Neuropharmacological potentials (antipsychotic-, anxiolytic-, and antidepressant-like activities) 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-HT2A 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-HT2A receptors but less than risperidone and aripiprazole at D2 and 5-HT2A, 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.