Berberine as a modulator in autism: Insights into mechanisms of action and therapeutic potential.

Autism spectrum disorder (ASD) is a broad neurodevelopmental disorder characterized by impairments in social communication and limited, repetitive patterns of behavior and interests. It is frequently associated with comorbidities, including gastrointestinal dysfunction, and immune and oxidative disturbances. Recent discoveries have revealed that nutritional therapies designed to target certain pathophysiological processes may serve as adjunctive treatments. Berberine is a natural isoquinoline alkaloid isolated from various medicinal herbs. It possesses anti-inflammatory and antioxidant activities and has demonstrated neuroprotective effects in preclinical models. Recent preclinical studies have shown that berberine may help modulate key pathways implicated in ASD, such as gut microbiota-brain axis, neuroinflammatory cascades, mitochondrial dysfunction and oxidative stress responses. Berberine can restore intestinal barrier integrity, suppress microglial activation, balance neurotransmitter systems, and regulate key signaling pathways including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2), which is considered a plausible basis for investigating it as an adjunctive strategy for ASD-associated biological pathways. Moreover, the impact of berberine on the composition of gut microbiota may be associated with behavioral modulation and immune homeostasis. This review explores the mechanistic basis of berberine activity in ASD. Existing preclinical evidence and indirect clinical data suggest that berberine can be regarded as an adjunct intervention and a biological therapeutic approach targeting ASD-related biological pathways. However, current evidence remains preliminary and needs to be further validated in subsequent clinical studies. Please cite this article as: Rodríguez-Vera D, Soriano-Ursúa MA, Pinto-Almazán R, Arciniega-Martínez IM, Reséndiz-Albor AA, Vergara-Castañeda A, Valadez-Vega C, Morales-González Á, Madrigal-Santillán EO, García-Machorro J, Ibañez-Cervantes G, Morales-González JA. Berberine as a modulator in autism: Insights into mechanisms of action and therapeutic potential. J Integr Med. 2026; Epub ahead of print.