Research Group on Quality, Safety and Bioactivity of Plant Foods, CEBAS-CSIC, 30100 Campus de Espinardo, Murcia, Spain.
Pharmacol Res. 2013 Jun;72:69-82. doi: 10.1016/j.phrs.2013.03.011. Epub 2013 Apr 1.
Numerous studies have shown that resveratrol (RES) exerts anti-inflammatory effects but human trials evidencing these effects in vivo are limited. Furthermore, the molecular mechanisms triggered in humans following the oral intake of RES are not yet understood. Therefore, the purpose of this study was to investigate the molecular changes in peripheral blood mononuclear cells (PBMCs) associated to the one-year daily intake of a RES enriched (8 mg) grape extract (GE-RES) in hypertensive male patients with type 2 diabetes mellitus (T2DM). We used microarrays and RT-PCR to analyze expression changes in genes and microRNAs (miRs) involved in the inflammatory response modulated by the consumption of GE-RES in comparison to a placebo and GE lacking RES. We also examined the changes in several serobiochemical variables, inflammatory and fibrinolytic markers. Our results showed that supplementation with GE or GE-RES did not affect body weight, blood pressure, glucose, HbA1c or lipids, beyond the values regulated by gold standard medication in these patients. We did not find either any significant change on serum inflammatory markers except for a significant reduction of ALP and IL-6 levels. The expression of the pro-inflammatory cytokines CCL3, IL-1β and TNF-α was significantly reduced and that of the transcriptional repressor LRRFIP-1 increased in PBMCs from patients taking the GE-RES extract. Also, a group of miRs involved in the regulation of the inflammatory response: miR-21, miR-181b, miR-663, miR-30c2, miR-155 and miR-34a were found to be highly correlated and altered in the group consuming the GE-RES for 12 months. Our results provide preliminary evidence that long-term supplementation with a grape extract containing RES downregulates the expression of key pro-inflammatory cytokines with the involvement of inflammation-related miRs in circulating immune cells of T2DM hypertensive medicated patients and support a beneficial immunomodulatory effect in these patients.
大量研究表明白藜芦醇（RES）具有抗炎作用，但在体内证实这些作用的人体试验有限。此外，口服 RES 后在人体内引发的分子机制尚不清楚。因此，本研究旨在研究与高血压 2 型糖尿病男性患者（T2DM）每日摄入 RES 富集（8mg）葡萄提取物（GE-RES）一年相关的外周血单个核细胞（PBMCs）的分子变化。我们使用微阵列和 RT-PCR 分析了与 RES 消耗相关的参与炎症反应的基因和 microRNAs（miRs）的表达变化，与安慰剂和不含 RES 的 GE 进行比较。我们还检查了几种血清生化变量、炎症和纤维蛋白溶解标志物的变化。我们的研究结果表明，补充 GE 或 GE-RES 不会影响体重、血压、血糖、HbA1c 或血脂，超出了这些患者标准药物治疗调节的范围。除了 ALP 和 IL-6 水平的显著降低外，我们没有发现任何血清炎症标志物的显著变化。服用 GE-RES 提取物的患者的 PBMC 中促炎细胞因子 CCL3、IL-1β 和 TNF-α的表达明显降低，转录抑制因子 LRRFIP-1 的表达增加。此外，一组参与炎症反应调节的 miRs：miR-21、miR-181b、miR-663、miR-30c2、miR-155 和 miR-34a 被发现高度相关，并在服用 GE-RES 12 个月的组中发生改变。我们的研究结果提供了初步证据，表明长期补充含有 RES 的葡萄提取物可下调关键促炎细胞因子的表达，涉及到循环免疫细胞中与炎症相关的 miRs，这为 T2DM 高血压药物治疗患者提供了有益的免疫调节作用。
