Andrographis paniculata, metformin attenuate hyperglycaemia-induced neuroendocrine toxicity via antioxidant and cholinergic modulation

Hyperglycemia is associated with neuroendocrine disruption, oxidative stress, and reproductive dysfunction, often accompanied by cholinergic imbalance and structural tissue damage. This study investigated the comparative effects of Andrographis paniculata (AP), metformin, and their combination on biochemical, hormonal, and histological alterations induced by hyperglycemia in the Wistar rats. Hyperglycemia significantly disrupted hormone profiles, increased oxidative stress and cholinesterase activities and caused degenerative changes in brain and testicles. AP and metformin each restored several parameters, but the combination therapy produced the most substantial improvements. Notably, the combination group exhibited the highest antioxidant levels, lowest cholinesterase activity, restored testosterone, and well-preserved histoarchitecture. Induced neuroendocrine and oxidative alterations. However, the metformin and AP combination therapy demonstrated superior efficacy, suggesting a synergistic interaction in mitigating neuroendocrine toxicity and oxidative stress.Metformin exerted beneficial effects on hyperglycemia-induced neuroendocrine and oxidative alterations. However, the metformin and AP combination therapy demonstrated superior efficacy, suggesting a synergistic interaction in mitigating neuroendocrine toxicity and oxidative stress.