Research Affairs, Faculty of Veterinary Medicine, Chiang Mai University, Chiang Mai, 50100, Thailand.
Research Center of Producing and Development of Products and Innovations for Animal Health and Production, Faculty of Veterinary Medicine, Chiang Mai University, Chiang Mai, 50100, Thailand.
Sci Rep. 2022 Jun 22;12(1):10548. doi: 10.1038/s41598-022-14888-2.
Our previous study demonstrated that purple rice bran extract (PRBE) could inhibit diethylnitrosamine (DEN)-induced hepatocarcinogenesis. Protocatechuic acid (PCA) is the major phenolic acid contained in the PRBE. Therefore, this study aimed to determine whether PCA is an anticarcinogenic compound in purple rice extract. Rats were intraperitoneally injected with DEN to induce glutathione S-transferase placental form (GST-P)-positive foci. Rats were fed with PRBE at 500 mg kg body weight or PCA at 4 mg kg body weight for 5 and 15 weeks. PCA administration attenuated DEN-induced hepatic GST-P positive foci to a degree similar to PRBE. The molecular mechanisms of PCA in the initiation stage were correlated with reduced activity of cytochrome P450 reductase and induction of glutathione S-transferase. In addition, PCA also downregulated the expression of TNF-α and IL-1β genes in rat liver. These genes are associated with the inhibition of inflammation. In the promotion stage, PCA suppressed cell proliferation correlated with the downregulation of Cyclin D1 expression. Moreover, it also induced apoptosis, indicated by increased expression of P53 and Bad genes, and decreased the expression of the anti-apoptotic Bcl-xl in DEN-initiated rats. These findings suggest that PCA is an active compound in the anticarcinogenic action of purple rice bran.
我们之前的研究表明，紫米糠提取物（PRBE）可以抑制二乙基亚硝胺（DEN）诱导的肝癌发生。原儿茶酸（PCA）是 PRBE 中主要的酚酸。因此，本研究旨在确定 PCA 是否是紫米提取物中的一种抗癌化合物。大鼠经腹腔注射 DEN 诱导谷胱甘肽 S-转移酶胎盘形式（GST-P）阳性病灶。大鼠分别用 PRBE（500mg/kg 体重）或 PCA（4mg/kg 体重）喂养 5 周和 15 周。PCA 给药可使 DEN 诱导的肝 GST-P 阳性病灶减轻到与 PRBE 相似的程度。PCA 在起始阶段的分子机制与细胞色素 P450 还原酶活性降低和谷胱甘肽 S-转移酶诱导有关。此外，PCA 还下调了大鼠肝脏中 TNF-α和 IL-1β基因的表达。这些基因与炎症抑制有关。在促进阶段，PCA 抑制细胞增殖与 Cyclin D1 表达下调有关。此外，它还通过增加 P53 和 Bad 基因的表达和降低 DEN 诱导大鼠中抗凋亡 Bcl-xl 的表达来诱导细胞凋亡。这些发现表明 PCA 是紫米糠抗癌作用的一种活性化合物。
