# Molecular Mechanisms and Therapeutic Potential of Baicalein in Acute Pancreatitis: A Comprehensive Review

## TL;DR

This paper reviews how baicalein, a plant compound, may treat acute pancreatitis by targeting multiple disease mechanisms, including inflammation and cell death.

## Contribution

The paper provides a novel synthesis of baicalein's multi-target mechanisms in acute pancreatitis, highlighting its potential as a precision therapeutic.

## Key findings

- Baicalein suppresses acute pancreatitis by modulating TLR4/NF-κB/MAPK signaling and reducing cytokine storms.
- It promotes macrophage polarization from M1 to M2 and inhibits neutrophil extracellular trap formation.
- Baicalein blocks pyroptosis and ferroptosis while scavenging systemic toxins like histones and pancreatic lipase.

## Abstract

Acute pancreatitis (AP) is a severe inflammatory disorder characterized by a complex molecular pathophysiology involving premature zymogen activation, organelle dysfunction, and systemic immune dysregulation. Current therapeutic strategies remain largely supportive, underscoring the critical need for specific molecular-targeted interventions. Baicalein, a bioactive flavonoid derived from Scutellaria baicalensis Georgi, has emerged as a potent pleiotropic agent. This review comprehensively synthesizes the molecular mechanisms underlying baicalein’s therapeutic efficacy in AP. Its capacity to intercept the pathological cascade at multiple checkpoints is elucidated, from mitigating the initiating cytosolic calcium overload and preserving mitochondrial integrity to suppressing the cytokine storm via the TLR4/NF-κB/MAPK signaling axis. Crucially, baicalein modulates the pancreatic immune microenvironment by driving the phenotypic polarization of macrophages from pro-inflammatory M1 to reparative M2 states and regulating neutrophil dynamics, specifically by inhibiting infiltration and neutrophil extracellular trap formation. Furthermore, its role in orchestrating regulated cell death pathways is highlighted, specifically by blocking pyroptosis and ferroptosis while modulating apoptosis, and its function as a biophysical scavenger of circulating histones and pancreatic lipase to neutralize systemic toxins. Consequently, this review emphasizes the multi-target biological activities of baicalein, providing a mechanistic rationale for its development as a precision therapeutic candidate for AP.