Anti-inflammatory and antinociceptive activities of a phenylpropanoid-enriched fraction of Duguetia furfuracea.

A previous study reported the in vivo anti-inflammatory and antinociceptive activities of essential oil of the underground stem bark of Duguetia furfuracea, termed EODf. This study aimed to obtain a phenylpropanoid-enriched fraction from the D. furfuracea (EFDf) essential oil and to investigate its anti-inflammatory and antinociceptive effects. The chemical composition of the EFDf was determined by gas chromatography-mass spectrometry (GC-MS). The in vivo anti-inflammatory activity was evaluated with a lipopolysaccharide (LPS)-induced paw oedema model. The effects of the EFDf on the polymorphonuclear leukocyte recruitment and the inducible nitric oxide synthase (iNOS) expression were evaluated in mice footpads. Moreover, the in vivo antinociceptive effect was assayed using the formalin test and the LPS-induced thermal hyperalgesia model. In the EFDf, 8 major compounds were identified, with α-asarone (36.4%) and 2,4,5-trimethoxystyrene (27.8%) the main constituents. A higher concentration of phenylpropanoid derivatives was found in the EFDf, 64.2% compared to the EODf (38%). The oral (p.o.) treatment with the EFDf at a dose of 3 mg/kg significantly attenuated the paw oedema, polymorphonuclear leukocyte migration, iNOS expression, and tumour necrosis factor alpha (TNF-α) production. The EFDf (10 and 30 mg/kg) also inhibited both phases of the formalin test and caused a significant increase in the reaction time in the LPS-induced thermal hyperalgesia model. Finally, EFDf-treated animals did not show any alteration of motor coordination. The results suggest that the enrichment of 2,4,5-trimethoxystyrene and α-asarone enhances the anti-inflammatory activity of the EFDf compared to the EODf. In contrast, the antinociception promoted by the EFDf was similar to the EODf and was mediated via activation of adenosinergic and opioidergic receptors.

Chemical composition, anti-inflammatory and antinociceptive effects of the butanolic fraction of Annona nutans (Annonaceae) leaves.

The species Annona nutans (R. E. Fries) is a plant found in Bolivia, Paraguay, Argentina and the Brazilian cerrado. Considering the anti-inflammatory and antinociceptive activities of the hydrometanolic fraction (FHMeOH) of A. nutans leaves previously reported, the present study aimed to evaluate in vivo anti-inflammatory and antinociceptive activities of a subfraction obtained from FHMeOH, the butanolic fraction (FBuOHf). Intraperitoneal (i.p.) treatment with FBuOHf (50 and 100 mg · kg-1) inhibited paw edema induced by carrageenan. Moreover, FBuOHf (100 mg · kg-1, i.p.) also suppressed polymorphonuclear (PMN) leukocyte migration in the footpad. Regarding the antinociceptive activity, FBuOHf (50, 100, and 200 mg · kg-1, i.p.) inhibited acetic acid-induced abdominal writhing. In the formalin test, this fraction (200 mg · kg-1, i.p.) reduced licking time only in the inflammatory phase. The FBuOHf contents flavonoids and cinnamic acid derivatives, such as quercetin-3-O-galactoside, quercetin-3-O-glucoside, isorhamnetin-3-O-galactoside, quercetin-3-O-ß-D-apio-furanosyl-(1→2)-galactopyranoside and chlorogenic acid, identified and quantified by LC-MS. The FBuOHf possesses anti-inflammatory and peripheral antinociceptive activities.

Anti-inflammatory and central and peripheral anti-nociceptive activities of α-asarone through the inhibition of TNF-α production, leukocyte recruitment and iNOS expression, and participation of the adenosinergic and opioidergic systems.

Alpha-asarone has been found to possess many pharmacological activities, which can improve cognitive function and exert anti-oxidant, anxiolytic, anti-epileptic and protective effects against endothelial cell injury. The anti-inflammatory activity of α-asarone was evaluated using lipopolysaccharide (LPS)-induced paw oedema. Moreover, leukocyte migration, inducible nitric oxide synthase (iNOS) expression and tumour necrosis factor-alpha (TNF-α) levels were quantified in footpads. Formalin and LPS-induced thermal hyperalgesia models were generated using adenosinergic, opioidergic, serotonergic and muscarinic receptor antagonists. The effects on motor coordination were evaluated by means of the rota-rod test. Oral treatment (p.o.) with α-asarone (3 mg/kg) significantly inhibited paw oedema by 62.12 and 72.22%, 2 and 4 h post LPS injection, respectively. Alpha-asarone (3 mg/kg, p.o.) attenuated the inflammatory infiltrate 1, 3 and 6 h after LPS injection. Furthermore, α-asarone (3 mg/kg, p.o.) suppressed iNOS expression and TNF-α production, 6 and 1 h after inflammatory stimulus, respectively. Alpha-asarone (3, 10 and 30 mg/kg, p.o.) inhibited both phases of formalin-induced licking. In the hot-plate test, α-asarone (10 and 30 mg/kg, p.o.) increased the latency to response 3 and 5 h post LPS stimulus. Caffeine and naloxone abolished the central anti-nociceptive effect of α-asarone (neurogenic phase of formalin and hot plate tests), suggesting the participation of the adenosinergic and opioidergic systems. Furthermore, naloxone reversed the peripheral activity of α-asarone (inflammatory phase of formalin test), indicating the possible involvement of the opioidergic pathway. In the rota-rod test, α-asarone did not change motor coordination. These findings suggest that α-asarone has anti-inflammatory, peripheral and central anti-nociceptive effects and could represent a promising agent for future research.

Are the Statins promising antifungal agents against invasive candidiasis?

The medical importance of intra-abdominal candidiasis (IAC) contrasts with the limited number of pharmacological treatment options available and the increasing rate of resistance to antifungal drugs. Thus, the repositioning of compounds in clinical use can contribute to the broadening of treatment possibilities for this infection. Statins, a class of drugs used to reduce cardiovascular event risk, have shown antiparasitic, antibacterial, and antiviral activities; however, their antifungal effects remain poorly studied. In this context, the present study aimed to elucidate the antifungal potential of six statins in vitro, as well as to evaluate the therapeutic use of fluvastatin in a mouse model of IAC. The biological effects of statins were evaluated against Candida spp., through the determination of the minimum inhibitory concentration (MIC). For the statins that showed activity, the fungicidal concentration, toxicity/selectivity, synergism with azoles and polyenes, phenotypic effects, and activity against virulence factors were also determined. Atorvastatin, rosuvastatin and fluvastatin were highly active, especially against C. albicans (MIC < 1-128 µg.mL-1) and C. glabrata (MIC 32-64 µg.mL-1). Fluvastatin and atorvastatin were selective for C. albicans in baby hamster kidney (BHK) cells. Moreover, all active statins in the antifungal assay showed high selectivity for fungal cells over bacteria. The combination of atorvastatin, rosuvastatin, and fluvastatin with azoles was associated with a synergistic effect. Active statins do not act on the fungal membrane or wall, but instead stimulate farnesol-dependent pathogenicity factors such as yeast-to-hyphal transition and biofilm generation. Fluvastatin treatment was evaluated in a mouse model of IAC, showing stimulation of the extra-hepatic dissemination of C. albicans but improvements in renal, splenic, and hepatic histological aspects. In conclusion, statins have potent antifungal activity in vitro, but the therapeutic effect in vivo is restricted to their anti-inflammatory activity.

Achyrocline alata potentiates repair of skin full thickness excision in mice.

Plants of the Asteraceae family have been traditionally used as medicinal plants. The species Achyrocline satureioides and Achyrocline alata present anti-inflammatory properties and great chemical similarity. However, no study has been performed to evaluate the influence of these plants on skin wound healing in vivo. Here, we have assessed the effect of these plants extracts on skin wound healing in mice. Mice were randomly arranged into three groups (n = 10), an injury was performed on the dorsal area of the animals, which received the following topical treatment: group 1, control (ointment base); group 2, A. satureioides extract; group 3, A. alata extract. The solution for treatment was prepared as 10% (w/w) concentration. The wound area was measured on days 1, 4, 9, 15 and 17 after treatment and tissues of local lesion were collected on the ninth day for histological analysis. A. alata was more effective since it induced earlier wound closure associated with decreasing initial inflammatory response, faster reepithelialization and collagen remodeling. A. satureioides improved the collagen renovation, but induced slower closure, which may be due to different concentrations of phenolic compounds among the plants here studied. Both plants did not alter the ultrastructural characteristics of cells in the healing process. In conclusion, our findings suggest the potent wound healing capacity of A. alata extracts, as demonstrated by more efficient and faster induction of wound closure. We believe this plant is a potential wound healing treatment for humans and further studies are necessary to assess its clinical practice.

Evaluation of healing wound and genotoxicity potentials from extracts hydroalcoholic of Plantago major and Siparuna guianensis.

Despite the large use of the Plantago major and Siparuna guianensis in traditional medicine, there are no studies demonstrating the effectiveness from extracts of these plants in the healing process by the present methodology. This study reported the effects and toxicity of the P. major and S. guianensis extracts in the wound healing compared with a commercial product used in Brazil by macroscopic and microscopic analysis. Following injury in cervical dorsal area of the mice, the extract from P. major and S. guianensis and ointment was applied after an injury in cervical dorsal area of the mice. Wound healing rates were calculated at 4, 9, 15 and 21 d after the wounding, and tissues were obtained on the ninth day for histological analysis. Moreover, mutagenic assay of extracts was performed. Mutagenicity studies carried out with plant extracts showed not mutagenic with or without metabolic activations. Reduction of the wound area occurred earlier in mice treated with P. major and control treatment. On the 15th day, the complete wound closure occurred in P. major-treated wounds. Throughout ointment and S. guianensis treatment it was not observed the wound closured. Microscopic analyses of the wound, on the ninth day, showed the more efficient formation of the neoepithelium and skin appendages in animals treated with S. guianensis and P. major, while ointment treatment presented no re-epithelialization and absent skin appendages in wound. Thus, P. major extract showed good effects on wound healing processes rendering it a promising candidate for the treatment of wounds what also justified its traditional usage in wound treatment.