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罗比(Roxb.)多酚富集部分有效逆转 NDEA 诱导 HCC 大鼠的肝癌。

Phenolics-Enriched Fraction of Roxb. efficiently Reverses the Hepatocellular Carcinoma in NDEA-Induced HCC Rats.

机构信息

Pharmacology Division, CSIR-National Botanical Research Institute, Lucknow, India.

Department of Biotechnology, Kumaun University, Nainital, India.

出版信息

Nutr Cancer. 2022;74(3):1106-1121. doi: 10.1080/01635581.2021.1922716. Epub 2021 May 21.

Abstract

Hepatocellular Carcinoma is one of the most frequently diagnosed cancer and highly refractory for chemotherapeutics agents. Therefore, the study aims to explore the new therapeutic agents for HCC. Phenolics rich fraction of leaves of was studied against hepatic cancer cell lines (HepG2) and NDEA-induced HCC rat model system. The obtained results showed that PLE induces reactive oxygen species (ROS) generation and chromatin condensation in nucleus and, alters the mitochondrial membrane potential (MMP) in HepG2 cell lines. The acridine orange/propidium iodide analysis and annexin-V FITC/PI analysis confirms that PLE induces apoptosis-mediated cell death in HepG2-cell lines. In In Vivo analysis, the administration of PLE in NDEA-induced rats declined the elevated biochemicals markers (ALT, AST, ALP, and GGT), interleukins, TNF-α, α-fetoprotein, carcinoembryonic antigen, and total bilirubin. PLE reinstated the level of antioxidant enzyme (GSH, GST, catalase, SOD, and GPX) and the expression of pro-apoptotic (p53, caspase-3, caspase-9, and Bax) and anti-apoptotic (Bcl-2) genes in a dose-dependent manner. The GC-MS analysis of fraction (PLE) represents the presence of palmitic acid, myristic acid, β-sitosterol, and catechin as major bioactive phytocompounds. The study discloses the new lead for HCC that can be further useful for development of new chemopreventive agent.

摘要

肝细胞癌是最常见的癌症之一,对化疗药物高度耐受。因此,本研究旨在探索治疗 HCC 的新方法。对 叶的多酚富集部分进行了研究,以对抗肝癌细胞系 (HepG2) 和 NDEA 诱导的 HCC 大鼠模型系统。结果表明,PLE 诱导活性氧 (ROS) 的产生和核内染色质凝聚,并改变 HepG2 细胞系中的线粒体膜电位 (MMP)。吖啶橙/碘化丙啶分析和 Annexin-V FITC/PI 分析证实,PLE 诱导 HepG2 细胞系中的凋亡介导的细胞死亡。在体内分析中,PLE 在 NDEA 诱导的大鼠中的给药降低了升高的生化标志物 (ALT、AST、ALP 和 GGT)、白细胞介素、TNF-α、甲胎蛋白、癌胚抗原和总胆红素。PLE 以剂量依赖的方式恢复抗氧化酶 (GSH、GST、过氧化氢酶、SOD 和 GPX) 和促凋亡 (p53、caspase-3、caspase-9 和 Bax) 和抗凋亡 (Bcl-2) 基因的表达。对 部分 (PLE) 的 GC-MS 分析表明存在棕榈酸、肉豆蔻酸、β-谷甾醇和儿茶素等主要生物活性植物化合物。该研究揭示了 HCC 的新线索,可为开发新的化学预防剂提供进一步的帮助。

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