Rutaecarpine alleviates acute pancreatitis in mice and AR42J cells by suppressing the MAPK and NF‐κB signaling pathways via calcitonin gene‐related peptide

Abstract

Acute pancreatitis (AP) is an acute inflammatory condition of the pancreas. Previous studies have shown that rutaecarpine (RUT), an important alkaloid component of Evodia rutaecarpa, exhibits certain protective effects against AP in rats by upregulating calcitonin gene-related peptide (CGRP). However, the molecular mechanism of RUT in AP remains unknown. This study aimed to investigate the effects of RUT on ceruleininduced AP in vivo and in vitro, and to explore the underlying molecular mechanisms.In cerulein/LPS-treated wild-type mice, but not CGRP gene knock-out mice, RUT significantly ameliorated pancreatic inflammation by alleviating histopathological changes, reducing IL-6 and TNF-α levels, and increasing in IL-10 levels. Moreover, RUT improved AP by suppressing the MAPK and NF-κB signaling pathways. These effects were mostly mediated through CGRP. Cell-based studies revealed that RUT significantly improved cell viability while suppressing the apoptosis of AR42J cells with cerulein-induced AP, downregulating IL-6 and TNF-α, stimulating IL-10 release, and inhibiting MAPK, NF-κB, and STAT3 signaling activation, all in a CGRP-dependent manner. RUT ameliorated cerulein/LPS-induced AP inflammatory responses in mice and AR42J cells in a CGRP-dependent manner and thus may represent a potential therapeutic option for AP patients. Our study provides valuable insights for AP drug development.

[Retracted] A Network Pharmacology Method Combined with Molecular Docking Verification to Explore the Therapeutic Mechanisms Underlying Simiao Pill Herbal Medicine against Hyperuricemia

“…Rutaecarpine, an alkaloid extracted from the unripe fruit of E. rutaecarpa, possesses an antiinflammatory function [73]. Rutaecarpine has been reported to inhibit the expression of IL1B, IL6, and TNF and promote IL10 expression to ameliorate the histopathology damage caused by inflammation [74][75][76]. Baicalin, a flavonoid compound isolated from radix scutellariae, is characterized by its potent anti-inflammatory effect [77].…”

Effectiveness of integrated approach of yoga therapy versus usual care in management on chronic low back pain patients: A randomized controlled pilot study

“…In inflammatory conditions like acute pancreatitis, TNFα, interleukins 3,6 are downregulated, and MAPK, NF-κB, and STAT3 signaling is inhibited in CGRP dependent manner. 57 Hence, we propose that further studies must be carried out after adjusting the confounders like age, gender, comorbidities and life style habits, with larger sample size will also add to the strength of the study.…”

Molecular mechanisms of pain in acute pancreatitis: recent basic research advances and therapeutic implications

“…It was also reported that rutaecarpine, a major alkaloid component of the Chinese herb Wu-Zhu-Yu (Evodia rutaecarpa), showed protective effects against NaTC-AP in mice, via promoting the release of CGRP ( Yan et al, 2018 ). Rutaecarpine was also found to inhibit tumor necrosis factor-α and IL-6 as well as upregulated IL-10 in CER/LPS-AP in mice ( Huang et al, 2021 ).…”