da Silva Lucas Henrique Domingos, Squarisi Iara Silva, de Freitas Karoline Soares, Barcelos Ribeiro Arthur, Ozelin Saulo Duarte, Aldana-Mejía Jennyfer Andrea, de Oliveira Lucas Teixeira Souza, Rodrigues Tábata Esperandim, de Melo Matheus Reis Santos, Nicolella Heloiza Diniz, Alves Bianca Silva, de Andrade Melo Alex Luiz, Ccana-Ccapatinta Gari Vidal, Bastos Jairo Kenupp, Tavares Denise Crispim
Postgraduate Program in Science, University of Franca, Franca, São Paulo, Brazil.
School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Ribeirão Preto, São Paulo, Brazil.
J Pharm Pharmacol. 2022 May 20;74(5):740-749. doi: 10.1093/jpp/rgac008.
Dalbergia ecastaphyllum (L.) Taub. is a semi-prostrate species associated with estuaries, mangroves and dunes. This plant species has great ecological and economic importance, especially concerning apiculture pasture and Brazilian red propolis production. In this study, non-clinical toxicological evaluations of the hydroalcoholic extract of D. ecastaphyllum stems (DEHE), the resin production source, were conducted. In addition, the action of DEHE on genomic instability and colon carcinogenesis was investigated.
The extract's chemical profile was analysed by HPLC, and medicarpin, vestitol and neovestitol were found as major compounds. DEHE showed an IC50 equivalent to 373.2 µg/ml and LC50 equal 24.4 mg/L, when evaluated using the XTT colorimetric test and the zebrafish acute toxicity assay, respectively. DEHE was neither genotoxic nor cytotoxic at the highest dose, 2000 mg/kg, by peripheral blood micronucleus test. The treatments DEHE (6 and 24 mg/kg) led to the reduction of micronuclei induced by doxorubicin (DXR) in mice. Furthermore, significantly higher serum levels of reduced glutathione were observed in animals treated with DEHE plus DXR, revealing an antioxidant effect. Treatments with DEHE (48 mg/kg) led to a significant reduction in pre-neoplastic lesions induced by the 1,2-dimethylhydrazine (DMH) carcinogen in the rat colon. Immunohistochemical analysis revealed significantly lower levels of expression of COX-2 (86%) and PCNA (83%) in the colon of rats treated with DEHE plus DMH, concerning those treated with the carcinogen.
These results indicate the involvement of anti-inflammatory and antiproliferative pathways in the protective effect of DEHE.
小叶黄檀（Dalbergia ecastaphyllum (L.) Taub.）是一种与河口、红树林和沙丘相关的半匍匐物种。该植物物种具有重要的生态和经济意义，特别是在养蜂牧场和巴西红蜂胶生产方面。在本研究中，对小叶黄檀茎部水醇提取物（DEHE）进行了非临床毒理学评估，DEHE是树脂的生产来源。此外，还研究了DEHE对基因组不稳定性和结肠癌发生的作用。
通过高效液相色谱法分析提取物的化学特征，发现主要化合物为紫铆因、vestitol和新vestitol。分别使用XTT比色法和斑马鱼急性毒性试验评估时，DEHE的IC50相当于373.2μg/ml，LC50等于24.4mg/L。通过外周血微核试验，在最高剂量2000mg/kg时，DEHE既无遗传毒性也无细胞毒性。DEHE（6和24mg/kg）处理可使小鼠中阿霉素（DXR）诱导的微核减少。此外，在DEHE加DXR处理的动物中观察到血清中还原型谷胱甘肽水平显著升高，显示出抗氧化作用。DEHE（48mg/kg）处理可使大鼠结肠中由1,2 - 二甲基肼（DMH）致癌物诱导的癌前病变显著减少。免疫组织化学分析显示，与仅用致癌物处理的大鼠相比，DEHE加DMH处理的大鼠结肠中COX - 2（86%）和PCNA（83%）的表达水平显著降低。
这些结果表明抗炎和抗增殖途径参与了DEHE的保护作用。
