The ethanolic extract of Terminalia argentea Mart. & Zucc. bark reduces the inflammation through the modulation of cytokines and nitric oxide mediated by the downregulation of NF-κB.

ETHNOPHARMACOLOGICAL RELEVANCE: Terminalia argentea Mart. & Zucc. (Combretaceae), popularly known as "capitão do campo", is native from the Brazilian cerrado, which is used in folk medicine to treat inflammatory diseases. AIM OF THE STUDY: We aimed to investigate the anti-inflammatory effects, toxicity and mechanisms of action regarding the use of the hydroalcoholic extract of T. argentea bark. MATERIALS AND METHODS: Toxicity was determinate in vitro using the macrophage lineage J774.1 without LPS. Cells were treated with 0.5; 2; 8; 32 and 125 µg/mL of the plant extract. Cell viability was assessed by MTT colorimetric assay. The production of nitrite and cytokines was also determined in the supernatants. A NF-κB reporter assay using RAW macrophages was employed to elucidate the impact of the plant extract on the expression of such molecule. In mice, toxicity was assessed by orally given an intermediate to high concentration of the plant extract on a single dose (1000 or 5000 mg/kg) or low and intermediate doses (300 or 1000 mg/kg) twice daily for 14 days. Blood samples were collected for biochemical analysis. The anti-inflammatory activity was assessed using the air-pouch model with or without pre-inoculation with the inflammatory stimuli LPS (0.5 µg/mL), followed by treatment with plant extract at 5, 60 or 300 mg/kg administered in the air pouch (subcutaneous injection). After 4 h, mice were euthanized and the air pouches washed with 2 mL heparinized PBS (10 IU/mL). Then, the local production in the air pouch wash of cytokines, total proteins and leukocytes was assessed. RESULTS: No signals of toxicity were observed either in cells or mice. Regardless the concentration used in vitro, the extract exhibited a significant anti-inflammatory activity, as perceived by the reduction of the inflammatory cytokines IL-1ß, TNF-α and IL-6 and nitrites on cell supernatants. This was concomitant with a downregulation in NF-κB and elevated levels of IL-10. In mice, similar effects were observed, especially when the plant extract was given at 300 mg/kg, inhibiting the release of IL-1ß, TNF-α, IL-6 and proteins, as well as increasing the release of IL-10. CONCLUSIONS: Altogether, our results demonstrated that the hydroalcoholic extract of T. argentea bark has anti-inflammatory activity without inducing toxicity in cells or living animals. This activity seems to be chiefly influenced by a downregulation in NF-κB, inflammatory cytokines and production of nitrite along with augmented concentration of IL-10.

Eicosanoid pathway on host resistance and inflammation during Mycobacterium tuberculosis infection is comprised by LTB4 reduction but not PGE2 increment.

The functions of eicosanoids, a family of potent biologically active lipid mediators, are not restricted to inflammatory responses and they also act as mediators of the pathogenesis process. However, the role of eicosanoids in tuberculosis remains controversial. To investigate the specific role of LTB4 in Mycobacterium tuberculosis (Mtb) infection, we used 5-lipoxygenase-deficient (5-LO-/-) mice and WT (sv129) mice inoculated intranasally with LTB4 (encapsulated in PLGA microspheres). We showed that deficiency of the 5-LO pathway was related to resistance to Mtb infection. LTB4 inoculation increased susceptibility to Mtb in 5-LO-/- mice but not in WT mice, resulting in worsening of lung inflammation and tissue damage. In infected WT mice, most supplementary LTB4 was metabolized to the inactive form 12-oxo-LTB4 in the lung. A high amount of PGE2 was detected during Mtb infection, and pharmacological inhibition of COX-2 induced a significant reduction of bacterial load and an improved innate immune response in the lungs, independently of baseline LTB4 levels. COX-2 inhibition with celecoxib significantly reduced PGE2 levels, enhanced IFN-γ production and NO release, and increased macrophage phagocytosis of Mtb. The results suggest that a balance between PGE2/LTB4 is essential in the pathogenesis process of tuberculosis to prevent severe inflammation. Moreover, optimal levels of PGE2 are required to induce an effective innate response in the early phase of Mtb infection. Thus, pharmacological modulation of eicosanoid production may provide an important host-directed therapy in tuberculosis.

Anti-inflammatory effects of Lafoensia pacari and ellagic acid in a murine model of asthma.

We have shown that the ethanolic extract of Lafoensia pacari inhibits eosinophilic inflammation induced by Toxocara canis infection, and that ellagic acid is the secondary metabolite responsible for the anti-eosinophilic activity seen in a model of beta-glucan peritonitis. In the present study, we investigated the preventive and curative effects of L. pacari extract and ellagic acid on allergic lung inflammation using a murine model of ovalbumin-induced asthma. In bronchoalveolar lavage fluid, preventive (22-day) treatment with L. pacari (200 mg/kg) and ellagic acid (10 mg/kg) inhibited neutrophil counts (by 75% and 57%) and eosinophil counts (by 78% and 68%). L. pacari reduced IL-4 and IL-13 levels (by 67% and 73%), whereas ellagic acid reduced IL-4, IL-5 and IL-13 (by 67%, 88% and 85%). To investigate curative anti-inflammatory effects, we treated mice daily with ellagic acid (0.1, 1, or 10 mg/kg), also treating selected mice with L. pacari (200 mg/kg) from day 18 to day 22. The highest ellagic acid dose reduced neutrophil and eosinophil numbers (by 59% and 82%), inhibited IL-4, IL-5, and IL-13 (by 62%, 61%, and 49%). Neither L. pacari nor ellagic acid suppressed ovalbumin-induced airway hyperresponsiveness or cysteinyl leukotriene synthesis in lung homogenates. In mice treated with ellagic acid (10 mg/kg) or L. pacari (200 mg/kg) at 10 min after the second ovalbumin challenge, eosinophil numbers were 53% and 69% lower, respectively. Cytokine levels were unaffected by this treatment. L. pacari and ellagic acid are effective eosinophilic inflammation suppressors, suggesting a potential for treating allergies.

Anti-asthmatic potential of a D-galactose-binding lectin from Synadenium carinatum latex.

Extracts from the plant Synadenium carinatum latex are widely and indiscriminately used in popular medicine to treat a great number of inflammatory disorders and although the mechanisms underlying these effects remain undefined, the lectin isolated from S. carinatum latex (ScLL) is thought to be in part responsible for these anti-inflammatory effects. In order to elucidate possible immunoregulatory activities of ScLL, we investigated the effects of ScLL administration in models of acute and chronic inflammation. Oral administration of ScLL significantly inhibited neutrophil and eosinophil extravasation in models of acute and chronic inflammation and reduced eosinophil and mononuclear blood counts during chronic inflammation. ScLL administration reduced IL(interleukin)-4 and IL-5 levels but increased interferon-gamma and IL-10 in an asthma inflammatory model, which suggested that it might induce a TH2 to TH1 shift in the adaptive immune response. ScLL also inhibited IkappaBalpha degradation, a negative regulator of proinflammatory NF-kappaB. Taken together, these results provide the first description of a single factor isolated from S. carinatum latex extract with immunoregulatory functions and suggest that ScLL may be useful in the treatment of allergic inflammatory disorders.

Anti-inflammatory, analgesic and anti-oedematous effects of Lafoensia pacari extract and ellagic acid.

Lafoensia pacari St. Hil. (Lythraceae) is used in traditional medicine to treat inflammation. Previously, we demonstrated the anti-inflammatory effect that the ethanolic extract of L. pacari has in Toxocara canis infection (a model of systemic eosinophilia). In this study, we tested the anti-inflammatory activity of the same L. pacari extract in mice injected intraperitoneally with beta-glucan present in fraction 1 (F1) of the Histoplasma capsulatum cell wall (a model of acute eosinophilic inflammation). We also determined the anti-oedematous, analgesic and anti-pyretic effects of L. pacari extract in carrageenan-induced paw oedema, acetic acid writhing and LPS-induced fever, respectively. L. pacari extract significantly inhibited leucocyte recruitment into the peritoneal cavity induced by beta-glucan. In addition, the L. pacari extract presented significant analgesic, anti-oedematous and anti-pyretic effects. Bioassay-guided fractionation of the L. pacari extract in the F1 model led us to identify ellagic acid. As did the extract, ellagic acid presented anti-inflammatory, anti-oedematous and analgesic effects. However, ellagic acid had no anti-pyretic effect, suggesting that other compounds present in the plant stem are responsible for this effect. Nevertheless, our results demonstrate potential therapeutic effects of L. pacari extract and ellagic acid, providing new prospects for the development of drugs to treat pain, oedema and inflammation.