关键词: DSS colitis MAPKs NF-κB signaling inflammatory bowel diseases β-myrcene

Mesh : Mice Animals NF-kappa B / metabolism Tumor Necrosis Factor-alpha / metabolism Signal Transduction Colitis / chemically induced drug therapy metabolism Colitis, Ulcerative / chemically induced drug therapy metabolism Mitogen-Activated Protein Kinases / metabolism Colon / metabolism Inflammatory Bowel Diseases / pathology Inflammation / metabolism Dextran Sulfate / adverse effects Disease Models, Animal

来  源:   DOI:10.3390/molecules27248744

Abstract:
Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders that include Crohn\'s disease (CD) and ulcerative colitis (UC). The incidence of IBD is rising globally. However, the etiology of IBD is complex and governed by multiple factors. The current clinical treatment for IBD mainly includes steroids, biological agents and need-based surgery, based on the severity of the disease. Current drug therapy is often associated with adverse effects, which limits its use. Therefore, it necessitates the search for new drug candidates. In this pursuit, phytochemicals take the lead in the search for drug candidates to benefit from IBD treatment. β-myrcene is a natural phytochemical compound present in various plant species which possesses potent anti-inflammatory activity. Here we investigated the role of β-myrcene on colon inflammation to explore its molecular targets. We used 2% DSS colitis and TNF-α challenged HT-29 adenocarcinoma cells as in vivo and in vitro models. Our result indicated that the administration of β-myrcene in dextran sodium sulfate (DSS)-treated mice restored colon length, decreased disease activity index (DAI), myeloperoxidase (MPO) enzyme activity and suppressed proinflammatory mediators. β-myrcene administration suppressed mitogen-activated protein kinases (MAPKs) and nuclear factor-κB (NF-κB) pathways to limit inflammation. β-myrcene also suppressed mRNA expression of proinflammatory chemokines in tumor necrosis factor-α (TNF-α) challenged HT-29 adenocarcinoma cells. In conclusion, β-myrcene administration suppresses colon inflammation by inhibiting MAP kinases and NF-κB pathways.
摘要:
炎症性肠病(IBD)是慢性炎症性疾病,包括克罗恩病(CD)和溃疡性结肠炎(UC)。IBD的发病率在全球范围内呈上升趋势。然而,IBD的病因复杂,受多种因素影响。目前IBD的临床治疗主要包括类固醇,生物制剂和基于需求的手术,根据疾病的严重程度。目前的药物治疗通常与不良反应有关,这限制了它的使用。因此,这就需要寻找新的候选药物。在这种追求中,植物化学物质率先寻找从IBD治疗中受益的候选药物。β-月桂烯是存在于各种植物物种中的天然植物化学化合物,其具有有效的抗炎活性。在这里,我们研究了β-月桂烯在结肠炎症中的作用,以探索其分子靶标。我们使用2%DSS结肠炎和TNF-α攻击的HT-29腺癌细胞作为体内和体外模型。我们的结果表明,在葡聚糖硫酸钠(DSS)处理的小鼠中施用β-月桂烯可以恢复结肠长度,疾病活动指数(DAI)下降,髓过氧化物酶(MPO)酶活性和抑制促炎介质。β-月桂烯给药抑制丝裂原激活的蛋白激酶(MAPK)和核因子-κB(NF-κB)途径以限制炎症。β-月桂烯还抑制了肿瘤坏死因子-α(TNF-α)攻击的HT-29腺癌细胞中促炎趋化因子的mRNA表达。总之,β-月桂烯给药通过抑制MAP激酶和NF-κB途径抑制结肠炎症。
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