts displayed the most phytochemicals out of the J. tanjorensis extracts whilst P. mildbraedii leaf extracts presented all phytochemicals tested. Overall, the results presented from the phytochemical analysis confirmed presence of key phytoconstituents within most extracts which was essential to know due to the biological actions of phytochemicals on insulin signalling pathways which are suggested to contribute to the antidiabetic effects of plant extracts. None of the plant extracts exhibited significant cytotoxicity, particularly at lower concentrations. A similar effect during a confirmation of cell viability was also observed for each plant extract tested. The extract of each plant species which demonstrated the best insulinotropic and the lowest cytotoxicity was selected for the investigation of the mechanism of actions. Specifically, these aqueous extracts of C. procera seed, aqueous extract of J. tanjorensis leaves, and ethanolic extract of P. mildbraedii leaves were selected. The analysis revealed that the insulin-releasing effects of these extracts were glucose-linked, and data generated strongly suggested the involvement of the KATP-dependent pathway in the actions of these plant extract. Further analyses revealed that all selected extracts enhanced membrane depolarisation and increased intracellular calcium concentration. All selected plant extracts produced significant anti glycation and antioxidant effects which would provide additional benefits to those diagnosed with diabetes. In vivo assessment of the ethanolic extract of P. mildbraedii leaves revealed that the plant significantly improved glucose tolerance and insulin secretion in animals with diet-induced obesity-diabetes. These effects were sustained for 2 hours (delayed effects) and in animals treated with the extract for 15 days. No adverse effect was observed in animals treated with the extract acutely or over a period of 15 days. These effects encourage future development of P. mildbraedii either for the prevention or treatment of type 2 diabetes. Overall, these results demonstrated that selected extracts are suitable candidates to be used for the management of diabetes. Further studies are recommended for consumption of these plants to be developed into therapeutic agents.

Citation

Heer, S.K. (2026) Investigation of cellular mechanisms underlying insulin-releasing or glucose-lowering effects of extracts of selected plants used in traditional medicinal practice for the management of diabetes. University of Wolverhampton. https://wlv.openrepository.com/handle/2436/626420

Publisher

University of Wolverhampton

URI

https://wlv.openrepository.com/handle/2436/626420

Type

Thesis or dissertation

Language

en

Description

A thesis presented for the degree of Doctor of Philosophy in the School of Sciences, Faculty of Science And Engineering, University Of Wolverhampton.

Collections

Theses and Dissertations