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The effects of herbal extracts and compounds on the glucose metabolism in HepG2 cells

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Kandunuri, Kiran Kumar (2023) The effects of herbal extracts and compounds on the glucose metabolism in HepG2 cells. Doctoral thesis, London Metropolitan University.

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Abstract

The aim of this study is to investigate the effects of herbal substances on glucose metabolism in HepG2 cellular models, this project's main objective was to evaluate and compare the metabolic activities of HepG2 cells following treatment with herbal compounds and botanical extracts like phloretin, ouabain, berberine, metformin, rebaudioside-A, and Stevia extracts, goldenseal extracts, goat's rue extracts, and Gymnema extracts.

In the screening tests, changes in glucose uptake in response to treatment with extracts and individual compounds were recorded. Extracts of goldenseal (Hydrastis candensis 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 biguanide drug metformin (p<0.01). As a result, goldenseal ethanolic extracts (10μL/mL) and berberine (10μM) were identified as the key candidates of the research to investigate glucose uptake using flowcytometry, Glucose transporter-1, estimation of glycogen content and glucose release, and seahorse metabolic analysis.

In glucose uptake studies using flowcytometry, berberine augmented 3.4 times more glucose uptake, goldenseal stimulated 2 times, and metformin upsurges 1.8 times compared to the control (p<0.001). In the glucose transporter-1 expression assays, goldenseal, and berberine were augmented the expression 1.7 times and 1.4 times compared to the control (p<0.05). Berberine was upregulated 2.4 times, metformin twice, and goldenseal twice in glycogen synthesis studies after long-term treatment (p<0.05). In glucose release assays, berberine, metformin, and goldenseal releasing 50%, 30%, and 23% less glucose 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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