State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, China.
Mol Nutr Food Res. 2017 Dec;61(12). doi: 10.1002/mnfr.201700332. Epub 2017 Oct 11.
Ursolic acid (UA) is a pentacyclicterpenoid carboxylic acid that is present in a wide variety of plant foods. There are many beneficial health effects that are attributed to the properties of UA. However, the specific cellular targets of UA and the mechanism underlying downstream signal transduction processes linked to the anti-inflammation pathway have not been thoroughly elucidated to date.
Chemical biology strategies such as target fishing, click reaction synthesis of a UA probe and molecular imaging were used to identify potential target proteins of UA. Cysteinyl aspartate specific proteinase 3 (CASP3) and its downstream signaling pathway were verified as potential targets by molecular docking, intracellular enzyme activity evaluation and accurate pathway analysis. The results indicated that UA acted on CASP3, ERK1 and JNK2 targets, alleviated inflammation-associated downstream multiple signal transduction factors, including ERK1, NF-κB and STAT3, and exhibited anti-inflammation activities.
As a natural dietary supplement, UA demonstrated anti-inflammation activity via inhibition of CASP3 and shows the potential to improve the therapy effect of several inflammation-associated diseases.
熊果酸（UA）是一种五环萜烯羧酸，存在于多种植物性食物中。UA 具有许多有益的健康作用，这归因于其特性。然而，UA 的特定细胞靶标以及与抗炎途径相关的下游信号转导过程的机制尚未得到彻底阐明。
采用化学生物学策略，如靶标捕捞、UA 探针的点击反应合成和分子成像，来鉴定 UA 的潜在靶标蛋白。半胱天冬氨酸特异性蛋白酶 3（CASP3）及其下游信号通路通过分子对接、细胞内酶活性评估和准确的途径分析被验证为潜在的靶标。结果表明，UA 作用于 CASP3、ERK1 和 JNK2 靶标，减轻炎症相关的下游多个信号转导因子，包括 ERK1、NF-κB 和 STAT3，表现出抗炎活性。
作为一种天然膳食补充剂，UA 通过抑制 CASP3 表现出抗炎活性，并显示出改善几种与炎症相关疾病的治疗效果的潜力。
