Department of Clinical Analysis, School of Pharmaceutical Sciences, São Paulo State University, Araraquara, Rua Expedicionários do Brasil, 1621, Brazil.
Mutagenesis. 2009 Nov;24(6):501-6. doi: 10.1093/mutage/gep034. Epub 2009 Sep 7.
Casearia sylvestris is used in Brazil as a popular medicine to treat ulcer, inflammation and tumour. Caseargrewiin F is a clerodane diterpene isolated from the ethanolic leaf extract of C.sylvestris. The aim of the study was to assess the capacity of the ethanolic extract of C.sylvestris leaves and caseargrewiin F to protect DNA and verify if both the compounds cause some DNA damage, using the micronucleus (MN) test and comet assay in mice. Balb-C mice were treated with the extract [3.13, 6.25, 12.5, 25, 50 and 75 mg/kg body weight (b.w.)] and caseargrewiin F (0.16, 0.32, 0.63, 1.3, 2.5 and 3.8 mg/kg b.w.) for 14 days. On day 15, DNA damage was induced by intra-peritoneal (i.p.) injection of cyclophosphamide (CP) (i.p.) at 50 mg/kg b.w. after the MN test and comet assay were performed. A protective effect of ethanolic extract was observed in MN test (6.25 and 12.5 mg/kg b.w.) and the comet assay (3.13 and 6.25, 12.5 and 25 mg/kg b.w.). Caseargrewiin F showed protective effect at 0.63, 1.3 and 2.5 mg/kg b.w. only in comet assay. We also tested the ability of compounds of C.sylvestris to induce MN and to increase the comet assay tail moment. The experimental design was similar to the DNA protection assay except that in test groups we omitted the CP challenge. We observed increased damage at 50 and 75 mg/kg b.w. of ethanolic extract of C.sylvestris and caseargrewiin F at 3.18 mg/kg b.w. in both the MN test and comet assay. We conclude that ethanolic extract of C. sylvestris and caseargrewiin F can protect cells against DNA damage induced by CP at low concentrations, but at high concentrations these compounds also induce DNA damage.
巴西有种药用植物名为山香圆,其叶子可用于治疗溃疡、炎症和肿瘤。从山香圆叶子的乙醇提取物中分离得到的 clerodane 二萜类化合物名为山香圆素 F。本研究旨在评估山香圆叶子的乙醇提取物和山香圆素 F 对 DNA 的保护能力,并通过微核(MN)试验和彗星试验在小鼠体内验证这两种化合物是否会引起 DNA 损伤。Balb-C 小鼠用提取物(3.13、6.25、12.5、25、50 和 75mg/kg 体重)和山香圆素 F(0.16、0.32、0.63、1.3、2.5 和 3.8mg/kg 体重)处理 14 天。第 15 天,经腹腔(i.p.)注射环磷酰胺(CP)(i.p.)(50mg/kg 体重)诱导 DNA 损伤,随后进行 MN 试验和彗星试验。在 MN 试验(6.25 和 12.5mg/kg 体重)和彗星试验(3.13 和 6.25、12.5 和 25mg/kg 体重)中观察到乙醇提取物的保护作用。山香圆素 F 仅在彗星试验中(0.63、1.3 和 2.5mg/kg 体重)表现出保护作用。我们还测试了山香圆化合物诱导 MN 和增加彗星试验尾部矩的能力。实验设计与 DNA 保护试验相似,只是在试验组中我们省略了 CP 挑战。我们观察到在 MN 试验和彗星试验中,山香圆叶子的乙醇提取物和山香圆素 F 在 50 和 75mg/kg 体重时均会增加损伤,在 3.18mg/kg 体重时。我们得出结论,山香圆叶子的乙醇提取物和山香圆素 F 可以在低浓度下保护细胞免受 CP 诱导的 DNA 损伤,但在高浓度下,这些化合物也会引起 DNA 损伤。