Neuropharmacological potentials (antipsychotic-, anxiolytic-, and antidepressant-like activity) of Methanol Leaf Extract of Andrographis paniculata Nees in vivo: Possible mechanisms, antioxidant activity, and in silico supportive evidence.

Ethnopharmacology relevance: In Asia and parts of Africa, extracts from Andrographis paniculata Nees (Acanthaceae) are used as traditional remedies for a number of ailments such as tuberculosis, sinusitis, syphilis, leprosy, diarrhea, and malaria. There has been extensive research detailing the various pharmacological actions of Andrographis paniculata Nees (Acanthaceae). However, there is a paucity of scientific information on its neuropharmacological potential despite its traditional use to manage depression and anxiety in West Africa.

Aim of study: This study aims to evaluate the neuropharmacological activities of Andrographis paniculata Nees (Acanthaceae) in mice.

Methods: Acute oral toxicity was evaluated on the methanol extract of Andrographis paniculata (MEAP) before screening it for neuropsychopharmacological properties including antipsychotic-like, anxiolytic-like, antidepressant-like, sedative-hypnotic, anticonvulsant, and motor coordination after administering it for 10 consecutive days using oral doses of 100, 200, 400 mg/kg. The principal constituent andrographolide was evaluated for antipsychotic-like property over a range of doses (2-32 mg/kg). The brains of MEAP-treated mice were assayed for antioxidant enzymes and lipid peroxidation. Molecular docking was used to evaluate the degree of binding of andrographolide to 5-HT_2A and D₂ receptors.

Results: MEAP is relatively safe with oral LD₅₀ >5000 mg/kg. It significantly dose- and time-dependently attenuated amphetamine- and ketamine-induced psychosis-like behavior. The effect of andrographolide on amphetamine-induced psychosis-like behavior was significant only at 8 mg/kg dose. MEAP showed anxiolytic-like and antidepressant-like properties but did not enhance phenobarbitone-induced sleep. It did not protect the mice against chemically induced convulsions and did not affect the motor-coordinating ability of mice. MEAP significantly increased the brain levels of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and reduced the levels of malondialdehyde. Andrographolide bound to D₂ and 5-HT_2A receptors but less than risperidone and aripiprazole at D₂ and 5-HT_2A, respectively.

Conclusion: The methanol extract of Andrographis paniculata possesses antipsychotic-like property possibly mediated by one or more of its constituents rather than solely by andrographolide. It also possesses anxiolytic- and antidepressant-like actions. The brain antioxidant property of the extract complements its neuropsychopharmacological actions.