...

Hyperglycemia is associated with hippocampal neuronal injury, apoptosis, and demyelination; Modulation of  apoptotic pathways, particularly Bcl-2 associated X protein (BAX) and B-cell lymphoma 2 (Bcl-2) signaling,  represents a potential therapeutic target for neuroprotection. Thirty-five male Wistar rats were divided into five  groups (n = 7). Hyperglycemia was induced in Groups B–E using alloxan (120 mg/kg) and nicotinamide (110  mg/kg). Group A served as the non-diabetic control while Group B served as the diabetic control. Group C  received A. paniculata (400 mg/kg), Group D received metformin (14 mg/kg), and Group E received both.   Hyperglycemia induced marked hippocampal degeneration characterized by increased BAX expression, reduced  BCL-2 signaling, neuronal vacuolation, loss of Nissl bodies, and disrupted myelin architecture, with CA1 and  CA2 showing greater vulnerability. Treatment with Andrographis paniculata attenuated apoptotic signaling,  preserved neuronal morphology, and improved myelin integrity, while metformin produced moderate  neuroprotective effects. Combination therapy demonstrated the most pronounced protection, characterized by  strong suppression of BAX, enhancement of BCL-2 expression, and preservation of neuronal and myelin  structures across hippocampal subfields. Andrographis paniculata, particularly in combination with metformin,  confers significant neuroprotection against hyperglycemia-induced hippocampal apoptosis and demyelination  through modulation of the BAX/BCL-2 pathway. These findings highlight the therapeutic potential of targeting  apoptotic mechanisms to preserve hippocampal integrity under metabolic stress. 

Key Words: Andrographis paniculata, metformin, hippocampus, apoptosis, BAX/BCL-2 pathway, diabetic  neurodegeneration