Da-Cheng-Qi decoction attenuates inflammatory edema and endoplasmic reticulum stress in acute pancreatitis via...

Da-Cheng-Qi Decoction (DCQD) is clinically used for acute pancreatitis (AP). AP is an inflammatory disorder, characterized by inflammatory edema (IE) and endoplasmic reticulum stress (ERS).

This study aims to investigate whether DCQD attenuates IE and ERS in AP via nuclear factor κB (NF-κB) pathway.

In vivo, an AP model was established in Balb/c mice via L-arginine intraperitoneal injection (24 h); in vitro, an AP model was induced in rat pancreatic exocrine cells (AR42J) using cerulein (24 h). Mice were treated with DCQD (18 g/kg, 9 g/kg, and 4.5 g/kg); cells received DCQD-containing serum (5%, 2.5% and 1.25%). Network pharmacology, transcriptomics and non-targeted metabolomics were performed to predict core pathway. Pharmacological modulation employed NF-κB agonist and inhibitor. Docking and molecular dynamics (MD) validated interactions between core DCQD compound and proteins. Several pharmacological indicators tests and molecular biological assessments were conducted.

Network pharmacology identified 138 DCQD targets overlapping with AP, with NF-κB pathway as a core pathway. Docking/MD demonstrated strong binding affinity between rhein and NF-κB. In vivo, DCQD (9 g/kg or 2.5% drug-containing serum) significantly lowered pancreas coefficient, decreased serum α-amylase and interleukin-6 (IL-6), and attenuated pancreatic Na⁺ accumulation and Ca²⁺ depletion. In vitro, DCQD-containing serum increased cell viability, suppressed IL-6, and modulated ion imbalance. Mechanistically, DCQD down-regulated NF-κB, IE-related proteins and ERS-related proteins. The NF-κB inhibitor enhanced DCQD's protective effects, while the NF-κB agonist counteracted them.

DCQD ameliorates IE and ERS in AP, primarily through suppressing NF-κB pathway.