Berberine ameliorates malathion-triggered rat brain cholinergic dysfunction besides attenuation of oxidative stress, pyroptosis, and apoptosis

Roghani, Mehrdad; Iranzadeh, Saeid; Sedaghat, Reza; Taheri, Mahdieh

doi:10.22038/ajp.2026.27919

Berberine ameliorates malathion-triggered rat brain cholinergic dysfunction besides attenuation of oxidative stress, pyroptosis, and apoptosis

Articles in Press

Document Type : Original Research Article

Authors

¹ Neurophysiology Research Center, Shahed University, Tehran, Iran.

² Faculty of Medicine, Shahed University, Tehran, Iran.

10.22038/ajp.2026.27919

Abstract

Objective: Exposure to pesticides such as malathion induces neurotoxic effects that may lead to brain injury. Berberine, a bioactive alkaloid isolated from Coptis chinensis, has demonstrated significant neuroprotective properties. This study aimed to evaluate the protective effects of berberine against malathion-induced brain injury in rats.
Materials and methods: Adult male rats were assigned to four groups: control, malathion, malathion + berberine 10 mg/kg, and malathion + berberine 50 mg/kg. Malathion (100 mg/kg/day, i.p.) was administered for two weeks to induce neuronal injury. Berberine was given orally daily for the same period. Oxidative stress parameters including malondialdehyde (MDA), reactive oxygen species (ROS), and glutathione (GSH) levels, and superoxide dismutase (SOD) and catalase (CAT) activities were assessed. Acetylcholinesterase (AChE) activity was measured as an index of cholinergic function. Moreover, caspase 1 and caspase 3 enzymatic activities were determined, and hippocampal CA1 pyramidal neuron density was evaluated histologically.
Results: Malathion exposure significantly impaired antioxidant activity and cholinergic function while increasing oxidative stress, pyroptosis, and apoptosis markers. Berberine treatment, particularly at 50 mg/kg, significantly reversed these malathion-induced alterations by restoring SOD, CAT, and AChE activities and reducing MDA and ROS levels, along with caspase 1 and caspase 3 activities. Although berberine improved GSH levels and CA1 neuronal density compared to the malathion group, these effects did not reach statistical significance.
Conclusion: Berberine exerts neuroprotective effects against malathion-induced brain injury by attenuating cholinergic dysfunction, oxidative stress, and pyroptotic and apoptotic pathways. These findings suggest that berberine may represent a promising therapeutic candidate for pesticide-induced neurotoxicity.

Keywords