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古日古木-7 毒性评估:传统蒙药对细胞存活或死亡的调控。

Gurgem-7 toxicity assessment: Regulation of cell survival or death by traditional Mongolian prescription.

机构信息

Mon-Intra CO., LTD, 23 sh/h 166 Mongolian, Ulaanbaatar, Mongolia; Department of Food and Nutrition, Medical University of Lublin, 20-093 Lublin, Poland.

Department of Biopharmacy, Medical University of Lublin, Lublin 20-093, Poland; Department of Biotechnology, Institute of Biology and Biotechnology, University of Rzeszow, Rzeszow 35-310, Poland.

出版信息

Ecotoxicol Environ Saf. 2022 Jul 1;239:113660. doi: 10.1016/j.ecoenv.2022.113660. Epub 2022 May 20.

DOI:10.1016/j.ecoenv.2022.113660
PMID:35605329
Abstract

Surgical treatments and chemotherapy are the most commonly used methods of colorectal cancer treatment (CRC), unfortunately, these therapies have many side effects. Moreover, despite advances in primary and adjuvant treatments, the survival time in CRC patients is still unsatisfactory. Treatment options for patients with CRC continue to advance and recent research has shown that colorectal cancer is sensitive to plant-derived substances. The use of natural compounds contained in herbal extracts for the treatment of colon cancer or as adjunctive therapy for CRC gives patients a wide range of treatment options. In this study, we evaluate the potential toxicity of the Mongolian preparation - Gurgem-7 composed of Crocus sativus, Veronica officinalis, Capsella bursa-pastoris, Arctostaphylos uva-ursi, Calendula officinalis, Gentiana lutea, and Terminalia chebula. Therefore, the aim of this study was to determine its biological activities, biochemical and molecular features in vitro and composition analysis by HPLC-ESI-QTOF-MS/MS platform. We identified 18 metabolites and 8 of them were quantified. Majority of the secondary metabolites belonged to the group of phenolic constituents with taxifolin, chlorogenic acids' family, hydroxysafflor yellow A and hydroxybenzoic acid as leading compounds. In turn, our in vitro results suggest that the preparation inhibits cell metabolic activity through oxidative stress, numerous DNA damage and cell cycle arrest. Simultaneously enzymatic and non-enzymatic cell protection mechanisms mediated by TP53/Keap1 and Nrf2/HO-1 pathways may be activated in a cell-specific manner in vitro. In conclusion, we provide preliminary molecular evidence of the toxic properties of Gurgem-7 preparation to Caco-2 and CT26. WT cells related to insufficient action of their repair and adaptive mechanisms to stress conditions.

摘要

手术治疗和化疗是结直肠癌(CRC)最常用的治疗方法(CRC),不幸的是,这些疗法有很多副作用。此外,尽管原发性和辅助治疗有所进展,但 CRC 患者的生存时间仍然不尽如人意。CRC 患者的治疗选择仍在不断发展,最近的研究表明,结直肠癌对植物源性物质敏感。使用草药提取物中含有的天然化合物治疗结肠癌或作为 CRC 的辅助治疗为患者提供了广泛的治疗选择。在这项研究中,我们评估了由藏红花、婆婆纳、荠菜、熊果酸、金盏花、秦艽和诃子组成的蒙古制剂——Gurgem-7 的潜在毒性。因此,本研究的目的是确定其在体外的生物活性、生化和分子特征以及通过 HPLC-ESI-QTOF-MS/MS 平台进行的成分分析。我们鉴定了 18 种代谢物,其中 8 种进行了定量。大多数次生代谢物属于酚类成分组,以杨梅素、绿原酸家族、羟基红花黄色 A 和羟基苯甲酸为主要化合物。反过来,我们的体外结果表明,该制剂通过氧化应激、大量 DNA 损伤和细胞周期停滞来抑制细胞代谢活性。同时,TP53/Keap1 和 Nrf2/HO-1 途径介导的酶和非酶细胞保护机制可能在体外以细胞特异性的方式被激活。总之,我们为 Gurgem-7 制剂对 Caco-2 和 CT26 的毒性特性提供了初步的分子证据。WT 细胞与它们的修复和适应应激条件的机制不足有关。

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