Evaluation of the Potential Hypoglycaemic Properties of Mimusops zeyheri Sond. and Aloe marlothii A.Berger, Two Plants Used by Traditional Healers in South Africa

<i>Mimusops zeyheri</i> Sond. And <i>Aloe marlothii</i> A.Berger are used traditionally in South Africa to manage many diseases, including diabetes mellitus. The mechanism through which these extracts exert blood glucose lowering is not well understood or reported. This study was aimed at assessing <i>M. zeyheri</i> and <i>A. marlothii</i> plant extracts for their potential to exhibit antidiabetic activity and their associated mechanisms. We evaluated the action of both extracts on major genes involved in the insulin signalling pathways in skeletal muscle cells. The in vitro cytotoxic effects of <i>M. zeyheri</i> and <i>A. marlothii</i> extracts were evaluated using the MTT assay and glucose uptake was evaluated using a glucose oxidase assay. The amount of translocated GLUT-4 was determined using the flow cytometry. Conventional PCR was used to determine the expression of GLUT-1 and GLUT-4 and RT-qPCR. IRS-1 total protein and Phospho-Akt were determined using ELISA. Plant extracts stimulated glucose absorption by skeletal muscle cells. <i>M. zeyheri</i> extract increased glucose absorption in muscle cells after 1 and 3 h of incubation. A 2-fold increase in translocated GLUT-4 was noted with <i>M. zeyheri</i>. The mRNA levels of GLUT-4 and GLUT-1 remained uniform in all treatments, while IRS-1, PI3K, Akt1, Akt2, and PPAR-γ were downregulated by both extracts. The expression of GLUT-4 was significantly increased by the action of insulin and <i>M. zeyheri</i> extract at 500 μg/mL. This study validates the traditional use of aqueous extracts of <i>A. marlothii</i> and <i>M. zeyheri</i> as hypoglycaemic plants and raises the assertion that the selected plant extracts utilise the IRS-1/PI3K/Akt pathway.