Tag Archives: antidiabetic

Acute toxicity of interruptin-rich extract in rats

J. Pharm. Pharmacogn. Res., vol. 10, no. 5, pp. 800-811, September-October 2022.

DOI: https://doi.org/10.56499/jppres22.1392_10.5.800

Original Article

Acute oral toxicological evaluation in Wistar rats of interruptin-rich extract from Cyclosorus terminans and its in vitro antidiabetic potential

[Evaluación toxicológica oral aguda en ratas Wistar del extracto de Cyclosorus terminans rico en interruptina y su potencial antidiabético in vitro]

Sujinda Songtrai1,2, Kwanchanok Dejyong3, Sireewan Kaewsuwan1,2*

1Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Songkhla, 90110, Thailand.

2Phytomedicine and Pharmaceutical Biotechnology Excellence Center, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Songkhla, 90110, Thailand.

3Laboratory Animal Facility Unit, Faculty of Science, Prince of Songkla University, Songkhla 90110, Thailand.

*E-mail: songsri.k@psu.ac.th


Context: Interruptins A and B derivatives from edible fern Cyclosorus terminans have been reported properties including anti-bacterial, anti-cancer, anti-oxidation, anti-inflammatory, and antidiabetic activities. Unfortunately, studies on its safety are still scarce.

Aims: To evaluate the acute oral toxicity of interruptin-rich extract (IRE) from C. terminans in Wistar rats and examine the antidiabetic potential of IRE in vitro.

Methods: IRE was evaluated cytotoxicity by MTT assay and potency of glucose consumption in hepatocyte and skeletal muscle cells. IRE was evaluated for acute toxicity in Wistar rats by following OECD 420 guidelines. Wistar rats were single oral administrated of 2000 mg/kg IRE and further observed for 14 days. LCMS was assessed for verifying IRE absorption into the bloodstream. Hematological, biochemical parameters and microscopic examination of heart, liver and kidney were evaluated.

Results: IRE demonstrated no cytotoxicity toward hepatocytes and skeletal muscle cells and facilitated glucose consumption into cells. In the acute toxicity study, on day 14, after a single oral administration of 2000 mg/kg IRE, no mortality and behavioral alterations. There was no change in metabolic parameters. Histopathology of heart, liver and kidney showed normal architecture.

Conclusions: Thus, LD50 of IRE was considered superior to 2000 mg/kg. Hence the extract can be utilized safely and could provide a capability for diabetic control.

Keywords: acute toxicity; antidiabetic; Cyclosorus terminans; histopathology; Wistar rats.



Contexto: Se han informado propiedades de los derivados de las interruptinas A y B del helecho comestible Cyclosorus terminans, que incluyen actividades antibacterianas, anticancerígenas, antioxidantes, antiinflamatorias y antidiabéticas. Desafortunadamente, los estudios sobre su seguridad aún son escasos.

Objetivos: Evaluar la toxicidad oral aguda del extracto rico en interruptina (IRE) de C. terminans en ratas Wistar y examinar el potencial antidiabético de IRE in vitro.

Métodos: Se evaluó la citotoxicidad de IRE mediante ensayo MTT y la potencia de consumo de glucosa en hepatocitos y células de músculo esquelético. Se evaluó la toxicidad aguda de IRE en ratas Wistar siguiendo las directrices de la OCDE 420. A ratas Wistar se les administró por vía oral una sola dosis de 2000 mg/kg de IRE y se observaron durante 14 días. Se evaluó mediante LCMS para verificar la absorción de IRE en el torrente sanguíneo. Se evaluaron parámetros hematológicos, bioquímicos y examen microscópico de corazón, hígado y riñón.

Resultados: IRE no demostró citotoxicidad hacia los hepatocitos y las células del músculo esquelético y facilitó el consumo de glucosa en las células. En el estudio de toxicidad aguda, el día 14, tras una única administración oral de 2000 mg/kg IRE, no hubo mortalidad ni alteraciones del comportamiento. No hubo cambios en los parámetros metabólicos. La histopatología de corazón, hígado y riñón mostró una arquitectura normal.

Conclusiones: Así, la DL50 de IRE se consideró superior a 2000 mg/kg. Por lo tanto, el extracto se puede utilizar de forma segura y proporcionaría una capacidad para el control de la diabetes.

Palabras Clave: toxicidad aguda; antidiabético; Cyclosorus terminans; histopatología; ratas Wistar.


Citation Format: Songtrai S, Dejyong K, Kaewsuwan K (2022) Acute oral toxicological evaluation in Wistar rats of interruptin-rich extract from Cyclosorus terminans and its in vitro antidiabetic potential. J Pharm Pharmacogn Res 10(5): 800–811. https://doi.org/10.56499/jppres22.1392_10.5.800

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© 2022 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

Curcuma zanthorrhiza as antidiabetic agent

J Pharm Pharmacogn Res 10(2): 206-217, 2022.

DOI: https://doi.org/10.56499/jppres21.1175_10.2.206

Original Article

Computational study of Curcuma zanthorrhiza Roxb compounds as potential antidiabetic towards alpha-amylase, alpha-glucosidase, and Keap1 inhibition

[Estudio computacional de compuestos de Curcuma zanthorrhiza Roxb como posibles antidiabéticos frente a la inhibición de alfa-amilasa, alfa-glucosidasa e Keap1]

Sasangka Prasetyawan1*, Anna Safitri1, Sri Rahayu2

1Department of Chemistry, Faculty of Mathematics and Natural Sciences, Brawijaya University, 65145, Malang, East Java, Indonesia.

2Department of Biology, Faculty of Mathematics and Natural Sciences, Brawijaya University, 65145, Malang, East Java, Indonesia.

*E-mail: sasangka@ub.ac.id


Context: Curcuma zanthorrhiza Roxb is traditionally used as a medicinal herb that is believed might cure some diseases. However, there is still a lack of information about the underlying mechanism of bioactive compounds from C. zanthorrhiza, which has antidiabetic properties.

Aims: To analyze the bioactive compounds of C. zanthorrhiza as inhibitors of alpha-amylase, alpha-glucosidase, and Keap1, which play a significant role in diabetes mellitus (DM) progression.

Methods: The bioactive compounds of C. zanthorrhiza were screened its antidiabetic activity by PASS server. To determine the interaction between selected active compounds of C. zanthorrhiza, molecular docking was performed by PyRx 0.8 software and visualized in Biovia Discovery Studio and PyMol, respectively. The pharmacological properties of selected active compounds of C. zanthorrhiza were then evaluated using the Lipinski rule and SwissADME.

Results: There were 20 from 60 bioactive compounds of C. zanthorrhiza, which have antidiabetic properties. The molecular docking analysis revealed that five from 20 bioactive compounds might be inhibiting alpha-amylase, alpha-glucosidase, and Keap1. Curcumin might be potential as an alpha-amylase, alpha-glucosidase, and Keap1 inhibitor. Curcumin and xanthorrizol were the compounds that meet pharmacological properties criteria.

Conclusions: The data suggested that C. zanthorriza compounds may be a promising inhibitor candidate of three key target proteins that have been highly involved in DM. Further research is needed to validate the in vitro and in vivo activity of the C. zanthorrhiza compounds or be used as a primary compound for target DM progression.

Keywords: alpha-amylase; alpha-glucosidase; antidiabetic; Curcuma zanthorrhiza; Keap1.


Contexto: Curcuma zanthorrhiza Roxb se usa tradicionalmente como una hierba medicinal que se cree que podría curar algunas enfermedades. Sin embargo, todavía falta información sobre el mecanismo subyacente de los compuestos bioactivos de C. zanthorrhiza, que tiene propiedades antidiabéticas.

Objetivos: Analizar los compuestos bioactivos de C. zanthorrhiza como inhibidores de la alfa-amilasa, alfa-glucosidasa y Keap1, que juegan un papel significativo en la progresión de la diabetes mellitus (DM).

Métodos: Los compuestos bioactivos de C. zanthorrhiza se cribaron su actividad antidiabética por el servidor PASS. Para determinar la interacción entre compuestos activos seleccionados de C. zanthorrhiza, se realizó el acoplamiento molecular mediante el software PyRx 0.8 y se visualizó en Biovia Discovery Studio y PyMol, respectivamente. A continuación, se evaluaron las propiedades farmacológicas de compuestos activos seleccionados de C. zanthorrhiza utilizando la regla de Lipinski y SwissADME.

Resultados: Se encontraron 20 de 60 compuestos bioactivos de C. zanthorrhiza, que tienen propiedades antidiabéticas. El análisis de acoplamiento molecular reveló que cinco de los 20 compuestos bioactivos podrían estar inhibiendo la alfa-amilasa, la alfa-glucosidasa y Keap1. La curcumina podría ser un inhibidor de la alfa-amilasa, alfa-glucosidasa e Keap1. La curcumina y el xanthorrizol fueron los compuestos que cumplieron con los criterios de propiedades farmacológicas.

Conclusiones: Los datos sugirieron que los compuestos de C. zanthorriza pueden ser un candidato inhibidor prometedor de tres proteínas diana clave que han estado altamente involucradas en la DM. Se necesitan más investigaciones para validar la actividad in vitro e in vivo de los compuestos de C. zanthorrhiza o para usarse como compuesto principal para la progresión de la DM diana.

Palabras Clave: alfa-amilasa; alfa-glucosidasa; antidiabético; Curcuma zanthorrhiza; Keap1.

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Citation Format: Prasetyawan S, Safitri A, Rahayu S (2022) Computational study of Curcuma zanthorrhiza Roxb compounds as potential antidiabetic towards alpha-amylase, alpha-glucosidase, and Keap1 inhibition. J Pharm Pharmacogn Res 10(2): 206–217. https://doi.org/10.56499/jppres21.1175_10.2.206

© 2022 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

Metabolic effects of M. charantia foliage extract

J Pharm Pharmacogn Res 9(4): 537-548, 2021.

Original article

Antidiabetic, hypolipidemic, antioxidant and anti-inflammatory effects of Momordica charantia L. foliage extract

[Efectos antidiabéticos, hipolipemiantes, antioxidantes y anti-inflamatorios del extracto foliar de Momordica charantia L.]

Alicia Lagarto Parra1, Roberto Menéndez Soto-del Valle2, Janet Piloto Ferrer1, Pham Thi Nguyet Hang3, Nguyen Thi Phuong3, Addis Bellma1, Orestes Darío López4, Dunia Casanave Guarnaluce1, Carlos Rodríguez Ferrada1, Alejandro S. Padrón Yaquis1, Nicte González Alfonso1, Gilberto L. Pardo-Andreu5*

1Center for Pharmaceuticals Research and Development. Av. 26 # 1605 b/ Av. Boyeros and Puentes Grandes, Havana, Cuba

2Cuban Center for Neurosciences (CNEURO), Ave 25 # 15202. Cubanacán, Playa. PO 11600. La Habana

3National Institute of Medicinal Material. 3B Quang Trung Str, Hoan Kiem Dist, Hanoi, Viet Nam.

4Facultad de Ciencia e Ingeniería en Alimentos, Universidad Técnica de Ambato, Ambato, Ecuador.

5Center for Research and Biological Evaluations, Institute of Pharmaceutical and Foods Sciences, University of Havana (UH), Av. 23 # 2317 b/ 214 and 222, La Coronela, La Lisa, PO 13600 Havana, Cuba.

*E-mail: gpardo@ifal.uh.cu


Context: Momordica charantia (Cucurbitaceae) is extensively distributed in tropical areas, and it is traditionally used as antidiabetic. Nevertheless, few studies supporting the metabolic effects of its foliage extracts have been reported elsewhere.

Aims: To evaluate the effects of M. charantia foliage extract (MCh) on blood glucose and lipids levels in animal models of hyperglycemia. The anti-inflammatory and antioxidant properties together with the acute toxicity and genotoxic effects were also assessed.

Methods: An MCh powder was obtained by spray-drying techniques. The anti-hyperglycemic and hypolipidemic effects of MCh were evaluated in the glucose tolerance test and the alloxan-induced diabetes, respectively. The in vitro and ex vivo MCh antioxidant effects were assessed against the 2,2´-azinobis3-ethylbenzothiazoline-6-sulfonic acid (ABTS), peroxyl, and superoxide anion radicals. The MCh anti-inflammatory effects were also assessed together with its toxicological profile by means of the Acute Toxic Class Method, and the chromosome aberration assay.

Results: MCh administered orally diminished the glucose and lipids levels in normoglycemic healthy rats and alloxan-induced hyperglycemic mice. Strong in vitro free radical scavenging effects was demonstrated by MCh against ABTS, peroxyl, and superoxide anion radicals. The extract also improved the free radical scavenging ability of diabetic mice serum. Moreover, MCh reduced the weight of cotton-induced granulomas in mice, the exudate volume, and its leukocyte counts in carrageenan-induced pleurisy in rats. Very low MCh toxicity was also verified.

Conclusions: The hypoglycemic, hypolipidemic, anti-inflammatory, and antioxidant activities here observed make the spray-drayed powder from M. charantia foliage extract an interesting alternative for the correction of diabetes and its complications.

Keywords: antidiabetic; anti-inflammatory; antioxidant; foliage extract; toxicity; Momordica charantia.

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Contexto: La Momordica charantia (Cucurbitaceae) se encuentra ampliamente distribuida en las áreas tropicales y se usa tradicionalmente como antidiabético. Sin embargo, pocos estudios sustentan los efectos metabólicos de sus extractos foliares.

Objetivos: Evaluar los efectos de un extracto foliar de M. charantia (MCh) sobre los niveles de glucosa y lípidos en modelos animales de hiperglicemia. También se evaluaron sus propiedades anti-inflamatorias y antioxidantes, así como su toxicidad aguda oral y efectos genotóxicos.

Métodos: Se obtuvo un polvo de MCh por técnicas de secado por aspersión. Sus efectos anti-hiperglicémicos e hipolipemiantes se evaluaron en modelos de tolerancia a la glucosa y de diabetes inducida por aloxano, respectivamente. Los efectos antioxidantes in vitro y ex vivo se evaluaron frente a los radicales 2,2´-azinobis3-ethylbenzotiazolina-6- ácido sulfónico, peroxilo, y el radical anión superóxido. Se evaluaron además los efectos anti-inflamatorios de MCh junto a su perfil toxicológico a través del Método de las Clases para la toxicidad aguda oral y el ensayo de aberración cromosómica.

Resultados: La administración oral de MCh disminuyó los niveles de glucosa y lípidos en ratas saludables normo-glicémicas y en ratones hiperglicémicos por acción del aloxano. Se demostró una potente actividad secuestradora de los radicales ABTS, peroxilo y superóxido, in vitro. El extracto también mejoró la actividad secuestradora de radicales libres del suero de ratones diabéticos. Además, el MCh redujo el peso de los granulomas inducidos por algodón en ratones, y en el modelo de pleuresía inducida por carragenina en ratas, redujo el volumen de exudado y su conteo de leucocitos. Se demostró una baja toxicidad para el MCh.

Conclusiones: Las actividades hipoglicémicas, hipolipemiantes, anti-inflamatorias y antioxidantes aquí observadas, hacen del extracto de M. charantia obtenido a partir de un secado por aspersión, una alternativa interesante para corregir la diabetes y sus complicaciones.

Palabras Clave: antidiabético; anti-inflamatorio; antioxidante; extracto foliar; toxicidad; Momordica charantia.

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Citation Format: Lagarto A, Menéndez R, Piloto J, Thi P, Thi N, Bellma A, Dario O, Casanave D, Rodríguez C, Padron AS, González N, Pardo-Andreu G (2021) Antidiabetic, hypolipidemic, antioxidant and anti-inflammatory effects of Momordica charantia L. foliage extract. J Pharm Pharmacogn Res 9(4): 537–548.

© 2021 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

Hibiscus surattensis: Insulin secretion and pancreatic tissue improvement

J Pharm Pharmacogn Res 9(4): 454-464, 2021.

Original article

Insulin secretion and repairing pancreatic tissue damage on diabetic mice treated with the extract and active fraction of Hibiscus surattensis L. leaves

[Secreción de insulina y reparación del daño del tejido pancreático en ratones diabéticos tratados con el extracto y la fracción activa de hojas de Hibiscus surattensis L.]

Yuliet1*, Elin Yulinah Sukandar2, Nur Atik3, I Ketut Adnyana2

1Department of Pharmacy, Faculty of Mathematics and Natural Sciences, Tadulako University, Palu 94148, Central Sulawesi, Indonesia.

2Department of Pharmacology and Toxicology, School of Pharmacy, Bandung Institute of Technology, Bandung 40132, West Java, Indonesia.

3Department of Biomedical Sciences, Faculty of Medicine, Padjadjaran University, Jatinangor 45363, West Java, Indonesia.

*E-mail: yuliet@untad.ac.id; yuliet_susanto@yahoo.com


Context: Diabetes is a chronic health condition with insulin disturbance. Hibiscus surattensis L. is a medicinal plant and plays a pivotal role in diabetes.

Aims: To evaluate the effect of H. surattensis leaves extract to increase insulin secretion and repair pancreatic tissue damage in streptozotocin (STZ)‑induced diabetic mice.

Methods: This research used male mice (Swiss Webster) administrated by STZ 100 mg/kg BW to induce diabetes. Animals were divided into eight groups (n = 6) consisting of normal control, diabetic control, glibenclamide, ethanol extract 50, ethyl acetate fraction, and water fraction with doses of 25 and 50 mg/kg BW, respectively. Treatment was given for 28 days. The evaluation was carried out on blood glucose levels, insulin levels, HOMA-β, and the pancreatic islets by the morphometric analysis were evaluated. All data were analyzed using SPSS 16.0.

Results: Extract and active fraction of H. surattensis leaves, especially ethyl acetate fractions (25 and 50 mg/kg BW) significantly (p<0.05) reduced fasting blood glucose levels, insulin levels, and the strength of pancreatic β cells (HOMA-β) increased in STZ induced diabetic mice. Histopathological results in pancreatic confirmed the effect of H. surattensis to increase the number of islets significantly in Langerhans and pancreatic β-cells compared to the diabetic control group (p<0.05).

Conclusions: Extract, and active fraction of H. surattensis leaves affect the insulin secretion and repairing the pancreatic tissue damage on diabetic mice, the most optimal therapy on the administration of ethyl acetate fraction.

Keywords: antidiabetic; Hibiscus surattensis L.; insulin; pancreas; streptozotocin.

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Contexto: La diabetes es una enfermedad crónica con alteración de la insulina. Hibiscus surattensis L. es una planta medicinal y juega un papel fundamental en la diabetes.

Objetivos: Evaluar el efecto del extracto de hojas de H. surattensis para aumentar la secreción de insulina y reparar el daño del tejido pancreático en ratones diabéticos inducidos por estreptozotocina (STZ).

Métodos: Esta investigación utilizó ratones macho (Swiss Webster) administrados por STZ 100 mg/kg BW para inducir diabetes. Los animales se dividieron en ocho grupos (n = 6) que consistían en control normal, control diabético, glibenclamida, extracto de etanol 50, fracción de acetato de etilo y fracción de agua con dosis de 25 y 50 mg/kg de peso corporal, respectivamente. El tratamiento se administró durante 28 días. La evaluación se realizó sobre niveles de glucosa en sangre, niveles de insulina, HOMA-β, y se evaluaron los islotes pancreáticos mediante análisis morfométrico. Todos los datos se analizaron con SPSS 16.0.

Resultados: El extracto y la fracción activa de hojas de H. surattensis, especialmente las fracciones de acetato de etilo (25 y 50 mg/kg de peso corporal) redujeron significativamente (p<0,05) los niveles de glucosa en sangre en ayunas, los niveles de insulina y la fuerza de las células β pancreáticas (HOMA-β) aumentó en ratones diabéticos inducidos por STZ. Los resultados histopatológicos en páncreas confirmaron el efecto de H. surattensis para aumentar significativamente el número de islotes en Langerhans y células β pancreáticas en comparación con el grupo de control diabético (p<0,05).

Conclusiones: El extracto y fracción activa de hojas de H. surattensis afectan la secreción de insulina y reparan el daño del tejido pancreático en ratones diabéticos, la terapia más óptima sobre la administración de fracción de acetato de etilo.

Palabras Clave: antidiabético; estreptozotocina; Hibiscus surattensis L.; insulina; páncreas.

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Citation Format: Yuliet, Sukandar EY, Atik N, Adnyana IK (2021) Insulin secretion and repairing pancreatic tissue damage on diabetic mice treated with the extract and active fraction of Hibiscus surattensis L. leaves. J Pharm Pharmacogn Res 9(4): 454–464.

© 2021 Journal of Pharmacy & Pharmacognosy Research (JPPRes)