Pancreatic diseases are a typical representative of clinically difficult diseases. The rapid progression of acute pancreatitis (AP), the impaired quality of life resulting from chronic pancreatitis (CP), the lethal nature of pancreatic ductal adenocarcinoma (PDAC), and the high rate of complications following pancreatectomy collectively contribute to this perspective(Petrov and Yadav, 2019; Scholten et al., 2019). Studies have shown that these diseases are closely related. For example, CP is promoted by recurrent AP and uncontrolled tobacco and alcohol abuse; furthermore, chronic inflammatory and stone irritation in CP and tobacco/alcohol consumption can accelerate the development of PDAC; in turn, high pressure in the pancreatic duct caused by tumour compression and tumour treatment are also important reasons for AP(Ma et al., 2023; Yadav and Lowenfels, 2013). Therefore, the key to enhancing the prognosis of pancreatic diseases lies in adopting a long-term perspective on their development, investigating the mechanisms underlying pancreatic diseases interactions, and identifying efficacious adjunctive medications.

Acinar-to-ductal metaplasia (ADM) and the pancreatic precancerous lesion named pancreatic intraepithelial neoplasia (PanIN) that evolved from it are the key links among AP, CP, and PDAC(Parte et al., 2022). ADM is a protective factor for pancreatic acinar cells (the main parenchymal cells in the pancreas) after pancreatitis, trauma and other stress injuries, characterized by the loss of the acinar phenotype and the gain of the ductal phenotype in the transcriptome and proteome(S. Li and Xie, 2022). Once the stress disappears, the ADM structure returns to the normal pancreatic acinar structure via regeneration(Storz, 2017). However, if stress injuries persist, such as the persistent activation of Kras signalling, ADM will be difficult to reverse and even develop into PanIN, which may progress to aggressive tumours with the assistance of other oncogenic factors(Nishikawa et al., 2019). Therefore, blocking the formation and development of ADM seems to be critical in the prevention and treatment of AP and PDAC.

Traditional Chinese medicine (TCM) and therapies are widely used to treat pancreatic diseases in China. For instance, the TCM formula Qingyi decoction exhibits a significant therapeutic effect on AP, while the TCM monomer emodin demonstrates a rapid reduction in serum inflammatory factors and amylase levels (J. Li et al., 2017). Additionally, various other TCM therapies are extensively employed in clinical practice, including topical application of mirabilite for AP management and formula enema for postpancreatectomy constipation (J. Li et al., 2017). Therefore, the pursuit of enhanced efficacy, reduced adverse effects, decreased cost, and simplified extraction methods for TCM is a crucial aspect in the comprehensive treatment of pancreatic diseases. Rutin is a prototypical flavonoid, and its analogue quercetin has been scientifically validated to possess antioxidant, anti-inflammatory, and anticancer properties, as well as therapeutic effects on various tumour or inflammatory diseases. Quercetin has been employed for several decades in the treatment of AP and PDAC; however, rutin remains relatively underexplored in pancreatic diseases(Ganeshpurkar and Saluja, 2017; Ghanbari-Movahed et al., 2022). In this study, we aimed to explore the therapeutic effect of rutin on pancreatic diseases and its potential mechanisms in the formation of ADM.