Sambucus australis Modulates Inflammatory Response via Inhibition of Nuclear Factor Kappa B (NF-kB) in vitro.

Medicinal plants have long been used as an alternative to traditional drugs for the treatment of inflammatory conditions due to the classical side effects and restricted access of various commercially available drugs, such as steroids (GCs) and nonsteroidal anti-inflammatory drugs (NSAIDs). Sambucus australis is a Brazilian herb that is commonly used to treat inflammatory diseases; however, few studies have examined the use of this species in the treatment of inflammatory conditions. The present study aims to evaluate the potential anti-inflammatory activity of S. australis in vitro. We established spleen cell cultures stimulated with pokeweed mitogen (PWM) to evaluate the production of proinflammatory cytokines, such as IL-4, IL-5, IFN-y, and IL-10 (by ELISA), and the expression of the transcription factor NF-kB (by RT-PCR). In addition, we evaluated the levels of nitric oxide in macrophage cultures and the membrane-stabilizing activity of S. australis methanolic extract (EMSA). Treatment with EMSA at concentrations of 100, 50, 25 and 12.5 µg/ml significantly decreased IL-4 (p<0.001) and IL-5 (p<0.001) levels. Treatment with 100 µg/ml EMSA reduced IFN-у (p<0.001) levels. Moreover, at 100 mg/ml, EMSA also increased IL-10 production and reduced NF-kB expression (p<0.01). In macrophage cultures stimulated with LPS, EMSA decreased nitric oxide levels (p<0.001) at all concentrations tested (100, 50, 25 and 12.5 µg/ml). Additionally, EMSA had a protective effect in the erythrocyte membrane stabilization assay. Taken together, these results suggest that S. australis has anti-inflammatory potential in vitro, characterized by the reduction of both inflammatory cytokines and the expression of NF-kB along with the up-regulation of IL-10.

Solanum paniculatum L. decreases levels of inflammatory cytokines by reducing NFKB, TBET and GATA3 gene expression in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: Solanum paniculatum L., popularly known as jurubeba, is a common subtropical plant from Brazil, Paraguay, Bolivia and Argentina, that is used in folk medicine for the treatment of anemia, gastrointestinal disorders and inflammatory conditions in general. In addition to that, an ethnobotanical survey in "Todos os Santos" Bay have pointed out S. paniculatum as an herb to treat asthma. Previous publications have shown that S. paniculatum possesses antibiotic, antioxidant and modulatory effects on gastric acid secretion; however, its anti-inflammatory potential remains unexplored. AIM OF THE STUDY: Herein, we analyzed the S. paniculatum fruits hexane extract (SpE) for the presence of stigmasterol and ß-sitosterol and investigated the anti-inflammatory effect of SpE in vitro. MATERIALS AND METHODS: SpE was subjected to high-performance liquid chromatography (HPLC) for standardization and quantification of stigmasterol and ß-sitosterol. Spleen cells from BALB/c mice were cultivated and stimulated with pokeweed mitogen and also exposed to 15, 30 and 60µg/mL of SpE. Following treatment, levels of IFN-γ, IL-4 and IL-10 in the culture supernatants were assessed by ELISA. We also evaluated nitric oxide (NO) production by murine LPS-stimulated peritoneal macrophages using the Griess technique. In addition, the ability of SpE to stabilize membranes was assessed using a model of hemolysis induced by heat on murine erythrocytes. Gene expression of Th1-cell-specific Tbx21 transcription factor (TBET), zinc-finger transcription factor-3 (GATA3), and nuclear factor-κB (NFKB) in murine spleen cells were assessed by quantitative Polymerase Chain Reaction (qRT-PCR). RESULTS: SpE at 15, 30 and 60µg/mL significantly attenuated cell proliferation, decreased IL-4 release, reduced NO production and improved erythrocyte membrane stabilization in a concentration-dependent manner. SpE was also able to decrease the release of IFN-γ without altering IL-10 levels. The mechanism whereby SpE decreased inflammatory markers may be related to the reduction of NFKB, TBET and GATA3 gene expression. CONCLUSIONS: This study is the first to test the anti-inflammatory action of S. paniculatum. Herein, we provided evidence for the popular use of S. paniculatum in inflammatory conditions. Additional studies must be conducted to further explore the anti-inflammatory potential of SpE and to elucidate possible clinical applications.

Protoflavanones from the Wood Stem of Salvertia convallariodora.

Phytochemical-analysis of the ethyl acetate extract of stem wood of Salvertia convallariodora A. St.-Hil. (Vochysiaceae), a Brazilian Cerrado species, led to the isolation and full characterization of three new non-aromatic B-ring flavanones (1-3) as well as the terpene mixture of sericic acid (4), 24-hydroxytormentic acid (5); 24-hydroxytormentic acid glucosyl ester (6), and sericoside (7), all identified for the first time from S. convallariodora. The structures of the new flavanones (1-3) were established from IR, LC-PDA-qTOF-MS, and NMR spectral data, including 2D NMR experiments.

Toxicological, Antidiarrheal and Spasmolytic Activities of Solanum paniculatum.

Solanum paniculatum is popularly known as "jurubeba-verdadeira". In folk medicine, its roots, stems, and leaves are used as tonics, anti-inflammatories, carminatives, diuretics, and for gastrointestinal disorders. This species is listed in the Brazilian Pharmacopoeia and belongs to the "Relação Nacional de Plantas Medicinais de Interesse ao SUS". Based on folk medicine data of the Solanum genus, we decided to investigate whether the crude ethanol extract from S. paniculatum aerial parts presents toxicological, antidiarrheal, and spasmolytic activities. The crude ethanol extract from S. paniculatum aerial parts did not produce in vitro or in vivo toxicity and showed dose-dependent antidiarrheal activity, inhibiting equipotently both the defecation frequency (ED50 = 340.3 ± 35.1 mg/kg) and liquid stool formation (ED50 = 370.1 ± 19.4 mg/kg) in mice. Conversely, the crude ethanol extract from S. paniculatum aerial parts did not inhibit normal intestinal transit, even though it has shown a dose-dependent reduction of both the castor oil-induced intestinal transit (Emax = 36.9 ± 1.3 %, ED50 = 242.0 ± 8.6 mg/kg) and intestinal fluid content (Emax = 74.8 ± 2.4 %, ED50 = 328.9 ± 15.9 mg/kg). Additionally, the crude ethanol extract from S. paniculatum aerial parts was approximately 2-fold more potent in antagonizing the phasic contractions induced with histamine (IC50 = 63.7 ± 3.5 µg/mL) than carbachol 10(-6) M (IC50 = 129.3 ± 14.1 µg/mL). Therefore, we concluded that the crude ethanol extract from S. paniculatum aerial parts presents antidiarrheal activity in mice related to the inhibition of small intestinal motility and secretion as well as nonselective spasmolytic activity on the guinea pig ileum.

Antileishmanial Phenylpropanoids from the Leaves of Hyptis pectinata (L.) Poit.

Hyptis pectinata, popularly known in Brazil as "sambacaitá" or "canudinho," is an aromatic shrub largely grown in the northeast of Brazil. The leaves and bark are used in an infusion for the treatment of throat and skin inflammations, bacterial infections, pain, and cancer. Analogues of rosmarinic acid and flavonoids were obtained from the leaves of Hyptis pectinata and consisted of two new compounds, sambacaitaric acid (1) and 3-O-methyl-sambacaitaric acid (2), and nine known compounds, rosmarinic acid (3), 3-O-methyl-rosmarinic acid (4), ethyl caffeate (5), nepetoidin A (6), nepetoidin B (7), cirsiliol (8), circimaritin (9), 7-O-methylluteolin (10), and genkwanin (11). The structures of these compounds were determined by spectroscopic methods. Compounds 1-5, and 7 were evaluated in vitro against the promastigote form of L. braziliensis, and the ethanol extract. The hexane, ethyl acetate, and methanol-water fractions were also evaluated. The EtOH extract, the hexane extract, EtOAc, MeOH:H2O fractions; and compounds 1, 2 and 4 exhibited antileishmanial activity, and compound 1 was as potent as pentamidine. In contrast, compounds 3, 5, and 7 did not present activity against the promastigote form of L. braziliensis below 100 µM. To our knowledge, compounds 1 and 2 are being described for the first time.