Mendonça Leonardo Meneghin, Machado Carla da Silva, Teixeira Cristiane Cardoso Correia, Freitas Luis Alexandre Pedro de, Bianchi Maria Lourdes Pires, Antunes Lusânia Maria Greggi
Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
Departamento de Ciências Farmacêuticas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
Genet Mol Biol. 2015 Dec;38(4):490-8. doi: 10.1590/S1415-475738420150046. Epub 2015 Nov 3.
Curcumin (CMN) is the principal active component derived from the rhizome of Curcuma longa (Curcuma longa L.). It is a liposoluble polyphenolic compound that possesses great therapeutic potential. Its clinical application is, however, limited by the low concentrations detected following oral administration. One key strategy for improving the solubility and bioavailability of poorly water-soluble drugs is solid dispersion, though it is not known whether this technique might influence the pharmacological effects of CMN. Thus, in this study, we aimed to evaluate the antioxidant and antigenotoxic effects of CMN formulated in a solid dispersion (CMN SD) compared to unmodified CMN delivered to Wistar rats. Cisplatin (cDDP) was used as the damage-inducing agent in these evaluations. The comet assay results showed that CMN SD was not able to reduce the formation of cDDP-DNA crosslinks, but it decreased the formation of micronuclei induced by cDDP and attenuated cDDP-induced oxidative stress. Furthermore, at a dose of 50 mg/kg b.w. both CMN SD and unmodified CMN increased the expression of Tp53 mRNA. Our results showed that CMN SD did not alter the antigenotoxic effects observed for unmodified CMN and showed effects similar to those of unmodified CMN for all of the parameters evaluated. In conclusion, CMN SD maintained the protective effects of unmodified CMN with the advantage of being chemically water soluble, with maximization of absorption in the gastrointestinal tract. Thus, the optimization of the physical and chemical properties of CMN SD may increase the potential for the therapeutic use of curcumin.
姜黄素(CMN)是从姜黄(Curcuma longa L.)根茎中提取的主要活性成分。它是一种脂溶性多酚化合物,具有巨大的治疗潜力。然而,其临床应用受到口服给药后检测到的低浓度的限制。提高难溶性药物溶解度和生物利用度的一个关键策略是固体分散体,尽管尚不清楚该技术是否会影响CMN的药理作用。因此,在本研究中,我们旨在评估与给予Wistar大鼠的未修饰CMN相比,固体分散体形式的CMN(CMN SD)的抗氧化和抗遗传毒性作用。顺铂(cDDP)在这些评估中用作损伤诱导剂。彗星试验结果表明,CMN SD不能减少cDDP-DNA交联的形成,但它减少了cDDP诱导的微核形成并减轻了cDDP诱导的氧化应激。此外,在50 mg/kg体重的剂量下,CMN SD和未修饰的CMN均增加了Tp53 mRNA的表达。我们的结果表明,CMN SD没有改变未修饰CMN观察到的抗遗传毒性作用,并且在所有评估参数上显示出与未修饰CMN相似的作用。总之,CMN SD保持了未修饰CMN的保护作用,具有化学水溶性的优点,在胃肠道中的吸收最大化。因此,优化CMN SD的物理和化学性质可能会增加姜黄素治疗应用的潜力。