Emerging research indicates that vitamin D metabolic disorder plays a major role in both acute pancreatitis (AP) and chronic pancreatitis (CP). This has been demonstrated by studies showing that vitamin D deficiency is associated with pancreatitis and its anti-inflammatory and anti-fibrotic effects by binding with the vitamin D receptor (VDR). However, the role of vitamin D assessment and its management in pancreatitis remains poorly understood. In this narrative review, we discuss the recent advances in our understanding of the molecular mechanisms involved in vitamin D/VDR signaling in pancreatic cells; the evidence from observational studies and clinical trials that demonstrate the connection among vitamin D, pancreatitis and pancreatitis-related complications; and the route of administration of vitamin D supplementation in clinical practice. Although further research is still required to establish the protective role of vitamin D and its application in disease, evaluation of vitamin D levels and its supplementation should be important strategies for pancreatitis management according to currently available evidence.

Coagulopathy is a critical pathophysiological mechanism of acute pancreatitis (AP), arising from the complex interplay between innate immune, endothelial cells and platelets. Although initially beneficial for the host, uncontrolled and systemic activation of coagulation cascade in AP can lead to thrombotic and hemorrhagic complications, ranging from subclinical abnormalities in coagulation tests to severe clinical manifestations, such as disseminated intravascular coagulation. Initiation of coagulation activation and consequent thrombin generation is caused by expression of tissue factor on activated monocytes and is ineffectually offset by tissue factor pathway inhibitor. At the same time, endothelial-associated anticoagulant pathways, in particular the protein C system, is impaired by pro-inflammatory cytokines. Also, fibrin removal is severely obstructed by inactivation of the endogenous fibrinolytic system, mainly as a result of upregulation of its principal inhibitor, plasminogen activator inhibitor type 1. Finally, increased fibrin generation and impaired break down lead to deposition of (micro) vascular clots, which may contribute to tissue ischemia and ensuing organ dysfunction. Despite the high burden of coagulopathy that have a negative impact on AP patients’ prognosis, there is no effective treatment yet. Although a variety of anticoagulants drugs have been evaluated in clinical trials, their beneficial effects are inconsistent, and they are also characterized by hemorrhagic complications. Future studies are called to unravel the pathophysiologic mechanisms involved in coagulopathy in AP, and to test novel therapeutics block coagulopathy in AP.

Chaiqinchengqi decoction, a traditional Chinese medicine, has shown promising effects in in vitro, animal and preliminary small human studies for acute pancreatitis, but evidence of clinical practice is limited. To investigate whether Chaiqinchengqi decoction could improve clinical outcomes in patients with acute pancreatitis. Prospective, pragmatic, randomized controlled trial. (Chictr.org.cn registration number: ChiCTR2000034325) METHODS: This trial was conducted at West China Hospital of Sichuan University, China. Patients with acute pancreatitis were randomly assigned to receive either Chaiqinchengqi decoction or placebo by oral and rectal enemas in addition to guideline-directed administrations using a 1:1 ratio. The intervention of Chaiqinchengqi and placebo was determined by the grading of acute gastrointestinal injury. Patients were assessed within 24 and 48 hours, and on 3, 5, and 7 days after admission, or organ failure normalized. Survivors were followed up at 1, 3, and 6 months after discharge. Primary outcome was the duration of respiratory failure to 28 days after enrollment. Secondary outcomes included other organ failure, local complications, 6-month all-cause mortality, inflammatory indicators, and related interventions. Among 248 patients enrolled, Chaiqinchengqi decoction shortened the duration of respiratory failure compared with the placebo (median [IQR], 1.0 [0.0 to 5.0] vs 3.0 [1.0-8.0] days; median difference, -1.0; 95% CI, -2.0 to 0.0, P=.001). There were significant differences in the duration of circulatory failure, the incidence of new-onset respiratory and cardiovascular and failure, the incidence of new organ failure, severity, intensive care unit need, pain visual analogue scale, pancreatitis activity scoring system, and EQ-5D-5L. Chaiqinchengqi decoction as an adjunctive therapy significantly reduced the duration of respiratory failure and improved 6-month clinical outcomes of acute pancreatitis in addition to guideline-directed treatments. Further study is needed to elucidate the mechanism of action.

Background: Acute pancreatitis (AP) is an inflammatory disorder of the exocrine pancreas without specific treatment. Shenmai injection (SMI) was reported to eliminate the severity of experimental AP. This study aimed to explore the mechanisms underlying the synergistic protective effects of SMI on AP based on network pharmacology and experimental validation. Methods: Network pharmacology analysis and molecular docking based on identified components were performed to construct the potential therapeutic targets and pathways. The principal components of SMI were detected via ultra-high-performance liquid chromatography-coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS). Effect of SMI and the identified components on cellular injury and IL6/STAT3 signaling was assessed on mouse pancreatic acinar cell line 266– 6 cells. Finally, 4% sodium taurocholate (NaT) was used to induce AP model to assess the effects of SMI in treating AP and validate the potential molecular mechanisms. Results: By searching the TCMSP and ETCM databases, 119 candidate components of SMI were obtained. UHPLC-QTOF/MS analysis successfully determined the representative components of SMI: ginsenoside Rb1, ginsenoside Rg1, ginsenoside Re, and ophiopogonin D. Fifteen hub targets and eight related pathways were obtained to establish the main pharmacology network. Subnetwork analysis and molecular docking indicated that the effects of these four main SMI components were mostly related to the interleukin (IL) 6/STAT3 pathway. In vitro, SMI, ginsenoside Rb1, ginsenoside Rg1, ginsenoside Re, and ophiopogonin D increased the cell viability of NaT-stimulated mouse pancreatic acinar 266– 6 cells and decreased IL6 and STAT3 expression. In vivo, 10 mL/kg SMI significantly alleviated the pancreatic histopathological changes and the expression of IL6 and STAT3 in the AP mice. Conclusion: This study demonstrated SMI may exert anti-inflammatory effects against AP by suppressing IL6/STAT3 activation, thus providing a basis for its potential use in clinical practice and further study in treating AP.