Analgesic and Anti-Inflammatory Properties of Ethanolic Extract of Piper vicosanum Leaves.

Nonclinical trials are important to validate the efficacy and safety of medicinal plants. Scientific toxicological studies with Piper vicosanum Yuncker have showed its safety; however, no studies have indicated the analgesic or antiarthritic potential of the ethanolic extract of P. vicosanum leaves (EEPV). The objective of the present work was to evaluate the antiarthritic and antinociceptive effects of EEPV in experimental mouse models. The oral administration of EEPV (100, 300, and 700 mg/kg) and dexamethasone (1 mg/kg) were performed in carrageenan-induced pleurisy, in formalin and acetic-acid-induced nociception, and in zymosan-induced articular inflammation models in Swiss mice. The EEPV (300 mg/kg) was tested in zymosan-articular inflammation, the complete Freund's adjuvant (CFA) inflammatory model, and in in situ intravitreal microscopy analysis of rolling and adhesion events of leukocytes in the mesenteric microcirculation in mice. EEPV significantly inhibited: (i) nociceptive response at phase 1 and 2, and also in the cold response in the formalin model; (ii) abdominal contortion induced by acetic acid; (iii) mechanical hyperalgesia after 4 and 6 h, knee edema after 6 h, and leukocyte migration in articular inflammation induced by zymosan. All doses of EEPV reduced the leukocyte migration to the inflamed pleural cavity and knee edema 4 h after the zymosan knee injection. The treatment with the EEPV significantly inhibited the CFA-induced edema, mechanical and cold hyperalgesia, and NAG and MPO. The EEPV also significantly inhibited carrageenan-induced leukocyte rolling and adhesion. The present study revealed, for the first time, the antiarthritic and antinociceptive effects of the EEPV.

Anti-inflammatory properties of ethanolic extract from Vatairea macrocarpa leaves.

ETHNOPHARMACOLOGICAL RELEVANCE: In Brazilian traditional folk medicine, the leaves and heartwood from Vatairea macrocarpa (Benth) Ducke (Angelim-of-Cerrado) (Fabaceae family) are used as remedy after cold maceration for the treatment of the condition popularly known as rheumatism, as well as for the general inflammatory aspects such as pains, injury and swelling. The rheumatological and rheumatic diseases affect 0.3-1.0% of the world population and all long-term treatment with conventional medications lead to adverse effects. AIM OF THE STUDY: To investigate the chemical composition and the anti-inflammatory properties and of the ethanolic extract from V. macrocarpa leaves (EEVM) in experimental models. MATERIAL AND METHODS: EEVM was chemically analyzed by spectrophotometry and the compounds characterization was performed by nuclear magnetic resonance and mass spectrometry. EEVM was evaluated in methylthiazolyldiphenyl-tetrazolium bromide (MTT) (3, 10, 30, and 90 µg/ml) and neutrophils phagocytic activity (1, 3, and 10 µg/ml) tests. For in vivo models, the EEVM (10, 30, 100, and 300 mg/kg) was orally administered (p.o.) for inflammatory evaluation in carrageenan-induced pleurisy in Swiss mice. The EEVM (30 and 100 mg/kg, p.o.) was tested against the Complete Freund Adjuvant (CFA)-induced paw persistent inflammation and Mycobacterium bovis (bacillus Calmette-Guerin - BCG)-induced pleurisy in C57bL6 mice. RESULTS: The chemical composition of EEVM showed 157.06 mg (GAE)/g in relation to phenolic compounds, 82.13 mg (RUE)/g in relation to flavonoids and 48.99 mg (TAE)/g in relation to tannins. The flavonoid compounds identified were catechin, epicatechin and kaempferol-3-O-a-l-rhamnopyranoside. EEVM did not present cytotoxicity in MTT assay, however EEVM reduced phagocytic neutrophils activity at all tested concentration. EEVM significantly inhibited leukocytes migration/proteins exudation in carrageenan-induced pleurisy model. The daily administration of EEVM inhibited the inflammatory parameters in BCG and CFA models. CONCLUSIONS: The present study showed anti-inflammatory features of EEVM (V. macrocarpa) as a natural agent against inflammatory diseases.

Aqueous extract from leaves of Doliocarpus dentatus (Aubl.) Standl. relieves pain without genotoxicity activity.

ETHNOPHARMACOLOGICAL RELEVANCE: In the State of Mato Grosso do Sul, the watery sap of Doliocarpus dentatus is used to alleviate thirst, and the leaves of this species are used to relieve pain and swelling associated with inflammatory processes. AIM OF THE STUDY: This study aimed to analyze the compounds of the leaves from the aqueous extract of D. dentatus (EADd) and evaluate its toxicogenetic and pain relief effects in animal models. MATERIALS AND METHODS: Compounds were identified in EADd by UHPLC-HRMS (Ultra high-performance liquid chromatography coupled to high resolution mass spectrometry). The oral dose of 17 mg/kg EADd, calculated according to ethnopharmacological uses, and doses between 30 and 300 mg/kg were used to test Swiss mice in formalin- and acetic acid-induced models of pain and behavior. EADd (100-2000 mg/kg) was assayed in mice by comet, micronucleus, and phagocytosis tests and by peripheral leukocyte counts. RESULTS: Phenolic compounds and flavonoids as well as trigonelline and isoquercetin were identified in EADd. All oral doses of EADd exhibited antinociceptive activity, as indicated by a decrease in pain in both phases, a decrease in cold hypersensitivity induced by formalin, and a decrease in abdominal contortions induced by acetic acid. EADd did not alter the exploratory, motor or motivational activities of the animals. The comet and micronucleus tests indicated that EADd was not genotoxic and did not change the phagocytic activity or peripheral leukocyte count. CONCLUSIONS: These results demonstrate that EADd could act as an antinociceptive agent that does not present genotoxicity. This study should contribute to justifying, in part, the popular use of D. dentatus in pain management, ensuring its safe use.