In vitro antitumor effects of aqueous extract and protease inhibitors from Sterculia striata st. Hil. et naud and metabolite profiling.

The present study aims to assess the cytotoxic effect of the aqueous and protease inhibitors extracts of Sterculia striata on breast cancer cell lines. The in vitro results showed significant reductions in the highest concentrations from the S. striata seed extract for all cell lines. The aqueous extract reduced the viability by up to 35% in the MCF-7, 25% in the 4T1, and 35% in the MDA-MB-231 cell lines. Regarding the protease inhibitor extract, a 50% reduction in cell viability was observed in the MDA-MB-231 at concentration of 333 µg/mL. The aqueous and the protease inhibitor extracts showed mild reduction in the viability of macrophage cell lines. Chemical characterisation analysis revealed several polyphenols such as flavonoids, tannins, phenolic acids, and other secondary metabolites including terpenes, steroids, fatty acids, and organic acids, which may be related to the promising bioactivity observed. The S. striata showed antitumor activity, emphasising its pharmacological potential.

Protease inhibitors characterisation by SDS-PAGE and MALDI-TOF from Alocasia macrorrhizos and their modulation of macrophage immune-inflammatory properties.

This study describes the extraction and identification by electrophoretic and spectrometric techniques of protease inhibitor from the medicinal plant Alocasia macrorrhizos as well as investigates their immunomodulatory properties and cell viability. The A. macrorrhizos tubers were subjected to protease inhibitor extractions and characterised using SDS-PAGE and MALDI-TOF. The protein extracts were assessed for activities trypsin inhibition stoichiometry, haemagglutinating, cell viability, NO and TNF-α production inhibition. Concerning the protease inhibitors analysis through SDS-PAGE, the results showed two bands with 11 and 24 kDa, and the MS analysis detected the ions more intense of m/z 4276.795 and 8563.361 in the roasted protein extract. The IC50 of trypsin inhibition was 0.119 and 0.302 mg L-1 in the roasted and crude tuber, respectively. The protease inhibitors extract from the roasted tubers showed a reduction in the production of NO and TNF-α at concentrations lower than 100 µg mL-1, without a reduction in cell viability.

Assessing the Effectiveness of Chemical Marker Extraction from Amazonian Plant Cupuassu (Theobroma grandiflorum) by PSI-HRMS/MS and LC-HRMS/MS.

Employing a combination of liquid chromatography electrospray ionization and paper spray ionization high-resolution tandem mass spectrometry, extracts from cupuassu (Theobroma grandiflorum) pulp prepared with either water, methanol, acetonitrile or combinations thereof were subjected to metabolite fingerprinting. Among the tested extractors, 100% methanol extracted preferentially phenols and cinnamic acids derivatives, whereas acetonitrile and acetonitrile/methanol were more effective in extracting terpenoids and flavonoids, respectively. And while liquid chromatography- mass spectrometry detected twice as many metabolites as paper spray ionization tandem mass spectrometry, the latter proved its potential as a screening technique. Comprehensive structural annotation showed a high production of terpenes, mainly oleanane triterpene derivatives. of the mass spectra Further, five major metabolites with known antioxidant activity, namely catechin, citric acid, epigallocatechin-3'-glucuronide, 5,7,8-trihydroxyflavanone, and asiatic acid, were subjected to molecular docking analysis using the antioxidative enzyme peroxiredoxin 5 (PRDX5) as a model receptor. Based on its excellent docking score, a pharmacophore model of 5,7,8-trihydroxyflavanone was generated, which may help the design of new antioxidants.

Metabolic profiling by LC-DAD-MS, FTIR, NMR and CE-UV of polyphenols with potential against skin pigmentation disorder.

In traditional Brazilian medicine, tubers extracts from Alocasia macrorrhizos are widely used in the treatment of skin pigmentation disorder. However, studies that evaluate its benefits in the treatment of this disorder are non-existent. Thus, this work aims to investigate the bioactivity of A. macrorrhizos extracts in cell culture and murine model of Vitiligo and correlating with its phenolic profile. The metabolic profiling from the bioactive extracts was obtained by LC-DAD-MS, FTIR, NMR, and CE-UV. The murine model of Vitiligo was induced with 5% hydroquinone in C57BL/6 male mice, which were treated or not with 100 mg/kg of roasted tuber aqueous extract. In Vitiligo model assay was observed hair follicle repigmentation and reduction of the epidermal layer thickness at the histopathological level, in the animals treated with aqueous extract of roasted tubers. The present study provides new molecular insight and scientific evidence on the potential utility of the extract of A. macrorrhizos against Vitiligo.

Dereplication of Siparuna brasiliensis extract with in vivo anti-inflammatory activity.

Siparuna brasiliensis is a medicinal plant widely used by indigenous communities of the Amazon rainforest to treat inflammatory diseases and related pathologies. Considering its ethnopharmacological application, it constitutes an important source of biologically active molecules in the development of anti-inflammatory drugs. This study describes a dereplication methodology of the bioactive extract from S. brasiliensis leaves and the evaluation of the anti-inflammatory potential in an in vivo inflammatory model with mice of the BALB/c lineage and in vitro using cell lines, as well as determining the production of an inflammatory mediator. From their charge-to-mass ratios (m/z) and elemental composition obtained through Ultrahigh-resolution mass spectrometry analysis by ESI(-)-Orbitrap MS and chromatographic profile by RP-HPLC-PDA, it was possible to annotate polyphenols with anti-inflammatory properties classified as flavonoids and organic acids. The administration of the extract significantly inhibited carrageenan-induced paw edema and showed effects similar to those of drug dexamethasone without affecting cell viability.

The Free Radical Scavenging Property of the Leaves, Branches, and Roots of Mansoa hirsuta DC: In Vitro Assessment, 3D Pharmacophore, and Molecular Docking Study.

In this work, a metabolic profile of Mansoa hirsuta was investigated, and in vitro assays and theoretical approaches were carried out to evaluate its antioxidant potential. The phytochemical screening detected saponins, organic acids, phenols, tannins, flavonoids, and alkaloids in extracts of leaves, branches, and roots. Through LC-MS analysis, the triterpenes oleanolic acid (m/z 455 [M-H]-) and ursolic acid (m/z 455 [M-H]-) were identified as the main bioactive components. The extracts of the leaves, branches, and roots revealed moderate antioxidant potential in the DPPH test and all extracts were more active in the ABTS test. The leaf extracts showed better antioxidant capacity, displaying IC50 values of 43.5 ± 0.14, 63.6 ± 0.54, and 56.1 ± 0.05 µg mL-1 for DPPH, ABTS, and kinetics assays, respectively. The leaf extract showed higher total flavonoid content (TFC) (5.12 ± 1.02 mg QR/g), followed by branches (3.16 ± 0.88 QR/g) and roots (2.04 ± 0.52 QR/g/g). The extract of the branches exhibited higher total phenolic content (TPC) (1.07 ± 0.77 GAE/g), followed by leaves (0.58 ± 0.30 GAE/g) and roots (0.19 ± 0.47 GAE/g). Pharmacophore and molecular docking analysis were performed in order to better understand the potential mechanism of the antioxidant activity of its major metabolites.

Metabolic Profiling of Inga Species with Antitumor Activity.

This work evaluated the metabolic profiling of Inga species with antitumor potential. In addition, we described the antigenotoxicity of polyphenols isolated from I. laurina and a proteomic approach using HepG2 cells after treatment with these metabolites. The in vitro cytotoxic activity against HepG2, HT-29 and T98G cancer cell lines was investigated. The assessment of genotoxic damage was carried out through the comet assay. The ethanolic extract from I. laurina seeds was subjected to bioassay-guided fractionation and the most active fractions were characterized. One bioactive fraction with high cytotoxicity against HT-29 human colon cancer cells (IC50 = 4.0 µg mL-1) was found, and it was characterized as a mixture of p-hydroxybenzoic acid and 4-vinyl-phenol. The I. edulis fruit peel (IC50 = 18.6 µg mL-1) and I. laurina seed (IC50 = 15.2 µg mL-1) extracts had cytotoxic activity against the cell line T98G, and its chemical composition showed a variety of phenolic acids. The chemical composition of this species indicated a wide variety of aromatic acids, flavonoids, tannins, and carotenoids. The high concentration (ranging from 5% to 30%) of these polyphenols in the bioactive extract may be responsible for the antitumor potential. Regarding the proteomic approach, we detected proteins directly related to the elimination of ROS, DNA repair, expression of tumor proteins, and apoptosis.

Phytochemical, metabolic profiling and antiparasitic potential from Inga semialata leaves (Fabaceae).

Natural Products phytochemical provide a rich source for therapeutic discovery and has led to the development of many drugs. Thus, the aim of this study was to obtaining a metabolic profiling from ethanol extract of Inga semialata leaves (EEIS) selected by bioassay antimalarial and nematostatic and identify metabolites in mixture by co-injection experiments and NMR spectroscopy. The chemical composition of this species indicated a wide variety of aromatic acids (vanillic acid, 3,4,5-trimethoxy benzoic acid, gallic acid, methyl gallate, p-coumaric acid and ferulic acid), flavonoids (quercetin, myricetin-3-O-rhamnoside and myricetin-3-O-(2"-O-galloyl)-α-rhamnopyranoside), triterpenes (lupeol, α-amyrin, friedelin and oleanolic acid) and the 2-hydroxyethyl-dodecanoate. The antimalarial assay showed that the I. semialata n-hexane fraction presented higher inhibition percentage than the Chloroquine standard and may be considered a potential source of compounds with antimalarial activity while the EEIS and its fractions showed nematostatic potential below 17% in the assay of nematostatic evaluation against the parasite Meloidogyne incognita.

Cytogenotoxic evaluation of the acetonitrile extract, citrinin and dicitrinin-A from Penicillium citrinum.

Endophytic fungi are promising sources of bioactive substances; however, their secondary metabolites are toxic to plants, animals, and humans. This study aimed toevaluate the toxic, cytotoxic, mutagenic and oxidant/antioxidant activities of acetonitrile extract (AEPc), citrinin (CIT) and dicitrinin-A (DIC-A) of Penicillium citrinum. For this, the test substances at 0.5; 1.0; 1.5 and 2 µg/mLwere exposed for 24 and 48 h in Artemia salina, and 48 h in Allium cepa test systems. The oxidant/antioxidant test was evaluated in pre-, co- and post-treatment with the stressor hydrogen peroxide (H2O2) in Saccharomyces cerevisiae. The results suggest that the AEPc, CIT and DIC-A at 0.5; 1.0; 1.5 and 2 µg/mL showed toxicity in A. saline, with LC50 (24 h) of 2.03 µg/mL, 1.71 µg/mL and 2.29 µg/mL, and LC50 (48 h) of 0.51 µg/mL, 0.54 µg/mL and 0.54 µg/mL, respectively.In A. cepa, the test substances also exerted cytotoxic and mutagenic effects. The AEPc, CIT and DIC-A at lower concentrations modulated the damage induced by H2O2 in the proficient and mutant strains of S. cerevisiae for cytoplasmic and mitochondrial superoxide dismutase. Moreover, the AEPc at 2 µg/mL and CIT at the two highest concentrations did not affect the H2O2-induced DNA damage in the test strains. In conclusion, AEPc, CIT and DIC-A of P. citrinum may exert their toxic, cytotoxic and mutagenic effects in the test systems possibly through oxidative stress induction pathway.

Dereplication of terpenes and phenolic compounds from Inga edulis extracts using HPLC-SPE-TT, RP-HPLC-PDA and NMR spectroscopy.

Inga edulis is traditionally used as anti-inflammatory and antidiarrheal and has been investigated as potential sources of biologically active natural products. In this study, dereplication strategy using HPLC-SPE-TT, RP-HPLC-PDA and NMR spectroscopy was employed, and this resulted in the identification of sixteen compounds from the leaves extract of I. edulis, including four triterpenes (lupeol, α-amirin, olean-18-ene acid and frideline), three flavonoids, eight phenolic acids, an anthocyanin derived from delphinidin-3-glycoside and a mixture of five acylated anthocyanins. The chemical identification was performed based on NMR data, chemosystematics aspects, UV spectra and by comparison with the retention time and UV spectra of authentic standards. The metabolic profile of the species indicated the presence of phenolic compounds as major constituents justifying its strong antioxidant potential performed in ß-carotene test. The techniques used have shown effective strategies for the early detection of active natural products from plant extracts, as these approaches are still crucially absent.[Formula: see text].

Medicinal Plants from Brazilian Cerrado Biome: Potential sources of new anti-inflammatory compounds and antitumor agents on Ehrlich carcinoma.

This work describes a pharmacological screening of Brazilian medicinal plants through their anti-inflammatory and cytotoxicity activities. Cytotoxicity activity of Mouriri elliptica and Alchornea glandulosa as well as the drugs celecoxib and doxorubicin were evaluated in cultures of peritoneal macrophages. The immune system influence of these samples was analyzed by determining production/inhibition of NO, production of tumor necrosis factor-α and production of interleukin-10. Regarding the production/inhibition of NO, there was NO production by M. elliptica and NO inhibition when the cells were exposed to A. glandulosa; Macrophages generally produce more NO, plus TNF-α and less IL-10, when associated to the tumor phenomenon, characterizing the inflammation involved in cancer. A. glandulosa showed anti-inflammatory effect, inhibited NO production and it was associated with low TNF-α production, although not as low as the macrophages associated with celecoxib and doxorubicin. These cytokines were not different in animals with tumor. Celecoxib confirms its anti-inflammatory action by markedly inhibiting NO and TNF-α, but also inhibiting IL-10 which is an anti-inflammatory cytokine. Doxorubicin inhibited NO in a higher percentage in the group of animals with tumor, although the literature reports that this drug stimulates the production of NO and this collaborates with its cytotoxic effect.

Effectiveness of different methods for the extraction of principle actives and phytochemicals content in medicinal herbals / Efectividad de diferentes métodos para la extracción de principios activos y contenido de fitoquímicos en hierbas medicinales

In this present study, we investigated the influence of various extraction methods including maceration, sonication, infusion, decoction, and microwave extraction, on the chemical and biological potential of phytochemicals extracted from three medicinal plants (Ageratum conyzoides, Plantago majorand Arctium lappa L). The results were subsequently analyzed by variance analysis. Our results suggested that sonication is the most effective extraction method among the five methods tested herein, for the extraction of phytochemicals that have a high antioxidant potential and high phenolic content. The three plants employed for this study had a high concentration of flavonoids and phenolics which was compatible with the chemosystematics of the species. All the samples possessed a Sun Protection Factor (SPF) of less than 6. Interestingly, a maximum reaction time of approximately 20 min was noted for the complexation of AlCl3 with the flavonoids present in the phytochemical extract during analyses of the kinetic parameters. We finally identified that the Ageratum conyzoides extract, prepared by sonication, possessed a significant pharmacological potential against hepatocarcinoma tumour cells, whose result can guide further studies for its therapeutic efficacy.

En el presente estudio, investigamos la influencia de varios métodos de extracción, incluyendo maceración, sonicación, infusión, decocción y extracción por microondas, sobre el potencial químico y biológico de los fitoquímicos extraídos de tres plantas medicinales (Ageratum conyzoides, Plantago majory Arctium lappa L). Los resultados se analizaron posteriormente mediante análisis de varianza. Nuestros resultados sugieren que la sonicación es el método de extracción más eficaz entre los cinco métodos aquí probados, para la extracción de fitoquímicos que tienen un alto potencial antioxidante y un alto contenido fenólico. Las tres plantas empleadas para este estudio tenían una alta concentración de flavonoides y fenólicos que era compatible con la quimiosistemática de las especies. Todas las muestras poseían un factor de protección solar (SPF) menor a 6. Curiosamente, se observó un tiempo máximo de reacción de aproximadamente 20 min para la complejación de AlCl3con los flavonoides presentes en el extracto fitoquímico durante los análisis de los parámetros cinéticos. Finalmente, identificamos que el extracto de Ageratum conyzoides, elaborado por sonicación, posee un importante potencial farmacológico frente a las células tumorales del hepatocarcinoma, cuyo resultado puede orientar nuevos estudios sobre su eficacia terapéutica.

Miconia albicans and Curcuma longa herbal medicines positively modulate joint pain, function and inflammation in patients with osteoarthritis: a clinical study.

This study aims to evaluate the analgesic and modulating effect of Curcuma longa and Miconia albicans herbal medicines in knee's osteoarthritis (OA) treatment. This longitudinal study evaluated 24 patients with OA. The patients were divided into three groups: ibuprofen (1200 mg/day), C. longa (1000 mg/day) and M. albicans (1000 mg/day). The medications were applied orally for 30 days. The synovial fluid of the knee joint was collect at the first (day 0) and the last medical (day 30) consultation. The groups treated with herbal medicines presented the same results when compared to Ibuprofen. The comparison of the means of Total WOMAC for M. albicans before and after treatment presented a statistically significant difference (mean day 0 = 57.19; mean day 30 = 31.02) as well as variation of Total WOMAC for C. longa (mean day 0 = 54.79; mean day 30 = 37.08). The WOMAC Total and the VASP were compared, it was found that there was a significant decrease in the means in the C. longa and M. albicans groups, as well as in the Ibuprofen group after treatment. The study demonstrated that the treatment of knee OA with C. longa or M. albicans positively interferes with patients pain and functionality, decreased WOMAC and VASP scores, leading to functional improvement of these patients. This is the first clinical study demonstrating the analgesic and anti-inflammatory effect on knee osteoarthritis from M. albicans comparable to Ibuprofen drug.

Citrinin against breast cancer: A cytogenotoxicological study.

Breast cancer is one of the most lethal types of cancer and a leading cause of mortality among Women worldwide. Citrinin (CIT), a polyketide extracted from the fungus Penicillium citrinum, exhibits a wide range of biological activities such as antibacterial, antifungal, and cytotoxic effects. The aim of the current study was to evaluate the antitumoral effects of CIT against 7,12-dimethylbenzanthracene (DMBA)-induced mammary carcinoma in Swiss mice For this, CIT, DMBA and the standard cyclophosphamide (CPA) induced behavioral changes in experimental animals, and these changes were screened by using the rota rod and open field tests. Additionally, hematological, biochemical, immuno-histochemical, and histopathological analyses were carried out. Results suggest that CIT did not alter behavioral, hematological, and biochemical parameters in mice. DMBA induced invasive mammary carcinoma and showed genotoxic effects in the breasts, bone marrow, lymphocytes, and hepatic cells. It also caused mutagenic effects in the formation of micronuclei, bridges, shoots, and binucleate cells in bone marrow and liver. CIT and CPA genotoxic effects were observed after 3 weeks of therapy, where CIT exhibited a repair capacity and induced significant apoptotic damage in mouse lymphocytes. In conclusion, CIT showed antitumoral effects in Swiss mice, possibly through induction of apoptosis.

Antiparasitic effects of ethanolic extracts of Piper arboreum and Jatropha gossypiifolia leaves on cercariae and adult worms of Schistosoma mansoni.

New treatment strategies for schistosomiasis should be evaluated, since resistant strains to the only available drug, Praziquantel, have already been described. Thus, we demonstrated antiparasitic effects of ethanolic extracts of Jatropha gossypiifolia and Piper arboreum on cercariae and adult worms of Schistosoma mansoni. The bioassays were performed at 0-10 000 µg mL-1 concentration for 0-72 h. Adult worms were stained with carmine to assess external and internal damage. The chemical screening was performed using high-performance liquid chromatography. P. arboreum displayed the best cercaricidal effect, with a 100% reduction in viability in just 60 min. The extract of J. gossypiifolia was more effective against adult worms, with 100% viability reduction of male and female worms after 12 and 24 h, respectively. P. arboreum and J. gossypiifolia were equally effective in inhibiting the oviposition of S. mansoni (93% reduction) and causing damage to internal and external structures in adult worms. Flavonoids were identified in both the extracts and phenolic compounds and amides only in P. arboreum. Thus, for the first time, it was proven that ethanolic extracts of P. arboreum and J. gossypiifolia leaves are biologically active against cercariae and adult worms of S. mansoni in vitro.

Hydroalcoholic extract of Caryocar brasiliense Cambess. leaves affect the development of Aedes aegypti mosquitoes.

INTRODUCTION: Curtailing the development of the aquatic immature stages of Aedes aegypti is one of the main measures to limit their spread and the diseases transmitted by them. The use of plant extracts is a promising approach in the development of natural insecticides. Thus, this research aimed to characterize the inhibitory effect of the hydroalcoholic extract of Caryocar brasiliense leaves on the emergence of adult A. aegypti and the main substances that constitute this extract. METHODS: C. brasiliense leaf extract was prepared by ethanol (70%) extraction. Bioassays using L3 larvae were performed at concentrations of 200, 300, 400, and 500 ppm. We identified the major secondary metabolites present in this extract, and performed toxicity tests on an off-target organism, Danio rerio. RESULTS: We observed a significant delay in the development of A. aegypti larvae mainly at a concentration of 500 ppm, and estimated an emergence inhibition for 50% of the population of 150 ppm. Moreover, the C. brasiliense leaf extracts exhibited low toxicity in D. rerio. The main compounds found in the extract were quercetin, violaxanthin, myricetin3-O-hexoside, methyl-elagic-3-arabinose acid, and isoquercitrin. CONCLUSIONS: Herein, we demonstrate the inhibition of mosquito development by the hydroalcoholic extract of C. brasiliense and suggest substances that may act as active principles.

Antitumor effects of citrinin in an animal model of Sarcoma 180 via cytogenetic mechanisms.

Citrinin (CIT) is a cytotoxic, hepatotoxic, nephrotoxic and cardiotoxic metabolite obtained from Penicillium citrinum, that has been increasingly searched as an anticancer drug candidate. In this study, we assessed the antitumor effects of citrinin, using cytogenetic biomarkers for genotoxicity in Sarcoma 180 (S-180) ascitic fluid cells of mice. Citrinin, extracted from P. citrinum acetonitrile extract, was characterized by LC-MS. Cytotoxic assessment was done through using comet (alkaline version) and micronucleus assays. In S-180 cells, CI50 of CIT was 3.77 µg/mL, while at 12.5 and 100 µg/mL, CIT was as cytotoxic as doxorubicin (2 µg/mL). At 0.5, 1.0 and 2.0 µg/mL, it induced genotoxicity and mutagenicity in S-180 cells, especially at 2 µg/mL, triggering oxidative damage similar to hydrogen peroxide (10 mM). The antitumor effects were evidenced by a marked increase in S-180 cells apoptosis and necrosis due to clastogenic and/or aneugenic cytogenetic effects (micronucleus formation), as well as by induction of nucleoplasm bridges and nuclear buds, culminating in S-180 apoptosis and necrosis. CIT has potential as drug candidate for antitumor purposesbyinvolving cytogenetic mechanisms.

Antitumoral effects of [6]-gingerol [(S)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-3-decanone] in sarcoma 180 cells through cytogenetic mechanisms.

BACKGROUND: [6]-Gingerol [(S)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-3-decanone] is a phenolic substance reported for several ethnopharmacological usage by virtue of its antioxidant, antiemetic, anti-inflammatory and anticancer properties. This study assessed the antitumoral effects of [6]-Gingerol in primary cells of Sarcoma 180 as well as in peripheral blood lymphocytes of mice. METHODS: The effect of [6]-Gingerol was assessed by applying cytogenetic biomarkers as indicative of genotoxicity, mutagenicity and apoptosis. Ascitic liquid cells were treated with [6]-Gingerol at concentrations of 21.33, 42.66 and 85.33 µM and subjected to the cytotoxicity assays using Trypan blue test and the comet assay, as well as the cytokinesis-block micronucleus assay. Doxorubicin (6 µM) and hydrogen peroxide (85.33 µM) were used as positive controls. RESULTS: [6]-Gingerol, especially at concentrations of 42.66 and 85.33 µM, showed notable cytotoxicity in Sarcoma 180 cells by reducing cell viability and cell division rates via induction of apoptosis. Genotoxicity at the concentrations used was punctuated by the increase in the index and frequency of DNA damage in tested groups. [6]-Gingerol, at all concentrations tested, did not induce significant aneugenic and/or clastogenic effects. It did, however, induced other nuclear abnormalities, such as nucleoplasmic bridges, nuclear buds and apoptosis. The genotoxic effects observed in the cotreatment with H2O2 (challenge assay) employing neoplastic and healthy cells, indicated that [6]-Gingerol may induce oxidative stress. CONCLUSIONS: Observations suggest that [6]-Gingerol may be a candidate for pharmaceutical antitumoral formulations due to its cytotoxicity and to mechanisms associated with genetic instability generated by nuclear alterations especially by apoptosis.

Hydroalcoholic extract of Caryocar brasiliense Cambess. leaves affect the development of Aedes aegypti mosquitoes

Abstract INTRODUCTION: Curtailing the development of the aquatic immature stages of Aedes aegypti is one of the main measures to limit their spread and the diseases transmitted by them. The use of plant extracts is a promising approach in the development of natural insecticides. Thus, this research aimed to characterize the inhibitory effect of the hydroalcoholic extract of Caryocar brasiliense leaves on the emergence of adult A. aegypti and the main substances that constitute this extract. METHODS: C. brasiliense leaf extract was prepared by ethanol (70%) extraction. Bioassays using L3 larvae were performed at concentrations of 200, 300, 400, and 500 ppm. We identified the major secondary metabolites present in this extract, and performed toxicity tests on an off-target organism, Danio rerio. RESULTS: We observed a significant delay in the development of A. aegypti larvae mainly at a concentration of 500 ppm, and estimated an emergence inhibition for 50% of the population of 150 ppm. Moreover, the C. brasiliense leaf extracts exhibited low toxicity in D. rerio. The main compounds found in the extract were quercetin, violaxanthin, myricetin3-O-hexoside, methyl-elagic-3-arabinose acid, and isoquercitrin. CONCLUSIONS: Herein, we demonstrate the inhibition of mosquito development by the hydroalcoholic extract of C. brasiliense and suggest substances that may act as active principles.

Toxic, cytogenetic and antitumor evaluations of [6]-gingerol in non-clinical in vitro studies.

Gingerol - [6]-gingerol ((S)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-3-decanone; [6]-G) - is a phenolic compound with several pharmacological properties. Herein, the aim of the study was to evaluate the toxicogenic effects of [6]-G on Artemia salina nauplii, Allium cepa, HL-60 cell line and Sarcoma 180 (S-180) ascitic fluid cells.For toxic and genotoxic analysis, it was used [6]-G concentrations of 5, 10, 20 and 40 µg mL-1. For cytotoxic evaluation using the MTT test (3- [4,5-dimethyl-thiazol-2-yl] -2,5-diphenyl tetrazolium bromide), serial [6]-G dilutions (1.56-100 µg mL-1) were performed, and S-180, HL-60 and peripheral blood mononuclear cells (PBMC) were treated for 72 h. The IC50 of [6]-G were 1.14, 5.73 and 11.18 µg mL-1 for HL-60, S-180 and PBMC, respectively, indicating a possible selectivity against tumor cell lines. At higher concentrations (>10 µg mL-1), toxicity and genotoxicity were observed in the A. cepa test, especially at 40 µg mL-1. Mechanisms indicating apoptosis, such as toxicity, cytotoxicity and nuclear abnormalities (bridges, fragments, delays, loose chromosomes and micronuclei) suggest that [6]-G has potential for antitumor pharmaceutical formulations.