A Novel Derivative of the Natural Product Danshensu Suppresses Inflammatory Responses to Alleviate Caerulein-Induced Acute Pancreatitis.
A Novel Derivative of the Natural Product Danshensu Suppresses Inflammatory Responses to Alleviate Caerulein-Induced Acute Pancreatitis.
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天然产物丹参素的新型衍生物可抑制炎症反应，减轻雨蛙素诱发的急性胰腺炎。
DOI：
10.3389/fimmu.2018.02513
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发表时间：
2018
影响因子：
7.3
通讯作者：
Sun J
中科院分区：
文献类型：
--
作者：
Ren Z;Li H;Zhang M;Zhao Y;Fang X;Li X;Chen W;Zhang H;Wang Y;Pan LL;Sun J
急性胰腺炎（acute pancreatitis，AP）是一种常见的腹部炎症性疾病，其特征是胰腺腺泡内消化酶的过早细胞内激活和连续的全身炎症反应。虽然其机制尚不完全清楚，但炎症是AP胰腺损伤的主要原因。丹参素衍生物[4-（2-乙酰氧基-3-（（R）-3-（苄硫基）-1-甲氧基-1-氧代丙-2-基氨基）-3-氧代丙基）-1，2-亚苯基二乙酸酯（DSC）]在体外具有抗炎和抗细胞凋亡作用。然而，其在AP中的潜在有益作用尚未得到证实。本研究旨在探讨DSC对小鼠实验性AP的治疗作用及其机制。结果发现，DSC通过抑制核因子-κB（NF-κB）、信号转导和转录激活因子3（STAT 3）和含亮氨酸重复序列的核结合域家族（NLRP 3）炎性体的活化，抑制AP的炎症反应。此外，DSC治疗调制的中性粒细胞的浸润和巨噬细胞的表型在小鼠诱导AP。有趣的是，我们发现，核因子-红细胞2相关因子2（Nrf 2）及其调节的抗氧化酶血红素加氧酶-1（HO-1）的表达，调节炎症活动，显着增加DSC治疗组。总之，我们的研究结果表明，DSC通过抑制NF-κB、STAT 3和NLRP 3炎性体的活化和调节免疫细胞应答来减轻AP中的胰腺炎症和损伤。
Acute pancreatitis (AP), a common abdominal inflammatory disorder, is characterized by premature intracellular activation of digestive proteases within pancreatic acini and a consecutive systemic inflammatory response. Although the mechanism remains to be fully understood, inflammation is the main cause of pancreatic damage in AP. A novel compound [4-(2-acetoxy-3-((R)-3-(benzylthio)-1-methoxy-1-oxopropan-2-ylamino)-3-oxopropyl)-1,2-phenylene diacetate (DSC)], derived from danshensu, exhibits anti-inflammatory and anti-apoptotic properties in vitro. However, its potential beneficial effect in AP has not been demonstrated. This study aimed to investigate the effects and underlying mechanisms of DSC in experimental AP in mice. We found that DSC suppressed inflammatory responses in AP by inhibiting the activation of nuclear factor-κB (NF-κB), signal transducer and activator of transcription 3 (STAT3) and nucleotide-binding domain leucine-rich repeat containing family, pyrin domain-containing 3 (NLRP3) inflammasome. Furthermore, treatment with DSC modulated the infiltration of neutrophils and the phenotypes of macrophages in mice induced with AP. Interestingly, we found that the expression of nuclear factor-erythroid 2 related factor 2 (Nrf2) and its regulated antioxidant enzyme heme oxygenase-1 (HO-1), which modulate inflammatory activities, was significantly increased in DSC-treated groups. Together, our findings demonstrate that DSC alleviates pancreatic inflammation and damage in AP by inhibiting the activation of NF-κB, STAT3, and NLRP3 inflammasome and modulating immune cell responses.
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影响因子：
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作者：
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发表时间：
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期刊：
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影响因子：
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作者：
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影响因子：
7.3
作者：
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通讯作者：
Sun J