Direito Rosa, Lima Ana, Rocha João, Ferreira Ricardo Boavida, Mota Joana, Rebelo Patrícia, Fernandes Adelaide, Pinto Rui, Alves Paula, Bronze Rosário, Sepodes Bruno, Figueira Maria-Eduardo
University of Lisbon, Faculty of Pharmacy and Research Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal.
Disease & Stress Biology Group, LEAF, Instituto Superior de Agronomia, Universidade de Lisboa, 1349-017 Lisbon, Portugal.
J Nutr Biochem. 2017 Aug;46:100-108. doi: 10.1016/j.jnutbio.2017.03.002. Epub 2017 Mar 30.
Polyphenols from persimmon (Diospyros kaki) have demonstrated radical-scavenging and antiinflammatory activities; however, little is known about the effects of persimmon phenolics on inflammatory bowel diseases (IBD) and colorectal cancer (CRC). Therefore, we aimed in this work to characterize the antiinflammatory and antiproliferative effects of a persimmon phenolic extract (80% acetone in water), using an in vivo model of experimental colitis and a model of cancer cell invasion. Our results show, for the first time, a beneficial effect of a persimmon phenolic extract in the attenuation of experimental colitis and a potential antiproliferative effect on cultured colon cancer cells. Administration of persimmon phenolic extract to mice with TNBS-induced colitis led to a reduction in several functional and histological markers of colon inflammation, namely: attenuation of colon length decrease, reduction of the extent of visible injury (ulcer formation), decrease in diarrhea severity, reduced mortality rate, reduction of mucosal hemorrhage and reduction of general histological features of colon inflammation. In vitro studies also showed that persimmon phenolic extract successfully impaired cell proliferation and invasion in HT-29 cells. Further investigation showed a decreased expression of COX-2 and iNOS in the colonic tissue of colitis mice, two important mediators of intestinal inflammation, but there was no inhibition of the gelatinase MMP-9 and MMP-2 activities. Given the role of inflammatory processes in the progression of CRC and the important link between inflammation and cancer, our results highlight the potential of persimmon polyphenols as a pharmacological tool in the treatment of patients with IBD.
柿子(柿属)中的多酚已显示出自由基清除和抗炎活性;然而,关于柿子酚类物质对炎症性肠病(IBD)和结直肠癌(CRC)的影响知之甚少。因此,在这项研究中,我们旨在利用实验性结肠炎的体内模型和癌细胞侵袭模型,来表征柿子酚类提取物(80%丙酮水溶液)的抗炎和抗增殖作用。我们的研究结果首次表明,柿子酚类提取物对减轻实验性结肠炎具有有益作用,并且对培养的结肠癌细胞具有潜在的抗增殖作用。给患有三硝基苯磺酸(TNBS)诱导结肠炎的小鼠施用柿子酚类提取物,可使结肠炎症的几种功能和组织学指标降低,具体如下:减轻结肠长度缩短、减少可见损伤(溃疡形成)的程度、降低腹泻严重程度、降低死亡率、减少粘膜出血以及减轻结肠炎症的一般组织学特征。体外研究还表明,柿子酚类提取物成功抑制了HT - 29细胞的增殖和侵袭。进一步研究表明,结肠炎小鼠结肠组织中环氧合酶 - 2(COX - 2)和诱导型一氧化氮合酶(iNOS)的表达降低,这两种是肠道炎症的重要介质,但并未抑制明胶酶基质金属蛋白酶 - 9(MMP - 9)和基质金属蛋白酶 - 2(MMP - 2)的活性。鉴于炎症过程在结直肠癌进展中的作用以及炎症与癌症之间的重要联系,我们的研究结果突出了柿子多酚作为治疗炎症性肠病患者的药理学工具的潜力。