Phytomedicines in preclinical and clinical research on antipsychotics-induced EPS/EPS-like behaviors: therapeutic effects and neurobiological mechanisms

Extrapyramidal syndrome (EPS) refers to a group of movement disorders resulting from dysfunction of the extrapyramidal system (motor pathways outside the pyramidal tract). Among the various pathogenic factors of EPS, chronic or long-term use of antipsychotic drugs (APDs) is worth special note. This article aims to provide a comprehensive review on the application of phytomedicines in preventing and treating the APDs-induced EPS or EPS-like behaviors by summarizing their therapeutic effects and outlining the underlying neurobiological mechanisms. An advanced search was done using the data bases PubMed, Web of Science, Google Scholar, and CNKI, employing the terms "antipsychotics, " "dopamine, " "extrapyramidal syndrome, " "movement disorder", "herbal, " "haloperidol, " "phytomedicine", and "traditional Chinese medicine". The Boolean operators "AND", "OR" were used to combine some of the above terms in the literature search. Except for a few negative reports, the extant clinical research reported beneficial effects of herb medicines on EPS in patients with schizophrenia. Most of all the research reviewed in this article are animal studies, in which herbal medicines prevented or improved the APDs-induced EPS-like behaviors in animal models of EPS. The neurobiological mechanisms underlying the observed therapeutic effects involve regulating monoaminergic neurotransmission, alleviating oxidative stress, maintaining mitochondrial function, suppressing neuroinflammation, and modulating the KEAP1/Nrf2 pathway, which regulates redox homeostasis and mitochondrial function and plays a crucial role in regulating neuroinflammation. The results of existing research support the combination of herbal medicines with antipsychotic drugs for the prevention and treatment of EPS in patients with schizophrenia.