The protective effects of rutaecarpine on acute pancreatitis

Abstract

Abstract. Acute pancreatitis (AP) is the acute inflammation of the pancreas. The morbidity of AP has increased in recent years. Certain patients eventually develop severe AP (SAP), which rapidly progresses to multiple organ dysfunction; the incidence of this occurring in patients with AP is 20-30%. To date, no specific drugs or methods exist to treat this disease. Rutaecarpine relaxes vascular smooth muscle by stimulating calcitonin gene-related peptide (CGRP) release via activation of vanilloid receptor subtype 1 (VR1). It has been demonstrated that rutaecarpine induces a therapeutic effect on SAP. The present study was conducted to characterize the molecular mechanisms underlying the protective effects of rutaecarpine against AP using a rat model of AP. Gross pathological changes of the pancreas, as well as the pancreatic tissue histopathological score, were assessed following treatment with rutaecarpine, capsazepine or a combination of the two. Serum amylase activity was detected using an automatic biochemistry analyzer. Changes in the serum concentrations of interleukin (IL)-6, tumor necrosis factor (TNF-α), IL-10 and CGRP were assessed by ELISA and radioimmunoassay. The results demonstrated that pre-treatment with rutaecarpine markedly decreased pancreatic inflammation and necrosis, reduced the volume of ascites, and significantly increased the plasma concentration of CGRP and the serum concentration of IL-10, an anti-inflammatory cytokine. However, serum concentrations of the inflammatory cytokines IL-6 and TNF-α were decreased. The effect of rutaecarpine treatment markedly improved with increases in the drug dose. Capsazepine, as a competitive vanilloid receptor antagonist, abolished these protective effects of rutaecarpine against AP. Therefore, the results of the present study indicate that rutaecarpine protects against AP in rats by upregulating endogenous CGRP release via activation VR1 of, to improving the microcirculation of the pancreatic tissue and regulate the expression of inflammatory factors. IntroductionAcute pancreatitis (AP) is a severe disease that affects the abdomen and its incidence is increasing from 13 to 45/100,000 (1,2). In the majority of cases, AP is a mild and self-limiting disease; however, ~30% of patients will develop severe acute pancreatitis (SAP), which is characterized by severe attacks, including pancreatic necrosis, intestinal barrier dysfunction and bacterial translocation, leading to multiple organ dysfunction (mortality rate, 15-30%) (3-5). Currently, the mechanisms involved in the pathogenesis of AP and associated pancreatic injury have not been fully elucidated. Among the various hypotheses used to explain the development of AP, microcirculatory disturbance and inflammatory mediation have attracted the most attention (6). Pancreatic microcirculatory disorders may be important pathogenic factors in determining acute pancreatitis (7) and it has been suggested that a number of factors are involved in the development of pancreatic microcirculatory disturbance (8). A num...

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“…Rutaecarpine (Rut) is an alkaloid isolated from Evodia rutaecarpa. Rut has obvious antioxidant6 and anti-inflammatory effects 7. Besides, Rut also has a certain cardiovascular protective effect,8 specifically in preventing hypertensive myocardial hypertrophy9 and preventing the dysfunction of vascular smooth muscle cells 10.…”

Murine Models of Acute Pancreatitis: A Critical Appraisal of Clinical Relevance

“…Pancreatic microcirculatory failure is the major cause of mortality in severe AP, and is thought to be crucial in the early events of AP with multiple organ dysfunction syndrome [130]. The decrease of pancreatic microcirculatory blood flow volume and velocity, and the increase of microvascular permeability lead to pancreas edema and inflammatory infiltration in the early phase of AP [131].…”

Evodiae fructus Extract Inhibits Interleukin-1β-Induced MMP-1, MMP-3, and Inflammatory Cytokine Expression by Suppressing the Activation of MAPK and STAT-3 in Human Gingival Fibroblasts In Vitro

“…Evodiae fructus (EF) is the dried, ripe fruit of Evodia rutaecarpa, which has been used as an analgesic, antidiarrheal, antiemetic, and anti-inflammatory drug in Chinese traditional medicine [30,31]. Alkaloids are the main active ingredients of EF, and recent studies have investigated the pharmacological activities of alkaloids such as evodiamine, hydroxyevocarpine, hydroxyevodiamine, evocarpine, isoevodiamine, higenamine, and rutaecarpine [31].…”