Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China; School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou China.
School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou China.
Phytomedicine. 2021 Jul;87:153570. doi: 10.1016/j.phymed.2021.153570. Epub 2021 Apr 20.
Croton crassifolius Geisel (CCG, also known as Ji-Gu-Xiang in Traditional Chinese Medicine), is traditionally prescribed for the therapy of rheumatic arthritis and gastrointestinal ulcer. However, the effect of CCG on ulcerative colitis (UC) has not been investigated.
To explore the therapeutic potential and underlying mechanism of CCG extract against UC by colonic and serum metabolomics.
In order to standardize the CCG extract, UPLC-QTOF-MS was used for quantitative and qualitative analysis of the representative terpenoids. C57BL/6J mice were divided into control, Dextran Sulfate Sodium (DSS), mesalazine (100 mg•kg), CCG extract (150 and 600 mg•kg) groups. The mice were provided 3% DSS dissolved in distilled water ad libitum for 7 days except control group. Weight change, disease activity index (DAI), colon lengths and expression of inflammatory mediators iNOS and COX-2 in colonic tissue were determined. Serum and colon metabolomics using UPLC-QTOF-MS technology coupled with multivariate data analysis were performed to reveal the underlying mechanism.
Thirty-five terpenoids in CCG were identified by fingerprint, in which ten representative terpenes were quantified. CCG could relieve the weight loss, the degree of bloody stool and ulcer of colon, as well as significantly lowering the expression level of iNOS and COX-2. Metabolomics analysis showed that 25 biomarkers were obviously interfered by CCG treatment and 16 of them were highly correlated with the efficacy of CCG. The analysis of metabolic pathway showed that the anti-UC effect of CCG was associated with the regulation on linoleic acid metabolism, sphingolipid metabolism, α-linolenic acid metabolism, and glycerophospholipids metabolism.
The oral administration of CCG significantly alleviated DSS-induced UC symptoms by reducing inflammation and rectifying the metabolic disorder. CCG may provide a new strategy for the management of UC.
巴豆（CCG，也称为中药鸡骨香）传统上用于治疗风湿性关节炎和胃溃疡。然而，CCG 对溃疡性结肠炎（UC）的影响尚未得到研究。
通过结肠和血清代谢组学探讨 CCG 提取物治疗 UC 的潜在机制。
为了标准化 CCG 提取物，使用 UPLC-QTOF-MS 对代表性萜类化合物进行定量和定性分析。将 C57BL/6J 小鼠分为对照组、葡聚糖硫酸钠（DSS）组、美沙拉嗪（100mg·kg）组、CCG 提取物（150 和 600mg·kg）组。除对照组外，其余各组均给予 3%DSS 溶解在蒸馏水中自由饮用 7 天。测定体重变化、疾病活动指数（DAI）、结肠长度和结肠组织中炎症介质诱导型一氧化氮合酶（iNOS）和环氧化酶-2（COX-2）的表达。使用 UPLC-QTOF-MS 技术结合多元数据分析进行血清和结肠代谢组学分析，以揭示潜在机制。
CCG 中鉴定出 35 种萜类化合物，其中 10 种代表性萜类化合物进行了定量。CCG 可缓解体重减轻、大便带血和结肠溃疡程度，显著降低 iNOS 和 COX-2 的表达水平。代谢组学分析表明，CCG 处理明显干扰了 25 种生物标志物，其中 16 种与 CCG 的疗效高度相关。代谢途径分析表明，CCG 的抗 UC 作用与调节亚油酸代谢、鞘脂代谢、α-亚麻酸代谢和甘油磷脂代谢有关。
CCG 口服给药可通过减轻炎症和纠正代谢紊乱显著缓解 DSS 诱导的 UC 症状。CCG 可能为 UC 的治疗提供新策略。
