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评估从安息香科(Salicaceae)野牡丹属(Casearia)植物中提取的 clerodane 二萜化合物——贝壳杉烯 B 的化学预防作用。

Assessment of the chemopreventive effect of casearin B, a clerodane diterpene extracted from Casearia sylvestris (Salicaceae).

机构信息

UNESP-Univ. Estadual Paulista, Araraquara, School of Pharmaceutical Sciences, Department of Clinical Analysis, Rua Expedicionários do Brasil 1621, Araraquara, SP, Brazil.

出版信息

Food Chem Toxicol. 2013 Mar;53:153-9. doi: 10.1016/j.fct.2012.11.029. Epub 2012 Nov 28.

Abstract

Studies have shown that Casearia sylvestris compounds protect DNA from damage both in vitro and in vivo. Complementarily, the aim of the present study was to assess the chemopreventive effect of casearin B (CASB) against DNA damage using the Ames test, the comet assay and the DCFDA antioxidant assay. The genotoxicity was assessed by the comet assay in HepG2 cells. CASB was genotoxic at concentrations higher than 0.30 μM when incubated with the FPG (formamidopyrimidine-DNA glycosylase) enzyme. For the antigenotoxicity comet assay, CASB protected the DNA from damage caused by H(2)O(2) in the HepG2 cell line in concentrations above 0.04 μM with post-treatment, and above 0.08 μM with pre-treatment. CASB was not mutagenic (Ames test) in TA 98 and TA 102. In the antimutagenicity assays, the compound was a strong inhibitor against aflatoxin B1 (AFB) in TA 98 (>88.8%), whereas it was moderate (42.7-59.4%) inhibitor against mytomicin C (MMC) in TA 102. Additionally, in the antioxidant assay using DCFDA, CASB reduced reactive oxygen species (ROS) generated by H(2)O(2). In conclusion, CASB was genotoxic to HepG2 cells at high concentrations; was protective of DNA at low concentrations, as shown by the Ames test and comet assay; and was also antioxidant.

摘要

研究表明,Casearia sylvestris 化合物在体外和体内均能保护 DNA 免受损伤。补充一点,本研究的目的是通过 Ames 试验、彗星试验和 DCFDA 抗氧化试验评估 casearin B(CASB)对 DNA 损伤的化学预防作用。在 HepG2 细胞中,通过彗星试验评估遗传毒性。当与 FPG((formamidopyrimidine-DNA glycosylase) 酶孵育时,CASB 的浓度高于 0.30 μM 时具有遗传毒性。对于抗原毒性彗星试验,CASB 在 0.04 μM 以上的浓度下具有后处理,在 0.08 μM 以上的浓度下具有预处理,可保护 HepG2 细胞系中的 DNA 免受 H(2)O(2) 引起的损伤。CASB 在 TA 98 和 TA 102 中没有致突变性(Ames 试验)。在抗突变试验中,该化合物是 TA 98 中黄曲霉毒素 B1(AFB)的强抑制剂(>88.8%),而在 TA 102 中是中等抑制剂(42.7-59.4%)。此外,在使用 DCFDA 的抗氧化试验中,CASB 减少了 H(2)O(2)产生的活性氧(ROS)。总之,CASB 在高浓度时对 HepG2 细胞具有遗传毒性;在低浓度时对 DNA 具有保护作用,如 Ames 试验和彗星试验所示;并且具有抗氧化作用。

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