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Cordycepin protects against acute pancreatitis by modulating NF-κB and NLRP3 inflammasome activation via AMPK.
Life Sciences ( IF 5.2 ) Pub Date : 2020-04-05 , DOI: 10.1016/j.lfs.2020.117645
Jing Yang 1 , Yiwen Zhou 1 , Jinsong Shi 1
Affiliation  

Acute pancreatitis (AP) is a noninfectious inflammatory disease with high morbidity and mortality, which is characterized by severe inflammation and tissue necrosis. Cordycepin (CRD), derived from Cordyceps militaris, possesses anti-inflammatory effects and immunomodulation properties. Here, we investigated the protective effects of CRD on pancreatic injury and clarified potential mechanisms in AP model. There were established caerulein-induced AP and CRD pretreatment models in vivo and in vitro, as showed by serum enzymes, histopathological alterations and pro-inflammatory cytokines. Pretreatment with CRD notably downregulated the serum amylase and lipase levels and apparently reduced pancreatic histopathological alterations in AP mice. Meanwhile, the MPO staining confirmed that CRD pretreatment modulated the infiltration of neutrophils in AP mice. Furthermore, CRD markedly decreased the levels of pro-inflammatory factors (IL-6, IL-1β, and TNF-α) though inhibiting the activation of nuclear factor-κB (NF-κB) and NLR family pyrin domain-containing protein 3 (NLRP3) inflammasome in AP mice. In pancreatic acinar cancer cell 266-6, CRD pretreatment decreased cholecystokinin(CCK)-induced inflammatory response was consistent with those in vivo. Mechanistically, CRD was also revealed to activate activated protein kinase (AMPK) and attenuated inflammation both in vivo and in vitro. On the whole, this study indicated that CRD protects mice from pancreatic inflammatory process and damage by suppressed NF-κB and NLRP3 inflammasome activation via AMPK, which probably contributed to the potential therapy for AP.

中文翻译:

虫草素通过调节AMPK调节NF-κB和NLRP3炎性小体的活化来预防急性胰腺炎。

急性胰腺炎(AP)是一种非传染性炎症疾病,具有高发病率和死亡率,其特征是严重的炎症和组织坏死。虫草衍生的虫草素(CRD)具有抗炎作用和免疫调节特性。在这里,我们调查了CRD对胰腺损伤的保护作用,并阐明了AP模型的潜在机制。如血清酶,组织病理学改变和促炎细胞因子所示,已经建立了体内和体外由轻油蛋白诱导的AP和CRD预处理模型。CRD预处理显着下调了AP小鼠的血清淀粉酶和脂肪酶水平,并明显减少了胰腺组织病理学改变。与此同时,MPO染色证实CRD预处理调节了AP小鼠中性粒细胞的浸润。此外,尽管CRD抑制了核因子-κB(NF-κB)和含有NLR家族含吡啶结构域的蛋白3( AP小鼠的NLRP3)炎性小体。在胰腺腺泡癌细胞266-6中,CRD预处理降低了胆囊收缩素(CCK)诱导的炎症反应,与体内的一致。从机理上讲,还发现CRD可在体内和体外激活活化的蛋白激酶(AMPK)并减轻炎症。总体而言,这项研究表明CRD通过抑制AMPK激活的NF-κB和NLRP3炎性小体激活来保护小鼠免受胰腺炎性过程和损害。
更新日期:2020-04-06
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