Acute and repeated dose 28-day oral toxicity of Chrysobalanusicaco L. leaf aqueous extract.

Chrysobalanus icaco L. is a native plant of Brazil used as a food source and traditionally for the treatment of various diseases. The aim of study was performed the phytochemical analysis by UPLC-DAD-ESI-QTOF-MS/MS, and evaluated acute and repeated dose oral toxicities of the C. icaco L. leaf aqueous extract (AECi). The acute toxicity study was performed using a dose of AECi 2000 mg/kg, while the repeated dose toxicity study, the AECi was administered daily at doses of 100, 200 and 400 mg/kg, for 28 days. Behavior and mortality of animals were observed during the test period and body weight, as well water and eating consumption. Hematological, biochemical parameters and histopathological examinations were carried out. Phytochemical analysis of the AECi revealed the presence of flavonoids and tannins. Oral single dose of 2000 mg/kg of AECi resulted in no mortalities or abnormal clinical signs. Studies of repeated dose toxicity promoted a reduction in the body weight of treated animals and an increase of hepatic enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in both, males and females. Histopathological analyzes showed alterations in the livers of animals treated with AECi. Thus, this study recommends the population take care when using this species, especially during prolonged periods.

Anti-inflammatory and antinociceptive activities of the leaf methanol extract of Miconia minutiflora (Bonpl.) DC. and characterization of compounds by UPLC-DAD-QTOF-MS/MS.

Some species of the genus Miconia are used in Brazilian folk medicine as analgesic and anti-inflammatory; however, several species of this genus are still poorly studied. Therefore, the aims of this study were to investigate the phytochemistry characterization by UPLC-DAD-QTOF-MS/MS, acute toxicity, anti-inflammatory and antinociceptive properties of Miconia minutiflora (Bonpl.) DC. The methanol extract of M. minutiflora (Mm-MeOH) was subjected to ultra-high-performance liquid chromatography (UPLC-DAD-QTOF-MS/MS) for the identification of the main phytocompounds. The anti-inflammatory properties of the extracts were studied using several inflammation models induced by carrageenan and acetic acid-induced vascular permeability. Antinociceptive effects of Mm-MeOH were assessed in nociception induced by intraperitoneal acetic acid or subplantar formalin injection. The role of α-adrenergic, cholinergic, and opioid receptors in modulating the extract's antinociceptive activity was determined. Analyses by UPLC-DAD-QTOF-MS/MS revealed the presence of ellagic acid, gallotannin, and terpenes in the methanol extract. Mm-MeOH (100 mg/kg) reduced carrageenan-induced paw edema and vascular permeability and inhibited leukocyte migration toward the air pouch and pleural cavity. Furthermore, Mm-MeOH decreased tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) levels. Administration of Mm-MeOH reduced the number of writhes by 58.9% and increased the pain threshold in the formalin test. The anti-inflammatory action mechanism of Mm-MeOH is associated with inhibition of proinflammatory cytokines TNF-α and IL-1ß, whereas the antinociceptive actions involve peripheral and central mechanisms with participation of α2-adrenergic receptors. These effects may be attributed to the presence of polyphenolics in the extract.

Gastroprotective effect of ethyl acetate extract from Avicennia schaueriana Stapf & Leechman and underlying mechanisms.

OBJECTIVE: Avicennia schaueriana Stapf is an endemic mangrove species widely used by traditional Brazilian communities as a folk remedy for the treatment of rheumatism, ulcers, and skin wounds. The aim of the present study was to evaluate the gastroprotective potential of the ethyl acetate extract from the leaves of A. schaueriana (As-AcOEt). METHODS: Ultra-performance liquid chromatography coupled with diode-array detection and quadrupole time-of-flight mass spectrometry (UPLC-DAD-QTOF-MS/MS) was performed to identify chemical constituents of the ethyl acetate extract from the leaves ofA. schaueriana. Total phenols, flavonoids and tannins were determined and antioxidant activity was evaluated using the DPPH and ABTS methods. The acute toxicity of As-AcOEt and gastroprotective activity on HCl/ethanol-induced gastric ulcers were assessed and mechanisms of action involving the role of nitric oxide, sulfhydryl compounds, and prostaglandins were investigated. RESULTS: Terpenes, flavonoids and tannins were detected in the extract. As-AcOEt exhibited antioxidant activity, with an EC50 of 42.2 ± 4.4 µg/mL (DPPH) and 73.2% inhibition of ABTS radicals. UPLC-DAD-QTOF-MS/MS analysis identified gallic acid, gallic acid derivative, ellagic acid, myricetin pentoside, myricetin deoxyhexose, quercetin pentoside, quercetin deoxyhexose, and other compounds. Gallic acid was isolated in this species for the first time. During the acute toxicity test, no deaths or changes occurred in the variables evaluated. In the ethanol-induced ulcer model, As-AcOEt reduced the ulcerative lesion index, with 50, 100 and 200 mg/kg achieving 83.8, 88.5 and 86.9% inhibition, respectively. MPO levels decreased and the gastric mucosa of the animals treated with the extract was preserved. Pre-treatment with N-omega-nitro-l-arginine methyl ester (L-NAME; NO blocker) or carbenoxolone (CBXN; NP-SH blocker) reversed the gastroprotective effect of As-AcOEt, but this effect was not reversed with the previous administration of indomethacin. CONCLUSION: The present findings reveal that the extract from the leaves ofA. schaueriana has gastroprotective effects, suggesting the involvement of nitric oxide and nonprotein sulfhydryl compounds, but not prostaglandin. Therefore, the use of A. schaueriana in Brazilian folk medicine for the treatment of gastric disorders has a scientific basis.

Evaluation of anti-inflammatory activity and molecular docking study of new aza-bicyclic isoxazoline acylhydrazone derivatives.

The aim of this study was to investigate the anti-inflammatory effects of two new isoxazoline-acylhydrazone derivatives: N'-(4-methoxybenzylidene)-6-(4-nitro-benzoyl)-3a,5,6,6a-tetrahydro-4H-pyrrolo[3,2-d]isoxazole-3-carbohydrazide (R-123) and N'-(4-chlorobenzylidene)-6-(4-chlorobenzoyl)-3a,5,6,6a-tetrahydro-4H-pyrrolo[3,2-d]isoxazole-3-carbohydrazide (R-99). An air pouch induced by carrageenan was used for screening the best dose of R-99 and R-123. Using this mouse model, leukocyte migration and cytokine levels (TNF-α and IL-1ß) were determined. Paw edema induced by several phlogistic agents and vascular permeability induced by acetic acid were employed to investigate the mechanism of action of the isoxazoline-acylhydrazone derivatives. A docking study was performed with the human histamine H1 receptor to investigate potential antihistaminic activity. Treatment with the compounds reduced leukocyte migration in the air pouch at all doses tested. TNF-α and IL-1ß levels were similarly reduced by the two compounds. Vasoactive amines were inhibited in models of paw edema induced by several agents and vascular permeability induced by acetic acid. The docking study suggests that R-99 and R-123 may be inhibitors of the histamine H1 receptor. In conclusion, the results indicate that R-99 and R-123 exhibit promising anti-inflammatory activity related to their ability to inhibit TNF-α, IL-1ß, and vasoactive amine production, as well as reduce leukocyte migration and inhibit mast cell degranulation.