Mitigating Hyperglycaemic Oxidative Stress in HepG2 Cells: The Role of Leaf and Root Extracts in Promoting Glucose Uptake and Antioxidant Defence.

Diabetes often goes undiagnosed, with 60% of people in Africa unaware of their condition. Type 2 diabetes mellitus (T2DM) is associated with insulin resistance and is treated with metformin, despite the undesirable side effects. Medicinal plants with therapeutic potential, such as , have shown promising anti-diabetic properties. This study explored the role of leaf and root extracts compared to metformin in reducing hyperglycaemia-induced oxidative stress and their impact on liver function using HepG2 as a reference. The cytotoxicity was assessed through the MTT assay. At the same time, glucose uptake and metabolism (ATP and ∆Ψm) in HepG2 cells treated with aqueous leaf and root extract were evaluated using a luminometry assay. Additionally, antioxidant properties (SOD2, GPx1, GSH, and Nrf2) were measured using qPCR and Western blot following the detection of MDA, NO, and iNOS, indicators of free radicals. The MTT assay showed that extracts did not exhibit toxicity in HepG2 cells and enhanced glucose uptake compared to the hyperglycaemic control (HGC) and metformin. The glucose levels in -treated cells increased ATP production ( < 0.05), while the ∆Ψm was significantly increased in HGR1000-treated cells ( < 0.05). Furthermore, leaf extract upregulated GPx1 ( < 0.05), GSH, and gene ( < 0.05), while SOD2 and Nrf2 proteins were reduced ( > 0.05), ultimately lowering ROS ( > 0.05). Contrarily, the root extract stimulated SOD2 ( > 0.05), GPx1 ( < 0.05), and GSH levels ( < 0.05), reducing Nrf2 gene and protein expression ( < 0.05) and resulting in high MDA levels < 0.05). Additionally, the extracts elevated NO levels and iNOS expression ( < 0.05), suggesting potential RNS activation. Taken together, the leaf extract stimulated glucose metabolism and triggered ROS production, producing a strong antioxidant response that was more effective than the root extract and metformin. However, the root extract, particularly at high concentrations, was less effective at neutralising free radicals as it did not stimulate Nrf2 production, but it did maintain elevated levels of SOD2, GSH, and GPx1 antioxidants.