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(UPLC/T-TOF-MS/MS)鉴定的提取物中的化合物通过调节 HNF-1α、Sirtuin-1、C/ebpα、miRNA-34a 和 miRNA-223 发挥体内肝保护作用。

Tentatively Identified (UPLC/T-TOF-MS/MS) Compounds in the Extract of Roots Exhibit In Vivo Hepatoprotection via Modulation of HNF-1α, Sirtuin-1, C/ebpα, miRNA-34a and miRNA-223.

机构信息

Department of Pharmacognosy, Faculty of Pharmacy, October 6 University (O6U), Giza 12585, Egypt.

Department of Pharmacognosy, School of Pharmacy, Newgiza University (NGU), Newgiza, km 22 Cairo-Alexandria Desert Road, Giza 12577, Egypt.

出版信息

Molecules. 2022 Apr 28;27(9):2802. doi: 10.3390/molecules27092802.

DOI:10.3390/molecules27092802
PMID:35566153
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9104236/
Abstract

is a plant traditionally used for the treatment of several ailments. Our study accomplished the UPLC/T-TOF-MS/MS analysis of a methanol extract of roots (MESC), in addition to lipoidal matter determination and assessment of its in vivo hepatoprotective activity. In this study, we were able to identify the major metabolites in MESC rather than the previously known isolated compounds, improving our knowledge of its chemical constituents. The flavones apigenin, acacetin, baicalein, luteolin, and diosmetin, and the flavonol aglycones quercetin, kaempferol, isorhamnetin, gossypetin, and myricetin and/or their glycosides and glucuronic derivatives were the major identified compounds. The hepatoprotective activity of MESC was evaluated by measuring catalase activity using UV spectrophotometry, inflammatory cytokines and apoptotic markers using ELISA techniques, and genetic markers using PCR. Paracetamol toxicity caused a significant increase in plasma caspase 2, cytokeratin 18 (CK18), liver tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), miRNA-34a, and miRNA-223, as well as a significant decrease in liver catalase (CAT) activity and in the levels of liver nuclear factor 1α (HNF-1α), sirtuin-1, and C/ebpα. Oral pretreatment with MESC (200 mg/kg) showed a significant decrease in caspase 2, CK18, TNF-α, IL-6 and a significant increase in liver CAT activity. MESC decreased the levels of liver miRNA-34a and miRNA-223 and induced HNF-1α, sirtuin-1, and C/ebpα gene expression. The histological examination showed a significant normalization in rats pretreated with MESC. Our findings showed that may exert a potent hepatoprotective activity through the modulation of the expression of cellular cytokines, miRNA-34a, and miRNA-223.

摘要

是一种传统上用于治疗多种疾病的植物。我们的研究完成了甲醇提取物(MESC)的 UPLC/T-TOF-MS/MS 分析,此外还确定了脂类物质并评估了其体内保肝活性。在这项研究中,我们能够识别 MESC 中的主要代谢物,而不是以前已知的分离化合物,从而提高了我们对其化学成分的认识。鉴定出的主要化合物为类黄酮芹菜素、木犀草素、黄芩素、木樨草素、芫花素和非瑟酮苷元、槲皮素、山奈酚、异鼠李素、棉子糖和杨梅素和/或它们的糖苷和葡萄糖醛酸衍生物。通过使用紫外分光光度法测量过氧化氢酶活性、使用 ELISA 技术测量炎症细胞因子和凋亡标志物以及使用 PCR 测量遗传标志物来评估 MESC 的保肝活性。扑热息痛毒性导致血浆 Caspase 2、细胞角蛋白 18(CK18)、肝肿瘤坏死因子-α(TNF-α)、白细胞介素 6(IL-6)、miRNA-34a 和 miRNA-223 显著增加,而肝过氧化氢酶(CAT)活性和肝核因子 1α(HNF-1α)、Sirtuin-1 和 C/ebpα 的水平显著降低。MESC(200mg/kg)口服预处理可显著降低 Caspase 2、CK18、TNF-α、IL-6 的水平,显著增加肝 CAT 活性。MESC 降低肝 miRNA-34a 和 miRNA-223 的水平,并诱导 HNF-1α、Sirtuin-1 和 C/ebpα 基因表达。组织学检查显示 MESC 预处理的大鼠明显正常化。我们的研究结果表明,可能通过调节细胞因子、miRNA-34a 和 miRNA-223 的表达发挥强大的保肝活性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f47f/9104236/9b9bfa4528d2/molecules-27-02802-g006a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f47f/9104236/a08c9f372a14/molecules-27-02802-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f47f/9104236/a919e82a33b1/molecules-27-02802-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f47f/9104236/2b337f9846e0/molecules-27-02802-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f47f/9104236/bef93a787458/molecules-27-02802-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f47f/9104236/ed6b27aed02a/molecules-27-02802-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f47f/9104236/9b9bfa4528d2/molecules-27-02802-g006a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f47f/9104236/a08c9f372a14/molecules-27-02802-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f47f/9104236/a919e82a33b1/molecules-27-02802-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f47f/9104236/2b337f9846e0/molecules-27-02802-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f47f/9104236/bef93a787458/molecules-27-02802-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f47f/9104236/ed6b27aed02a/molecules-27-02802-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f47f/9104236/9b9bfa4528d2/molecules-27-02802-g006a.jpg

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