Signaling Pathways in Pancreatic Stellate Cell Activation: A Review of Therapeutic Mechanisms by Traditional Chinese Medicine for Pancreatic Fibrosis

Pancreatic fibrosis, a major pathological feature of chronic pancreatitis, is primarily driven by the abnormal activation of pancreatic stellate cells (PSCs) and excessive deposition of extracellular matrix. Traditional Chinese medicine (TCM) offers a holistic and synergistic approach to preventing and treating pancreatic fibrosis through multi-target regulation of PSC activation. This review systematically elucidates the mechanisms by which TCM—encompassing both bioactive monomers and compound formulations—modulates key signaling pathways involved in PSC activation, including the mitogen-activated protein kinase, transforming growth factor-β/Smad, platelet-derived growth factor, nuclear factor kappa B, and Wingless/β-catenin pathways. By simultaneously targeting these interconnected signaling networks, TCM strategies effectively inhibit PSC activation, attenuate inflammatory responses, and reduce extracellular matrix deposition. In contrast to single-target pharmacological inhibitors, TCM embodies a “multi-component, multi-pathway” therapeutic paradigm that aligns with the complex pathophysiology of pancreatic fibrosis. This review also draws comparative insights from liver fibrosis, highlighting conserved pathways and organ-specific regulatory contexts. Ultimately, TCM represents a promising integrative avenue for the prevention and treatment of pancreatic fibrosis, supported by growing preclinical evidence and aligned with the principles of holistic intervention.