Department of Gastroenterology, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Zhangjiagang, 215600, China.
Department of Nephrology, Changshu Hospital Affiliated to Nanjing University of Chinese medicine, Changshu, 215500, China.
Curr Gene Ther. 2024;24(1):73-92. doi: 10.2174/1566523223666230731115236.
Isoliquiritin belongs to flavanol glycosides and has a strong antiinflammatory activity. This study sought to investigate the anti-inflammatory effect of isoliquiritin and its underlying mechanism.
The inflammatory (trinitro-benzene-sulfonic acid-TNBS-induced ulcerative colitis (UC)) model was established to ascertain the effect of isoliquiritin on the caspase-3/HMGB1/TLR4 pathway in rats. We also explored its protective effect on intestinal inflammation and its underlying mechanism using the LPS-induced inflammation model of Caco-2 cells. Besides, Deseq2 was used to analyze UCassociated protein levels.
Isoliquiritin treatment significantly attenuated shortened colon length (induced by TNBS), disease activity index (DAI) score, and body weight loss in rats. A decrease in the levels of inflammatory mediators (IL-1β, I IL-4, L-6, IL-10, PGE2, and TNF-α), coupled with malondialdehyde (MDA) and superoxide dismutase (SOD), was observed in colon tissue and serum of rats after they have received isoliquiritin. Results of techniques (like western blotting, real-time PCR, immunohistochemistry, and immunofluorescence-IF) demonstrated the potential of isoliquiritin to decrease expressions of key genes in the TLR4 downstream pathways, viz., MyD88, IRAK1, TRAF6, NF-κB, p38, and JNK at mRNA and protein levels as well as inhibit HMGB1 expression, which is the upstream ligand of TLR4. Bioinformational analysis showed enteritis to be associated with a high expression of HMGB1, TLR4, and caspase-3.
Isoliquiritin could reduce intestinal inflammation and mucosal damage of TNBS-induced colitis in rats with a certain anti-UC effect. Meanwhile, isoliquiritin treatment also inhibited the expression of HMGB1, TLR4, and MyD88 in LPS-induced Caco-2 cells. These results indicated that isoliquiritin could ameliorate UC through the caspase-3/HMGB1/TLR4-dependent signaling pathway.
异甘草素属于黄烷醇糖苷，具有很强的抗炎活性。本研究旨在探讨异甘草素的抗炎作用及其机制。
建立炎症（三硝基苯磺酸-TNBS 诱导的溃疡性结肠炎（UC））模型，确定异甘草素对大鼠 caspase-3/HMGB1/TLR4 通路的影响。我们还使用 LPS 诱导的 Caco-2 细胞炎症模型探讨了其对肠道炎症的保护作用及其机制。此外，使用 Deseq2 分析 UC 相关蛋白水平。
异甘草素治疗可显著减轻 TNBS 诱导的大鼠结肠缩短、疾病活动指数（DAI）评分和体重减轻。大鼠结肠组织和血清中炎症介质（IL-1β、IL-4、IL-6、IL-10、PGE2 和 TNF-α）水平下降，同时观察到丙二醛（MDA）和超氧化物歧化酶（SOD）水平下降。Western blot、实时 PCR、免疫组化和免疫荧光 IF 等技术结果表明，异甘草素可降低 TLR4 下游途径关键基因（MyD88、IRAK1、TRAF6、NF-κB、p38 和 JNK）的 mRNA 和蛋白水平表达，并抑制 TLR4 的上游配体 HMGB1 的表达。生物信息学分析表明，肠炎与 HMGB1、TLR4 和 caspase-3 的高表达有关。
异甘草素可减轻 TNBS 诱导的大鼠结肠炎的肠道炎症和黏膜损伤，具有一定的抗 UC 作用。同时，异甘草素治疗还抑制了 LPS 诱导的 Caco-2 细胞中 HMGB1、TLR4 和 MyD88 的表达。这些结果表明，异甘草素通过 caspase-3/HMGB1/TLR4 依赖性信号通路改善 UC。
