Cirsiliol is a flavone found in many Lamiaceae species with high cytotoxic activity against tumor cell lines. Although cirsiliol is being used in cancer therapy, its pharmacological potential is limited by its low solubility and bioavailability. In this paper, a cirsiliol-β-cyclodextrin inclusion complex was developed in order to increase its solubility and bioavailability. The formation of inclusion complex was proved by scanning electron microscopy, Fourier-transform infrared spectroscopy (FTIR) and nuclear magnetic resonance (NMR) and solubility increment was verified through the ultraviolet-visible (UV-Vis) method. The cytotoxic effect against tumor cells (PC3, HCT-116 and HL-60 human cell lines, and S-180 murine cell line) and the antitumor activity in mice bearing sarcoma S-180 were also investigated. The inclusion complex was obtained with 71.45% of total recovery and solubility 2.1 times higher compared to the compound in its free form. This increment in solubility was responsible by a tumor growth inhibition potentiation (1.5 times greater compared to compound in its free form). In addition, this study showed that cirsiliol and its inclusion complex in β-cyclodextrin have strong antitumor potential at low doses without promoting side effects commonly observed for conventional drugs as doxorubicin.

Atividade Citotóxica de Constituintes Químicos e Óleo Essencial das Folhas de Leonotis nepetifolia (Lamiaceae) Resumo: O câncer é um problema de saúde que afeta grande parte da população mundial. Nesse contexto, vários grupos de pesquisa têm investigado moléculas com maior eficiência e menores efeitos colaterais. A espécie Leonotis nepetifolia é um arbusto pertencente à família Lamiaceae com atividade citotóxica relatada na literatura. Este trabalho descreve o isolamento dos compostos hentriacontano, palmitato de fitila, estigmasterol glicosídeo, 6,7-dimetoxi-5,3',4'-trihidroxiflavona, apigenina-7-O-glicosídeo e luteolina-7-O-glicosídeo a partir de extratos e a composição química do óleo essencial das folhas de espécimes brasileiras de L. nepetifolia, além das suas atividades citotóxicas in vitro. Os compostos foram identificados por uma série de métodos espectroscópicos e espectrométricos, principalmente RMN (1D e 2D) e CG-EM, bem como por comparação com dados da literatura. A atividade citotóxica de compostos isolados e óleo essencial foi realizada utilizando o ensaio de brometo de 3-(4,5-dimetiltiazol-2-il)-2,5-difeniltetrazólio (MTT), contra linhagens de células tumorais HCT-116 (cólon humano) e SF-295 (glioblastoma). O álcool 1-octen-3-ol foi o composto majoritário do óleo essencial e os compostos hentriacontano, palmitato de fitila, estigmasterol glicosídeo, apigenina-7-O-glicosídeo e luteolina-7-O-glicosídeo foram descritos pela primeira vez nesta espécie. Todos os compostos testados e o óleo essencial apresentaram baixa atividade citotóxica para as linhagens celulares testadas, sugerindo que outros estudos fitoquímicos devam ser conduzidos para a descoberta de outros compostos responsáveis pela atividade citotóxica da espécie.

BackgroundLeonotis nepetifolia (Family Lamiaceae) is a medicinal plant from which the flavonoid cirsiliol with sedative, hypnotic, anti-inflammatory and cytotoxic activity has been extracted.MethodsSeedlings were cultivated under different levels of shade in native or fertilized modes. The content of cirsiliol was measured monthly by high-performance liquid chromatography and the total phenolic content by the Folin-Ciocalteu method. Monitoring of growth was carried out with the weekly measurement of height until the stabilization of growth.ResultsThe application of fertilizing and/or shading does not alter significantly the cirsiliol content. However, this content varies throughout the year, reaching the peak production in the summer, independently of the treatment applied. This same profile, with production in the summer, was also verified for phenolic compounds, reaching 58.15 ± 9.35 mg of equivalents of gallic acid per g of extract in the summer, content 1.84 times greater than the content verified in winter (31.56 ± 4.09 mg of gallic acid/g of extract). Although shading and fertilizing had no effect on cirsiliol content, the results also showed a positive influence on the height and biomass of the plant, which can causes a higher yield of extractable material.DiscussionBiotic and abiotic stresses are able to increase or decrease the production of secondary metabolites, including phenolic compounds in medicinal plants and, as the stress response is peculiar to each species, cultivation studies become necessary. The present study reports by the first time the influence of shading, fertilizing and seasons in cirsiliol content in L. nepetifolia. Among analyzed variables, the seasons showed a larger influence in expression of cirsiliol and among seasons, our results showed that the summer is the ideal season for collections. In summer, the photoperiod is larger than in other seasons of the year and due to that, the plants need greater protection against the long photoperiod. For this, the plants increase the production of phenolic compounds as observed in this study. Although they do not influence the production of cirsiliol, the shading and nutrients in soil favor growth and leaf area of several plants, explaining, thus, the higher height and biomass obtained.

In Brazil, the leather industry is an important economic segment moving around U$ 3 billions of dollars a year. However, high amounts of water are requested to transform skin animals into leather, causing high wastewater amounts to be consequently produced. A major problem is attached to the presence of chromium in the wastewater from the tanning process. Chromium is a heavy metal potentially toxic both to the environment and to the human health. In order to control the levels of chrome dumped into the environment, Brazilian agencies require the treatment of effluents by the generating source. Thus, this study aimed to develop an alternative method to the removal of chromium in wastewater from the leather industry using the Opuntia ficus-indica biomass as ecofriendly biosorbent. Crude waste samples were collected in a tannery stabilization pond for chromium quantification and further treatments. The powdered Opuntia ficus-indica was obtained from species collected in Pernambuco, Brazil, and its physical parameters and pH PCZ were characterized. Adsorptions studies and acute toxicity were also carried out. The biomass remaining after the sorption was analyzed through scanning electron microscopy and Fourier-transform infrared spectroscopy. The chromium content was above the limit allowed by the Brazilian regulatory agency. In sorption studies, biomass was able to remove 74.8% and 84.88% of Cr (III) using 2.0 g and 4.0 g of biomass, respectively. The surface of biomass is very favorable to biosorption and the chemical bindings among oxygen atoms present in the chemical components of this biomass and the heavy metal was confirmed through infrared spectrum. This study proved that Opuntia ficus-indica is effectively biosorbent to chromium, promising and with low costs for the leather industry, able to reduce its ecotoxicity as proven by chemical and biological assays.