Work

Therapeutic Potentials of Phytochemicals in Pancreatitis: Targeting Calcium Signaling, Ferroptosis, microRNAs, and Inflammation with Drug-Likeness Evaluation

Year: 2025

Type: article

Abstract: BACKGROUND: Pancreatitis, encompassing acute (AP), severe acute (SAP), and chronic (CP) forms, is a life-threatening inflammatory disorder with limited therapeutic options. Current management is largely supportive, highlighting the urgent need for novel interventions targeting underlying molecular pathways. AIM: This review summarizes recent advances in the pathogenesis of pancreatitis, focusing on calcium dysregulation, ferroptosis, and microRNA-mediated mechanisms while exploring the therapeutic potential of phytochemicals as disease-modifying agents. SUMMARY: Aberrant calcium signaling, iron-dependent lipid peroxidation, and microRNA imbalance drive acinar cell injury, inflammatory cascades, and pancreatic fibrosis. Phytochemicals, including flavonoids, terpenoids, alkaloids, and phenolics, have shown protective effects in preclinical models through multi-targeted mechanisms. These include suppression of NF-κB-driven inflammation, activation of the Nrf2/HO-1 antioxidant pathway, modulation of ferroptosis via GPX4 and iron efflux, regulation of calcium signaling, and modulation of microRNA expression. Importantly, several phytochemicals attenuate acinar cell death, reduce cytokine release, and limit fibrosis, thereby improving outcomes in experimental pancreatitis. However, poor solubility, bioavailability, and pharmacokinetic limitations remain significant barriers. Emerging strategies such as nanotechnology-based formulations, prodrug design, and pharmacokinetic profiling, as well as bioavailability studies, may enhance their clinical applicability. CONCLUSIONS: Phytochemicals represent a promising reservoir of multitarget therapeutic agents for pancreatitis. Their ability to modulate oxidative stress, inflammatory and calcium signaling, ferroptosis, and microRNA networks highlights their translational potential. Future studies should focus on clinical validation, bioavailability optimization, and advanced delivery platforms to bridge the gap from bench to bedside.

Source: Nutrients

DOI: 10.3390/nu17243841

Authors: Fatma Farhat, Balaji Venkataraman, Bhoomendra A. Bhongade, Mauro Pessia, Shreesh Ojha, Sandeep B. Subramanya

Institutions: United Arab Emirates University, Helwan University, Ras al-Khaimah Medical and Health Sciences University

Language: English

Topic: Pancreatitis Pathology and Treatment

Subfield: Surgery

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,499