Category Archives: Diabetes

Effect of mouse sex on pharmacological investigations

J. Pharm. Pharmacogn. Res., vol. 8, no. 6, pp. 569-579, November-December 2020.

Original Article

Effect of sex differences in antinociceptive, antipyretic, hypoglycemia, hepatoprotective and antidiarrheal activities in mice model

[Efecto de las diferencias sexuales en las actividades antinociceptiva, antipirética, hipoglucemia, hepatoprotectora y antidiarreica en modelo de ratones]

Irin Karim#, Roni Roy#, Md Rafiul Hoque, Sazzad Hosen, Tanaya Bhowmik, Israt Jahan Liya, Afroza Akter, Mohammad Anwarul Basher

Department of Pharmacy, Noakhali Science and Technology University, Sonapur, Noakhali-3814, Bangladesh.
#These two authors contributed equally.


Context: The use of animal models is a longstanding practice in biological research. Among different models, the mouse is the most widely used and accepted model. In designing the mouse model, a male mouse is generally preferred over a female to avoid the effect of changing hormonal state in females. However, it is not known whether mouse sex affects all experiments.

Aims: To determine the effect of mouse sex on pharmacological responses in antinociceptive, antipyretic, hypoglycemia, hepatoprotective and antidiarrheal experiments.

Methods: Antinociceptive study was performed by three different experiments. An antipyretic experiment was performed by yeast induced hyperthermia test. The effect on hypoglycemic response was assessed by an oral glucose tolerance test. The effect on the hepatoprotective study was evaluated by carbon tetrachloride-induced liver damage. The antidiarrheal study was conducted by a castor oil-induced diarrhea test.

Results: Antinociceptive studies demonstrated mixed effects. Hot plate test showed significant differences; the licking test showed variation only in the late phase, while no significant variation was observed. In the antipyretic experiment, female mice showed higher body temperature in both control and standard that varied significantly with male mice. Hypoglycemia and hepatoprotective tests did not show significant variation between sexes; however, liver enzymes levels were found higher in males while the percentage liver weight was higher in females. In the antidiarrheal test, the male mouse was observed to have higher responses than the female.

Conclusions: Antinociceptive and antipyretic investigations should be performed separately on both male and female mice. On the other hand, hypoglycemic, hepatoprotective and antidiarrheal tests can be conducted on any mouse sex, and findings on particular sex can be extrapolated to the opposite sex.

Keywords: drug discovery; sex dimorphism; Swiss albino mice.


Contexto: El uso de modelos animales es una práctica de larga data en la investigación biológica. Entre los diferentes modelos, el ratón es el modelo más utilizado y aceptado. Al diseñar el modelo de ratón, generalmente se prefiere un ratón macho a una hembra para evitar el efecto del cambio de estado hormonal en las hembras. Sin embargo, no se sabe si el sexo del ratón afecta a todos los experimentos.

Objetivos: Determinar el efecto del sexo del ratón sobre las respuestas farmacológicas en experimentos antinociceptivos, antipiréticos, hipoglucémicos, hepatoprotectores y antidiarreicos.

Métodos: Se realizaron experimentos para demostrar efectos anti-nociceptivo (tres experimentos diferentes), antipirético (hipertermia inducida por levaduras), hipoglucémico (prueba de tolerancia a la glucosa oral), hepatoprotector (daño hepático inducido por tetracloruro de carbono) y antidiarreico (diarrea inducida por aceite de ricino).

Resultados: Los estudios antinociceptivos demostraron efectos mixtos. La prueba de la placa caliente mostró diferencias significativas; la prueba de lamido mostró variación solo en la fase tardía, mientras que no se observó variación significativa. En el experimento antipirético, las hembras mostraron una temperatura corporal más alta tanto en el control como en el estándar que varió significativamente con los ratones machos. Las pruebas de hipoglucemia y hepatoprotección no mostraron variación significativa entre sexos; sin embargo, los niveles de enzimas hepáticas se encontraron más altos en los machos mientras que el porcentaje de peso del hígado fue más alto en las hembras. En la prueba antidiarreica, se observó que el ratón macho tenía respuestas más altas que la hembra.

Conclusiones: Las investigaciones antinociceptivas y antipiréticas debían realizarse por separado en ratones machos y hembras. Por otro lado, las pruebas hipoglucémicas, hepatoprotectoras y antidiarreicas podrían realizarse en cualquier sexo de ratón, y los hallazgos sobre un sexo particular se pueden extrapolar al sexo opuesto.

Palabras Clave: dimorfismo sexual; investigación en medicamento; ratones albinos suizos.

Download the PDF file .

Citation Format: Karim I, Roy R, Hoque MR, Hosen S, Bhowmik T, Liya IJ, Akter A, Basher MA (2020) Effect of sex differences in antinociceptive, antipyretic, hypoglycemia, hepatoprotective and antidiarrheal activities in mice model. J Pharm Pharmacogn Res 8(6): 569–579.

Afonso-Pereira F, Dou L, Trenfield SJ, Madla CM, Murdan S, Sousa J, Veiga F, Basit AW (2018) Sex differences in the gastrointestinal tract of rats and the implications for oral drug delivery. Eur J Pharm Sci 115: 339–344.

Awouters F, Niemegeers CJ, Lenaerts FM, Janssen PA (1978) Delay of castor oil diarrhoea in rats: a new way to evaluate inhibitors of prostaglandin biosynthesis. J Pharm Pharmacol 30: 41–45.

Ballou LR, Botting RM, Goorha S, Zhang J, Vane JR (2000) Nociception in cyclooxygenase isozyme-deficient mice. Proc Natl Acad Sci USA 97: 10272–10276.

Balmain A, Harris C (2000) Carcinogenesis in mouse and human cells: parallels and paradoxes. Carcinogenesis 21: 347–371.

Beery AK, Zucker I (2011) Sex bias in neuroscience and biomedical research. Neurosci Biobehav Rev 35: 565–572.

Berkenkopf JW, Weichman BM (1988) Production of prostacyclin in mice following intraperitoneal injection of acetic acid, phenylbenzoquinone and zymosan: its role in the writhing response. Prostaglandins 36: 693–709.

Craft RM (2003) Sex differences in opioid analgesia: “From mouse to man”. Clin J Pain 19: 175–186.

Cragg GM, Kingston DG, Newman DJ (2011) Anticancer agents from natural products. CRC press.

DeHaven-Hudkins D, Burgos LC, Cassel J, Daubert J, DeHaven R, Mansson E, Nagasaka H, Yu G, Yaksh T (1999) Loperamide (ADL 2-1294), an opioid antihyperalgesic agent with peripheral selectivity. J Pharmacol Exp Ther 289: 494–502.

Dubuisson D, Dennis SG (1977) The formalin test: A quantitative study of the analgesic effects of morphine, meperidine, and brain stem stimulation in rats and cats. Pain 4: 161–174.

European Union (2020) Report of European Union, The Statistics on the Number of Animals Used for Experimental and Other Scientific Purposes.

Fabricant DS, Farnsworth NR (2001) The value of plants used in traditional medicine for drug discovery. Environ Health Perspect 109: 69–75.

Fatehi-Hassanabad Z, Jafarzadeh M, Fafehi M, Razavi-Tossi MT (2005) Sex affects the feeling of pain in the mice, possible involvement of nitric oxide. DARU J Pharm Sci 13: 116–119.

Field M, Rao MC, Chang EB (1989) Intestinal electrolyte transport and diarrheal disease. N Engl J Med 321: 800–806.

Gregory MS, Duffner AL, Hahn LE, Hsin-Hsiung T, Faunce ED, Kovacs JE (2000) Differential production of prostaglandin E2 in male and female mice subjected to thermal injury contributes to the gender difference in immune function: possible role for 15-hydroxyprostaglandin dehydrogenase. Cell Immunol 205: 94–102.

Kaikaew K, Steenbergen J, van Dijk TH, Grefhorst A, Visser JA (2019) Sex difference in corticosterone-induced insulin resistance in mice. Endocrinology 160: 2367-2387.

Kaur N, Kishore L, Singh R (2016) Attenuating diabetes: What really works? Curr Diabetes Rev 12: 259–278.

Koster R, Anderson M, de Beer EJ (1959) Acetic acid for analgesic screening. Fed Proceed 18: 412–417.

Linhart O, Obreja O, Kress M (2003) The inflammatory mediators serotonin, prostaglandin E2 and bradykinin evoke calcium influx in rat sensory neurons. Neuroscience 118: 69–74.

Lwoff A (1971) Protoza to bacteria and viruses-fifty years with microbes. Annu Rev Microbiol 25: 1–27.

Mascolo N, Izzo AA, Barbato F, Capasso F (1993) Inhibitors of nitric oxide synthetase prevent castor-oil-induced diarrhoea in the rat. Br J Pharmacol 108: 861–864.

Mia S, Roy R, Akter A, Barek MA, Basher MA (2019) Hypoglycemic effect of leaf extract of Fimbristylis miliacea in mice model. Clin Phytoscience 5: 26.

Pace S, Rossi A, Krauth V, Dehm F, Troisi F, Bilancia R, Weinigel C, Rummler S, Werz O, Sautebin L (2017) Sex differences in prostaglandin biosynthesis in neutrophils during acute inflammation. Sci Rep 7: 3759.

Pathan H, Williams J (2012) Basic opioid pharmacology: An update. Br J Pain 6: 11–16.

Shore R, Björne H, Omoto Y, Siemiatkowska A, Gustafsson J-Å, Lindblad M, Holm L (2017) Sex differences and effects of oestrogen in rat gastric mucosal defence. World J Gastroenterol 23: 426–436.

Siegmund E, Cadmus R, Lu G (1957) A method for evaluating both non-narcotic and narcotic analgesics. Proc Soc Exp Biol Med 95: 729–731.

Sorge RE, Mapplebeck JCS, Rosen S, Beggs S, Taves S, Alexander JK, Martin LJ, Austin J-S, Sotocinal SG, Chen D, Yang M, Shi XQ, Huang H, Pillon NJ, Bilan PJ, Tu Y, Klip A, Ji R-R, Zhang J, Salter MW, Mogil JS (2015) Different immune cells mediate mechanical pain hypersensitivity in male and female mice. Nat Neurosci 18: 1081–1083.

Stitt JT (1973) Prosaglandin E1 fever induced in rabbits. J Physiol 232: 163–179.

Suzuki Y, Nakahara K, Ensho T, Murakami N (2017) Sex difference of hyperinsulinemia in the C57BL/6J-Daruma (obese) mouse. J Vet Med Sci 79: 1284–1293.

Tomazetti J, Avila DS, Ferreira AP, Martins JS, Souza FR, Royer C, Rubin MA, Oliveira MR, Bonacorso HG, Martins MA, Zanatta N, Mello CF (2005) Baker yeast-induced fever in young rats: characterization and validation of an animal model for antipyretics screening. J Neurosci Methods 147: 29–35.

Vecchio I, Tornali C, Bragazzi NL, Martini M (2018) The Discovery of Insulin: An Important Milestone in the History of Medicine. Front Endocrinol (Lausanne) 9: 613.

Wald C, Wu C (2010) Of mice and women: The bias in animal models. Science 327(5973): 1571–1572.

Woo H, Okamoto S, Guiney D, Gunn JS, Fierer J (2008) A model of Salmonella colitis with features of diarrhea in SLC11A1 wild-type mice. PLoS One 3: e1603.

Woolfe G, MacDonald AD (1944) The evaluation of the analgesic action of pethidine hydrochloride (demerol). J Pharmacol Exp Ther 80: 300–307.

Yoshitake I, Ohishi E, Kubo K (1991) Hepatoprotective effects of 1-[(2-thiazolin-2-yl)-amino]acetyl-4-(1,3-dithiol-2-ylidene)-2,3,4,5-tetrahydro-1H-1-benzazepin-3,5-dione hydrochloride (KF-14363) in various experimental liver injuries. Jpn J Pharmacol 57: 127–136.

© 2020 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

Kombucha from Rhizophora mucronata

J Pharm Pharmacogn Res 8(5): 410-421, 2020.

Original Article

The kombucha from Rhizophora mucronata Lam. herbal tea: Characteristics and the potential as an antidiabetic beverage

[Kombucha del té de hierbas de Rhizophora mucronata: Características y potencial como bebida antidiabética]

Hardoko*, Evi K. Harisman, Yunita E. Puspitasari

Department of Fisheries and Product Technology, Faculty of Fisheries and Marine Science, Brawijaya University, Jalan Veteran No. 1, Malang 65145, East Java, Indonesia.

Context: Kombucha from tea is reported to be beneficial for health. Moreover, it can be used as a hepatoprotective, antiproliferative, antimicrobial, antidiabetic, and antilipidemic agent and is capable of healing stomach ulcers. But kombucha from other herbal has not been studied, including kombucha from the mangrove (Rhizophora mucronata) fruit.

Aims: To evaluate the characteristics and the antidiabetic potential of kombucha herbal tea from R. mucronata fruit based on in vitro, chemistry, and physical analysis.

Methods: This study was conducted by an experimental method using R. mucronata herbal tea as a kombucha drink with different sugar concentrations (10, 20, 30%) and fermentation time (7, 14, 21 days) with three replications on each experiment. The analyzed parameters were the inhibition of the α-glucosidase enzyme for antidiabetic activity, total phenolics, total acids, and organoleptic characteristics.

Results: The sugar concentration and fermentation time significantly affected the characteristics of the produced kombucha in inhibiting α-glucosidase. The optimum treatment in inhibition was at 10% sugar concentration and 14 days of fermentation time with IC50 of 33.95 ppm. The kombucha from R. mucronata fruit had a pH of 3.11 and contained a total phenolics of 19,679.82 mg GAE/100g, 0.52% of total acids, and was quite preferred by panelists.

Conclusions: Kombucha herbal tea of R. mucronata fruit has the potential as an antidiabetic drink with a lower IC50 value than acarbose drug and commercial kombucha tea.

Keywords: antidiabetic; fruit; a-glucosidase; herbal tea; kombucha; Rhizophora mucronata.


Contexto: Se informa que la kombucha del té es beneficiosa para la salud. Además, puede usarse como un agente hepatoprotector, antiproliferativo, antimicrobiano, antidiabético y antilipidémico y es capaz de curar úlceras estomacales. Pero no se ha estudiado la kombucha de otras hierbas, incluida la kombucha de la fruta del mangle (Rhizophora mucronata).

Objetivos: Evaluar las características y el potencial antidiabético del té de hierbas kombucha de la fruta de R. mucronata con base en análisis in vitro, químicos y físicos.

Métodos: Este estudio se realizó mediante un método experimental utilizando té de hierbas de R. mucronata como bebida de kombucha con diferentes concentraciones de azúcar (10, 20, 30%) y tiempo de fermentación (7, 14, 21 días) con tres repeticiones en cada experimento. Los parámetros analizados fueron la inhibición de la enzima α-glucosidasa para la actividad antidiabética, fenoles totales, ácidos totales y características organolépticas.

Resultados: La concentración de azúcar y el tiempo de fermentación afectaron significativamente las características de la kombucha producida en la inhibición de la α-glucosidasa. El tratamiento óptimo en la inhibición fue a una concentración de azúcar del 10% y 14 días de tiempo de fermentación con IC50 de 33,95 ppm. La kombucha de la fruta de R. mucronata tuvo un pH de 3.11 y contenía un contenido de fenoles totales de 19.679,82 mg GAE/100g, 0,52% del ácido total, y fue muy preferida por los panelistas.

Conclusiones: La kombucha del té de hierbas de la fruta de R. mucronata tiene el potencial de ser una bebida antidiabética con un valor de CI50 más bajo que el fármaco de acarbosa y la kombucha del té comercial.

Palabras Clave: antidiabético; fruta; a-glucosidasa; té de hierbas; kombucha; Rhizophora mucronata.

Download the PDF file .

Citation Format: Hardoko, Harisman EK, Puspitasari YE (2020) The kombucha from Rhizophora mucronata Lam. herbal tea: Characteristics and the potential as an antidiabetic beverage. J Pharm Pharmacogn Res 8(5): 410–421.

© 2020 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

Medicación potencialmente inapropiada en ancianos

J Pharm Pharmacogn Res 7(4): 288-296, 2019.

Original Article | Artículo Original

Medicación potencialmente inapropiada en pacientes ancianos en Santiago de Cuba

[Potentially inappropriate medication in elderly patients in Santiago de Cuba]

Irma L. Ortega López1*, Ivette Reyes Hernández2, Niurka M. Dupotey Varela1, Danneris Lores Delgado3, Yoenia Veranes Vera4, Lilisbeth Pupo Benítez5, Erenis Guerra Prado6

1Departamento de Farmacia Universidad de Oriente. Santiago de Cuba, Cuba.
 2Área Académica de Farmacia. Universidad Autónoma del Estado de Hidalgo. México.
3Farmacia Principal Municipal. Santiago de Cuba, Cuba.
4Hogar de Ancianos “América Labadi Arce”. Santiago de Cuba, Cuba.
5Departamento de Farmacia. Dirección Provincial de Salud. Holguín. Cuba.
6Farmacia Principal Municipal. Colombia. Las Tunas. Cuba.



Context: Several studies have reported the high use of inappropriate medication in the elderly, as well as the associated risks; for this reason, it has become a major health problem.

Aim: To characterize the use of potentially inappropriate medication in the elderly based on the reality observed in Santiago de Cuba.

Methods: A descriptive cross-sectional study was carried out, with a random selection that included elderly patients from the community and institutional care in Santiago de Cuba. The data were obtained by reviewing medical records and interviews with patients/caregivers. The potentially inappropriate medication was identified through the Beer’s Criteria and the Screening Tool of Older Person’s Prescriptions/ Screening Tool to Alert doctors to Right; i.e., appropriate indicated treatment.

Results: There were detected 895 potentially inappropriate medications in 632 patients, which affected 81.01% of them, for an average of 1.41 problems per patient. The predominantly inappropriate medication was independent of the diagnosis, which represented 61.7% of the total detected. The most commonly used drugs or groups of drugs were oral hypoglycemic agents, β-blockers, platelet antiaggregants, psychotropic drugs, inhibitors of angiotensin converting enzyme, nifedipine, digoxin, and non-steroidal anti-inflammatory.

Conclusions: There is a high use of potentially inappropriate medication in the elderly, in the health context of Santiago de Cuba, which may be an expression of the limited attention to health needs related to the use of medications in these patients.

Keywords: drug-related problems; elderly; inadequate prescription; potentially inappropriate medications.


Contexto: Varios estudios han referido el elevado uso de medicación inapropiada en el anciano, así como los riesgos asociados; por tal razón ésta se ha convertido en un problema sanitario de primer orden.

Objetivo: Caracterizar el uso de medicación potencialmente inapropiada en el anciano en base a la realidad observada en Santiago de Cuba.

Métodos: Se realizó un estudio descriptivo de corte transversal, con selección aleatoria que incluyó a pacientes ancianos de la atención comunitaria e institucional, en Santiago de Cuba. Los datos fueron obtenidos por revisión de las historias clínicas y entrevistas a pacientes/cuidadores. La medicación potencialmente inapropiada fue identificada mediante los Criterios de Beer’s y los Screening Tool of Older Person’s Prescriptions / Screening Tool to Alert doctors to Right; i.e., appropriate, indicated treatment.

Resultados: Fueron detectadas 895 medicación potencialmente inapropiada en 632 pacientes, las cuales afectaron al 81,01% de ellos, para un promedio de 1,41 problemas por pacientes. Predominó la medicación inapropiada independiente del diagnóstico, la cual representó el 61,7% del total detectadas. Los fármacos o grupos de fármacos que más se utilizaron fueron: los hipoglucemiantes orales, los β bloqueantes, los antiagregantes plaquetarios, los psicofármacos, los Inhibidores de la enzima convertidora de angiotensina, la nifedipina, la digoxina y los antiinflamatorios no esteroideos.

Conclusiones: Existe elevado uso de medicación potencialmente inapropiada en los ancianos, en el contexto sanitario de Santiago de Cuba, lo cual puede constituir una expresión de la limitada atención a las necesidades de salud relativas al uso de medicamentos en estos pacientes.

Palabras Clave: ancianos; medicación potencialmente inapropiada; prescripción inadecuada; problemas relacionados con medicamentos.

Download the PDF file .

Citation Format: Ortega López IL, Reyes Hernández I, Dupotey Varela NM, Lores Delgado D, Veranes Vera Y, Pupo Benítez L, Guerra Prado E (2019) Medicación potencialmente inapropiada en pacientes ancianos en Santiago de Cuba [Potentially inappropriate medication in elderly patients in Santiago de Cuba].  J Pharm Pharmacogn Res 7(4): 288–296.

© 2019 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

Beneficios de la suplementación con zinc en ratas diabéticas

J Pharm Pharmacogn Res 7(2): 144-155, 2019.

Original Article | Artículo Original

Beneficios de la suplementación con zinc sobre el estado metabólico, redox y de elementos traza en un modelo de diabetes moderada en ratas

[Benefits of zinc supplementation on the metabolic, redox and trace elements status in mild diabetic rats]

Tahiry Gómez1*, Leticia Bequer1, Ángel Molineda2, José L. Molina1, Alain O. Álvarez1, Mayrelis Lavastida1, Geidy Cruz1, Cindy Freire1, Sonia Clapés3

1Unidad de Investigaciones Biomédicas. Universidad de Ciencias Médicas de Villa Clara, Santa Clara, Villa Clara, Cuba.
2Centro de Investigaciones Agropecuarias. Universidad Central “Marta Abreu” de las Villas, Santa Clara, Villa Clara, Cuba.
3Departamento de Bioquímica, Instituto de Ciencias Básicas y Preclínicas “Victoria de Girón”. Universidad de Ciencias Médicas de La Habana, La Habana, Cuba.

*E-mail: :


Context: The function of zinc in the diabetes prevention, its management and complications are not clear.

Aim: To determine the effect of zinc supplementation on the metabolic, redox and trace element status in mild diabetic Wistar rats.

Methods: Thirty-two female Wistar rats equally distributed in four groups were studied: C: Control, CZn: Control-Zn-supplemented, D: Diabetic, DZn: Diabetic-Zn-supplemented. Diabetes was induced by streptozotocin (STZ-100 mg/kg-sc, second postnatal day). In adulthood, the corresponding groups were supplemented with zinc sulfate (ZnSO4x7H2O-100 mg/kg) for 14 days.

Results: Zn supplementation in diabetic rats: -alleviated diabetes markers such as HbA1C, HOMA cell-β index, tolerance to glucose and insulin, polydipsia and polyuria; -decreased the Cu/Zn ratio levels in serum and tissues; -in liver and kidney improved excessive accumulation of Cu and increased the Zn concentrations, without causing toxicity; -increased the reduced glutathione (GSH) levels in liver and kidney and decreased the malonyldialdehyde (MDA) levels in liver, without changes in advanced oxidation protein products (AOPP); -evidenced negative correlation between tissue levels of Zn Vs MDA and AOPP.

Conclusions: Zn supplementation favored glycemic control in rats with moderate diabetes, contributing to recovery of the metabolic, redox and trace elements status. Regulation of diabetes complications was associated with the antioxidant action of Zn. Nutritional supplementation with zinc may be suggested to prevent complications of diabetes in conditions of deficiency of this micronutrient.

Keywords: diabetes mellitus; oxidative stress; rats; zinc.


Contexto: La función del zinc en la prevención de la diabetes, su manejo y complicaciones no está esclarecida.

Objetivo: Determinar el efecto de la suplementación con zinc sobre el estado metabólico, redox y de elementos traza en ratas con diabetes moderada.

Métodos: Se estudiaron 32 ratas Wistar hembras distribuidas equitativamente en cuatro grupos: C: Control, CZn: Control-Zn-suplementado, D: Diabético, DZn: Diabético-Zn-suplementado. La diabetes se indujo con estreptozotocina (STZ-100 mg/kg-sc, segundo día-postnatal). En la adultez los grupos correspondientes se suplementaron con sulfato de zinc (ZnSO4x7H2O-100 mg/kg) durante 14 días.

Resultados: La suplementación con Zn a ratas diabéticas: -moderó marcadores de diabetes como HbA1C, índice HOMA célula-β, tolerancia a la glucosa y la insulina, polidipsia y poliuria; -disminuyó los niveles de la relación Cu/Zn en suero y tejidos; -mejoró en hígado y riñón la excesiva acumulación de Cu e incrementó las concentraciones de Zn, sin provocar toxicidad; -aumentó los niveles de glutatión reducido (GSH) en hígado y riñón y disminuyó los de malonildialdehido (MDA) en hígado, sin cambios en los productos avanzados de oxidación de proteínas (PAOP); -evidenció correlación negativa entre los niveles tisulares de Zn Vs MDA y PAOP.

Conclusiones: La suplementación con Zn favoreció el control glucémico en ratas con diabetes moderada, contribuyendo a la recuperación del estado metabólico, redox y de elementos traza. La regulación de las complicaciones de la diabetes se asoció a la acción antioxidante del Zn. La suplementación nutricional con Zn puede sugerirse para prevenir las complicaciones de la diabetes en condiciones de deficiencia de este micronutriente.

Palabras Clave: diabetes mellitus; estrés oxidativo; ratas; zinc.

Download the PDF file .

Citation Format: Gómez T, Bequer L, Mollineda A, Molina JL, Álvarez AO, Lavastida M, Cruz G, Freire C, Clapés S (2019) Beneficios de la suplementación con zinc sobre el estado metabólico, redox y de elementos traza en un modelo de diabetes moderada en ratas [Benefits of zinc supplementation on the metabolic, redox and trace elements status in mild diabetic rats]. J Pharm Pharmacogn Res 7(2): 144–155.

© 2019 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

Oxidative stress index in arterial hypertension and diabetes mellitus

J Pharm Pharmacogn Res 7(2): 103-115, 2019.

Original Article | Artículo Original

The oxidative stress index in human population with arterial hypertension and diabetes mellitus

[El índice de estrés oxidativo en una población humana con hipertensión arterial y diabetes mellitus]

Alberto J. Núñez Sellés1,2*, Wilfredo I. Mañon Rossi1, Rodolfo Núñez Musa2, Rafael Guillén Marmolejos2, Gregorio Martínez-Sánchez3

1National Evangelic University (UNEV), Paseo de los Periodistas 54, Miraflores, CP 10203, Santo Domingo, Distrito Nacional, Dominican Republic.
2Dominican Institute of Clinical and Pharmacological Research (IDICF), Calle Primera, Bloque VI No. 12, Buenos Aires del Mirador, CP 11109, Santo Domingo, Distrito Nacional, Dominican Republic.
3Independent Consultor, Via Dalmazia 16A, 60126, Ancona, Italy.



Context: A clinical study was conducted in a cohort of human subjects from 60 to 75 years of age in order to assess the correlation between disease diagnosis and oxidative stress (OS) damage in diabetes mellitus (DM) and arterial hypertension (AHT).

Aims: To provide a sound basis to design a clinical protocol for antioxidant adjuvant therapy for DM and AHT.

Methods: The values of the OS index were determined from the experimental values of biomarkers in erythrocyte lysates obtained from human blood samples including total antioxidant levels, specific biomarkers of oxidative damage, and antioxidant enzyme activities. Three study groups were formed: Group I: DM patients (110 subjects), group II: AHT patients (112 subjects); and Control group: Healthy volunteers (123 subjects). The data of all groups were analyzed using SPSS 9.0 software. A nonparametric Friedman test was used to compare several related subgroups, and changes within the groups and subgroups were tested using the Wilcoxon paired test. A Mann-Whitney U test was used to estimate significant differences (p<0.05) between the subgroups.

Results: Severe OS was observed in subgroup IIc (AHT III), moderate OS was observed in subgroups Ib (DM II) and IIb (AHT II), mild OS was observed in subgroup Ia (DM I), and no OS was observed in subgroup IIa (AHT I).

Conclusions: The results support the possible design of clinical trial protocols for adjuvant antioxidant therapy in order to increase the efficacy of standard therapies for AHT II and III and for DM II. Antioxidant therapies for DM I and AHT I are not recommended due to the presence of only mild OS or no OS, respectively.

Keywords: antioxidant therapy; diabetes mellitus; hypertension; oxidative stress; redox biomarkers.


Contexto: Se realizó un estudio clínico en una cohorte de sujetos humanos entre 60 y 75 años de edad para determinar la correlación entre diagnóstico de la enfermedad y daño por estrés oxidativo (EO) en diabetes mellitus (DM) e hipertensión arterial (HTA).

Objetivos: Proporcionar una base sólida para el diseño de un protocolo clínico para la terapia adyuvante antioxidante en DM e HTA.

Métodos: Se determinaron los valores del índice de EO a partir de las determinaciones experimentales de niveles de antioxidantes totales, biomarcadores específicos del daño oxidativo y actividades de enzimas antioxidantes en lisados de eritrocitos obtenidos de muestras de sangre. Se conformaron tres grupos de estudio: Grupo I; pacientes DM (110 sujetos), grupo II; pacientes HTA (112 sujetos), y grupo III; voluntarios sanos (123 sujetos). Los datos de los grupos se analizaron con el programa SPSS 9.0. Se utilizó la prueba no paramétrica de Friedman para comparar entre subgrupos, y los cambios entre grupos se analizaron mediante la prueba de pares de Wilcoxon. Las diferencias significativas entre subgrupos (p<0.05) se estimaron con la prueba de Whitney U.

Resultados: Se observó EO severo en el subgrupo IIc (HTA III), EO moderado en los subgrupos Ib (DM II) y IIb (HTA II), EO leve en el subgrupo Ia (DM I), y no se observó EO en el subgrupo IIa (HTA I).

Conclusiones: Los resultados demuestran el posible diseño de protocolos de ensayos clínicos para incrementar la eficacia de las terapias estándar de la HTA II y III, y DM II, con el uso de terapias antioxidantes adyuvantes, las que no son recomendables para DM I y HTA I, debido a que el EO es leve o no existente, respectivamente.

Palabras Clave: biomarcadores redox; estrés oxidativo; diabetes mellitus; hipertensión arterial; terapia antioxidante.

Download the PDF file .


Citation Format: Núñez Sellés AJ, Mañon Rossi WI, Núñez Musa R, Guillén Marmolejos R, Martínez-Sánchez G (2019) The oxidative stress index in human population with arterial hypertension and diabetes mellitus. J Pharm Pharmacogn Res 7(2): 103–115.

© 2019 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

Fagonia cretica and Citrus paradise effects in diabetic rabbits

J Pharm Pharmacogn Res 5(6): 365-380, 2017.

Original Article | Artículo Original

Antidiabetic and renoprotective effect of Fagonia cretica L. methanolic extract and Citrus paradise Macfad. juice in alloxan induced diabetic rabbits

[Efecto antidiabético y renoprotector del extracto metanólico de Fagonia cretica L. y el jugo de Citrus paradise Macfad. en conejos diabéticos inducidos por aloxano]

Sairah H. Kamran1*, Rana M. Shoaib1, Mobasher Ahmad2, Saiqa Ishtiaq1, Rukhsana Anwar1

1Punjab University College of Pharmacy, University of the Punjab, Allama Iqbal Campus, Lahore – 54000, Pakistan.
2Pharmacy College, Gulab Devi Educational complex, Lahore, Pakistan.



Context: Fagonia cretica is a medicinal herb reported to have flavanoids of potential therapeutic value and Citrus paradisi is a fruit, whose juice is of great therapeutic value due to its anti-hyperglycemic effects.

Aims: To determine anti-hyperglycemic and renal protective effect of methanolic extract of Fagonia cretica and Citrus paradisi juice (grapefruit juice) in alloxan induced diabetic rabbits.

Methods: Diabetes was induced in rabbits by alloxan monohydrate (150 mg/kg, i.p.). The therapies including Fagonia cretica methanolic extract (500 mg/kg), Citrus paradisi juice (7 mL/kg) and sitagliptin (10 mg/kg) were administered (p.o.) to diabetic groups for 14 days. The biochemical parameters, glucose, creatinine, urea, bilirubin, albumin, total protein, globulins and albumin/globulin ratio were estimated.

Results: Fagonia cretica extract and grapefruit juice therapy significantly (p<0.05) reduced glucose levels in diabetic rats. Fagonia cretica extract was more effective anti-hyperglycemic agent than Citrus paradisi juice and sitagliptin. Significant (p<0.05) improvement in kidney function was observed in treated groups, the plant extract showing significant improvement as compared to the other two treatments. The histopathological results verified improvement in structural damage of kidney, liver and pancreas with these treatments.

Conclusions: Fagonica cretica and Citrus paradisi juice therapy markedly improved hyperglycemia and kidney functions in alloxan-induced diabetic rabbits.

Keywords: alloxan; Citrus paradise; diabetes; Fagonia cretica; kidney.


Contexto: Fagonia cretica es una hierba medicinal que posee flavonoides de potencial valor terapéutico y Citrus paradisi es una fruta cuyo jugo es de gran valor terapéutico debido a sus efectos antihiperglicémicos.

Objetivos: Determinar el efecto antihiperglicémico y protector renal del extracto metanólico de Fagonia cretica y el jugo de Citrus paradisi (jugo de toronja) en conejos diabéticos inducidos por aloxano.

Métodos: La diabetes fue inducida en conejos por monohidrato de aloxano (150 mg/kg, i.p.). Se administraron (p.o.) los tratamientos incluyendo el extracto metanólico de Fagonia cretica (500 mg/kg), jugo de Citrus paradisi (7 mL/kg) y sitagliptina (10 mg/kg) a grupos diabéticos durante 14 días. Se estimaron los parámetros bioquímicos, glucosa, creatinina, urea, bilirrubina, albúmina, proteína total, globulinas y relación albúmina/globulina.

Resultados: El extracto de Fagonia cretica y la terapia con jugo de toronja (p<0,05) redujeron significativamente los niveles de glucosa en ratas diabéticas. El extracto de Fagonia cretica fue un agente anti-hiperglucémico más eficaz que el jugo de Citrus paradisi y sitagliptina. Se observó una mejoría significativa (p<0,05) en la función renal en los grupos tratados, el extracto de la planta mostró una mejoría significativa en comparación con los otros dos tratamientos. Los resultados histopatológicos verificaron mejoría en el daño estructural del riñón, hígado y páncreas con estos tratamientos.

Conclusiones: La terapia con extracto de Fagónica cretica y jugo de Citrus paradisi mejoró notablemente la hiperglucemia y las funciones renales en conejos diabéticos inducidos por aloxano.

Palabras Clave: aloxano; Citrus paradise; diabetes; Fagonia cretica; riñón.

Download the PDF file .



Citation Format: Kamran SH, Shoaib RM, Ahmad M, Ishtiaq S, Anwar R (2017) Antidiabetic and renoprotective effect of Fagonia cretica L. methanolic extract and Citrus paradise Macfad. juice in alloxan induced diabetic rabbits. J Pharm Pharmacogn Res 5(6): 365–380.
This article has been cited by:
Dimple, Kumar A, Kumar V, Tomer V (2018) Traditional medicinal systems for treatment of diabetes mellitus: a review. International Journal of Pharmacy and Pharmaceutical Sciences 10(5): 7-17.

© 2017 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

Nephroprotective activity of Pterocarpus marsupium

J Pharm Pharmacogn Res 4(5): 174-186, 2016.

Original Article | Artículo Original

Nephroprotective role of alcoholic extract of Pterocarpus marsupium heartwood against experimentally induced diabetic nephropathy

[Papel nefroprotector del extracto alcohólico del duramen de Pterocarpus marsupium contra la nefropatía diabética inducida experimentalmente]

Pankaj Gupta1*, Preeti Sharma2, Kumari Shanno3, Vivek Jain3, Ashutosh Pareek3, Priyanka Agarwal4, Randhir Singh5, Veena Sharma2*

1Department of Pharmacology, DDPR Central Research Institute for Homoeopathy, Noida, India.
2Department of Biosciences & Biotechnology, Banasthali Vidyapeeth University, Banasthali, India.
3Department of Pharmacy, Banasthali Vidyapeeth University, Banasthali, India.
4Department of Plant Molecular Biology, University of Delhi, South Campus, New Delhi, India.
5College of Pharmacy, Maharishi Markandeshwar University, Mullana, Ambala, Harayana, India.

*E-mail: (PG); (VS)


Context: Heartwood of Pterocarpus marsupium has been widely reported for its effect on diabetes clinical or preclinically. However, role in diabetic complications is yet to be revealed.

Aims: To investigate the effect of alcoholic extract of the heartwood of Pterocarpus marsupiumin experimentally induced diabetic nephropathy in rats.

Methods: The streptozotocin (STZ) 55 mg/kg, i.p., once daily induced diabetes in Sprague-Dawley rats. These animals were treated orally with alcoholic extract of P. marsupium (100, 200 and 400 mg/kg) or glimepiride (10 mg/kg) for 60 days. Body weight, blood glucose, glycosylated hemoglobin (HBA1c), biochemical markers of renal function were estimated on day 30 and at the end of study (day 60). Kidney weight measurement, oxidative stress markers such as lipid peroxidation (TBARS), catalase, superoxide dismutase, reduced glutathione were estimated in kidney tissues, and histopathological evaluation was carried out at the end of study period.

Results: The administration of an alcoholic extract of P. marsupium showed a decrease in blood glucose, HBA1c, kidney weight, serum creatinine, blood urea nitrogen, serum uric acid, urea, urine volume, urine albumin and the level of TBARS. While the increase in urine creatinine, the activity of superoxide dismutase and glutathione were observed when compared to the diabetic control group. This effect was observed significantly at the highest dose of the plant extract. The histopathological study also confirmed that alcoholic extract prevented structural kidney damage.

Conclusions: These results suggest that the alcoholic extract of P. marsupium has renoprotective effects against STZ induced diabetic nephropathy.

Keywords: Antioxidant; biochemical markers; diabetic nephropathy; oxidative stress markers; Pterocarpus marsupium; renoprotective.


Contexto: El duramen de Pterocarpus marsupium ha sido reportado ampliamente por su efecto sobre la diabetes, tanto clínica o preclínicamente. Sin embargo, el papel de las complicaciones diabéticas aún no se ha revelado.

Objetivos: Investigar el efecto del extracto alcohólico del duramen de Pterocarpus marsupiumin sobre la nefropatía diabética inducida experimentalmente en ratas.

Métodos: La estreptozotocina (STZ) 55 mg/kg, i.p., indujo diabetes en ratas Sprague-Dawley. Los animales se trataron oralmente con extracto alcohólico de P. marsupium (100, 200 y 400 mg/kg) o glimepirida (10 mg/kg) durante 60 días. El peso corporal, la glucosa en sangre, la hemoglobina glicosilada (HbA1c), los marcadores bioquímicos de la función renal se determinaron en el día 30 y al final del estudio (día 60). El peso del riñón, los marcadores de estrés oxidativo, tales como peroxidación lipídica (TBARS), catalasa, superóxido dismutasa y glutatión reducido se estimaron en los tejidos renales. La evaluación histopatológica se llevó a cabo al final del período de estudio.

Resultados: El extracto alcohólico de P. marsupium mostró una disminución en la glucosa en sangre, la HbA1c, el peso del riñón, creatinina sérica, nitrógeno ureico en sangre, ácido úrico en suero, urea, el volumen de orina, la albúmina de la orina y la concentración de TBARS. Se observó el aumento de la creatinina en orina, la actividad de la superóxido dismutasa y el glutatión en comparación con el grupo de control diabético. Este efecto se observó significativamente en la dosis más alta del extracto vegetal. El estudio histopatológico confirmó también que el extracto alcohólico impidió el daño renal estructural.

Conclusiones: El extracto alcohólico de P. marsupium tiene efectos nefroprotectores contra la nefropatía diabética inducida por STZ.

Palabras Clave: Antioxidante; marcadores bioquímicos; marcadores de estrés oxidativo; nefropatía diabética; Pterocarpus marsupium; renoprotectivo.

Download the PDF file .

Citation Format: Gupta P, Sharma P, Shanno K, Jain V, Pareek A, Agarwal P, Singh R, Sharma V (2016) Nephroprotective role of alcoholic extract of Pterocarpus marsupium heartwood against experimentally induced diabetic nephropathy. J Pharm Pharmacogn Res 4(5): 174-186.

© 2016 Journal of Pharmacy & Pharmacognosy Research (JPPRes)


J Pharm Pharmacogn Res 2(Suppl. 1): S84, 2014

Special supplement with the abstract book of LATINFARMA 2013



Marrero Faz E1, Sánchez Calero E1, Young L2 and Harvey A.2

1Grupo de Desarrollo Biofarmacéutico, Centro Nacional de Sanidad Agropecuaria (CENSA), Mayabeque, Cuba. E-mail:
2Strathclyde Institute for Biomedical Sciences, Strahclyde University, Scotland, United Kingdom.

The present study is aimed to determine the underlying mechanism of the antidiabetic efficacy of seven medicinal Cuban plants: Allophylus cominia (L.) Sw., Ocimum tenuiflorum, Persea americana, Sechium edule green and white varieties, Momordica charantia and Jatropha aethiopica, some of them reported in Cuban ethnomedicine. The aqueous extracts from these plants and their fractions were evaluated on type 2 diabetes therapeutic targets: protein tyrosine phosphatase 1B (PTP1B) and dipeptidyl peptidase-IV (DPPIV) enzymatic activities and glucose uptake, in order to identify the candidate plants that can be used more effectively in treating diabetes. All in vitro assays were performed on 96 micro well plates. In PTP1B enzymatic assay (6, 8-difluoro-4-methylumbelliferyl phosphate) (DiFMUP) was used as substrate and as standard inhibitor [Bis(4-Trifluoromethylsulfonamidophenyl)-1,4-diisopropylbenzine] (TFMS); in DPPIV enzymatic assay [Gly-Pro-7-amido-4-methylcoumarin hydrobromide] (Gly-proAMC) was used as substrate and as standard inhibitor [(3N-[(2S, 3S)-2amino-3-methyl-pentanoyl]-1,3-thiazolidine) hemifumarate] (P32/98); in both assays, the enzymatic activity inhibition was calculated with the fluorescence values using an excitation wavelength of 360 nm and an emission wavelength of 460 nm. Glucose uptake studies were performed on fully differentiated 3T3-L1 adipocytes using 2-deoxy-D[3H] glucose and insulin as a positive control, the radioactivity incorporated into the cells was measured with a microplate scintillation counter. The results revealed that only aqueous extracts from A cominia, O tenuiflorum and P americana inhibited the enzymatic activity of PTP1B in an extract concentration dependent manner, resulting more active the more polar fractions from A. cominia and P. americana extracts and fraction 2 from O. tenuiflorum extract. All the extracts and fractions showed only a slight inhibition of enzymatic activity of DPPIV, at higher concentrations, A cominia aqueous extract also inhibited the enzymatic activity of this protease in an extract concentration dependent manner, only fraction 1 from P americana aqueous extract showed a moderate inhibitory effect. A. cominia, O. tenuiflorum and P. americana extracts exhibited a moderate enhance of glucose uptake in 3T3-L1 adipocytes, resulting more active fractions 6 and 10 from A. cominia extract and fraction 10 from P. americana extract. The present research demonstrated that aqueous extracts from A. cominia, P. americana and O. tenuiflorum and some of its fractions (AcF6, AcF10 and PaF10), are promising candidates for the development of antidiabetic phytopharmaceuticals and for drug discovery issues as well. Further research will be necessary in order to explore new molecular targets related with this metabolic disorder, such as: biomarkers of carbohydrates and lipids metabolism as well as to identify the secondary metabolites responsible of antidiabetic activity.