Inhibition of HIF-1α through Suppression of NF-κB Activation by Compounds Isolated from Senecio graveolens

One of the characteristics of cancer is that the lack of oxygen in the cancer cells triggers changes in their gene expression. This hypoxia activates hypoxia-inducible factor 1-alpha and this in turn sets in motion the whole family of important angiogenic genes for the tumour. Hypoxia-inducible factor 1-alpha therefore increases the density and vascular permeability within the tumours, facilitating their rapid growth and, later, the metastasis. Senecio graveolens is a South American medicinal plant commonly used for mountain sickness (lack of adaptation of the organism to hypoxia). Additionally, pharmacological studies showed that its alcoholic extracts have cytotoxic properties. This research aimed to perform a guided phytochemical study of S. graveolens to identify compounds capable of inhibiting hypoxia-inducible factor 1-alpha through suppression of nuclear factor kappa-light-chain-enhancer of activated B cell activation. The isolation led to the characterisation of phanurane (1), damsine (2), and scoparone (3), first reported in the S. graveolens species. Phanurane (1) showed inhibitory activity of hypoxia-inducible factor 1-alpha on the cancer cell lines U-373 MG (IC50 = 20.66 ± 0.04 μM), A549 (IC50 =25.80 ± 0.04 μM), Hep G2 (IC50 =29.21 ± 0.03 μM), and Caco-2 (IC50 =38.58 ± 0.02 μM). Damsine (2) hypoxia-inducible factor 1-alpha displayed inhibitory activity of hypoxiainducible factor 1-alpha on the cancer cell lines U-373 MG (IC50 =2.29 ± 0.07 μM), A549 (IC50 =4.13 ± 0.04 μM), Hep G2 (IC50 =6.40 ± 0.03 μM), and Caco-2 (IC50 =9.80 ± 0.04 μM). Finally, scoparone (3) displayed inhibitory activity of y poxiainducible factor 1-alpha on the cancer cell lines U-373 MG (IC50 =15.22±0.01μM), A549 (IC50 =17.47±0.02μM), Hep G2 (IC50=18.26±0.06μM), and Caco-2 (IC50=19.75±0.04μM). In addition, phanurane (1) displayed inhibitory activity over nuclear factor kappa-light-chain-enhancer of activated B cells on cancer cell lines U-373 MG (IC50 =7.13 ± 0.03 μM), A549 (IC50 = 8.64 ± 0.03 μM), Hep G2 (IC50 = 8.87 ± 0.04 μM), and Caco-2 (IC50 =15.11 ± 0.01 μM). Likewise, damsine (2) showed inhibitory activity over nuclear factor kappa-light-chainenhancer of activated B cells on cancer cell lines U-373 MG (IC50 =2.28 ± 0.01 μM), A549 (IC50 =3.79 ± 0.02 μM), Hep G2 (IC50 = 3.98 ± 0.05 μM), and Caco-2 (IC50 = 6.41 ± 0.02 μM). Lastly, scoparone (3) displayed inhibitory activity of nuclear factor kappa-light-chain-enhancer of activated B cells on cancer cell lines U-373 MG (IC50 = 3.62 ± 0.06 μM), A549 (IC50 = 4.48 ± 0.03 μM), Hep G2 (IC50 = 5.25 ± 0.01 μM), and Caco-2 (IC50 =11.90 ± 0.02 μM). This study corroborates the cytotoxic activity of the isolated compounds through the inhibition of hypoxia-inducible factor 1-alpha as well as its modulator nuclear factor kappa-light-chain-enhancer of activated B cellsThis work was supported by the National Herbarium of Bolivia, the Fundación de la Universidad Autónoma de Madrid (FUAM

Anti-inflammatory Potential of Macamides Isolated from Yellow Tubers of Mashua (Tropaeolum Tuberosum)

AbstractAlthough Tropaeolum tuberosum tubers have been consumed cooked as a folk remedy for the treatment of skin, lungs, liver and kidneys diseases, these uses have very limited scientific basis. Therefore, this article develops a phytochemical analysis of the yellow tubers of T. tuberosum with the objective to assess whether the isolated compounds have anti-inflammatory potential in the CCD-1109Sk, MRC-5 and RWPE-1 cell lines. We performed an extraction of T. tuberosum tubers using different organic solvents, followed by a bioguided chromatographic separation. Four macamides were identified by LC/MS techniques, but only N-benzyllinoleamide (1) and N-benzyloleamide (2) were isolated and elucidated by NMR/MS techniques, given that they were present in a larger proportion in the tubers. The anti-inflammatory potential of macamides was evaluated by the inhibition of NF-κB and STAT3 activation. Both compounds displayed inhibition of NF-κB activation with IC50 values of 2.28±0.54 µM; 3.66±0.34 µM and 4.48±0.29 µM for compound (1) and 6.50±0.75 µM; 7.74±0.19 µM and 8.37 ±0.09 µM for compound (2) in CCD-1109Sk, MRC-5 and RWPE-1 cell lines, respectively. Moreover, both compounds inhibited the STAT3 activation with IC50 of 0.61±0.76 µM; 1.24±0.05 µM and 2.10±0.12 µM for compound (1) and 5.49±0.31 µM; 7.73 ±0.94 µM and 7.79±0.30 µM for compound (2). Therefore, isolated macamides of T. tuberosum tubers showed promising anti-inflammatory effects, suggesting a possible beneficial use to combat inflammatory processes of skin, lung and prostate

Anti-inflammatory and anti-arthritic activities of glycosylated flavonoids from syzygium jambos in edematogenic agent-induced paw edema in mice

Two glycosylated flavonoids, the quercetin-3-O-β-D-xylofuranosyl-(1 → 2)-α-l-rhamnopyranoside and myricetin-3-O-β-d-xylofuranosyl-(1 → 2)-α-l-rhamnopyranoside, were isolated from the CH2Cl2/MeOH fraction of Syzygium jambos (L.) Alston, Myrtaceae. The structures of these compounds were elucidated by spectroscopic means. The cytotoxicity of the compounds was evaluated against the RAW 264.7 cell lines by the lactate dehydrogenase assay. All analyzed compounds were less cytotoxic than the positive control (actinomycin D, CC50 = 0.008 μM). The anti-inflammatory and anti-arthritic activities were evaluated by measuring inflammatory parameters in murine models. The two glycosylated flavonoids inhibited the production of tumor necrosis factor-α in RAW 264.7 cell line with IC50 of 1.68 and 1.11 μM, respectively. In addition, all flavonoids decreased the levels of tumor necrosis factor-α, C-reactive protein, and fibrinogen at a dose of 5 mg/kg in murine modelsThis work was supported by the National Herbarium of Bolivia and the Fundación de la Universidad Autónoma de Madrid (FUAM

Hydroalcoholic extract of Tagetes minuta L. inhibits inflammatory bowel disease through the activity of pheophytins on the NF-κB signalling pathway

Ethno-pharmacological relevance: Species of the genus Tagetes are well known for their anti-inflammatory properties. Tagetes minuta “Huacatay” is an endemic species of South America that has been used in traditional medicine since ancient times as a remedy for stomach and intestinal discomfort. Aim of the study: The aim of this study is to investigate the anti-inflammatory activity of the aqueous and hydroalcoholic extracts of the Huacatay, identifying the compounds responsible for this activity. Materials and methods: Anti-inflammatory activity of the compounds, fractions and extracts was evaluated in Hs 746T (stomach), HIEC-6 (intestine) and THP-1 (monocytes peripheral blood) cells by measuring their inhibitory capacity against the NF-κB production. Results: Aqueous and hydroalcoholic extracts of Tagetes minuta displayed anti-inflammatory activity in vitro, the hydroalcoholic extract being the most active (IC50 between 59.72 and 66.42 μg/mL) in all cell lines. Bio-guided hydroalcoholic extract fractionation led to the isolation and characterisation of two pheophytins, pheophytin a (1) and 132-hydroxy pheophytin a (2). Both compounds inhibited the production of NF-κB with IC50 values in the low micromolar range, with an IC50 between 12.32 and 16.01 μM for compound 1 and 7.91–9.87 μM for compound 2. Conclusions: The two pheophytins isolated in this study inhibit the production of NF-κB, thus showing that the traditional anti-inflammatory use of Tagetes minuta can be proved through pharmacological assays. This contributes to understanding the anti-inflammatory activity of the Huacatay extracts and their use in the treatment of stomach and intestinal discomfortThis work was supported by the National Herbarium of Bolivia and the Fundación de la Universidad Autónoma de Madrid (FUAM

Synthesis and biological screening of a library of macamides as TNF-α inhibitors

Thirty-five macamide analogues were synthesised by modifying the initial molecular structure. The resulting structures were confirmed using NMR and MS. Cytotoxicity and the anti-inflammatory activity of these synthetic macamides were evaluated in the THP-1 cell line. Preliminary biological evaluation indicated that most of these synthetic macamides did not present cytotoxicity (MTT assay) in the tested cell line with respect to the control (actinomycin D). Regarding the anti-inflammatory activity, several analogues had a greater potential for inhibition of TNF-α than natural macamides. Synthetic macamide 4a was the most active (IC50 = 0.009 ± 0.001 μM) compared to the C87 (control). Through looking at the link between the chemical structure and the activity, our study proves that changes made to natural macamides at the level of the alkyl chain, the benzyl position, the amide bond, and the addition of two methyl groups to the aromatic ring (meta position) lead us to obtaining new macamides with greater anti-inflammatory activityThis work was supported by the Fundación de la Universidad Autónoma de Madrid (FUAM

Observaciones de intranquilidad en el volcán Sabancaya iniciada el 22 de febrero de 2013

El 22 de Febrero 2013 en un lapso de solo 95 minutos han ocurrido 3 sismos de magnitudes 4.6, 5.2 y 5.0 ML en inmediaciones del volcán Sabancaya (15.78° S, 71.85°W, 5976 m, Fig 1), en el sur del Perú, causando destrucción de 18 viviendas en Maca, poblado situado en el valle del Colca, a 20 km al NE del cráter

Evaluación del riesgo volcánico en el sur del Perú, situación de la vigilancia actual y requerimientos de monitoreo en el futuro. Informe técnico

En el presente trabajo se efectúa una estimación semicuantitativa, orientada a la evaluación objetiva del riesgo volcánico que representa la actividad volcánica a nivel nacional. Este sistema es una adaptación del modelo utilizado por el Servicio Geológico de los Estados Unidos (USGS) denominado “National Volcano Early Warning System” (NVEWS) desarrollado por Ewert et al. (2005). En todas las etapas de análisis (factores de peligro, y de factores de exposición) para la determinación del nivel de riesgo volcánico, así como la compilación de la instrumentación actualmente instalada sobre los volcanes del sur del Perú, se ha trabajado conjunta y coordinadamente entre especialistas del Observatorio Vulcanológico del Sur (OVS), Observatorio Vulcanológico de INGEMMET (OVI) y del Observatorio Geofísico de la Universidad Nacional de San Agustín (UNSA). Con este trabajo se busca clasificar a los 16 volcanes activos y potencialmente activos de nuestro país, en grupos de nivel de Riesgo Volcánico Relativo. Por otro lado, en este trabajo se establece también el grado o nivel óptimo de monitoreo y vigilancia actual para cada uno de los volcanes según su respectivo nivel de riesgo, de modo que posteriormente se hace una comparación entre el nivel óptimo y el nivel de vigilancia actualmente alcanzado. Se determina así cuánto falta aún por avanzar en la implementación de instrumental especializado para alcanzar una adecuada vigilancia de la actividad volcánica en el Perú

Ensayos sobre aplicación de la Teoría del Estado en las algunas culturas del Perú antiguo

Investigations of State Theory on the cultures of ancient Peru.Capítulos de libro con investigaciones de Teoría del Estado sobre las culturas del Perú antiguo, realizado por docentes y estudiantes de la Escuela Profesional de Derecho de la Universidad Nacional del Altiplano de Puno.      

Ensayos sobre aplicación de la Teoría del Estado en las algunas culturas del Perú antiguo

Investigations of State Theory on the cultures of ancient Peru.Capítulos de libro con investigaciones de Teoría del Estado sobre las culturas del Perú antiguo, realizado por docentes y estudiantes de la Escuela Profesional de Derecho de la Universidad Nacional del Altiplano de Puno.      

Ensayos sobre aplicación de la Teoría del Estado en las algunas culturas del Perú antiguo

Investigations of State Theory on the cultures of ancient Peru.Capítulos de libro con investigaciones de Teoría del Estado sobre las culturas del Perú antiguo, realizado por docentes y estudiantes de la Escuela Profesional de Derecho de la Universidad Nacional del Altiplano de Puno.