Category Archives: Cellular Pharmacology

Cytotoxic activity of Vismia baccifera and V. macrophylla

J Pharm Pharmacogn Res 5(5): 320-326, 2017.

Original Article | Artículo Original

Cytotoxic activity of different polarity fractions obtained from methanolic extracts of Vismia baccifera and Vismia macrophylla (Hypericaceae) collected in Venezuela

[Actividad citotóxica de fracciones de diferentes polaridades obtenidas a partir de extractos metanólicos de Vismia baccifera y Vismia macrophylla (Hypericaceae) colectadas en Venezuela]

Janne del C. Rojas1*, Alexis A. Buitrago1,2, Francisco A. Arvelo3,4, Felipe J. Sojo3,4, Alírica I. Suarez5

1Organic Biomolecules Research Group, Research Inst., Faculty of Pharmacy and Bioanalysis, University of Los Andes, Humberto Tejera Ave., Mérida 5101, Venezuela.
2Analysis and Control Department. Faculty of Pharmacy and Bioanalysis, University of Los Andes, Humberto Tejera Avenue, Mérida 5101, Venezuela.
3Bioscience Center, Fundation of Advanced Studies Institute, Sartenejas Valley, Miranda State, 1080A. Venezuela.
4Tissue Cultivation and Tumor Biology Laboratory, Experimental Biology Institute, Central University of Venezuela, Los Ilustres Avenue, Caracas 1051, Venezuela.
5Natural Products, Faculty of Pharmacy, Central University of Venezuela, Los Ilustres Avenue, Caracas 1051, Venezuela.

*E-mail: janner@ula.ve; janne.rojas24@gmail.com

Abstract

Context: Cancer is a complex disease involving numerous changes in cell physiology and abnormal cell growth, which lead to malignant tumors. Many investigations are still carrying on in different areas including, natural products, to find a possible break point to this pathology.

Aims: To evaluate the cytotoxic activity on different polar extracts from Vismia baccifera and Vismia macrophylla collected in two locations of the Venezuelan Andes.

Methods: Cytotoxic activity assay was carried out following the colorimetric (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) MTT assay. Human tumor cell Lines from breast carcinoma without gene over-expression (MCF-7), breast carcinoma with overexpressed gene (SKBr3), prostate carcinoma (PC3) and cervix epithelial carcinoma (HeLa) were tested with different polarity solvent extracts (hexane, dichloromethane, ethyl acetate, butanol, water) from the two species under investigation. Human dermis fibroblasts were used as control cells. Mean inhibitory concentration (IC50) was calculated.

Results: Extracts from V. macrophylla showed significant inhibition of cervix epithelial carcinoma with values ranging from 6.09 µg/mL to 17.51 µg/mL; breast carcinoma with an overexpressed gene with values from 12.14 µg/mL to 16.90 µg/mL and prostate carcinoma from 10.91 µg/mL to 17.70 µg/mL. V. baccifera extracts showed the strongest activity against prostate carcinoma with an IC50 value of 2.92 µg/mL.

Conclusions: The present study showed evidence for the anticancer activity of Vismia baccifera and Vismia macrophylla extracts since caused growth inhibition in different cell lines at low concentrations, thus, it is considered not only an important contribution to the natural products research but bring supportive data for further investigations on cancer research.

Keywords: cytotoxic activity; HeLa; MCF-7; PC3; SKBr3; Vismia baccifera; Vismia macrophylla.

Resumen

Contexto: El cáncer es una enfermedad que envuelve cambios en la fisiología y crecimiento anormal de las células, conduciendo a la aparición de tumores malignos. Investigaciones están realizándose en diferentes áreas, incluyendo productos naturales, para conseguir el tratamiento que elimine en forma definitiva esta patología.

Objetivos: Evaluar actividad citotóxica de extractos de diferentes polaridades obtenidos de Vismia baccifera y Vismia macrophylla colectadas en dos regiones de los andes venezolanos.

Métodos: La actividad citotóxica se realizó siguiendo el método colorimétrico del MTT. Líneas celulares tumorales de carcinoma de mama sin sobreexpresión del oncogen (MCF-7), carcinoma de mama con sobreexpresión del oncogen (SKBr3), carcinoma de próstata (PC3) y carcinoma de cuello uterino (HeLa) fueron probadas con extractos de diferentes polaridades (hexano, diclorometano, acetato de etilo, butanol, agua) obtenidos de las dos especies en estudio. Fibroblastos de la dermis humana fueron usados como células de control. Se calculó la concentración mínima inhibitoria (IC50).

Resultados: Los extractos de V. macrophylla mostraron inhibición del carcinoma de cuello uterino con valores de IC50 entre 6,09 a 17,51 µg/mL; carcinoma de mama con sobreexpresión del oncogen (12,14 a 16,90 µg/mL) y carcinoma de próstata (10,91 a 17,70 µg/mL). Los extractos de V. baccifera mostraron la mayor actividad frente al carcinoma de próstata con una IC50 de 2,92 µg/mL.

Conclusiones: El presente estudio mostró actividad anticancerígena de los extractos de V. baccifera y V. macrophylla, al causar inhibición del crecimiento en las líneas celulares a bajas concentraciones. Se considera una contribución a la investigación de productos naturales ya que se aportan datos para futuras investigaciones.

Palabras Clave: actividad citotóxica; HeLa; MCF-7; PC3; SKBr3; Vismia baccifera; Vismia macrophylla.

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Citation Format: Rojas JC, Buitrago AA, Arvelo FA, Sojo FJ, Suarez AI (2017) Cytotoxic activity of different polarity fractions obtained from methanolic extracts of Vismia baccifera and Vismia macrophylla (Hypericaceae) collected in Venezuela. J Pharm Pharmacogn Res 5(5): 320–326.

© 2017 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

Depigmentation effect of Quercus infectoria and Terminalia chebula

J Pharm Pharmacogn Res 5(5): 270-277, 2017.

Original Article | Artículo Original

Quercus infectoria and Terminalia chebula decrease melanin content and tyrosinase activity in B16/F10 cell lines

[Quercus infectoria y Terminalia chebula disminuyen el contenido de melanina y la actividad tirosinasa en las líneas celulares B16/F10]

Akram Jamshidzadeh1, Yaser Shokri2**, Nahid Ahmadi1, Neda Mohamadi3, Fariba Sharififar3*

1Toxicology Department, Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
2Herbal and Traditional Medicines Research Center, Department of Pharmacognosy, Kerman University of Medical Sciences, Kerman, Iran.
3Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.

E-mail: *fa.sharififar@gmail.com, **yashokri@yahoo.com

Abstract

Context: One of the most complained skin cares in ethnic skin like Asian women is hyperpigmentation, and lightening preparations have been long-standing desired. Due to the side effects of current drugs, medicinal plants have attracted more attentions as a source of novel drugs. Mazo (Quercus infectoria galls) and Terminalia chebula fruits have been suggested in Persian Traditional Medicine as a safe treatment for hyperpigmentation.

Aims: To evaluate the cytotoxicity and the effect on melanin synthesis in B16/F10 melanoma of Q. infectoria and T. chebula extracts.

Methods: After collection and scientific authentication, plants were extracted by maceration method with methanol and were standardized based on total phenolic content. MTT assay and colorimetric method were used for cytotoxicity and determination of melanin content and tyrosinase activity in B16/F10 cells, respectively. Kojic acid was used as a reference compound.

Results: Total phenolic content of Q. infectoria and T. chebula was determined as 287.34 ± 4.21 and 172.61 ± 8.67 mg gallic acid equivalent/g dried extract, respectively. Both plants decreased cell viability at 100 µg/mL and significantly reduced intercellular melanin to 66.25% and 71.1%, respectively in comparison to kojic acid (56.63%) at 50 µg/mL. In the same concentration, 65.7% and 71.2% tyrosinase activity was inhibited by Q. infectoria and T. chebula, which significantly were different from control (p<0.001).

Conclusions: These findings suggest that both plants especially Q. infectoria could inhibit melanogenesis in non-toxic concentrations and would be a good candidate for further studies.

Keywords: B16/F10 melanoma cells; depigmentation; melanin; Quercus infectoria; Terminalia chebula.

Resumen

Contexto: Uno de los cuidados de la piel más reclamados en la piel étnica de las mujeres asiáticas es la hiperpigmentación, y se han deseado, desde hace mucho tiempo, preparaciones de aclaramiento. Debido a los efectos secundarios de los fármacos actuales, las plantas medicinales han atraído más atenciones como fuente de nuevos fármacos. Mazo (agallas de Quercus infectoria) y frutos de Terminalia chebula han sido sugeridos en la medicina tradicional persa como un tratamiento seguro para la hiperpigmentación.

Objetivos: Evaluar la citotoxicidad y el efecto sobre la síntesis de melanina en células de melanoma B16/F10 de los extractos de Q. infectoria y T. chebula.

Métodos: Después de la recolección y la autenticación científica, las plantas se extrajeron por método de maceración con metanol y se normalizaron en base al contenido fenólico total. El ensayo MTT y el método colorimétrico se utilizaron para la citotoxicidad y la determinación del contenido de melanina y la actividad tirosinasa en células B16/F10, respectivamente. Se usó ácido kójico como compuesto de referencia.

Resultados: El contenido fenólico total de Q. infectoria y T. chebula se determinó como 287,34 ± 4,21 y 172,61 ± 8,67 mg equivalente de ácido gálico/g de extracto seco, respectivamente. Ambas plantas disminuyeron la viabilidad celular a 100 μg/mL y redujeron significativamente la melanina intercelular a 66,25% y 71,1%, respectivamente, en comparación con el ácido kójico (56,63%) a 50 μg/mL. En la misma concentración, Q. inhiboria y T. chebula inhibieron el 65,7% y el 71,2% de actividad tirosinasa, que fueron significativamente diferentes del control (p <0,001).

Conclusiones: Estos hallazgos sugieren que ambas plantas, especialmente Q. infectoria, podrían inhibir la melanogénesis en concentraciones no tóxicas y sería un buen candidato para estudios posteriores.

Palabras Clave: células de melanoma B16/F10; despigmentación; melanina; Quercus infectoria; Terminalia chebula.

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Citation Format: Jamshidzadeh A, Shokri Y, Ahmadi N, Mohamadi N, Sharififar F (2017) Quercus infectoria and Terminalia chebula decrease melanin content and tyrosinase activity in B16/F10 cell lines. J Pharm Pharmacogn Res 5(5): 270–277.
This article has been cited by:
Şenol FS, Şekeroğlu N, Gezici S, Kiliç E, Erdoğan Orhan İ (2018) Neuroprotective potential of the fruit (acorn) from Quercus coccifera L. Turkish Journal of Agriculture and Forestry 42(2): 82-87. DOI: 10.3906/tar-1711-18

© 2017 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

Anti-inflammatory effect of amitriptyline

J Pharm Pharmacogn Res 5(3): 144-155, 2017.

Original Article | Artículo Original

In vitro and in vivo modulation of LPS and carrageenan-induced expression of inflammatory genes by amitriptyline

[Modulación in vitro e in vivo por amitriptilina de la expresión de genes inflamatorios inducidos por LPS y carragenina]

Laleh Rafiee1, Valiollah Hajhashemi2*, Shaghayegh Haghjooy Javanmard3

1Applied Physiology Research Center, Isfahan Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran.
2Department of Pharmacology and Toxicology, Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.
3Applied Physiology Research Center, Isfahan Cardiovascular Research Institute and Department of Physiology, Isfahan University of Medical Sciences, Isfahan, Iran.

*E-mail: vhajhashemi@gmail.com

Abstract

Context: Amitriptyline, a tricyclic antidepressant is used for the management of psychological disorders and various types of pain. In the previous work, it is founded that amitriptyline inhibited the migration of polymorphonuclear (PMN) into the site of inflammation.

Aims: To evaluate the effect of amitriptyline on the expression of some inflammatory mediators such as intercellular adhesion molecule (ICAM-1), vascular cell adhesion molecule (VCAM-1), cyclooxygenase 2 (COX2) and inducible nitric oxide synthase (iNOS).

Methods: An in vitro model system of LPS-stimulated human endothelial cells and U937 macrophages and also in vivo model of carrageenan-induced paw edema in rat were used. The expression of inflammatory mediator genes was determined by qRT-Real-time PCR. In endothelial cells, soluble forms of ICAM-1 and VCAM-1 were quantified by ELISA.

Results: The expression of ICAM-1, VCAM-1, COX2, iNOS, sICAM-1 and sVCAM-1 significantly decreased by amitriptyline. The finding of this study also confirmed that intraperitoneal (i.p.) injection of amitriptyline inhibited carrageenan-induced inflammation in rat paw edema.

Conclusions: The results of the present study provide further evidence for the anti-inflammatory effect of amitriptyline. This effect appears to be mediated by down-regulation of inflammatory genes.

Keywords: amitriptyline; cyclooxygenase 2; inducible nitric oxide synthase; inflammation; intercellular adhesion molecule-1; vascular cell adhesion molecule-1.

Resumen

Contexto: La amitriptilina, un antidepresivo tricíclico, se utiliza para el tratamiento de los trastornos psicológicos y diversos tipos de dolor. En un trabajo anterior se demostró el efecto inhibidor de la amitriptilina sobre la migración de polimorfonucleares (PMN) en el sitio de la inflamación.

Objetivos: Evaluar el efecto de la amitriptilina sobre la expresión de algunos mediadores inflamatorios tales como molécula de adhesión intracelular (ICAM-1), molécula de adhesión celular vascular (VCAM-1), ciclooxigenasa 2 (COX2) y óxido nítrico sintasa inducible (iNOS).

Métodos: Se utilizó un modelo in vitro de células endoteliales humanas estimuladas con LPS y macrófagos U937 y también un modelo in vivo de edema de la pata inducido por carragenina en rata. La expresión de genes mediadores inflamatorios se determinó por PCR qRT-Real-time. En las células endoteliales, las formas solubles de ICAM-1 y VCAM-1 se cuantificaron por ELISA.

Resultados: La expresión de ICAM-1, VCAM-1, COX2, iNOS, sICAM-1 y sVCAM-1 disminuyó significativamente por la amitriptilina. También se confirmó que la amitriptilina intraperitoneal (i.p.) inhibió la inflamación inducida por carragenina en el edema de la pata de la rata.

Conclusiones: Los resultados de este estudio proporcionan evidencia adicional para el efecto antiinflamatorio de la amitriptilina. Este efecto parece estar mediado por la regulación hacia abajo de los genes inflamatorios.

Palabras Clave: amitriptilina; ciclooxigenasa 2; inflamación; molécula de adhesión celular vascular-1; molécula de adhesión intracelular-1; óxido nítrico sintasa inducible.

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Citation Format: Rafiee L, Hajhashemi V, Haghjooy Javanmard S (2017) In vitro and in vivo modulation of LPS and carrageenan-induced expression of inflammatory genes by amitriptyline. J Pharm Pharmacogn Res 5(3): 144-155.

© 2017 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

Antibiotics, cytokine production and cross-talk with cancer cells

J Pharm Pharmacogn Res 4(4): 134-143, 2016.

Original Article | Artículo Original

The effect of antibiotics on cytokine production by mononuclear cells and the cross-talk with colon cancer cells

[Efecto de antibióticos sobre la producción de citocinas por células mononucleares y la interacción con células de cáncer de colon]

Meir Djaldetti1*, Nimrod Nachmias2, Hanna Bessler1

1Laboratory for Immunology and Hematology Research, 2Department of Orthopedics, Rabin Medical Center, Hasharon Hospital, 7, Keren Kayemet St Petah Tiqva, and the Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Israel.

*E-mail: meird@clalit.org.il

Abstract

Context: Antibiotics belong to the powerful weapons applied against microbial infections. It is notable that in addition to their antimicrobial effect they express immunomodulatory and anti-cancer activities.

Aims: To explore the effect of four antibiotics on the immune cross-talk between peripheral blood mononuclear cells (PBMC) and colon carcinoma cells from two human lines.

Methods: Cefotaxime, meropenem, ampicillin and vancomycin were separately added to PBMC co-incubated with cells from two human colon carcinoma cell lines, i.e. HT-29 and RKO. After 24 hours, the level of the following cytokines produced by PBMC was evaluated: IL-6, IL-1ra, IL-1β, TNFα, IFNγ and IL-10.

Results: All four antibiotics did not affect the generation of IL-6 and IL-1ra in both co-cultures. On the other hand all of them restrained the production of IL-1β by PBMC incubated with HT-29 cells. In the same incubation mixture cefotaxime, vancomycin and meropenem decreased IFNγ and IL-10 production, while ampicillin and vancomycin inhibited TNFα. As for PBMC incubated with RKO carcinoma cells, cefotaxime inhibited the production of IL-1β, IFNγ and mildly of IL-10, whereas vancomycin repressed that of IL-1β, TNFα and IFNγ. Notably, vancomycin increased the production of IL-1β and decreased that of TNFα and IFNγ. The results indicate that the four antibiotics examined exert a modulatory effect on the immune cross-talk between PBMC and human colon cancer cells from two lines expressed by a different impact on pro-and anti-inflammatory cytokines generation.

Conclusions: These findings support the conception that antibiotics may express not only an anti-microbial effect, but also possess an anti-cancer activity that may be considered for integration to the therapeutic arsenal against cancer.

Keywords: Ampicillin; cefotaxime; colon carcinoma cells; cytokines; meropenem; mononuclears; vancomycin.

Resumen

Contexto: Los antibióticos son armas poderosas aplicadas contra las infecciones microbianas. Además de su efecto antimicrobiano expresan actividades inmunomoduladoras y contra el cáncer.

Objetivos: Explorar el efecto de cuatro antibióticos sobre la interacción inmune entre las células mononucleares de sangre periférica (PBMC) y células de carcinoma de colon de dos líneas humanas.

Métodos: Cefotaxima, meropenem, ampicilina y vancomicina se añadieron por separado a PBMC co-incubadas con células de dos líneas de carcinoma de colon humano (HT-29 y RKO). Después de 24 horas, se evaluaron las concentraciones de las siguientes citocinas producidas por PBMC: IL-6, IL-1ra, IL-1β, TNFα, IFNγ e IL-10.

Resultados: Los cuatro antibióticos no afectaron la generación de IL-6 e IL-1ra en ambos co-cultivos. Por otra parte, todos contuvieron la producción de IL-1β por PBMC incubadas con células HT-29. En la misma mezcla de incubación cefotaxima, vancomicina y meropenem disminuyeron la producción de IFNγ e IL-10, mientras que la ampicilina y vancomicina inhibieron TNFα. Cuando PBMC se incubaron con células RKO, cefotaxima inhibió la producción de IL-1β, IFNγ y ligeramente de IL-10, mientras que la vancomicina reprimió las de IL-1β, TNFα e IFNγ. En particular, la vancomicina aumentó la producción de IL-1β y disminuyó las de TNFα e IFNγ. Los resultados indican que los cuatro antibióticos examinados ejercieron un efecto modulador sobre la interacción inmune entre PBMC y las células de cáncer de colon humano a partir de dos líneas, expresadas por un impacto diferente sobre la generación de citocinas pro- y anti-inflamatorias.

Conclusiones: Estos hallazgos apoyan la idea de que los antibióticos pueden presentar no sólo un efecto anti-microbiano, también poseen una actividad anti-cancerígena que pudiera ser considerada para la integración de éstos al arsenal terapéutico contra el cáncer.

Palabras Clave: Ampicilina; cefotaxima; células de carcinoma de colon; citocinas; meropenem; mononucleares; vancomicina.

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Citation Format: Meir Djaldetti, Nimrod Nachmias, Hanna Bessler (2016) The effect of antibiotics on cytokine production by mononuclear cells and the cross-talk with colon cancer cells. J Pharm Pharmacogn Res 4(4): 134-143.
This article has been cited by:
Krishnananthasivam S, Jayathilaka N, Sathkumara HD, Corea E, Natesan M, De Silva AD (2017) Host gene expression analysis in Sri Lankan melioidosis patients. PLoS Negl Trop Dis 11(6): e0005643. DOI: 10.1371/journal.pntd.0005643
Krishnananthasivam S, Sathkumara HD, Corea E, Natesan M, De Silva AD (2017) Gene expression profile of human cytokines in response to Burkholderia pseudomallei infection. mSphere 2: e00121-17. DOI: 10.1128/mSphere.00121-17

© 2016 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

Cytotoxicity of 1-O-undecylglycerol in melanoma

J Pharm Pharmacogn Res 4(2): 84-94, 2016.

Original Article | Artículo Original

Selective cytotoxic effect of 1-O-undecylglycerol in human melanoma cells

[Efecto citotóxico selectivo del 1-O-undecilglicerol en células de melanoma humano]

Marian Hernández-Colina1*, Alberto Martín Cermeño1, Alexis Díaz García2

1Instituto de Farmacia y Alimentos, Universidad de la Habana, Calle 222, No. 2317, entre 23 y 31, La Coronela, La Lisa, CP 13600, La Habana, Cuba.
2Laboratorios de Producciones Biofarmacéuticas y Químicas (LABIOFAM). Ave. Boyeros Km 16½, Rpto. Mulgoba, Boyeros, La Habana, Cuba.
Abstract

Context: 1-O-alkylglycerols are ether-linked glycerols derived from shark liver oil and found in small amounts in human milk. Previous studies showed antineoplastic activity for this family of compounds, structurally related to alkylphospholipids, but the activity of linear chain synthetic alkylglycerols in cancer cell lines is less documented. Melanoma is a high incidence cancer, highly resistant to potential treatments. Finding new anti-cancer compounds to improve melanoma prognosis is a relevant research issue.

Aims: To study the cytotoxic effect of 1-O-undecylglycerol in primary cultured normal fibroblasts and A375 human melanoma cell line.

Methods: Cells were treated with different concentrations of 1-O-undecylglycerol and viability assessed by MTT assay. Morphological changes were visualized by DAPI and acridine orange-ethidium bromide staining. Mitochondrial membrane potential was evaluated, and gene expression of P53 and BcL-2 was semi-quantified.

Results: 1-O-undecylglycerol decreased viability of A375 cells and exerted very low cytotoxicity on primary cultured normal fibroblasts. Necrosis appeared in A375 cells but not in fibroblasts, and no apoptotic changes were visualized in DAPI staining experiments. After 24 h fibroblasts and melanoma cells developed mitochondrial potential changes similar to valinomycin. The gene expression of P53 and BcL-2 decreased in treated cells.

Conclusions: 1-O-undecylglycerol exhibited selective cytotoxic activity in A375 melanoma cells when compared with primary cultured fibroblast. Its toxicity is mediated by necrosis that may be related with mitochondrial events and decrease in P53 and BcL-2 expression. The results suggest that UDG could be a useful strategy to combine with other chemotherapeutic agents in melanoma treatment.

Keywords: Alkylglycerols, cytotoxicity, melanoma, primary cultured fibroblasts.

Resumen

Contexto: Los 1-O-alquilgliceroles son éteres presentes en el aceite de hígado de tiburón y en la leche materna. Han mostrado actividad antineoplásica, pero está poco documentada para alquilgliceroles sintéticos de cadena lineal. La búsqueda de nuevos antitumorales para mejorar el pronóstico del melanoma resulta relevante, debido a su alta incidencia y resistencia.

Objetivos: Estudiar el efecto citotóxico del 1-O-undecilglicerol en cultivo primario de fibroblastos normales y la línea celular A375 de melanoma humano.

Métodos: En células tratadas con diferentes concentraciones de 1-O-undecilglicerol se monitoreó la viabilidad mediante ensayo con MTT. Los cambios morfológicos se visualizaron por tinción con DAPI y naranja acridina- bromuro de etidio. Se evaluó el potencial de membrana mitocondrial, y se semi-cuantificó la expresión de los genes P53 y BcL-2.

Resultados: El 1-O-undecilglicerol redujo la viabilidad de las células A375, y ejerció poca citotoxicidad en el cultivo primario de fibroblastos normales. Ocurrió necrosis en las células A375 pero no en los fibroblastos, y no se visualizaron cambios apoptóticos en la tinción con DAPI. Luego de 24 h ambas células desarrollaron cambios en el potencial de membrana mitocondrial similar a la valinomicina, y disminuyó la expresión de los genes p53 y BcL-2.

Conclusiones: El 1-O-undecilglicerol mostró actividad citotóxica selectiva en células A375 al compararlo con cultivo primario de fibroblastos humanos. Su toxicidad es mediada por necrosis, probablemente por eventos mitocondriales y disminución en la expresión de P53 y BcL-2. Ello sugiere que el 1-O-undecilglicerol pudiera ser útil en combinación con otros quimioterapéuticos en el tratamiento del melanoma.

Palabras Clave: Alquilgliceroles, citotoxicidad, cultivo primario de fibroblastos melanoma, necrosis.

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Citation Format: Marian Hernández-Colina, Alberto Martín Cermeño, Alexis Díaz García (2016) Selective cytotoxic effect of 1-O-undecylglycerol in human melanoma cells. J Pharm Pharmacogn Res 4(2): 84-94.

© 2016 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

In vitro antimycobacterial activity of G. glabra

J Pharm Pharmacogn Res 3(4): 80-86, 2015.

Original Article | Artículo Original

In vitro antimycobacterial activity of acetone extract of Glycyrrhiza glabra

[Actividad antimicobacteriana in vitro del extracto de acetona de Glycyrrhiza glabra]

Swapna S. Nair1, Rajesh R. Pharande2, Anilkumar S. Bannalikar2, Alka P. Mukne1

1Department of Pharmacognosy & Phytochemistry, Bombay College of Pharmacy, Kalina, Santacruz (East), Mumbai- 400 098, India.
2Department of Microbiology, Bombay Veterinary College, Parel, Mumbai- 400 012. India.*E-mail: alka.mukne@gmail.com
Abstract

Context: Glycyrrhiza glabra (licorice) has been used since ages as expectorant, antitussive and demulcent. G. glabra has been indicated in Ayurveda as an antimicrobial agent for the treatment of respiratory infections and tuberculosis.

Aims: To evaluate the antimycobacterial activity of acetone extract of G. glabra by in vitro techniques.

Methods: The anti-tubercular activity of acetone extract of G. glabra, obtained by Soxhlet extraction, was evaluated against Mycobacterium tuberculosis H37Rv (ATCC 27294). The in vitro anti-tubercular activity was determined by Resazurin Microtiter Plate Assay (REMA) and colony count method. Further, the anti-tubercular activity of acetone extract of G. glabra was determined in human macrophage U937 cell lines and was compared against that of the standard drugs isoniazid, rifampicin and ethambutol.

Results: G. glabra extract showed significant activity against Mycobacterium tuberculosis, when evaluated by REMA/colony count methods and in U937 human macrophage cell lines infected with Mycobacterium tuberculosis H37Rv. The activity of the extract was comparable to those of standard drugs. It was observed that the extract showed time and concentration dependent antimycobacterial activity.

Conclusions: The present study reveals that G. glabra extract has promising anti-tubercular activity by preliminary in vitro techniques and in U937 macrophage cell line. Therefore, it has the definite potential to be developed as an affordable, cost-effective drug against tuberculosis.

Keywords: Infections; licorice; macrophage; Mycobacterium tuberculosis H37Rv.

Resumen

Contexto: La especie Glycyrrhiza glabra (regaliz) ha sido usada desde la antigüedad como expectorante, antitusiva, y demulcente. G. glabra ha sido indicada en la medicina ayurvédica como un agente antimicrobiano para el tratamiento de infecciones respiratorias y tuberculosis.

Objetivos: Evaluar la actividad antimicobacteriana del extracto de acetona de G. glabra por técnicas in vitro.

Métodos: La actividad anti-tuberculosa del extracto de acetona de G. glabra, obtenido por Soxhlet, fue evaluada contra Mycobacterium tuberculosis H37Rv (ATCC 27294). La actividad anti-tuberculosa in vitro  fue determinada por Ensayo de Placa de Microtitulación Resazurin (REMA) y el método de conteo de colonias. Además, la actividad anti-tuberculosa de este extracto fue determinada en células de macrófagos humanos U937 y fue comparada contra aquella de fármacos de referencia como isoniacida, rifampicina y etambutol.

Resultados: El extracto de G. glabra mostró una actividad significativa contra Mycobacterium tuberculosis cuando fue evaluado por los métodos REMA/conteo de colonias y en macrófagos U937 infectados con M. tuberculosis. La actividad del extracto fue comparable a aquella observada con los fármacos de referencia. El extracto mostró una actividad antimicobacteriana dependiente de la concentración y el tiempo.

Conclusiones: El presente estudio revela que el extracto en acetona de G. glabra tiene actividad anti-tuberculosa prometedora, demostrada por técnicas preliminares in vitro y en la línea de macrófagos U937. De esta manera, esta especie tiene un potencial definido para desarrollar un producto asequible contra la tuberculosis.

Palabras Clave: Infectiones; regaliz; macrófago; Mycobacterium tuberculosis H37Rv.

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Citation Format: Nair SS, Pharande RR, Bannalikar AS, Mukne AP (2015) In vitro antimycobacterial activity of acetone extract of Glycyrrhiza glabra. J Pharm Pharmacogn Res 3(4): 80-86.
This article has been cited by:
Viswanathan V, Pharande R, Bannalikar A, Gupta P, Gupta U, Mukne A (2018) Inhalable liposomes of Glycyrrhiza glabra extract for use in tuberculosis: formulation, in vitro characterization, in vivo lung deposition, and in vivo pharmacodynamic studies. Drug Development and Industrial Pharmacy. DOI: 10.1080/03639045.2018.1513025
Sasikumar K, Ranjan Ghosh A, Dusthackeer A (2018) Antimycobacterial potentials of quercetin and rutin against Mycobacterium tuberculosis H37Rv. 3 Biotech 8:427. DOI: 10.1007/s13205-018-1450-5
Viswanathan V, Mehta H, Pharande R, Bannalikar A, Gupta P, Gupta U, Mukne A (2018) Mannosylated gelatin nanoparticles of licorice for use in tuberculosis: Formulation, in vitro evaluation, in vitro cell uptake, in vivo pharmacokinetics and in vivo anti-tubercular efficacy. Journal of Drug Delivery Science and Technology 45: 255-263. DOI: 10.1016/j.jddst.2018.01.017
Kahaliw W, Aseffa AAbebe MTeferi M, Engidawork E (2017) Evaluation of the antimycobacterial activity of crude extracts and solvent fractions of selected Ethiopian medicinal plants. BMC Complementary and Alternative Medicine 17: 143. DOI: 10.1186/s12906-017-1563-0
Jadhav SG, Viswanathan V, Mukne AP (2016) Validated HPTLC method for simultaneous quantification of isoniazid, rifampicin and glabridin. J Pharm Biomed Sci 6(7): 453–459. DOI: 10.20936/jpbms/160270
Viswanathan V, Mukne AP (2016) Development and validation of HPLC and HPTLC methods for estimation of glabridin in extracts of Glycyrrhiza glabra. Journal of AOAC International 99(2): 374-379. DOI: 10.5740/jaoacint.15-0239
Wubayehu Kahaliw (2016) Activity testing, toxicity assay and characterization of chemical constituents of medicinal plants used to treat tuberculosis in Ethiopian Traditional Medicine. A Thesis Submitted to the School of Graduate Studies of Addis Ababa University in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy in Pharmacology. Website

© 2015 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

SEPSIS, INFLAMMATION AND CELL RESPONSE

J Pharm Pharmacogn Res 2(Suppl. 1): S77, 2014

Special supplement with the abstract book of LATINFARMA 2013

Plenary Lecture

PL 007: SEPSIS, INFLAMMATION AND CELL RESPONSE

Salomao R.

Laboratório de Imunologia Universidade Federal de São Paulo/Escola Paulista de Medicina. Rua Pedro de Toledo, 781 – 15º andar – Vila Clementino. São Paulo, Brasil.
Abstract

Since the definition of systemic inflammatory response syndrome/sepsis was originally proposed, a large amount of new information has been generated showing a much more complex scenario of inflammatory and counter inflammatory responses during sepsis. Moreover, some fundamental mechanisms of sensing and destroying invading microorganisms have been uncovered, which include the discovery of TLR4 as the lipopolysaccharide (LPS) gene, implications of innate immune cells as drivers of the adaptive response to infection, and the modulation of multiple accessory molecules that stimulate or inhibit monocyte/macrophage and lymphocyte interactions. The complexity of the infection/injury-induced immune response could be better appreciated with the application of genomics and proteomics studies, and LPS was a useful tool in many of these studies. In this review, we discuss aspects of bacterial recognition and induced cellular activation during sepsis. Because of the relevance of endotoxin (LPS) research in the field, we focus on LPS and host interactions as a clue to understand microorganisms sensing and cell signaling, then we discuss how this response is modulated in septic patients.

Memory enhancing effects of Mangifera indica in SCA-2 disease

J Pharm Pharmacogn Res 2(3): 63-72, 2014.

Original Article | Artículo Original

Mangifera indica L. extract (Vimang) improves the aversive memory in spinocerebellar ataxia type 2 transgenic mice.

[El extracto de Mangifera indica L. (Vimang) mejora la memoria aversiva en ratones transgénicos portadores de ataxia espinocerebelosa tipo 2]

Natasha Maurmanna,b, Caroline B. de Fariasa,c,d, Gilberto Schwartsmannc,e, Rafael Roeslera,c,f, René Delgado-Hernándezg, Gilberto L. Pardo-Andreub*

aNational Science and Technology Institute (INCT) for Translational Medicine (TM), Brazil. bCentro de Estudio para las Investigaciones y Evaluaciones Biológicas, Instituto de Farmacia y Alimentos, Universidad de La Habana, Ave. 23, Nº 21425 e/214 y 222, La Coronela, La Lisa, CP 13600, La Habana, Cuba. cCancer Research Laboratory, University Hospital Research Center (CPE-HCPA), eDepartment of Internal Medicine, School of Medicine, fLaboratory of Neuropharmacology and Neural Tumor Biology, Department of Pharmacology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul; dChildren’s Cancer Institute (ICI-RS) and Pediatric Oncology Service, Porto Alegre, RS, Brazil.
gCentro de Investigación y Desarrollo de Medicamentos, Ave 26, Nº. 1605 Boyeros y Puentes Grandes, CP 10600, La Habana, Cuba.
*E-mail: gilbertopardo@infomed.sld.cu
Abstract

Context: The spinocerebellar ataxia type 2 (SCA-2) is a progressive neurodegenerative disorder without specific therapy identified, and it is related to the loss of function in the cerebellum, mitochondrial dysfunction, oxidative stress and neurotoxic processes. Scientific evidence indicates that Mangifera indica L. aqueous extract (MiE) and its major constituent (mangiferin) display antioxidant, anti-inflammatory and neuroprotective actions.

Aims: To investigate the MiE and mangiferin effects on behavioral outcomes of neurological function in SCA-2 transgenic mice.

Methods: The SCA-2 transgenic mice were daily and orally administered during 12 months with MiE (10, 50, and 100 mg/kg), mangiferin (10 mg/kg) or vehicle. It was evaluated locomotion (open-field), aversive memory (inhibitory avoidance) and declarative memory (object recognition). To explore possible cellular mechanisms underlying the in vivo effects was also evaluated their effects on nerve grow factor (NGF) and tumor necrosis factor-α (TNF-α) levels in the human glioblastoma cell line U138-MG supernatant.

Results: MiE administration did not affect the object recognition memory, but mangiferin did. The natural extract improved selectively the aversive memory in SCA-2 mice, indicating that MiE can affect behavioral parameters regarding fear-related memory. MiE also induced a significant increase in supernatant levels of NGF and TNF-α in vitro in human U138-MG glioblastoma cells.

Conclusions: The results suggest that MiE enhances the aversive memory through a mechanism that might involve an increase in neurotrophin and cytokine levels. These findings constitute the basis for the use of the natural extract in the prevention/treatment of memory deficits in SCA-2.

Keywords: Mangifera indica; memory; nerve growth factor; spinocerebellar ataxia type 2; tumor necrosis factor; Vimang.

Resumen

Contexto: La ataxia espinocerebelosa tipo 2 (SCA-2) es una enfermedad neurodegenerativa progresiva, sin una terapia específica. Se asocia con pérdida de la función del cerebelo, disfunción mitocondrial, estrés oxidativo y neurotoxicidad. Evidencias científicas indican que el extracto acuoso de Mangifera indica L. (MiE) y su componente mayoritario (mangiferina) poseen propiedades antioxidantes, anti-inflamatorias y neuroprotectoras.
Objetivos: Investigar los efectos de MiE y mangiferina sobre parámetros conductuales de la función neurológica en ratones transgénicos portadores de la SCA-2.
Métodos: Los animales se trataron diariamente y por vía oral, durante 12 meses con MiE (10, 50, y 100 mg/kg), mangiferina (10 mg/kg) o vehículo. Se evaluaron la locomoción, la memoria aversiva y la memoria declarativa. También se evaluaron sus efectos sobre los niveles del factor de crecimiento neuronal (NGF) y el factor de necrosis tumoral- α (TNF- α) en un cultivo de células neuronales.
Resultados: El extracto no afectó la memoria de reconocimiento de objetos, pero la mangiferina sí la modificó. También mejoró selectivamente la memoria aversiva de los ratones SCA-2, indicando que puede afectar la memoria asociada al temor en esta patología. Además, el MiE indujo significativamente los niveles de NGF y TNF- α in vitro, en los sobrenadantes del glioblastoma humano U138-MG.
Conclusiones: Los resultados sugieren que el MiE mejora la memoria aversiva por medio de mecanismos que pueden involucrar un incremento en los niveles de neurotrofinas y citocinas y constituyen las bases para el uso del extracto natural en la prevención/tratamiento del déficit de memoria en la SCA-2.

Palabras Clave: Ataxia espinocerebelosa tipo 2; factor de crecimiento neuronal; factor de necrosis tumoral; Mangifera indica; memoria; Vimang.

Download the PDF file .

Citation Format: Natasha Maurmann, Caroline B. de Farias, Gilberto Schwartsmann, Rafael Roesler, René Delgado-Hernández, Gilberto L. Pardo-Andreu (2014) Mangifera indica L. extract (Vimang) improves the aversive memory in spinocerebellar ataxia type 2 transgenic mice. J Pharm Pharmacogn Res 2(3): 63-72. 
This article has been cited by:
Eduardo Jesús Rodríguez-Delgado, Héctor García-Pérez, Leónides Castellanos-González, Maricela Capote-del Sol (2015) Estabilidad y adaptabilidad de tres cultivares de mango (Mangifera indica L.) en la unidad especial de frutales de Cienfuegos.  CitriFrut 32(2): 11-20, 2015. Website
Md. Reyad-Ul-Ferdous, Shahnur Parvez, Subash Pandaya, Kawsar Mahamud, Manson Pandey, Sharmi Sultana Ayshi, Dan Babu Barman, Nusrat Jahan (2015) Traditionally medicinal plants uses in the village of Bangladesh. World Journal of Pharmaceutical Research 4(1): 397-404. Website

© 2014 Journal of Pharmacy & Pharmacognosy Research (JPPRes)