Investigador Emérito, reconocido por Colciencias desde el 2017. Químico de la Universidad Nacional de Colombia, con una amplia experiencia en la aplicación de técnicas espectroscópicas en investigación de productos naturales, obtenidos a partir de plantas nativas, y aplicación de técnicas en actividad biológica. Actual líder del Grupo de Investigación en Productos Naturales U.D.C.A.
Rubén Darío Torrenegra Guerrero
LÍNEAS DE INVESTIGACIÓN: Fitoquímica; Actividad Biológica de Plantas; Actividad Farmacológica Plantas medicinales; Química microbiológica; Biotransformación.
CATEGORÍA COLCIENCIAS: Emérito
NIVEL DE FORMACIÓN: Pregrado/Universitario
Quantification of two isomeric flavones in rat colon tissue using reverse phase high performance liquid chromatography
Fecha de publicación: 07/01/2017
Background: Antineoplastic activity has been previously shown for two isomeric flavones, 5,7-dihydroxy-3,6,8-trimethoxy flavone (flavone A) and 3,5-dihydroxy-6,7,8-trimethoxy flavone (flavone B), against colon cancer cell lines (Thomas et al. in PLoS ONE 7:e39806, 5). Here, we present modified methods for the extraction and quantification of flavones A and B in rat colon tissue after intravenous dosing via high performance liquid chromatography, from the originally described procedure for extraction and quantification in rat plasma (Whitted et al. in J Chromatogr B Analyt Technol Biomed Life Sci 1001:150-155, 7). Results: Modifications included tissue homogenization (1 g tissue: 2 mL water), filtration of the supernatant with a PVDF membrane, and the use of only one calibration curve to determine the concentration of each flavone in colon tissue. Good separation was achieved and representative equations were linear with r 2 ≥ 0.99 for both flavones. Precision and accuracy for flavone A ranged from 0.88-24.03 and 109-116%. Precision and accuracy for flavone B ranged from 1.62-33.56 and 98-113%. Concentrations of 1639 ± 601 ng/g flavone A and 5975 ± 2480 ng/g of flavone B were detected in rat colon tissue 6 h post dosing. Conclusions: Modifications to the extraction methods for flavone A and flavone B from rat colon tissue had good separation, precision, and accuracy. © 2017 The Author(s).
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Mechanism of Action of Two Flavone Isomers Targeting Cancer Cells with Varying Cell Differentiation Status
Fecha de publicación: 01/11/2015
Apoptosis can be triggered in two different ways, through the intrinsic or the extrinsic pathway. The intrinsic pathway is mediated by the mitochondria via the release of cytochrome C while the extrinsic pathway is prompted by death receptor signals and bypasses the mitochondria. These two pathways are closely related to cell proliferation and survival signaling cascades, which thereby constitute possible targets for cancer therapy. In previous studies we introduced two plant derived isomeric flavonoids, flavone A and flavone B which induce apoptosis in highly tumorigenic cancer cells of the breast, colon, pancreas, and the prostate. Flavone A displayed potent cytotoxic activity against more differentiated carcinomas of the colon (CaCo-2) and the pancreas (Panc28), whereas flavone B cytotoxic action is observed on poorly differentiated carcinomas of the colon (HCT 116) and pancreas (MIA PaCa). Apoptosis is induced by flavone A in better differentiated colon cancer CaCo-2 and pancreatic cancer Panc 28 cells via the intrinsic pathway by the inhibition of the activated forms of extracellular signal-regulated kinase (ERK) and pS6, and subsequent loss of phosphorylation of Bcl-2 associated death promoter (BAD) protein, while apoptosis is triggered by flavone B in poorly differentiated colon cancer HCT 116 and MIA PaCa pancreatic cancer cells through the extrinsic pathway with the concomitant upregulation of the phosphorylated forms of ERK and c-JUN at serine 73. These changes in protein levels ultimately lead to activation of apoptosis, without the involvement of AKT. © 2015 LeJeune et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Antiproliferative activity of extracts of Gnaphalium Gracile H.B.K. against cancer cell lines
Fecha de publicación: 30/08/2018
Ethanol and n-hexane extracts obtained from the leaves and inflorescences of Gnaphalium gracile, were tested at different concentrations to evaluate their antineoplastic activities on pancreatic, colon, and prostate cancer cell lines by examining mitochondrial function. The polar extracts of both, leaves and inflorescences which contain gnaphalin, quercetin, and 3-methoxy quercetin, exhibited cytotoxicity against every cell line tested with EC50 values ranging between 20.23±1.185 µg/mL and 70.71±1.1419 µg/mL. The most remarkable values were observed in pancreatic cancer Panc 28 and androgen-dependent prostate LnCaP cells, with EC50 values of 20.23±1.185 and ˂25µg/mL, and androgen-independent prostate cancer PC-3, colon HCT-116 and pancreatic MIA PaCa cells with values ranging between 28.84±1.1766 and 34.41±1.057 µg/mL. The non-polar extract derived from leaves demonstrated significant cytotoxicity towards colon cancer HCT-116 cells, with an EC50 of 39.46±1.0617 µg/mL. However, the non-polar extract from the inflorescences did not have an appreciable effect on cell proliferation of any of the cell lines tested except for androgen-independent prostate cancer PC-3 cells with an EC50 of 62.05±1.237 µg/mL. The data obtained support the traditional use of G. gracile and suggest the polar extracts from aerial parts, as an interesting source for the development of novel antineoplastic agents. © 2018, SILAE (Italo-Latin American Society of Ethnomedicine). All rights reserved.
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Antiproliferative activity of chloroformic fractions from leaves and inflorescences of Ageratina gracilis
Fecha de publicación: 01/01/2017
To obtain a scientific basis and justification of plant domestication in the use of Ageratina gracilis, we did an in vitro study of the anticancer potential of extracts and fractions from its leaves and inflorescences. Firstly, cytotoxicity was evaluated against five human tumorigenic cell lines by MTT assay. Subsequently, the chloroformic fractions, considered the most cytotoxic were tested for genotoxicity by comet assay, morphological effects were analyzed by fluorescent microscopy, cell cycle arrest by flow cytometry and early apoptosis induction through fluorescein-5-isothiocyanate (FITC) labeled Annexin-V assay. Non-polar extracts with IC50 values of <53μg/ml showed a high cytotoxicity. The highest cytotoxicity was achieved by chloroformic fraction from petroleum ether extract of leaves and inflorescences and chloroformic fraction from ethanolic extract of leaves, displaying a significant inhibition of cell viability particularly on A549 cells with an IC50 value of 25.9 μg/mL. Chloroformic fractions caused a high percent of DNA damage above 60 percent on A549 and MDAMB-231.The fractions also induced G1/S phase arrest of the cell cycle in A549 cells, furthermore it was confirmed the apoptotic activity chloroformic fraction from petroleum ether extract of inflorescences and chloroformic fraction from ethanolic extract of leaves on those cells by Annexin-V assay. These preliminary results indicate that A. gracilis has an antiproliferative activity against cancer cells, being a starting point for forthcoming studies about the antineoplastic activity and its domestication conditions.
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Acute toxicity evaluation of the ethanolic extract from leaves and flowers of chromolaena perglabra (b. l. robinson) king & h. rob.
Fecha de publicación: 30/12/2018
At present, there is a great variety of plant species widely distributed in different geographical regions worldwide, with phytopharmacological potential; however, its indiscriminate use has limited access to vegetal resources by the population in general and the scientific community. Additionally, the lack of toxicological studies that provide knowledge on the safety of their use makes the problem more critical. According to traditional knowledge, the species that belong to the genus Chromolaena, have a high pharmacological potential, but currently, there are no studies that validate traditional use and safety. Therefore, the purpose of this investigation was to evaluate the acute toxicity of the leaf and flower extract of Chromolaena perglabra (C. perglabra) in mice. To develop this aim, 25 female ICR-CD1 mice were divided into two groups with three and two subgroups respectively, to which they were administered intraperitoneally 125, 250, 500, 1000 and 2000 mg/ kg of the ethanolic extract of leaves and flowers of C. perglabra; another 5 mice were administered the vehicle (control group); 72 hours after inoculation, they were sacrificed for histopathological study (macroscopic and microscopic). An increase in size was observed with mild lymphoid hyperplasia in the spleen and toxic hepatitis in all the animals, the rest of the organs analyzed were in normal conditions. © 2019, SILAE (Italo-Latin American Society of Ethnomedicine). All rights reserved.
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