Systems pharmacology and translational insights into herbal therapeutics for schizophrenia: Mechanistic advances, network-based approaches, and future directions

Schizophrenia (SCZ) is a complex and heterogeneous neuropsychiatric disorder that is characterized by disturbances in neurotransmission, neuroinflammation, oxidative stress, synaptic dysfunction and neurodevelopmental abnormalities. Current antipsychotic drugs mainly modulate dopaminergic signaling, thus they are not fully effective in improving negative symptoms, cognitive deficits and treatment-resistant cases. Herbal therapeutics and polyherbal formulations have been gaining attention due to their inherent polypharmacological profiles and traditional ethnomedicinal use in psychiatric disorders. This review highlights recent mechanistic insights of herbal approaches for SCZ, focusing on bioactive phytochemicals, traditional polyherbal formulations, and multi-target molecular actions. The use of recent advances in systems biology, in silico studies, and integrative tools to decode herb–compound–target–pathway interactions underlying therapeutic effects is also discussed. Experimental validation of computational predictions through neuronal cell lines, stem cell–based systems, and animal models were also discussed. This review also discusses the translational potential of integrative mechanistic approaches by framing SCZ as a network disorder and herbal formulations as systems-level modulators.