Cytotoxicity, oral toxicity, genotoxicity, and mutagenicity evaluation of essential oil from Psidium glaziovianum Kiaersk leaves.

ETHNOPHARMACOLOGICAL RELEVANCE: Members of the Psidium genus have been suggested in ethnobotanical research for the treatment of various human diseases, and some studies have already proven their popular uses through research, such as Psidium glaziovianum, which is found in Brazil's northeast and southeast regions and has antinociceptive and anti-inflammatory properties; however, the safety of use has not yet been evaluated. AIM OF THE STUDY: This study investigated the safety of using essential oil obtained from P. glaziovianum leaves (PgEO) in vitro and in vivo models. MATERIALS AND METHODS: Cytotoxicity was evaluated in murine erythrocytes, while acute toxicity, genotoxicity (comet assay) and mutagenicity (micronucleus test) studies were performed using Swiss albino mice. RESULTS: In the cytotoxicity assay, the hemolysis rate indicated a low capacity of PgEO to cause cell lysis (0.33-1.78%). In the acute oral toxicity study, animals treated with up to up to 5000 mg/kg body weight did not observe mortality or physiological changes. Neither dosage caused behavioral problems or death in mice over 14 days. The control and 2,000 mg/kg groups had higher feed intake and body weight than the 5,000 mg/kg PgEO group. Erythrocyte count, hemoglobin level, mean corpuscular volume, and MCV decreased, but serum alanine and aspartate aminotransferases increased. In the genotoxic evaluation, 5000 mg/kg PgEO enhanced nucleated blood cell DI and DF. CONCLUSIONS: The present study describes that PgEO can be considered well tolerated in acute exposure at doses up to 2000 mg/kg, however the dose of 5000 mg/kg of PgEO should be used with caution.

Oral administration of essential oil from Psidium glaziovianum Kiaersk leaves alleviates pain and inflammation in mice.

Plants of the genus Psidium have been employed in "in natura" consumption and agroindustry, and owing to the diversity of phytochemicals, the development of new pharmaceutical forms has received remarkable research interest. In this study, the essential oil obtained from Psidium glaziovianum (PgEO) leaves were evaluated antinociceptive and anti-inflammatory activities were evaluated in mouse models. Initially, PgEO was characterized by gas chromatography-mass spectrometry and gas chromatography with flame ionization detection, and the profile was dominated by sesquiterpene compounds. In the evaluation of acute antinociceptive activity (abdominal contortions induced by acetic acid, formalin, tail immersion, and hot plate tests), PgEO promoted a reduction in nociception in the chemical and thermal models. Additionally, the potential underlying mechanism was investigated using pain pathway blockers, and the results revealed a combined action of opioidergic and muscarinic pathways. The anti-inflammatory potential was confirmed by anti-edematogenic action, reduced cell migration, pro-inflammatory cytokine production, and granuloma formation in chronic processes. This study provides evidence that PgEO can be effective for the treatment of pain and acute and chronic inflammation.

Flavonoid-Rich Fraction from Croton blanchetianus (Euphorbiaceae) Leaves Exerts Peripheral and Central Analgesic Effects by Acting via the Opioid and Cholinergic Systems.

The ethanolic extract from Croton blanchetianus leaves has been shown to have antinociceptive activity in mice. Here, we investigated the antinociceptive activity of an ethyl acetate fraction (EAF) from this extract in mice and the possible pathways involved in the analgesic effect. Adverse effects on behavior and motor coordination were also evaluated. The EAF was characterized by liquid chromatography coupled with mass spectrometry and evaluated (12.5, 25, and 50 mg/kg per os) in the acetic acid-induced abdominal writhing, formalin, hot plate, and tail immersion assays. Naloxone, atropine, glibenclamide, prazosin, or yohimbine was pre-administered to mice to investigate the involved pathways in the formalin test. The open-field, rotarod, and elevated plus-maze tests were used to assess behavior and locomotion. The main components of the EAF were quercetin-3-O-(2-rhamnosyl) rutinoside, hyperoside, quercetin rutinoside pentoside, and quercetin hexoside deoxyhexoside. EAF showed antinociceptive effects in all models and was effective against both neurogenic and inflammatory pain. The reversion of the effects in the formalin test by naloxone and atropine revealed that the EAF acted via the opioid and cholinergic systems. In the open-field test, the behavior of the animals treated with the EAF was like that of control, except at the highest dose, when hypnosis, eyelid ptosis, decreased walking, hygiene, and rearing behaviors were observed. No muscle relaxant effect was observed, but an anxiogenic effect was observed at all doses. This study provides new scientific evidence on the pharmacological properties of C. blanchetianus leaves and their potential for the development of phytomedicines with analgesic properties.