The incidence of pancreatic exocrine diseases including acute pancreatitis (AP), chronic pancreatitis (CP), and pancreatic cancer (PC) continues to rise and becomes a significant and growing global health burden. While current clinical management for pancreatic exocrine diseases remains largely supportive rather than curative, it is necessary to explore novel therapeutic strategies targeting the underlying complex pathophysiology. Traditional Chinese Medicine (TCM) has long been recognized for its multi-targets, holistic approach to complex diseases. Based on the TCM etiological understanding of exocrine diseases, formulas such as Dazhihu Decoction and Chaiqin Chengqi Decoction (with Huang Qin as an important ingredient) have shown good therapeutic effects in the clinical treatment of AP, CP, and PC. Baicalin, a major bioactive flavonoid derived from the root of Scutellaria baicalensis Georgi (Huang Qin), has emerged as a compound which possesses a broad spectrum of pharmacological properties including anti-inflammatory, antioxidant, anti-fibrotic, and anti-tumor activities. Many studies have shown baicalin plays an important therapeutic role in various preclinical models of gastrointestinal and metabolic disorders. This article systematically reviews the recent advances about the therapeutic potential and molecular mechanisms of baicalin against major pancreatic exocrine diseases, providing a foundation for its future clinical translation. In AP, the therapeutic effects of baicalin are mainly achieved through anti-inflammatory and antioxidant actions. Its anti-inflammatory effect is mainly manifested by inhibiting key signaling pathways, especially NF-κB, JAK2/STAT3, and MAPK/JNK, to further reduce the production of proinflammatory cytokines (eg., TNF-α, IL-6, IL-1β) in the pancreas. Simultaneously, baicalin exerts potent antioxidant effects by activating the Nrf2/Keap1 pathway, which enhances the activity of antioxidant enzymes (SOD, GSH-Px) and reduces oxidative stress markers. Additionally, baicalin regulates cell fate by influencing autophagy (via Akt/mTOR) and apoptosis (through Bcl-2/Bax and Caspase-3). It also exhibits systemic protection by mitigating AP-associated injury to distant organs such as the lungs, liver, and kidneys. In CP, baicalin targets the key processes of fibrosis and chronic inflammation. It inhibits acinar-to-ductal metaplasia (ADM) that is an early pathological event of CP, by downregulating the IL-6/STAT3 pathway. Its anti-fibrotic activity is achieved by suppressing the activation of pancreatic stellate cells (PSCs) through interfering with the TGF-β1/Smad and NF-κB signaling cascades, thereby reducing the deposition of extracellular matrix proteins such as collagen and fibronectin. In PC, baicalin exhibits antitumor properties at multiple levels. It not only inhibits cancer cell proliferation by inducing cell cycle arrest and promotes apoptosis via mechanisms involving the JNK/FoxO1/BIM axis and caspase activation, but also suppresses cell migration, invasion, and epithelial-mesenchymal transition (EMT) by attenuating TGF-β1/Smad signaling. In summary, baicalin exerts broad-spectrum beneficial effects against pancreatic exocrine diseases through interconnected mechanisms targeting inflammation, oxidative stress, fibrosis, and tumor progression. While preclinical evidence is compelling, its clinical translation requires rigorous evidence through well-designed clinical trials to prove its efficacy, optimal dosing, and safety in patients with pancreatic exocrine diseases.
CAO et al. (Mon,) studied this question.