School of Third Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, PR China; Laboratories of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, PR China.
Laboratories of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, PR China; School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 210009, PR China.
J Ethnopharmacol. 2021 Oct 28;279:114108. doi: 10.1016/j.jep.2021.114108. Epub 2021 Apr 8.
Aloe vera (L.) Burm. f. (Aloe vera) is a medicinal herb that used in Traditional Chinese Medicine (TCM) practice for the treatment of gastrointestinal diseases such as constipation and colitis. Recent studies also reported its beneficial effect in mitigating ulcerative colitis (UC). Nevertheless, the underlying mechanisms of Aloe vera against UC remain largely unknown.
This study aimed to explore a relation between the therapeutical effects of Aloe vera in UC and colonic mucus secretion, and further investigate the underlying pathways through which Aloe vera regulates colon mucus as well as preliminarily studied the main active constitute of Aloe vera to alleviate UC.
UPLC-MS/MS were employed to analyze the Aloe vera extract. The rat models of UC were induced by free subjected to fresh 3% dextran sulfate sodium (DSS) solution for 8 days and then accessed to tap water for 2 days. Aloe vera extract (18 mg/kg and 72 mg/kg) or 5-ASA (400 mg/kg) was administered orally from day 1-10. At the end of experiment, rats were sacrificed and the colon tissues were harvested for analysis. UC symptoms was evaluated by disease activity index (DAI), colon length and H&E staining. The Alcian blue stain were determined colon mucus layer. Myeloperoxidase (MPO) activity, mucin and inflammatory cytokines in colon tissues were determined by ELISA. The expression of related proteins on PI3K/AKT and PKC/ERK signaling pathway was analyzed by Western blot. We then evaluated the effects of three main components of Aloe vera (Aloe-emodin, aloin A and B) on mucin secretion and cytokine expression in vitro by ELISA.
Oral supplement with Aloe vera extract resulted in a significantly decreased DSS-induced UC symptoms, including decreased DAI, prevention of the colon length shortening, and alleviation of the pathological changes occurring in colon. The expression of colonic pro-inflammatory mediators, including IL-6, IL-1β and TNF-α were suppressed, yet the expression of IL-10 was up-regulated by Aloe vera treatment. Moreover, Aloe vera significantly up-regulated the expressions of mucin proteins (e.g., MUC2 and MUC5AC) and increased the thickness of mucus layer in the colon. Further, we revealed that Aloe vera significantly upregulated p-PKC and p-ERK expression and downregulated p-PI3K and p-AKT expression. Finally, we discovered that treat with aloin A markedly decreased IL-6 levels and increased MUC2 expression in LPS-stimulated LS174T cell.
These results support that Aloe vera improved UC by enhancing colon mucus barrier functions in addition to reducing inflammation. Moreover, aloin A might be a main active components of Aloe vera to ameliorate UC.
库拉索芦荟(L.)伯曼。 f. (库拉索芦荟)是一种药用植物,在中国传统医学(TCM)实践中用于治疗便秘和结肠炎等胃肠道疾病。最近的研究还报道了其在减轻溃疡性结肠炎(UC)方面的有益作用。然而,库拉索芦荟对 UC 的作用机制在很大程度上仍然未知。
本研究旨在探讨库拉索芦荟治疗 UC 的疗效与结肠粘液分泌之间的关系,并进一步探讨库拉索芦荟调节结肠粘液的潜在途径,初步研究库拉索芦荟缓解 UC 的主要活性成分。
采用 UPLC-MS/MS 分析库拉索芦荟提取物。通过自由给予新鲜 3%葡聚糖硫酸钠(DSS)溶液 8 天,然后给予自来水 2 天,诱导大鼠 UC 模型。从第 1-10 天,给予库拉索芦荟提取物(18mg/kg 和 72mg/kg)或 5-ASA(400mg/kg)口服治疗。实验结束时,处死大鼠并采集结肠组织进行分析。通过疾病活动指数(DAI)、结肠长度和 H&E 染色评估 UC 症状。用阿尔辛蓝染色法测定结肠粘液层。通过 ELISA 测定结肠组织中髓过氧化物酶(MPO)活性、粘蛋白和炎症细胞因子。通过 Western blot 分析 PI3K/AKT 和 PKC/ERK 信号通路相关蛋白的表达。然后,通过 ELISA 评估库拉索芦荟的三种主要成分(大黄素、芦荟苷 A 和 B)对体外粘蛋白分泌和细胞因子表达的影响。
口服库拉索芦荟提取物可显著减轻 DSS 诱导的 UC 症状,包括降低 DAI、预防结肠长度缩短和减轻结肠发生的病理变化。库拉索芦荟治疗可抑制结肠促炎介质的表达,包括 IL-6、IL-1β 和 TNF-α,同时上调 IL-10 的表达。此外,库拉索芦荟还显著上调粘蛋白蛋白(如 MUC2 和 MUC5AC)的表达,并增加结肠粘液层的厚度。进一步研究表明,库拉索芦荟可显著上调 p-PKC 和 p-ERK 的表达,下调 p-PI3K 和 p-AKT 的表达。最后,我们发现用芦荟苷 A 处理可显著降低 LPS 刺激的 LS174T 细胞中 IL-6 的水平并增加 MUC2 的表达。
这些结果表明,库拉索芦荟通过增强结肠粘液屏障功能来改善 UC,同时减轻炎症。此外,芦荟苷 A 可能是库拉索芦荟改善 UC 的主要活性成分之一。