Evaluation of central neuroprotective effects of anti-snake venom, methanolic extract of Andrographis paniculata and andrographolide in envenomation with Naja naja

Background: Currently a partially purified polyvalent Anti-snake Venom (ASV) is the definitive treatment available against the venoms of snakes of India which is accompanied by allergic and anaphylactic reactions, especially at higher doses. No studies have reported the effectiveness of the Indian ASV on central nervous system dysfunction in envenomation with Naja naja. Aim and Objectives: This study investigated the effectiveness of the multipronged strategy of supplementation of ASV with Methanolic Extract of Andrographis paniculata (MAP), and Andrographolide (AP), to ameliorate deleterious changes in brain dopamine and histology in Naja naja envenomed rats. Material and Methods: Seventy female Wistar rats were divided into Group 1 (normal control), Group 2 (venom control), and Groups 3 to 7 were treated with ASV/MAP/AP/50% reduced ASV+MAP, or 50% reduced ASV+AP, respectively. For Groups 4 to 7, treatment with MAP/AP was continued for 14 days, after which animals were sacrificed. The brains were processed for biochemical and histopathological studies. Results: Of the envenomed rats, 60% survived. Their behaviour and physiological functions were drastically altered with blockade of sensory and motor pathways. Dopamine levels were significantly (p = 0.001) reduced with multifocal histopathological changes observed in all layers of the cerebral and cerebellar cortex. Rats treated with ASV showed persistent aggressive behaviour, decreased alertness, and slow reflexes. Dopamine levels were significantly (p = 0.001) improved. MAP/AP treatment reduced aggressiveness, fear response, and improved reflexes. Dopamine levels were 10-40% higher than the ASV-treated group (p > 0.05), along with the normal appearance of cells in the cerebrum and cerebellum. In animals treated with 50% reduced ASV+MAP/AP behavioural patterns, dopamine levels (p = 0.001) and brain cellular architecture were normalized. Conclusion: This study unequivocally demonstrated the central neuroprotective effect and the superiority of the multipronged strategy of addressing Naja naja envenomation and pave the way for more effective strategies to combat neurodegenerative diseases.