Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Department of Pharmaceutical and Pharmacological Science, University of Padova, Padova, Italy.
PLoS One. 2018 Apr 11;13(4):e0195502. doi: 10.1371/journal.pone.0195502. eCollection 2018.
Apigenin can exert beneficial actions in the prevention of obesity. However, its putative action on obesity-associated bowel motor dysfunctions is unknown. This study examined the effects of apigenin on colonic inflammatory and motor abnormalities in a mouse model of diet-induced obesity.
Male C57BL/6J mice were fed with standard diet (SD) or high-fat diet (HFD). SD or HFD mice were treated with apigenin (10 mg/Kg/day). After 8 weeks, body and epididymal fat weight, as well as cholesterol, triglycerides and glucose levels were evaluated. Malondialdehyde (MDA), IL-1β and IL-6 levels, and let-7f expression were also examined. Colonic infiltration by eosinophils, as well as substance P (SP) and inducible nitric oxide synthase (iNOS) expressions were evaluated. Motor responses elicited under blockade of NOS and tachykininergic contractions were recorded in vitro from colonic longitudinal muscle preparations.
When compared to SD mice, HFD animals displayed increased body weight, epididymal fat weight and metabolic indexes. HFD mice showed increments in colonic MDA, IL-1β and IL-6 levels, as well as a decrease in let-7f expression in both colonic and epididymal tissues. HFD mice displayed an increase in colonic eosinophil infiltration. Immunohistochemistry revealed an increase in SP and iNOS expression in myenteric ganglia of HFD mice. In preparations from HFD mice, electrically evoked contractions upon NOS blockade or mediated by tachykininergic stimulation were enhanced. In HFD mice, Apigenin counteracted the increase in body and epididymal fat weight, as well as the alterations of metabolic indexes. Apigenin reduced also MDA, IL-1β and IL-6 colonic levels as well as eosinophil infiltration, SP and iNOS expression, along with a normalization of electrically evoked tachykininergic and nitrergic contractions. In addition, apigenin normalized let-7f expression in epididymal fat tissues, but not in colonic specimens.
Apigenin prevents systemic metabolic alterations, counteracts enteric inflammation and normalizes colonic dysmotility associated with obesity.
芹菜素在预防肥胖方面具有有益作用。然而，其在肥胖相关肠动力障碍方面的作用尚不清楚。本研究探讨了芹菜素对饮食诱导肥胖小鼠模型结肠炎症和运动异常的影响。
雄性 C57BL/6J 小鼠喂食标准饮食（SD）或高脂肪饮食（HFD）。SD 或 HFD 小鼠用芹菜素（10mg/Kg/天）处理。8 周后，评估体重和附睾脂肪重量，以及胆固醇、甘油三酯和葡萄糖水平。还检测了丙二醛（MDA）、IL-1β 和 IL-6 水平以及 let-7f 表达。评估嗜酸性粒细胞浸润，以及 SP 和诱导型一氧化氮合酶（iNOS）的表达。在体外从结肠纵行肌标本中记录在 NOS 和速激肽能收缩阻断下引起的运动反应。
与 SD 小鼠相比，HFD 动物的体重、附睾脂肪重量和代谢指标增加。HFD 动物的结肠 MDA、IL-1β 和 IL-6 水平升高，结肠和附睾组织中的 let-7f 表达降低。HFD 动物的结肠嗜酸性粒细胞浸润增加。免疫组织化学显示 HFD 小鼠的肌间神经节中 SP 和 iNOS 表达增加。在 HFD 小鼠的制剂中，电刺激 NOS 阻断或由速激肽能刺激介导的收缩增强。在 HFD 小鼠中，芹菜素拮抗体重和附睾脂肪重量的增加，以及代谢指标的改变。芹菜素还降低了 MDA、IL-1β 和 IL-6 结肠水平以及嗜酸性粒细胞浸润、SP 和 iNOS 表达，并使电刺激引起的速激肽能和硝氮能收缩正常化。此外，芹菜素使附睾脂肪组织中的 let-7f 表达正常化，但结肠标本中未正常化。
芹菜素可预防全身性代谢改变，拮抗肠道炎症，使肥胖相关的结肠运动障碍正常化。
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