Acute pancreatitis (AP) represents a predominant cause of hospitalization related to digestive system disorders, marked by significant morbidity and mortality rates [1]. The condition can be precipitated by various etiological factors, including alcohol consumption, biliary tract disease, hyperlipidemia, and certain medications, which may induce the self-activation of trypsinogen. This activation leads to acinar cell death and subsequent local and systemic inflammation [2]. Although most AP cases are mild and self-limiting, about 20 % advance to moderate or severe stages, potentially leading to significant local complications and systemic organ failure [3]. Consequently, early intervention is imperative in the management of AP. Nonetheless, there remains a lack of specific or highly effective treatments for AP at present [4].

Neutrophils are the initial leukocytes to infiltrate pancreatic tissue at the onset of AP. Upon infiltration, neutrophils release reactive oxygen species (ROS), enzymes, and inflammatory cytokines, thereby exacerbating pancreatic injury [5,6]. Activated neutrophils can generate neutrophil extracellular traps (NETs), consisting of decondensed chromatin, histones, and granular proteins [7]. Increasing evidence suggests that NETs are markedly elevated in AP patients and play a crucial role in pancreatic tissue damage by triggering trypsinogen activation. [8,9]. In murine models of AP, the administration of DNase I to degrade NETs or the inhibition of key components essential for NETs formation has been shown to significantly reduce inflammation and tissue damage [8,10]. The results indicate that inhibiting NETs formation could be a viable therapeutic approach for AP.

Phellodendron bark is a crucial medicinal herb with notable therapeutic potential, characterized by pharmacological effects that include anti-arrhythmic, antibacterial, anti-ulcer, and antihypertensive activities [11]. Phellodendrine (PHE), a bioactive alkaloid extracted from Phellodendron bark, has been shown in recent studies to exhibit a range of pharmacological properties, such as the inhibition of inflammatory cytokine production, mitigation of intestinal inflammation, and the provision of anti-allergic and anti-arthritic effects [[12], [13], [14]]. Nonetheless, the impact of PHE on neutrophils and AP remains to be investigated.

This study employed a phorbol 12-myristate 13-acetate (PMA)-induced NETs formation model and a Caerulein (Cae)-induced AP mouse model to examine PHE's impact on NETs formation and assess its therapeutic potential and mechanisms in AP.