Postgraduate Program in Cardiovascular Sciences, Fluminense Federal University (UFF), Niterói, RJ, Brazil.
Postgraduate Program in Pathology, Fluminense Federal University (UFF), Niterói, RJ, Brazil.
Nutr Res. 2022 Nov;107:96-116. doi: 10.1016/j.nutres.2022.09.001. Epub 2022 Sep 9.
Chronic inflammation is associated with the development and progression of several noncommunicable diseases, such as diabetes, cardiovascular disease, chronic kidney disease, cancer, and nonalcoholic fatty liver disease. Evidence suggests that pattern recognition receptors that identify pathogen-associated molecular patterns and danger-associated molecular patterns are crucial in chronic inflammation. Among the pattern recognition receptors, Toll-like receptor 4 (TLR4) stimulates several inflammatory pathway agonists, such as nuclear factor-κB, interferon regulator factor 3, and nod-like receptor pyrin domain containing 3 pathways, which consequently trigger the expression of pro-inflammatory biomarkers, increasing the risk of noncommunicable disease development and progression. Studies have focused on the antagonistic potential of bioactive compounds, following the concept of food as a medicine, in which nutritional strategies may mitigate inflammation via TLR4 modulation. Thus, this review discusses preclinical evidence concerning bioactive compounds from fruit, vegetable, spice, and herb extracts (curcumin, resveratrol, catechin, cinnamaldehyde, emodin, ginsenosides, quercetin, allicin, and caffeine) that may regulate the TLR4 pathway and reduce the inflammatory response. Bioactive compounds can inhibit TLR4-mediated inflammation through gut microbiota modulation, improvement of intestinal permeability, inhibition of lipopolysaccharide-TLR4 binding, and decreasing TLR4 expression by modulation of microRNAs and antioxidant pathways. The responses directly mitigated inflammation, especially nuclear factor-κB activation and inflammatory cytokines release. These findings should be considered for further clinical studies on inflammation-mediated diseases.
慢性炎症与多种非传染性疾病的发展和进展有关，如糖尿病、心血管疾病、慢性肾脏病、癌症和非酒精性脂肪性肝病。有证据表明，识别病原体相关分子模式和危险相关分子模式的模式识别受体在慢性炎症中至关重要。在模式识别受体中，Toll 样受体 4（TLR4）刺激几种炎症途径激动剂，如核因子-κB、干扰素调节因子 3 和含 NOD 样受体 pyrin 域蛋白 3 途径，从而触发促炎生物标志物的表达，增加非传染性疾病发展和进展的风险。研究集中在生物活性化合物的拮抗潜力上，遵循食物作为药物的概念，其中营养策略可能通过 TLR4 调节减轻炎症。因此，本综述讨论了来自水果、蔬菜、香料和草药提取物（姜黄素、白藜芦醇、儿茶素、肉桂醛、大黄素、人参皂苷、槲皮素、大蒜素、咖啡因）的生物活性化合物的临床前证据，这些化合物可能调节 TLR4 途径并减少炎症反应。生物活性化合物可以通过调节肠道微生物群、改善肠道通透性、抑制脂多糖-TLR4 结合以及通过调节 microRNAs 和抗氧化途径来减少 TLR4 表达来抑制 TLR4 介导的炎症。这些反应直接减轻了炎症，特别是核因子-κB 激活和炎症细胞因子的释放。这些发现应在针对炎症介导疾病的进一步临床研究中加以考虑。
