Characterization of ßN-Octadecanoyl-5-hydroxytryptamide Anti-Inflammatory Effect.

BACKGROUND: N-octadecanoyl-5-hydroxytryptamide (C18-5HT) is an amide that can be obtained by the coupling of serotonin and octadecanoic acid. This study aims to characterize the in vivo and in vitro anti-inflammatory activity of C18-5HT. METHODS: A subcutaneous air pouch model (SAP) was used. The exudates were collected from SAP after carrageenan injection to assess cell migration and inflammatory mediators production. RAW 264.7 cells were used for in vitro assays. RESULTS: C18-5HT significantly inhibited leukocyte migration into the SAP as well as nitric oxide (NO) and cytokines production and protein extravasation. We also observed an reduction in some cytokines and an increase in IL-10 production. Assays conducted with RAW 264.7 cells indicated that C18-5HT inhibited NO and cytokine produced. CONCLUSIONS: Taken together, our data suggest that C18-5HT presents a significant effect in different cell types (leukocytes collected from exudate, mainly polumorphonuclear leukocytes and cell culture macrophages) and is a promising compound for further studies for the development of a new anti-inflammatory drug.

Pharmacological Evaluation of Artemisia cina Crude CO2 Subcritical Extract after the Removal of Santonin by Means of High Speed Countercurrent Chromatography.

Artemisia species are highly important due to their economic significance as medicines, fodder and food. Artemisia cina is an endemic species to Kazakhstan. In folk medicine, water extract of A. cina was used in the treatment of bronchial asthma while the alcohol extract has larvicidal and antituberculosis activity. The most common and most extensively studied compound from this species is the terpenoid santonin. The toxicity of this compound occurs at the doses of 60 mg for children and 200 mg for adults causing among other issues xanthopsia, leading to blindness. Having this in mind, the main idea of this work was to remove santonin from the crude extract and to check if the santonin-free extract would still be of any pharmacological importance. A CO2 subcritical extract was chromatographed using high-speed countercurrent chromatography (HSCCC) for the removal of santonin. The santonin-free CO2 subcritical extract (SFCO2E) as well as the isolated compound pectolinarigenin, a flavonoid, were assessed for their pharmacological actions. From the results obtained we can safely suggest that HSCCC is an efficient methodology to completely remove santonin from the CO2 subcritical extract. It was also possible to observe promising antinociceptive and anti-inflammatory activities for both SFCO2E and pectolinarigenin at concentrations that can justify the production of a phytomedicine with this endemic plant from Kazakhstan.

Study on the Antinociceptive Activity and Mechanism of Action of Isolated Saponins from Siolmatra brasiliensis (Cogn.) Baill.

Infusions of roots of Siolmatra brasiliensis (Cogn.) Baill, ("taiuiá", "cipó-tauá") are used for toothache pain and ulcers. We aimed to study the antinociceptive effects and identify the possible mechanism of action of this plant and its isolated substances (cayaponoside A1, cayaponoside B4, cayaponoside D, and siolmatroside I). Hydroethanol extract (HE), ethyl acetate fraction (EtOAc), and isolated saponins were evaluated in chemical and thermal models of pain in mice. Animals were orally pretreated and evaluated in the capsaicin- or glutamate-induced licking and in the hot plate tests. The antinociceptive mechanism of action was evaluated using the hot plate test with the following pretreatments: Atropine (cholinergic antagonist), naloxone (opioid antagonist), or L-NAME (nitric oxide synthase inhibitor). All extracts and isolated saponins increased the area under the curve in the hot plate test. Tested substances induced a higher effect than the morphine-treated group. Our data suggest that stems of S. brasiliensis and their isolated substances present antinociceptive effects. Cholinergic and opioidergic pathways seem to be involved in their mechanism of action. Taken together our data corroborate the traditional use of the plant and expands the information regarding its use.

Effects of Euphorbia characias subsp. characias flower extracts on nociceptive pain and acute inflammatory models in mice.

Pain and inflammation are major health issues worldwide, leading to negative consequences. Despite several drugs being available to manage these conditions, their effectiveness can be limited by cost, adverse reactions, and potential tolerance and dependence with long-term use. Euphorbia characias traditionally used in folk medicine for its diverse biological activities - including antiproliferative, antimicrobial, and anti-inflammatory effects - has not been extensively studied in vivo for its analgesic and anti-inflammatory properties. In this study, the antinociceptive and anti-inflammatory properties of the water and ethanolic extracts of E. characias flowers (ECAEFl and ECEEFl) were evaluated using various models. Both extracts significantly reduced paw licking time in a formalin-induced paw licking model, with ECAEFl specifically targeting and ECEEFl affecting both the neurogenic and inflammatory phases. Additionally, in the carrageenan-induced cell migration model, both extracts showed a significant decrease in leukocyte migration, protein extravasation and nitric oxide levels, further demostrating their anti-inflammatory activity. High-Resolution HPLC-ESI-QTOF-MS-MS and HPLC-PDA analysis characterized the chemical composition of the extracts, identifying a significant presence of phenolic compounds, particularly quercetin and its derivatives, which likely contribute to the observed biological activities. These findings highlight the potential of E. characias extracts as natural sources of compounds with antinociceptive and anti-inflammatory properties. Further investigations are needed to elucidate the underlying mechanisms and explore their therapeutic potential in pain and inflammation-related disorders.

Phenylbenzohydrazides Obtained from Isatoic Anhydride Present Anti-Inflammatory Activity In Vivo and In Vitro.

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-1ß, 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.

Pharmacognostic Study on Elsholtzia ciliata (Thumb.) Hyl: Anatomy, Phytochemistry and Pharmacological Activities.

Elsholtzia ciliata (Thunb.) Hyl, family Lamiaceae, is an important and popular anti-bacterial and anti-inflammatory Traditional Chinese Medicine (TCM). However, there are limited scientific studies on its anatomy and pharmacological activities. Moreover, the information of chemical constituents in relation to its non-volatile constituents are still missing. The current study aimed to evaluate the anatomic, pharmacological and phytochemical profile of Elsholtzia ciliata, providing means for the quality control of this herbal drug. The methodology designed for this study included the preparation of anatomic sections and their description, extraction, chromatography, structural elucidation of isolated compounds by NMR techniques and their quantification by HPLC using pharmacological assays (Formalin, hot plate, DPPH, antimicrobial-Gram positive, Gram Negative and fungus, and MTT assays) to confirm the activities described for this species. Results of the anatomic study are aligned with the pattern expected for plants belonging to the Lamiaceae family; Ursolic acid and Oroxylin were isolated from this plant species. The findings observed in this study indicate that Elsholtzia ciliata possess anti-inflammatory, antinociceptive, antioxidant, antimicrobial and anticancer activities. The chemical compounds isolated from its leaves and the anatomy profile of its parts provide the basis for further quality control for this plant.

Chemical composition and evaluation of antinociceptive activity of the essential oil of Stevia serrata Cav. from Guatemala.

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.

New ßN-octadecanoyl-5-hydroxytryptamide: antinociceptive effect and possible mechanism of action in mice.

The present study examined the potential antinociceptive activity of C18 5-HT (ßN-octadecanoyl-5-hydroxytryptamide) using chemical and thermal nociception models in mice. Orally administered C18 5-HT (0.1, 1 and 10 mg/kg) produced significant dose-dependent antinociceptive effects in formalin-, capsaicin- and glutamate-induced licking models. This compound also induced a significant increase in the response to thermal stimuli in the hot plate test, and its antinociceptive effect was not related to muscle relaxant or sedative actions. In a thermal hyperalgesia model, C18 5-HT presented an anti-hyperalgesic profile as evidenced by the increase in the response time of the animals. Furthermore, intraperitoneal (i.p) pretreatment with naloxone (a non-selective opioid receptor antagonist, 1 mg/kg), ondansetron (serotoninergic receptor antagonist (5-HT3 subtype), 0.5 mg/kg) or AM241 (CB1 cannabinoid receptor antagonist, 1 mg/kg) reversed the antinociceptive effects of C18 5-HT in the hot plate model. In the formalin-induced licking model, pretreatment with naloxone reversed the antinociceptive effects of C18 5-HT, as demonstrated by an increase in the paw licking response when compared with the C18 5-HT-treated group. These findings suggest that C18 5-HT has peripheral and central antinociceptive effects and that its mechanism of action involves, ate least in part, opioid, serotoninergic and cannabinoid pathways.

Antinociceptive effect and mechanism of action of isatin, N-methyl isatin and oxopropyl isatin in mice.

AIMS: There has been growing interest in the synthesis of new derivatives from isatin, found in Isatis genus. Our objectives were to characterize the antinociceptive mechanism of action of isatin, N-methyl-isatin (MI) and N-methyl-3-(2-oxopropyl)-3-hydroxy-2-oxindole (MOI). MATERIALS AND METHODS: Substances (0.1-10mg/kg, p.o.) were studied in chemical (paw licking induced by formalin, capsaicin or glutamate) or thermal (hot plate) models of nociception. The involvement of several systems was evaluated using different receptor antagonists. KEY FINDINGS: All three substances inhibit both phases of formalin-induced licking, increase the area under the curve and MI and MOI have a higher effect than that of morphine (in hot plate). Capsaicin and glutamate-induced licking were also reduced by all three substances. In the hot plate model, the antinociceptive effect of isatin was reduced by naloxone and atropine; naloxone, atropine and L-NAME reduced MI effect while naloxone, atropine, L-NAME, mecamylamine and ondansetron reduced MOI effect. SIGNIFICANCE: Our results suggest that isatin, MI and MOI: 1) present activity in models of nociception; 2) capsaicin and glutamate receptors seems to participate in the mechanism of action; 3) opioid, cholinergic, serotoninergic, nitrergic and adrenergic systems may be involved, at least in part, in the mechanism of action of some of these substances.

Central and peripheral antinociceptive activity of 3-(2-oxopropyl)-3-hydroxy-2-oxindoles.

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.