Baccharis dracunculifolia DC (Asteraceae) Root Extract and Its Triterpene Baccharis Oxide Display Topical Anti-Inflammatory Effects on Different Mice Ear Edema Models.

B. dracunculifolia is popularly used to treat skin diseases. This work aimed to evaluate the topical anti-inflammatory properties of B. dracunculifolia root extract (BdR) and its major compound baccharis oxide (BOx) on mice ear edema models. BdR was analyzed by GC-MS, and BOx was isolated by chromatographic fractionation. Topical anti-inflammatory activities were determined by using the croton oil, capsaicin, histamine, and phenol-induced mouse ear edema models. N-acetyl-ß-D- glucosaminidase (NAG) and myeloperoxidase (MPO) activities, as well as NO dosage and histopathological analyses, were also evaluated. Phytochemical analysis of BdR showed BOx as one of the major constituents. BdR and BOx (both at 0.1, 0.5, and 1.0 mg/ear) significantly reduced croton oil, histamine, and phenol-induced ear edema, while only BOx was effective in reducing capsaicin-induced edema. MPO and NAG activities, as well as NO production, were significantly inhibited by BdR and BOx. Histopathological analysis confirmed the topical anti-inflammatory properties of BdR and BOx. Our findings showed that BdR and BOx demonstrated significant topical anti-inflammatory effects in mouse ear edema induced by different agents, suggesting their possible application on skin inflammatory diseases.

Vernonia polyanthes Less. (Asteraceae Bercht. & Presl), a Natural Source of Bioactive Compounds with Antibiotic Effect against Multidrug-Resistant Staphylococcus aureus.

Vernonia polyanthes is a medicinal plant used to treat many disorders, including infectious diseases. This study investigated the chemical constituents and the antibacterial activity of V. polyanthes leaf rinse extract (Vp-LRE). The chemical characterization of Vp-LRE was established using ultra-high performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UHPLC/Q-TOF-MS), and glaucolide A was identified through 1H and 13C nuclear magnetic resonance (NMR) and mass fragmentation. The cytotoxicity was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT). The antibacterial activity was assessed by minimal inhibitory concentration and minimal bactericidal concentration. Interactions between ligands and beta-lactamase were evaluated via molecular docking. UHPLC/Q-TOF-MS detected acacetin, apigenin, chrysoeriol, isorhamnetin, isorhamnetin isomer, kaempferide, 3',4'-dimethoxyluteolin, 3,7-dimethoxy-5,3',4'-trihydroxyflavone, piptocarphin A and glaucolide A. Vp-LRE (30 µg/mL) and glaucolide A (10 and 20 µg/mL) were cytotoxic against RAW 264.7 cells. Glaucolide A was not active, but Vp-LRE inhibited the Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), Escherichia coli, Salmonella Choleraesuis and Typhimurium, with a bacteriostatic effect. The compounds (glaucolide A, 3',4'-dimethoxyluteolin, acacetin and apigenin) were able to interact with beta-lactamase, mainly through hydrogen bonding, with free energy between -6.2 to -7.5 kcal/mol. These results indicate that V. polyanthes is a potential natural source of phytochemicals with a significant antibiotic effect against MRSA strains.

Pharmacological investigation of antioxidant and anti-inflammatory activities of leaves and branches extracts from Plinia cauliflora (Jaboticaba).

ETHNOPHARMACOLOGICAL RELEVANCE: Among all native Brazilian plant species, Plinia cauliflora (DC.) Kausel (Jaboticaba), is well known for producing "superfruits", due to their high phenolic content and antioxidant property. The fruit has astringent characteristics, and it is popularly known for the treatment of diarrhea, rash, and intestinal inflammation. However, there are only a few studies on the use of leaves and branches of this species in the literature, mainly to treat oxidative stress and inflammation. AIM OF THE STUDY: The present study aimed to investigate the antioxidant and anti-inflammatory potential of leaves and branches extracts from P. cauliflora. MATERIAL AND METHODS: The phytochemical analysis of P. cauliflora extracts was performed by the total phenolic, flavonoid, and tannin dosage method. Moreover, the compounds were identified by HPLC-MS-Q-TOF. Antioxidant capacity was determined by DPPH, ß-carotene/linoleic acid system, MDA formation, and phosphomolybdenum assays. In vitro and in vivo anti-inflammatory activities of P. cauliflora were evaluated by the reduction of nitric oxide in the J774A.1 cell line and inhibition of ear edema in mice, respectively. RESULTS: The ethanolic extract of the leaves exhibited greater flavonoid content whereas the ethanolic extract of the branches showed higher tannins content. Twenty-two and seventeen compounds were identified by HPLC-MS-Q-TOF in the leaves and branches, respectively, being tellimagrandin I, castalagin, and valoneic acid dilactone reported for the first time in P. cauliflora. The antioxidant potential of extracts was confirmed through different oxidation pathways from oxidizing radicals, which might be related to the presence of phenolic compounds. For the anti-inflammatory assay, the leaves and branches extracts showed promising results, with a reduction of nitric oxide ear edema inhibition around 95% and 80%, respectively. CONCLUSIONS: Herein, the great biological potential of leaves and branches extracts from P. cauliflora was highlighted. These parts of the plant are underused and poorly reported in the literature, especially for the antioxidant and anti-inflammatory activities.

Potato apyrase reduces granulomatous area and increases presence of multinucleated giant cells in murine schistosomiasis.

Granulomas are inflammatory tissue responses directed to a set of antigens. Trapped Schistosoma mansoni eggs promote productive granulomas in the tissues, and they are the main damage caused by schistosomiasis. Some S. mansoni antigenic proteins may have a direct involvement in the resolution of the granulomatous response. The ATP diphosphohydrolases isoforms of this parasite are immunogenic, expressed in all phases of the parasite life cycle and secreted by eggs and adult worms. Potato apyrase is a vegetable protein that cross-reactive with parasite ATP diphosphohydrolases isoforms. In this study, the vegetable protein was purified, before being inoculated in C57BL/6 mice that were later infected with cercariae. Sixty days after infection, adult worms were recovered, antibodies and cytokines were measured, and morphological granuloma alterations evaluated. Immunization of the animals induced significant levels of IgG and IgG1 antibodies and IFN-γ, IL-10 and IL-5 cytokines, but not IL-13, suggesting that potato apyrase is an immunoregulatory protein. Supporting this hypothesis, it was found that liver damage associated with schistosomiasis was mitigated, reducing the size of the areas affected by granuloma to 35% and increasing the presence of multinucleated giant cells in this environment. In conclusion, potato apyrase was found to be effective immunomodulatory antigen for murine schistosomiasis.

Anti-inflammatory and antinociceptive activity of Siparuna guianensis Aublet, an amazonian plant traditionally used by indigenous communities.

ETHNOPHARMACOLOGICAL RELEVANCE: Siparuna guianensis Aublet leaves, known as negramina, are used by indigenous and local communities in Brazil and other countries in the Americas to treat pain and inflammatory diseases. AIM OF THE STUDY: To characterize the chemical constituents and to evaluate the antioxidant, anti-inflammatory, antinociceptive and locomotor activities of the dichloromethane fraction (DF) of S. guianensis leaves. Also, an acute oral toxicity test was accomplished. MATERIAL AND METHODS: The chemical characterization of DF was performed by ultra-high pressure liquid chromatography (UHPLC) analyses coupled with a high-resolution mass spectrometer. The antioxidant potential of DF was investigated using nitric oxide (NO) and hydroxyl radical (OH) scavenging test. The evaluation study of the anti-inflammatory activity was carried out in vitro by NO measurement in stimulated macrophages and, in vivo, by croton oil-induced ear edema, LPS-induced peritonitis, and zymosan-induced arthritis in mice. Different mechanisms of central and peripheral nociception were stimulated by acetic acid-induced writhing, formalin, and tail-flick tests. Besides that, the open field assay was performed. RESULTS: UHPLC analyses of DF showed the presence of a mixture of glycosylated and methoxylated flavonoids. DF was able to scavenge NO and OH radicals in vitro and showed anti-inflammatory activity by inhibiting NO production in LPS-stimulated murine macrophages. Oral administration of DF considerably inhibited the ear edema after croton oil application and reduced the leukocyte infiltrated in LPS-induced peritonitis. In the inflammatory intra-articular zymosan-induced process, DF showed a significant reduction in the inflammatory area and of the cells in the synovial and connective tissues adjacent to the joint. Also, DF was able to reduce the intra-articular edema. In nociception models, the oral administration of DF considerably inhibited the acetic acid-induced writhings. The formalin test showed that DF attenuated the licking time in both phases, which suggested that DF reduce the nociception by central and peripheral mechanisms. In the tail-flick test, DF showed no activity. Besides that, DF did not affect the animal locomotion, and no acute toxicity was observed. CONCLUSIONS: For the first time, the anti-inflammatory and antinociceptive activities of S. guianensis were reported, supporting its ethnopharmacological uses for some inflammatory diseases and painful conditions.

In vitro antifungal activity of organic compounds derived from amino alcohols against onychomycosis

Abstract Onychomycosis is a fungal infection of the nail caused by high densities of filamentous fungi and yeasts. Treatment for this illness is long-term, and recurrences are frequently detected. This study evaluated in vitro antifungal activities of 12 organic compounds derived from amino alcohols against standard fungal strains, such as Trichophyton rubrum CCT 5507 URM 1666, Trichophyton mentagrophytes ATCC 11481, and Candida albicans ATCC 10231. The antifungal compounds were synthesized from p-hydroxybenzaldehyde (4a-4f) and p-hydroxybenzoic acid (9a-9f). Minimum inhibitory concentrations and minimum fungicidal concentrations were determined according to Clinical and Laboratory Standards Institute protocols M38-A2, M27-A3, and M27-S4. The amine series 4b-4e, mainly 4c and 4e compounds, were effective against filamentous fungi and yeast (MIC from 7.8 to 312 µg/mL). On the other hand, the amide series (9a-9f) did not present inhibitory effect against fungi, except amide 9c, which demonstrated activity only against C. albicans. This allowed us to infer that the presence of amine group and intermediate carbon number (8C-11C) in its aliphatic side chain seems to be important for antifungal activity. Although these compounds present cytotoxic activity on macrophages J774, our results suggest that these aromatic compounds might constitute potential as leader molecules in the development of more effective and less toxic analogs that could have considerable implications for future therapies of onychomycosis.

In vitro antifungal activity of organic compounds derived from amino alcohols against onychomycosis.

Onychomycosis is a fungal infection of the nail caused by high densities of filamentous fungi and yeasts. Treatment for this illness is long-term, and recurrences are frequently detected. This study evaluated in vitro antifungal activities of 12 organic compounds derived from amino alcohols against standard fungal strains, such as Trichophyton rubrum CCT 5507 URM 1666, Trichophyton mentagrophytes ATCC 11481, and Candida albicans ATCC 10231. The antifungal compounds were synthesized from p-hydroxybenzaldehyde (4a-4f) and p-hydroxybenzoic acid (9a-9f). Minimum inhibitory concentrations and minimum fungicidal concentrations were determined according to Clinical and Laboratory Standards Institute protocols M38-A2, M27-A3, and M27-S4. The amine series 4b-4e, mainly 4c and 4e compounds, were effective against filamentous fungi and yeast (MIC from 7.8 to 312µg/mL). On the other hand, the amide series (9a-9f) did not present inhibitory effect against fungi, except amide 9c, which demonstrated activity only against C. albicans. This allowed us to infer that the presence of amine group and intermediate carbon number (8C-11C) in its aliphatic side chain seems to be important for antifungal activity. Although these compounds present cytotoxic activity on macrophages J774, our results suggest that these aromatic compounds might constitute potential as leader molecules in the development of more effective and less toxic analogs that could have considerable implications for future therapies of onychomycosis.

Parthenolide Modulates Immune Response in Cells from C57BL/6 Mice Induced with Experimental Autoimmune Encephalomyelitis.

Multiple sclerosis is a chronic inflammatory and autoimmune disease of the central nervous system that affects more than 2.5 million people worldwide. Experimental autoimmune encephalomyelitis is a murine autoimmune disease used to study multiple sclerosis. Parthenolide, a natural sesquiterpene lactone found in Tanacetum parthenium L., is known for its strong anti-inflammatory activity. Herein, we have investigated the in vitro immunomodulatory effects of parthenolide on cytokine production and nitric oxide in cultured cells from myelin oligodendrocyte glycoprotein 35-55 amino acid peptide mice. Experimental autoimmune encephalomyelitis was induced in C57BL/6 mice with myelin oligodendrocyte glycoprotein 35-55 amino acid peptide, and parthenolide was isolated from T. parthenium. Splenocytes and peritoneal cells were obtained from experimental autoimmune encephalomyelitis-induced mice and incubated with parthenolide (1, 5, and 20 µM). After in vitro treatment with parthenolide, supernatants were collected, and nitric oxide and cytokines were measured. The results suggested that parthenolide may regulate the activity of Th17 and Th1 cells, mainly by decreasing IL-17, TNF-α, and interferon gamma production. This modulation may be related to the lower levels of IL-12p40 and IL-6 after treatment with parthenolide. It was shown, for the first time, that parthenolide presents in vitro immunomodulatory effects on inflammatory mediators produced by cells from experimental autoimmune encephalomyelitis-induced mice.