Monnieriside A from Evolvulus linarioides promotes antinociceptive effects in models of inflammatory and postoperative pain in male mice.

Monnieriside A (MoA) is a chromone isolated from Evolvulus linarioides. This study investigated the antinociceptive potential of MoA in mice. MoA (0.01-100 mg/kg, i.p.) inhibited nociception in the inflammatory phase of the formalin test without causing motor impairment. MoA (0.1-100 mg/kg, i.p.) also reduced hindpaw mechanical allodynia caused by either intraplantar injection of Complete Freund's Adjuvant (CFA) or surgical paw incision to simulate postoperative pain. Postoperative antinociception was accompanied by reduced IL-1ß levels in the incised paw, assessed by ELISA. The antinociceptive action of MoA (100 mg/kg, i.p.) was preserved in IL-10 knockout mice submitted to paw incision, indicating that IL-10 is not essential to the antinociceptive effect. Interestingly, MoA (100 mg/kg, i.p.) increased the expression of TGF-ß in IL-10 knockout mice, which could be a compensation mechanism leading to an antinociceptive effect in the absence of IL-10.

Exploiting tropical fruit processing coproducts as circular resources to promote the growth and maintain the culturability and functionality of probiotic lactobacilli.

This study evaluated the use of acerola (Malpighia glabra L., CACE), cashew (Anacardium occidentale L., CCAS), and guava (Psidium guayaba L., CGUA) fruit processing coproducts as substrates to promote the growth, metabolite production, and maintenance of the viability/metabolic activity of the probiotics Lactobacillus acidophilus LA-05 and Lacticaseibacillus paracasei L-10 during cultivation, freeze-drying, storage, and exposure to simulated gastrointestinal digestion. Probiotic lactobacilli presented high viable counts (≥8.8 log colony-forming units (CFU)/mL) and a short lag phase during 24 h of cultivation in CACE, CCAS, and CGUA. Cultivation of probiotic lactobacilli in fruit coproducts promoted sugar consumption, medium acidification, and production of organic acids over time, besides increasing the of several phenolic compounds and antioxidant activity. Probiotic lactobacilli cultivated in fruit coproducts had increased survival percentages after freeze-drying and during 120 days of refrigerated storage. Moreover, probiotic lactobacilli cultivated and freeze-dried in fruit coproducts had larger subpopulations of live and metabolically active cells when exposed to simulated gastrointestinal digestion. The results showed that fruit coproducts not only improved the growth and helped to maintain the viability and metabolic activity of probiotic strains but also enriched the final fermented products with bioactive compounds, being an innovative circular strategy for producing high-quality probiotic cultures.

Anti-Leishmania amazonensis Activity of Morolic Acid, a Pentacyclic Triterpene with Effects on Innate Immune Response during Macrophage Infection.

Leishmaniasis is a group of infectious diseases transmitted to humans during vector bites and caused by protozoans of the genus Leishmania. Conventional therapies face challenges due to their serious side effects, prompting research into new anti-leishmania agents. In this context, we investigated the effectiveness of morolic acid, a pentacyclic triterpene, on L. amazonensis promastigotes and amastigotes. The present study employed the MTT assay, cytokine analysis using optEIATM kits, an H2DCFDA test, and nitric oxide dosage involving nitrite production and Griess reagent. Morolic acid inhibited promastigote and axenic amastigote growth forms at IC50 values of 1.13 µM and 2.74 µM, respectively. For cytotoxicity to macrophages and VERO cells, morolic acid obtained respective CC50 values of 68.61 µM and 82.94 µM. The compound causes damage to the parasite membrane, leading to cellular leakage. In the infection assay, there was a decrease in parasite load, resulting in a CI50 of 2.56 µM. This effect was associated with immunomodulatory activity, altering macrophage structural and cellular parasite elimination mechanisms. Morolic acid proved to be an effective and selective natural compound, making it a strong candidate for future in vivo studies in cutaneous leishmaniasis.

Anadenanthera colubrina regulated LPS-induced inflammation by suppressing NF-κB and p38-MAPK signaling pathways.

We aimed to determine the chemical profile and unveil Anadenanthera colubrina (Vell.) Brenan standardized extract effects on inflammatory cytokines expression and key proteins from immunoregulating signaling pathways on LPS-induced THP-1 monocyte. Using the RT-PCR and Luminex Assays, we planned to show the gene expression and the levels of IL-8, IL-1ß, and IL-10 inflammatory cytokines. Key proteins of NF-κB and MAPK transduction signaling pathways (NF-κB, p-38, p-NF-κB, and p-p38) were detected by Simple Western. Using HPLC-ESI-MSn (High-Performance Liquid-Chromatography) and HPLC-HRESIMS, we showed the profile of the extract that includes an opus of flavonoids, including the catechins, quercetin, kaempferol, and the proanthocyanidins. Cell viability was unaffected up to 250 µg/mL of the extract (LD50 = 978.7 µg/mL). Thereafter, the extract's impact on the cytokine became clear. Upon LPS stimuli, in the presence of the extract, gene expression of IL-1ß and IL-10 were downregulated and the cytokines expression of IL-1ß and IL-10 were down an upregulated respectively. The extract is involved in TLR-4-related NF-κB/MAPK pathways; it ignited phosphorylation of p38 and NF-κB, orchestrating a reduced signal intensity. Therefore, Anadenanthera colubrina's showed low cytotoxicity and profound influence as a protector against the inflammation, modulating IL-1ß and IL-10 inflammatory cytokines gene expression and secretion by regulating intracellular NF-κB and p38-MAPK signaling pathways.

Syzygium aromaticum essential oil and its major constituents: Assessment of activity against Candida spp. and toxicity.

Syzigium aromaticum essential oil (EO), eugenol, and ß-caryophyllene were evaluated regarding antifungal, antibiofilm, and in vitro toxicity. Additionally, in vivo toxicity of EO was observed. Anti-Candida activity was assessed through broth microdilution assay for all compounds. Time-kill assay (0, 1, 10, 30 min, 1, 2, and 4 h) was used to determine the influence of EO and eugenol on Candida Growth kinetics. Thereafter, both compounds were evaluated regarding their capacity to act on a biofilm formation and on mature biofilm, based on CFU/ml/g of dry weight. Cell Titer Blue Viability Assay was used for in vitro cytotoxicity, using oral epithelial cells (TR146) and human monocytes (THP-1). Lastly, Galleria mellonella model defined the EO in vivo acute toxicity. All compounds, except ß-cariofilene (MIC > 8000 µg/ml), presented antifungal activity against Candida strains (MIC 500-1000 µg/ml). The growth kinetics of Candida was affected by the EO (5xMIC 30 min onward; 10xMIC 10 min onward) and eugenol (5xMIC 10 min onward; 10xMIC 1 min onward). Fungal viability was also affected by 5xMIC and 10xMIC of both compounds during biofilm formation and upon mature biofilms. LD50 was defined for TR146 and THP1 cells at, respectively, 59.37 and 79.54 µg/ml for the EO and 55.35 and 84.16 µg/ml for eugenol. No sign of toxicity was seen in vivo up to 10mg/ml (20 x MIC) for the EO. S. aromaticum and eugenol presented antifungal and antibiofilm activity, with action on cell growth kinetics. In vivo acute toxicity showed a safe parameter for the EO up to 10 mg/ml.

Metabolomic analysis of retinopathy stages and amputation in type 2 diabetes.

BACKGROUND: Diabetic retinopathy (DR) and limb amputation are frequent complications of diabetes that cannot always be explained by blood glucose control. Metabolomics is a science that is currently being explored in the search for biomarkers or profiles that identify clinical conditions of interest. OBJECTIVE: This study aimed to analyze, using a metabolomic approach, peripheral blood samples from type 2 diabetes mellitus (DM2) individuals, compared with those with diabetic retinopathy and limb amputation. METHODS: The sample consisted of 128 participants, divided into groups: control, DM2 without DR (DM2), non-proliferative DR (DRNP), proliferative DR (DRP), and DM2 amputated (AMP). Metabolites from blood plasma were classified by spectra using nuclear magnetic resonance (NMR), and the metabolic routes of each group using metaboanalyst. RESULTS: We identified that the metabolism of phenylalanine, tyrosine, and tryptophan was discriminant for the DRP group. Histidine biosynthesis, on the other hand, was statistically associated with the AMP group. The results of this work consolidate metabolites such as glutamine and citrulline as discriminating for DRP, and the branched-chain amino acids as important for DR. CONCLUSIONS: The results demonstrate the relationship between the metabolism of ketone bodies, with acetoacetate metabolite being discriminating for the DRP group and histidine being a significant metabolite in the AMP group, when compared to the DM2 group.

Nutritional and antioxidant potential of Pleurotus djamor (Rumph. ex Fr.) Boedijn produced on agronomic wastes banana leaves and sugarcane bagasse substrates.

Global food production faces challenges concerning access to nutritious and sustainably produced food. Pleurotus djamor, however, is an edible mushroom that can be cultivated on agricultural waste. Considering that nutritional and functional potential of mushrooms can change based on cultivation conditions, we examined the influence of substrates with different compositions of banana leaf and sugarcane bagasse on the nutritional, mycochemical, and antioxidant properties of P. djamor. The mushrooms were grown for 120 days and dried in a circulating air oven at 45 °C for three days. We conducted bromatological analyses and mycochemical characterization (1H-NMR, total phenolics, and flavonoids) of the mushrooms and assayed the antioxidant activity of extracts from the dried mushrooms using an ethanol/water solution (70:30 v/v). In general, the substrates produced mushrooms with high protein (18.77 ± 0.24% to 17.80 ± 0.34%) and dietary fiber content (18.02 ± 0.05% to 19.32 ± 0.39%), and with low lipid (0.28 + 0.08% to 0.4 + 0.6%), and caloric content (maximum value: 258.42 + 8.49), with no significant differences between the groups (p ≥ 0.05). The mushrooms also exhibited high levels of total phenolics and flavonoids. The mushrooms cultivated on sugarcane bagasse substrates presented the highest values (p < 0.05). Analysis of the 1H-NMR spectra indicates an abundant presence of heteropolysaccharides, ß-glucans, α-glucans, and oligosaccharides, and all the mushroom extracts exhibited high antioxidant activity. In conclusion, our study demonstrates that agricultural residues permit sustainable production of edible mushrooms while maintaining nutritional and functional properties.

Larvicidal activity of diterpenes from Xylopia langsdorfiana St. Hilaire & Tulasne (Annonaceae) against Aedes aegypti linn. (diptera: culicidae).

Mosquitoes of the Aedes genus are responsible for transmitting many vector-borne viral diseases worldwide. Hundreds of thousands of people die annually from vector-borne diseases, including West Nile fever, dengue, tick-borne diseases, yellow fever, chikungunya, Rift Valley fever, and Zika. Billions of people are at the risk of infection on all continents, which is a cause of international concern. Therefore, new vector-control methods are essential for mitigating these illnesses. The bioactive hydrocarbons isolated from Xylopia langsdorfiana St. Hilaire & Tulasne are trachylobanes, a rare class of diterpenes found in the n-hexane fraction of the stem and leaf ethanolic extracts. These were tested against Ae. aegypti fourth-instar larvae over 48 h of exposure, with LC50 values ranging from 19.84 to 72.9 µg/mL, comparable to that of the positive control. The findings highlight the potential of Xylopia langsdorfiana St. Hilaire & Tulasne metabolites for controlling the main vectors of arthropod-borne viruses.

Antioxidant activity, cytotoxicity, phenolic content, and phytochemical composition of Pithecellobium Diversifolium benth: a pilot study / Atividade antioxidante, citotóxica, conteúdo fenólico e composição fitoquímica de Pithecellobium Diversifolium benth: um estudo piloto / Actividad antioxidante, citotóxica, contenido fenólico y composición fitoquímica de Pithecellobium Diversifolium benth: un estudio piloto

Species of Pithecellobium (Fabaceae) are used in traditional medicine to treat diabetes, cough, bronchitis, and inflammation. This study aims to evaluate the content and determine the antioxidant activity, phenolic compounds content, and cytotoxicity of the extract and the fractions of Pithecellobium diversifolium. This is unprecedented research with an exotic species from the Caatinga, northeastern Brazil, using High-performance Liquid Chromatography-Electrospray Ionization-Mass Spectrometry (HPLC-ESI-MS). The MeOH fractions of leaves and stem barks showed a high content of flavonoids (198.1 ± 106.50 and 542.7 ± 2.52 mg EqQ/g). The CH2Cl2 fraction of peels showed a high content of total phenolic compounds (516.7 ± 3.00 mg EqAG /g). The DPPH test showed that the CH2Cl2 fraction (leaves) held an EC50 of 0.08 ± 0.02, a higher value than that observed for the standards used in the test­Butylated hydroxyanisole (BHA), Butylated hydroxytoluene (BHT), and ascorbic acid. The AcOEt and MeOH fractions of peels presented moderate cytotoxicity with values below 500 µg/mL. The MeOH fraction of leaves showed seven major compounds: myricetin, quercetin, quercetin-arabinofuranoside, apigenin-triglycosides, and apigenin-diglucoside, being the last three unpublished in studies involving the genus. The tests conducted in this study show the potential of P. diversifolium as a promising source of biomolecules with therapeutic applicability.

Espécies de Pithecellobium (Fabaceae) são usadas na medicina tradicional para tratar diabetes, tosse, bronquite e inflamação. Este estudo teve como objetivo avaliar o teor e determinar a atividade antioxidante, o teor de compostos fenólicos e a citotoxicidade do extrato e das frações de Pithecellobium diversifolium, uma pesquisa inédita com uma espécie exótica da Caatinga do Nordeste do Brasil, utilizando a instrumentação Clae-IES. As frações MeOH das folhas e cascas do caule apresentaram alto teor de flavonoides (198,1 ± 106,50 e 542,7 ± 2,52 mg EqQ/g). A fração CH2Cl2 das cascas apresentou um elevado teor de compostos fenólicos totais (516,7 ± 3,00 mg EqAG/g). O teste DPPH mostrou que a fração CH2Cl2 (folhas) apresentou um EC50 de 0,08 ± 0,02, valor superior ao observado para os padrões utilizados no teste ­ Butil hidroxianisol (BHA), Butil hidroxitolueno (BHT) e ácido ascórbico. As frações AcOEt e MeOH das cascas apresentaram citotoxicidade moderada com valores inferiores a 500 µg/mL. A fração MeOH das folhas apresentou sete compostos majoritários: miricetina, quercetina, quercetina-arabinofuranosídeo, apigenina-triglicosídeos e apigenina-diglucosídeo, sendo os três últimos inéditos em estudos envolvendo o gênero. Os testes realizados demonstram o potencial de P. diversifolium, uma promissora fonte de biomoléculas com aplicabilidade terapêutica.

Las especies de Pithecellobium (Fabaceae) se utilizan en la medicina tradicional para tratar diabetes, tos, bronquitis e inflamación. Este estudio tuvo como objetivo evaluar el contenido y determinar la actividad antioxidante, el contenido de compuestos fenólicos y la citotoxicidad del extracto y de las fracciones de Pithecellobium diversifolium, un estudio inédito con una especie exótica de la Caatinga de la región Nordeste de Brasil, que utilizó la instrumentación HPLC-ESI. Las fracciones MeOH de hojas y cortezas de tallo mostraron un alto contenido de flavonoides (198,1 ± 106,50 y 542,7 ± 2,52 mg EqQ/g). La fracción CH2Cl2 de las cortezas presentó un alto contenido de compuestos fenólicos totales (516,7 ± 3,00 mg EqAG/g). El ensayo DPPH mostró que la fracción CH2Cl2 (hojas) tenía EC50 de 0,08 ± 0,02, valor superior a lo observado para los estándares utilizados en el ensayo ­Butilhidroxianisol (BHA), butilhidroxitolueno (BHT) y ácido ascórbico. Las fracciones AcOEt y MeOH de las cortezas presentaron una citotoxicidad moderada con valores inferiores a 500 µ g/mL. La fracción MeOH de las hojas contiene siete compuestos principales: miricetina, quercetina, quercetina-arabinofuranosido, apigenina-triglucósidos y apigenina-diglucósido, de los cuales los tres últimos son inéditos en estudios sobre el género. Las pruebas realizadas demuestran el potencial de P. diversifolium, una fuente prometedora de biomoléculas con aplicabilidad terapéutica.

Effects of Simulated Gastrointestinal Conditions on Combined Potentially Probiotic Limosilactobacillus fermentum 296, Quercetin, and/or Resveratrol as Bioactive Components of Novel Nutraceuticals.

This study evaluated the effects of simulated gastrointestinal conditions (SGIC) on combined potentially probiotic Limosilactobacillus fermentum 296 (~ 10 log CFU/mL), quercetin (QUE, 160 mg), and/or resveratrol (RES, 150 mg) as the bioactive components of novel nutraceuticals. Four different nutraceuticals were evaluated during exposure to SGIC and analyzed the plate counts and physiological status of L. fermentum 296, contents and bioaccessibility of QUE and RES, and antioxidant capacity. Nutraceuticals with QUE and RES had the highest plate counts (4.94 ± 0.32 log CFU/mL) and sizes of live cell subpopulations (28.40 ± 0.28%) of L. fermentum 296 after SGIC exposure. An index of injured cells (Gmean index, arbitrary unit defined as above 0.5) indicated that part of L. fermentum 296 cells could be entered the viable but nonculturable state when the nutraceuticals were exposed to gastric and intestinal conditions while maintaining vitality. The nutraceuticals maintained high contents (QUE ~ 29.17 ± 0.62 and RES ~ 23.05 mg/100 g) and bioaccessibility (QUE ~ 41.0 ± 0.09% and RES ~ 67.4 ± 0.17%) of QUE and RES, as well as high antioxidant capacity (ABTS assay ~ 88.18 ± 1.16% and DPPH assay 75.54 ± 0.65%) during SGIC exposure, which could be linked to the protective effects on L. fermentum 296 cells. The developed nutraceuticals could cross along the gastrointestinal tract with high concentrations of functioning potentially probiotic cells and bioavailable phenolic compounds to exert their beneficial impacts on consumer health, being an innovative strategy for the co-ingestion of these bioactive components.

Highlights of three metabolites HDL and reduction in blood pressure values after dietary fiber supplementation in overweight and obese normotensive women: a metabolomic study.

INTRODUCTION: The prevalence of hypertension and obesity are a worldwide concern. OBJETIVES: Assess the metabolites profile after intervention with mixed dietary fiber in overweight and obese normotensive women. METHODS: This is a randomized double blind placebo-controlled study. Through a simple randomization process, two groups were allocated, with eleven women (group 1) receiving 12 g of mixed dietary fiber and thirteen women (group 2) receiving 12 g of placebo (corn starch) for eight weeks. Anthropometric and biochemical tests and lifestyle were analyzed. As for evaluation metabolomics, used a 1H NMR. The data matrix generated 96 samples and 225 variables, which was exported in the ASCII format for the "The Unscrumbler" statistics software (version 9.7, CAMO Process). RESULTS: After the intervention with mixed dietary fiber, significant differences were observed between the main types of metabolites, referring to the increase in the relative peak areas of in three HDL metabolites 4.94 ppm (0.0086*), HDL 1.28 ppm (0 .0337*), HDL 0.88 ppm (0.0224*) and an α-glucose metabolite 4.90 ppm (0.0106) and the reduction in systolic blood pressure (SBP) (0.0292*) of 7 mmHg in the reference range and in the placebo group there was a reduction in SBP (0.0118*) of 4 mmHg and of a choline metabolite 3.65 ppm (0.0266*), which does not call into question the validity of these results in the literature. CONCLUSION: The synergism of the functions of these statistically highlighted metabolites contributed to prevention the increase in SBP after fiber intervention in overweight and obese normotensive women.

Unrevealing the in vitro impacts of Cereus jacamaru DC. cladodes flour on potentially probiotic strains, selected bacterial populations, and metabolic activity of human intestinal microbiota.

This study investigated the potential impacts of the flour from Cereus jamacaru cactus cladodes (CJF), a cactus native to the Brazilian Caatinga biome, on the growth and metabolism of different potentially probiotic strains, as well as on the abundance of selected intestinal bacterial populations and microbial metabolic activity during in vitro colonic fermentation with a pooled human fecal inoculum. Cultivation of the probiotics in a medium with C. jamacaru cladodes flour (20 g/L) resulted in viable cell counts of up to 9.8 log CFU/mL, positive prebiotic activity scores (0.73-0.91), decreased pH and sugar contents, and increased lactic, acetic, and propionic acid production over time, indicating enhanced probiotic growth and metabolic activity. CJF overall increased the relative abundance of Lactobacillus spp./Enterococcus spp. (2.12-3.29%) and Bifidobacterium spp. (4.08-4.32%) and decreased the relative abundance of Bacteroides spp./Prevotella spp. (8.35-6.81%), Clostridium histolyticum (6.91-3.59%), and Eubacterium rectale/Clostridium coccoides (7.70-3.95%) during 48 h of an in vitro colonic fermentation using a pooled human fecal inoculum. CJF stimulated the microbial metabolic activity, with decreased pH, sugar consumption, lactic and short-chain fatty acid production, alterations in overall metabolic profiling and phenolic compound contents, and maintenance of high antioxidant capacity during colonic fermentation. These results show that CJF stimulated the growth and metabolic activity of distinct potential probiotics, increased the relative abundance of beneficial intestinal bacterial groups, and stimulated microbial metabolism during in vitro colonic fermentation. Further studies using advanced molecular technologies and in vivo experimental models could forward the investigation of the potential prebiotic properties of CJF.

Tonantzitlolone B Modulates the Endogenous Opioid System to Promote Antinociception in Mice.

Tonantzitlolone B (TZL-B) is a diterpene isolated from the roots of Stillingia loranthacea. Its antinociceptive effects were investigated in male Swiss mice using the following models of pain: formalin test, inflammation induced by Complete Freund's Adjuvant (CFA), tail flick test, and cold plate test. The influence of TZL-B on the opioid system was assessed in vivo, using opioid antagonists; in silico, investigating the chemical similarity among TZL-B and opioid agonists; and ex vivo, measuring preproenkephalin (PENK) gene expression in the spinal cord by RT-qPCR. TZL-B (10-1000 µg/kg) promoted antinociception in the four experimental models without impairing mice's motor function. TZL-B did not alter paw edema during CFA-induced inflammation. The antinociceptive effects of TZL-B in the tail flick and cold plate tests were diminished by the opioid antagonists naloxone (5 mg/kg), NOR-BNI (0.5 mg/kg), naltrindole (3 mg/kg), and CTOP (1 mg/kg), indicating the involvement of κ-, δ-, and µ-opioid receptors. TZL-B showed no significant chemical similarity to opioid agonists, but the treatment with TZL-B (1000 µg/kg) increased PENK gene expression in the spinal cord of mice. These data suggest that TZL-B promotes antinociception by enhancing the transcription of PENK, hence modulating the endogenous opioid system.

Cleomin Exerts Acute Antinociceptive Effects in Mice via GABAB and Muscarinic Receptors.

Cleomin, a 1,3-oxazolidine-2-thione, was recently isolated from Neocalyptrocalyx longifolium, a species traditionally used for treating painful conditions. Reports about the pharmacological activities of cleomin are lacking. Here, the antinociceptive effects of cleomin were investigated using mice models of pain, namely the formalin, the cold plate, and the tail flick tests. Motor integrity was assessed in the rota-rod test. Antagonism assays and in silico docking analyses were performed to investigate the putative mechanisms of action. Cleomin (12.5-25 mg/kg), at doses that did not induce motor impairment, induced dose-dependent antinociception in both early and late phases of the formalin test and reduced nociceptive behaviors in both the cold plate and tail flick tests. Pretreatments with phaclofen and atropine attenuated the antinociceptive effects of cleomin, implicating the involvement of GABAB and muscarinic receptors. In silico docking studies suggested satisfactory coupling between cleomin and GABAB and M2 receptors, hence corroborating their role in cleomin's activity. Pretreatments with naloxone, yohimbine, bicuculline, and methysergide did not affect the antinociception of cleomin. In silico pharmacokinetics prediction showed a good drug ability profile of cleomin. In conclusion, cleomin promoted antinociception mediated by GABAB and muscarinic receptors. These findings support further investigation of the analgesic potential of cleomin.

The Essential Oil from Conyza bonariensis (L.) Cronquist (Asteraceae) Exerts an In Vitro Antimelanoma Effect by Inducing Apoptosis and Modulating the MAPKs, NF-κB, and PKB/AKT Signaling Pathways.

The characterization and cytotoxicity of the essential oil from Conyza bonariensis (L.) aerial parts (CBEO) were previously conducted. The major compound was (Z)-2-lachnophyllum ester (EZ), and CBEO exhibited significant ROS-dependent cytotoxicity in the melanoma cell line SK-MEL-28. Herein, we employed the Molegro Virtual Docker v.6.0.1 software to investigate the interactions between the EZ and Mitogen-Activated Protein Kinases (MAPKs), the Nuclear Factor kappa B (NF-κB), and the Protein Kinase B (PKB/AKT). Additionally, in vitro assays were performed in SK-MEL-28 cells to assess the effect of CBEO on the cell cycle, apoptosis, and these signaling pathways by flow cytometry and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay using MAPKs inhibitors. CBEO induced a significant increase in the sub-G1 peak, as well as biochemical and morphological changes characteristic of apoptosis. The in-silico results indicated that EZ interacts with Extracellular Signal-Regulated Kinase 1 (ERK1), c-Jun N-terminal Kinase 1 (JNK1), p38α MAPK, NF-κB, and PKB/AKT. Moreover, CBEO modulated the ERK1/2, JNK, p38 MAPK, NF-κB, and PKB/AKT activities in SK-MEL-28 cells. Furthermore, CBEO's cytotoxicity against SK-MEL-28 cells was significantly altered in the presence of MAPKs inhibitors. These findings support the in vitro antimelanoma effect of CBEO through apoptosis induction, and the modulation of ERK, JNK, p38 MAPK, NF-κB, and PKB/AKT activities.

Cactus flour (Opuntia ficus-indica) reduces brain lipid peroxidation and anxious-like behavior in old Wistar rats.

The aim of this research was to evaluate the effect of cactus flour on the anxious-like behavior and cerebral lipid peroxidation in elderly rats (18 months of life). The rats were divided into four groups (n=10). control (CG) - received the AIN-93M ration. P5%. P10% and P15%. treated with the AIN-93M ration with the addition of 5, 10 and 15% of cactus flour respectively. In the elevated plus maze (EPM) groups P5%, P10% and P15% remained longer in the open arms. P15% remained longer in this region and less time in the closed arms. No significant differences were observed between the groups regarding the time the rats remained in the center of the apparatus. P5%. P10% and P15% performed a greater number of head dips. Regarding the open field animals P5%. P10% and P15% performed a greater number of rearing and stayed for a longer time in the center of the apparatus with P15% being the group that remained for the longest time when compared to the other groups. There was no difference in locomotion and grooming. As for the light-dark box. P15% spent more time in the light part. less time in the dark part and performed a smaller number of transitions. P5%. P10% and P15% had the lowest concentrations of brain lipid peroxidation. Our data demonstrated that consumption of cactus flour by rats promoted anxiolytic effects and minimized brain lipid peroxidation in aging. Given the above, it can be deduced that cactus pear can contribute to the prevention and/or treatment of anxiety in the aging phase.Due to its concentrations of mono and polyunsaturated fatty acids, soluble fibers and antioxidant contents such as vitamin E and selenium.

Chemical Composition, In Vitro Antitumor Effect, and Toxicity in Zebrafish of the Essential Oil from Conyza bonariensis (L.) Cronquist (Asteraceae).

The essential oil from Conyza bonariensis (Asteraceae) aerial parts (CBEO) was extracted by hydrodistillation in a Clevenger-type apparatus and was characterized by gas chromatography-mass spectrometry. The antitumor potential was evaluated against human tumor cell lines (melanoma, cervical, colorectal, and leukemias), as well as non-tumor keratinocyte lines using the MTT assay. The effect of CBEO on the production of Reactive Oxygen Species (ROS) was evaluated by DCFH-DA assay, and a protection assay using the antioxidant N-acetyl-L-cysteine (NAC) was also performed. Moreover, the CBEO toxicity in the zebrafish model was assessed. The majority of the CBEO compound was (Z)-2-lachnophyllum ester (57.24%). The CBEO exhibited selectivity towards SK-MEL-28 melanoma cells (half maximal inhibitory concentration, IC50 = 18.65 ± 1.16 µg/mL), and induced a significant increase in ROS production. In addition, the CBEO's cytotoxicity against SK-MEL-28 cells was reduced after pretreatment with NAC. Furthermore, after 96 h of exposure, 1.5 µg/mL CBEO induced death of all zebrafish embryos. Non-lethal effects were observed after exposure to 0.50-1.25 µg/mL CBEO. Additionally, significant alterations in the activity of enzymes associated with oxidative stress in zebrafish larvae were observed. These results provide evidence that CBEO has a significant in vitro antimelanoma effect by increasing ROS production and moderate embryotoxicity in zebrafish.

Dereplication of tropane alkaloids from four Erythroxylum species using liquid chromatography coupled with ESI-MSn and HRESIMS.

RATIONALE: Tropane alkaloids represent an important class of secondary metabolites, but many of these compounds are already described in the scientific literature, so the use of guided identification and isolation strategies, such as dereplication, represent a fast and safe alternative. METHODS: For the annotation of the tropane alkaloids the chloroform phases of the four Erythroxylum species were analyzed by high-performance liquid chromatography coupled to mass spectrometry with positive-mode electrospray ionization, then the ions of their protonated molecules, molecular formulas and fragmentation patterns were observed and a comparison of the obtained data with those present in the scientific literature was performed. The compounds not fully annotated were isolated and characterized by 1 H and 13 C nuclear magnetic resonance spectroscopy. RESULTS: The annotation of 29 tropane alkaloids was performed, some being described for the first time in the family Erythroxylaceae. The chemical profiles of these secondary metabolites in the four Erythroxylum species analyzed were traced and compared. Isolation of three compounds whose mass spectral data were not sufficient for their full annotation was performed. They were 6-(benzoyloxy)-3-(3,5-dimethoxy-4-hydroxybenzoyloxy)tropane, 6-(benzoyloxy)-3-(3,4,5-trimethoxybenzoyloxy)tropane and 6-(benzoyloxy)-3-(3,4,5-trimethoxycinamoyloxy)tropane, first reported in the species Erythroxylum revolutum Mart. CONCLUSIONS: This work contributes to the phytochemical knowledge of the genus Erythroxylum, and demonstrates the efficiency and importance of using guided isolation methodologies of secondary metabolites in natural products research. Since safe results were presented in the annotation of the compounds evidenced, employing small quantities of organic solvents, when compared to classical methodologies, besides promoting an optimization in the research time.

The potential of Acmella oleracea as a nutraceutical source for the symptomatic treatment of Burning Mouth Syndrome.

This study analysed the phytochemical profile of Acmella oleracea extract and the molecular interactions of its main compounds with TRPV1 and CB2, target receptors in the Burning Mouth Syndrome (BMS) pathogenesis. The phytochemical profile of A. oleracea's floral buds extract treated with activated charcoal (TCEE) was analysed by High-Performance Liquid Chromatography (HPLC) coupled to Mass Spectrometry (LC-MS). The quantification of spilanthol was analysed by HPLC coupled to a Diode-Array Detector (HPLC-DAD). The phytochemical analysis revealed the presence of nine alkylamides and phenolic compounds. The TCEE showed a significant increase in spilanthol content compared to the crude extract (CEE), going from 28.33 mg/g to 117.96 mg/g. The molecular docking indicated a behaviour of the alkylamides as partial TRPV1 agonists and CB2 agonists and, for the first time, indicates the action of these compounds in the symptomatic management of BMS.

Evaluation of the acute toxicity and antidiabetic activity of Coutoubea spicata "nicolau" ethanolic extract and ethyl acetate fraction / Evaluación de la toxicidad aguda y la actividad antidiabética del extracto etanólico y la fracción de acetato de etilo de Coutoubea spicata "nicolau"

In order to understand antidiabetic potential and toxicity, this study aimed to evaluate the acute toxicity and antidiabetic activity of ethanolic extract and ethyl acetate fraction obtained from Coutoubea spicata "nicolau" shoots. Chemical constituents and acute toxicity were investigated. In alloxan-induced diabetic rats, extract and fraction were tested at dose of 100 mg/kg, p.o. Body weight gain, glucose, lipid profile and oxidative stress markers in serum and tissues were determined. In vitro antioxidant activity was performed. Swertiamarin, gentiopicrin, deoxyloganic acid, clovin and robinin, and their p-coumaric ester were identified. Extract and fraction were classified as safe (category 5). In diabetic rats, Coutoubea spicata reduced glycaemia, which was accompanied by body weight recovery gain and attenuation in oxidative stress markers. Fraction showed scavenging activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH), and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) radical (ABTS) radicals and reducing power higher than that of the extract. Extract and fraction of Coutoubea spicata didn't present significant toxicity and it can be investigated as a therapeutic alternative in diabetes.

Con el fin de conocer el potencial antidiabético y la toxicidad, este estudio tuvo como objetivo evaluar la toxicidad aguda y la actividad antidiabética del extracto etanólico y la fracción de acetato de etilo obtenidos de los brotes de Coutoubea spicata "Nicolau". Se investigaron los componentes químicos y la toxicidad aguda. En ratas diabéticas inducidas por alloxan, se probaron el extracto y la fracción en dosis de 100 mg/kg, p.o. Se determinó el aumento de peso corporal, la glucosa, el perfil lipídico y los marcadores de estrés oxidativo en suero y tejidos. Se realizó una actividad antioxidante in vitro. Se identificaron la suertiamarina, la gentiopicrina, el ácido desoxilogánico, la clovina y la robinina, así como su éster p-cumárico. El extracto y la fracción se clasificaron como seguros (categoría 5). En ratas diabéticas, Coutoubea spicata redujo la glicemia, lo que se acompañó de una recuperación del peso corporal y de la atenuación de los marcadores de estrés oxidativo. La fracción mostró una actividad de barrido contra los radicales 1,1-difenil-2-picrilhidrazilo (DPPH) y 2,2'-azino-bis (ácido 3-etilbenzotiazolina-6-sulfónico) y un poder reductor superior al del extracto. El extracto y la fracción de Coutoubea spicata no presentaron una toxicidad significativa y pueden ser investigados como alternativa terapéutica en la diabetes.