Isoliquiritigenin ameliorates caerulein-induced chronic pancreatitis by inhibiting the activation of PSCs and pancreatic infiltration of macrophages.
Isoliquiritigenin ameliorates caerulein-induced chronic pancreatitis by inhibiting the activation of PSCs and pancreatic infiltration of macrophages.
复制标题
异甘草素通过抑制 PSC 的活化和巨噬细胞的胰腺浸润来改善雨蛙素诱导的慢性胰腺炎
DOI：
10.1111/jcmm.15498
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发表时间：
2020-09
影响因子：
5.3
通讯作者：
Hu LH
中科院分区：
文献类型：
--
作者：
Wang LJ;He L;Hao L;Guo HL;Zeng XP;Bi YW;Lu GT;Li ZS;Hu LH
慢性胰腺炎（CP）的特征是胰腺持续炎症，由于萎缩和/或纤维化组织替代，导致内分泌和外分泌室逐渐丧失。目前，CP的临床治疗方案主要是对症治疗，包括胰酶替代、血糖控制和营养支持治疗，缺乏特异性的治疗药物来预防和抑制CP中炎症和纤维化的加重。在此，我们研究了异尿酸原素（ILG），一种从甘草中提取的查尔酮型膳食化合物，对小白鼠CP模型中胰腺纤维化和炎症的影响。结果表明，ILG明显减轻了胰腺纤维化和巨噬细胞的浸润。进一步在人胰星状细胞（hPSCs）的体外研究表明，ILG对hPSCs的增殖和活化具有显著的抑制作用，这可能是由于其负调控ERK1/2和JNK1/2活性所致。此外，ILG通过抑制NF - κB信号通路显著抑制巨噬细胞的M1极化（RAW 264.7），而M2极化几乎不受影响。这些发现表明，ILG可能是一种潜在的抗炎和抗纤维化治疗CP的药物。
Chronic pancreatitis (CP) is characterized by persistent inflammation of the pancreas that results in progressive loss of the endocrine and exocrine compartment owing to atrophy and/or replacement with fibrotic tissue. Currently, the clinical therapeutic scheme of CP is mainly symptomatic treatment including pancreatic enzyme replacement, glycaemic control and nutritional support therapy, lacking of specific therapeutic drugs for prevention and suppression of inflammation and fibrosis aggravating in CP. Here, we investigated the effect of isoliquiritigenin (ILG), a chalcone‐type dietary compound derived from licorice, on pancreatic fibrosis and inflammation in a model of caerulein‐induced murine CP, and the results indicated that ILG notably alleviated pancreatic fibrosis and infiltration of macrophages. Further in vitro studies in human pancreatic stellate cells (hPSCs) showed that ILG exerted significant inhibition on the proliferation and activation of hPSCs, which may be due to negative regulation of the ERK1/2 and JNK1/2 activities. Moreover, ILG significantly restrained the M1 polarization of macrophages (RAW 264.7) via attenuation of the NF‐κB signalling pathway, whereas the M2 polarization was hardly affected. These findings indicated that ILG might be a potential anti‐inflammatory and anti‐fibrotic therapeutic agent for CP.
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DOI：
10.1073/pnas.90.11.5292
发表时间：
1993-06-01
影响因子：
11.1
作者：
CHARLES, CH;SUN, H;TONKS, NK
通讯作者：
TONKS, NK
Wnt/Dkk负反馈失衡促进慢性胰腺炎胰腺星状细胞持续激活
影响因子：
3.7
作者：
Hu Y;Wan R;Yu G;Shen J;Ni J;Yin G;Xing M;Chen C;Fan Y;Xiao W;Xu G;Wang X;Hu G
通讯作者：
Hu G
影响因子：
24.5
作者：
Jaster, R;Sparmann, G;Liebe, S
通讯作者：
Liebe, S
影响因子：
81.5
作者：
Kleeff, Jorg;Whitcomb, David C.;Neoptolemos, John P.
通讯作者：
Neoptolemos, John P.
影响因子：
29.7
作者：
Van Dyken SJ;Locksley RM
通讯作者：
Locksley RM