The composition and the antinociceptive activity of the essential oil of Stevia serrata Cav. from a population located in the west highlands of Guatemala were evaluated. A yield of 0.2% (w/w) of essential oil was obtained by hydrodistillation of the dried aerial parts of the plant. The essential oil analysed by GC-FID and GC-MS showed a high content of sesquiterpenoids, with chamazulene (60.1%) as the major component and 91.5% of the essential oil composition was identified. To evaluate antinociceptive activity in mice, the essential oil of S. serrata Cav. was administered as gavage, using three different doses. In the formalin test, the animals were pre-treated with oral doses of the essential oil before the administration of formalin. Oral administration of S. serrata Cav. essential oil produced a marked antinociceptive activity. Therefore, the plant could be domesticated as a source of essential oil rich in chamazulene for developing medicinal products.

Convolutamydine A has been shown to develop a significant antinociceptive effect. Here we demonstrated that new analogues (5-iodo-3-(2-oxopropyl)-3-hydroxy-2-oxindole (5-Iisa), 5-fluoro-3-(2-oxopropyl)-3-hydroxy-2-oxindole (5-Fisa), 5-chloro-3-(2-oxopropyl)-3-hydroxy-2-oxindole (5-Clisa) and 5-methyl-3-(2-oxopropyl)-3-hydroxy-2-oxindole (5-Meisa)), at 0.1-10mg/kg doses, have significant peripheral and central antinociceptive effects in thermal and chemical models of nociception. Oral administered analogues demonstrated more pronounced antinociceptive effects than that obtained with the classical opioid drug morphine (5mg/kg) in the first and second phases of formalin-induced licking. In the tail flick model, 5-Clisa and 5-Meisa antinociceptive effect was almost twice as that observed with the same dose of morphine. The concomitant administration of diverse antagonists and the analogues indicates that 5-Iisa effects involve the activation of opioid pathway. On the other hand, 5-Fisa and 5-Clisa have the participation of opioid, nitrergic, cholinergic adrenergic and serotoninergic pathways and 5-Meisa has the involvement of opioid, serotoninergic and cholinergic pathways. In conclusion, our results suggest that the new four analogues from Convolutamydine A have significant antinociceptive effects in thermal and chemical induced nociception and could be used in development of new drugs to be used in pain treatment with reduced side effects.

Through dereplication strategies using gas chromatography-mass spectrometry (GC-MS) and ultra fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS), the ethanol extract from Psycotria nemorosa leaves (Rubiaceae) showed to be composed of: cinnamic acid, dihydroactinidiolide, 4-hydroxy-β-ionone, phytol, isophytol, 4,8,12,16-tetramethylheptadecan-4-olide, lupeol, a mixture of α/β-amyrin, the keto and acetylated derivatives, besides stigmast-4-en-3-one, campesterol, stigmasterol and γ-sitosterol by GC-MS. Likewise, by UFLC-MS/MS, the main compounds identified were: butin, resveratrol, rutin, kaempferol 7-O-β-D-glucopyranoside, deacetylasperuloside, epiloganin, hordenine, strictosidine, N-methyl-1,2,3,4-tetrahydro-β-carboline and N-formyl-tryptamine. The antinociceptive activity of the crude extract ant its fractions was reported.

Background: Stevia serrata Cav. (Asteraceae), widely found in Guatemala, is used to treat gastrointestinal problems. The aim of this study was to demonstrate the antinociceptive and anti-inflammatory effects of the essential oil (EO) and the mechanism of action. Methods: EO was tested in chemical (capsaicin- and glutamate-induced licking response) or thermal (hot plate) models of nociception at 10, 30 or 100 mg/kg doses. The mechanism of action was evaluated using two receptor antagonists (naloxone, atropine) and an enzyme inhibitor (L-NAME). The anti-hyperalgesic effect was evaluated using carrageenan-induced nociception and evaluated in the hot plate. Results: All three doses of EO reduced licking response induced by glutamate, and higher doses reduced capsaicin-induced licking. EO also increased area under the curve, similar to the morphine-treated group. The antinociceptive effect induced by EO was reversed by pretreatment of mice with naloxone (1 mg/kg, ip), atropine (1 mg/kg, ip) or L-NAME (3 mg/kg, ip). EO also demonstrated an anti-hyperalgesic effect. The 100 mg/kg dose increased the latency time, even at 1 h after oral administration and this effect has been maintained until the 96th hour, post-administration. Conclusions: Our data suggest that essential oil of S. serrata presents an antinociceptive effect mediated, at least in part, through activation of opioid, cholinergic and nitrergic pathways.

Background: Despite the existence of a wide variety of anti-inflammatory drugs, the vast majority are classified as steroidal or non-steroidal. Both classes present a variety of side effects that limit usage. Thus, the search for new molecules with anti-inflammatory potential is still important. Methods: Five phenylbenzohydrazides were synthetized and evaluated in pre-clinical models of acute inflammation in vivo and in vitro. Results: The new substances (INL-06, -07, -10, and -11), as well as AISCT, significantly reduced cell migration induced by carrageenan. It was also observed that all INLs inhibited protein extravasation as well as cytokines (IL-6, IL-1β, and TNF-α) and nitric oxide (NO) production. The INL-11 was demonstrated to be the most potent, since the inhibition observed in several parameters was significant even when compared with dexamethasone. In vitro INLs also reduced cytokines and NO production and inducible nitric oxide (iNOS) enzyme activity. The INL-11 was the most effective in reducing cell migration in vitro. Conclusions: Our data suggest that these substances are suitable for further development into a new series of compounds that could lead to new hits and future drug prototypes for anti-inflammatory conditions.