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The effects of herbal extracts and compounds on the glucose metabolism in Hep G2 cells

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Kandunuri, Kiran Kumar (2023) The effects of herbal extracts and compounds on the glucose metabolism in Hep G2 cells. Doctoral thesis, London Metropolitan University.

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Abstract

The aim of this study is to explore the effects of phyto-derived secondary metabolites and extracts on glucose metabolism in Hep G2 cellular models. The primary objective of this project is to evaluate and compare the metabolic activities of Hep G2 cells after treatment with pure compounds phloretin, ouabain, berberine, and metformin, rebaudioside-A, and extracts of Stevia rebaudiana Bertoni, Hydrastis Canadensis L., Galega officinalis L., and Gymnema sylvestre (Retz.) R.Br. ex Sm.

In the screening tests, changes in glucose uptake in response to treatment with extracts and individual compounds were recorded. Extracts of goldenseal (Hydrastis canadensis L.), and the alkaloid berberine induced remarkable glucose uptake, and consumption, compared with the other compounds and extracts. And demonstrated significant glucose uptake (p<0.05, p<0.01), and consumption activity (p<0.05, p<0.001), when compared to the biguanides class of oral anti-hyperglycaemic agent metformin (p<0.01). Consequently, goldenseal ethanolic extract (10 µL/mL) and berberine (10 µM) have emerged as key candidates for further research into glucose uptake using flow cytometry, the expression of glucose transporter-1, and the assessment of glycogen content, glucose release, and Seahorse metabolic analysis.

In studies on glucose uptake using flowcytometry, metformin increases 1.8-fold, goldenseal stimulates 2-fold, and berberine augments 3.4-fold more glucose uptake than the control (p<0.001). In glucose transporter-1 expression assays, goldenseal and berberine increased the expression by 1.7-fold and 1.4-fold, respectively, compared to the control (p<0.05). In glycogen synthesis studies, berberine was upregulated by 2.4-fold, metformin by 2-fold, and goldenseal by 2-fold compared to the control (p<0.05). In glucose release assays, berberine, metformin, and goldenseal decreased glucose release by 50%, 30%, and 23% respectively, compared to the control (p<0.05).

The Seahorse XF analysis, which is more in line with the literature, shows that the three treatments increase the rate of lactate production (p<0.01) while also improving glucose metabolism. When compared to the pure compound alkaloid berberine, goldenseal extract was found to be less effective in improving glucose metabolism. Nonetheless, both appear promising for the development of new oral anti-diabetic agents.

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