Nimbolide ameliorates pancreatic inflammation and apoptosis by modulating NF-κB/SIRT1 and apoptosis signaling in acute pancreatitis model
Nimbolide ameliorates pancreatic inflammation and apoptosis by modulating NF-κB/SIRT1 and apoptosis signaling in acute pancreatitis model
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DOI：
10.1016/j.intimp.2020.107246
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发表时间：
2021-01-01
影响因子：
5.6
通讯作者：
Godugu, Chandraiah
中科院分区：
文献类型：
--
作者：
Bansod, Sapana;Godugu, Chandraiah
急性胰腺炎（AP）是一种潜在的胃肠道疾病，最常见的是胰腺炎症和腺泡细胞损伤。印楝内酯（NB）是从印楝中提取的一种抗氧化、抗炎的有效成分。在此，我们的目的是研究NB在AP模型中改善蛙皮素诱导的胰腺炎症和凋亡的胰腺保护作用，并评估潜在的作用机制。通过每六小时腹腔内暴露雨蛙肽（50微克/公斤/小时）并在暴露雨蛙肽前7天预处理NB（0.3和1毫克/公斤），在瑞士白化病小鼠中诱导AP。评价血浆和胰腺组织中与AP相关的各种参数。NB可有效减轻AP的严重程度，如降低胰腺水肿、血浆淀粉酶和脂肪酶水平、MPO水平和雨蛙素诱导的组织学损伤。此外，NB的抗氧化作用与Raw 264.7细胞和雨蛙素诱导的AP小鼠中的氧化-亚硝化应激的显著抑制有关。此外，NB抑制促炎细胞因子，iNOS和硝基酪氨酸的表达。此外，NB抑制NF-κ B B活化并增加雨蛙肽攻击小鼠中SIRT 1的表达。此外，NB还通过下调裂解的caspase 3和Bax，同时上调Bcl 2的表达，抑制胰腺细胞凋亡在雨蛙素治疗的小鼠。胰腺炎症和细胞凋亡的抑制导致蛙皮素诱导的AP的衰减。这些结果表明，NB通过SIRT 1激活对抗炎症和凋亡信号，对蛙皮素诱导的AP发挥强大的抗胰腺炎作用。
Acute pancreatitis (AP) is a potential gastrointestinal problem most commonly associated with pancreatic inflammation and acinar cells injury. Nimbolide (NB), isolated from the tree Azadirachta indica, possesses antioxidant and anti-inflammatory effects. Here, we aimed to investigate the pancreatic protective effects of NB in ameliorating cerulein-induced pancreatic inflammation and apoptosis in AP model and evaluate the potential mechanism of action. AP was induced in Swiss albino mice by six-hourly intraperitoneal exposures of cerulein (50 mu g/kg/hr) and pre-treatment of NB (0.3 and 1 mg/kg) 7 days prior to the cerulein exposure. Various parameters associated with AP in plasma and pancreatic tissues were evaluated. Severity of AP was effectively ameliorated by NB as shown by reducing pancreatic edema, plasma amylase and lipase levels, MPO levels and in cerulein-induced histological damage. Further, the antioxidant effect of NB was associated with a significant inhibition of oxidative-nitrosative stress in Raw 264.7 cells and cerulein-induced AP mice. Moreover, NB suppressed proinflammatory cytokines, iNOS and nitrotyrosine expression. In addition, NB inhibited NF-kappa B activation and increased SIRT1 expression in cerulein challenged mice. Furthermore, NB also inhibited pancreatic apoptosis by downregulating cleaved caspase 3 and Bax while upregulating Bcl2 expression in cerulein-treated mice. Inhibition of pancreatic inflammation and apoptosis resulted in attenuation of cerulein-induced AP. These results suggest that NB exerts strong anti-pancreatitis effects against cerulein-induced AP by combating inflammatory and apoptosis signaling via SIRT1 activation.