Elucidating the Complex Etiology of Schizophrenia: Comprehensive Insights into the Therapeutic Roles of Natural Compounds and Pharmacological Interventions

Md Ali Mujtaba; Purushottam Gangane; Mohammed Kaleem; Naiyer Shahzad; Ali F Almutairy; Anwar Abbas N Alshmmari; Mandar Thool; Wasim Ahmad; Turky Omar Asar; Ameeduzzafar Zafar; Danish Mahmood

doi:10.2174/0113816128362637250621113743

Elucidating the Complex Etiology of Schizophrenia: Comprehensive Insights into the Therapeutic Roles of Natural Compounds and Pharmacological Interventions

Curr Pharm Des. 2025 Jun 27. doi: 10.2174/0113816128362637250621113743. Online ahead of print.

Authors

Affiliations

¹ Department of Pharmaceutics, Faculty of Pharmacy, Northern Border University, Arar, Saudi Arabia.
² Center for Health Research, Northern Border University, Arar, Saudi Arabia.
³ Department of Pharmaceutics, Dadasaheb Balpande College of Pharmacy, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur, 440037, India.
⁴ Department of Pharmacology, Dadasaheb Balpande College of Pharmacy, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur, 440037, India.
⁵ Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia.
⁶ Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Buraydah, 51452, Saudi Arabia.
⁷ Department of Pharmaceutical Care, Security Forces Hospital, Dammam 31413, Saudi Arabia.
⁸ Department of Kuliyate Tib, National Institute of Unani Medicine, Kottigepalya, Bengaluru, 560091, India.
⁹ Department of Biology, College of Science and Arts at Alkamil, University of Jeddah, Jeddah, 23218, Saudi Arabia.
¹⁰ Department of Pharmaceutics, College of Pharmacy, Jouf University, Sakaka, 72341, Al-Jouf, Saudi Arabia.

PMID: 40588996
DOI: 10.2174/0113816128362637250621113743

Abstract

Schizophrenia (SCZ) remains a captivating mental disorder marked by complex symptomatology. Despite the success of the current therapeutic options for psychosis, a definitive cure remains elusive. Hence, this review explores mechanisms underlying SCZ pathophysiology, examining their potential as novel therapeutic targets. This is a narrative review of literature that has been critically analyzed following retrieval from PubMed, PubMed Central, and Google Scholar. Nearly 30% of patients of SCZ show no response to first- and second-generation antipsychotic drugs and continue to suffer from cognitive and negative symptoms, including medication-induced adverse effects. Apart from the social and environmental factors, SCZ has been strongly linked to epigenetic factors and alterations in protein expression. Epigenetic modifications include histone modification and DNA methylation. Epigenetic alterations gained through environmental factors, known as molecular scars, also influence, to some extent, the brain functions throughout the life span of a human being. Epigenetic mechanisms are now recognized as significant contributors to the development and progression of SCZ. Epigenetics is critical in SCZ etiology through DNA methylation and histone modification. Herbal medicines offer promise by targeting genetic and epigenetic pathways, albeit with safety concerns. These approaches offer potential as supplementary therapies alongside conventional treatments or alternative preventive measures. By thoroughly investigating these methods, we may uncover new possibilities in SCZ care, ultimately paving the path for more effective and holistic therapeutic approaches.

Keywords: DNA methylation; Schizophrenia; epigenetic mechanisms; etiological factors; histone modification; natural drugs..