Baicalin ameliorates acute pancreatitis by inhibiting cGAS/STING pathway activation in vivo and in vitro

Acute pancreatitis (AP) is a severe inflammatory disorder of the pancreas that can lead to systemic complications and multi-organ dysfunction. Despite advancements in supportive care, there remains a critical lack of specific and effective drug therapies for AP. Current treatments primarily focus on symptom management, leaving a significant unmet need for targeted interventions that can mitigate pancreatic damage and systemic inflammation. Baicalin, a natural compound, has demonstrated anti-inflammatory and analgesic properties, making it a promising candidate for exploring novel therapeutic strategies in AP by targeting underlying inflammatory pathways.

Researchers evaluated Baicalin's role in AP using both in vivo mouse models and in vitro pancreatic acinar cell lines (AR42J). Pancreatic damage was assessed through histopathological examinations and measurements of serum enzyme levels (lipase, amylase). Apoptosis and reactive oxygen species (ROS) were quantified using TUNEL and DHE staining assays. The activation of the cGAS/STING signaling pathway was investigated in both models. To confirm the pathway's involvement, cGAS knockdown was performed in AR42J cells. Conversely, cGAS overexpression and a STING agonist were employed to explore how baicalin exerts its protective effects against AP.

Baicalin treatment significantly reduced serum levels of lipase and amylase, and alleviated pancreatic edema in AP mice. Furthermore, apoptosis and reactive oxygen species (ROS) levels in AP mice were diminished, as evidenced by TUNEL and DHE staining. In both in vivo and in vitro studies, baicalin notably inhibited the expression of the cGAS/STING signaling pathway, along with its downstream inflammatory factors, including NLRP3, IL-1β, and IL-18. Knockdown of cGAS in the AR42J pancreatic acinar cell line resulted in a significant reduction of apoptosis and inflammation. Conversely, both genetic and pharmacological overexpression of the cGAS/STING pathway negated the protective effects of baicalin on anti-apoptosis and anti-inflammation. This indicates a direct mechanistic link between baicalin's action and the cGAS/STING pathway.

Baicalin significantly reduced serum lipase and amylase levels, along with pancreatic edema, and diminished apoptosis and reactive oxygen species in acute pancreatitis models.