J. Pharm. Pharmacogn. Res., vol. 11, no. 2, pp. 243-254, March-April 2023.

DOI: https://doi.org/10.56499/jppres22.1566_11.2.243

Original Article

System optimization and validation to improve thin-layer chromatography of roselle calyces (Hibiscus sabdariffa L.) required by the Indonesian Herbal Pharmacopoeia Edition II

[Optimización y validación del sistema para mejorar la cromatografía en capa fina de cálices de rosa mosqueta (Hibiscus sabdariffa L.) requerida por la Farmacopea Herbal Indonesia Edición II]

Bhujangga Agung Ayu Sri Kartika Dewi, Kartini Kartini^*

Department of Pharmaceutical Biology, Faculty of Pharmacy, University of Surabaya, Surabaya, Indonesia.

*E-mail: kartini@staff.ubaya.ac.id

Abstract

Context: Roselle (Hibiscus sabdariffa L.) is one of the traditional crude drugs monographed in the Indonesian Herbal Pharmacopoeia Edition II (IHP II). As per IHP II requirements, a TLC pattern should be used in its authentication. However, the TLC system described for this purpose does not produce a clear reference chromatogram, often leading to inconclusive results.

Aims: To develop and validate TLC systems of H. sabdariffa calyces for a better-quality chromatogram than those listed in the IHP II, thereby facilitating crude drugs authentication.

Methods: To optimize TLC for H. sabdariffa, sixteen systems, differing in stationary phase, mobile phase composition, and/or visualization reagent were tested. The TLC system was then validated using several parameters such as analyte stability during chromatography, analyte stability in the extract solution and on the TLC plate, stability of the derivatization result, and precision on a plate as well as intermediate precision.

Results: Two systems (I and II) were successfully designed and applied to evaluate H. sabdariffa quality. System I used Si gel 60 F₂₅₄ for the stationary phase, ethyl acetate-formic acid-glacial acetic acid-water (100:11:11:2) for the mobile phase, H. sabdariffa’s ethanol extract (5%, 20 µL) for the test solution, cyanidin 3-O-glucoside (100 ppm, 4 µL) as a reference, no derivatization, and detection with visible light. System II combined Si gel 60 F₂₅₄ for the stationary phase, ethyl acetate-formic acid-glacial acetic acid-toluene-water (80:11:11:20:19), H. sabdariffa’s ethanol extract (5%, 20 µL) for the test solution, chlorogenic acid (1000 ppm, 2 µL) and caffeic acid (50 ppm, 2 µL) as references, the visualizing reagent NP/PEG, and investigation under 366 nm UV light.

Conclusions: Both systems are simple but have good stability and precision, thus facilitating H. sabdariffa calyx authentication and paving the way for developing content analysis methods for H. sabdariffa markers.

Keywords: authenticity; herbal pharmacopoeia; quality evaluation; roselle; TLC pattern.

Resumen

Contexto: La rosa mosqueta (Hibiscus sabdariffa L.) es una de las drogas crudas tradicionales monografiadas en la segunda edición de la Farmacopea Herbal Indonesia (PHI II). Según los requisitos de la PHI II, se debe utilizar un patrón de TLC para su autentificación. Sin embargo, el sistema de TLC descrito para este fin no produce un cromatograma de referencia claro, lo que a menudo conduce a resultados no concluyentes.

Objetivos: Desarrollar y validar sistemas de TLC de cálices de H. sabdariffa para obtener un cromatograma de mejor calidad que los listados en el PHI II, facilitando así la autentificación de drogas crudas.

Métodos: Para optimizar la TLC para H. sabdariffa, se probaron dieciséis sistemas, que diferían en la fase estacionaria, la composición de la fase móvil y/o el reactivo de visualización. A continuación, se validó el sistema de TLC utilizando varios parámetros, como la estabilidad del analito durante la cromatografía, la estabilidad del analito en la solución del extracto y en la placa de TLC, la estabilidad del resultado de la derivatización y la precisión en una placa, así como la precisión intermedia.

Resultados: Se diseñaron y aplicaron con éxito dos sistemas (I y II) para evaluar la calidad de H. sabdariffa. El sistema I utilizó Si gel 60 F254 como fase estacionaria, acetato de etilo-ácido fórmico-ácido acético glacial-agua (100:11:11:2) como fase móvil, extracto de etanol de H. sabdariffa (5%, 20 µL) como solución de prueba, cianidina 3-O-glucósido (100 ppm, 4 µL) como referencia, sin derivatización, y detección con luz visible. El sistema II combinó Si gel 60 F254 para la fase estacionaria, acetato de etilo-ácido fórmico-ácido acético glacial-tolueno-agua (80:11:11:20:19), extracto de etanol de H. sabdariffa (5%, 20 µL) para la solución de prueba, ácido clorogénico (1000 ppm, 2 µL) y ácido cafeico (50 ppm, 2 µL) como referencias, el reactivo de visualización NP/PEG, y la investigación bajo luz UV de 366 nm.

Conclusiones: Ambos sistemas son sencillos pero tienen buena estabilidad y precisión, facilitando así la autentificación del cáliz de H. sabdariffa y allanando el camino para desarrollar métodos de análisis de contenido para marcadores de H. sabdariffa.

Palabras Clave: autenticidad; farmacopea herbal; evaluación de la calidad; rosa mosqueta; patrón TLC.

Citation Format: Dewi BAASK, Kartini K (2023) System optimization and validation to improve thin-layer chromatography of roselle calyces (Hibiscus sabdariffa L.) required by the Indonesian Herbal Pharmacopoeia Edition II. J Pharm Pharmacogn Res 11(2): 243–254. https://doi.org/10.56499/jppres22.1566_11.2.243

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© 2023 Journal of Pharmacy & Pharmacognosy Research

J. Pharm. Pharmacogn. Res., vol. 11, no. 2, pp. 229-242, March-April 2023.

DOI: https://doi.org/10.56499/jppres22.1505_11.2.229

Original Article

Chitosan–alginate porous scaffold incorporated with hydroalcoholic Zingiber officinale Roscoe extract for neural tissue engineering

[Estructura porosa de quitosano-alginato incorporada con extracto hidroalcohólico de Zingiber officinale Roscoe para la ingeniería del tejido neural]

Hassan Sohrabian Kafraj¹, Maryam Alipour², Abdolhosein Shiravi¹, Vida Hojati¹, Mojtaba Khaksarian²*

¹Department of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran.

²Razi Herbal Medicines Research Center and Department of Physiology, Lorestan University of Medical Sciences, Khorramabad, Iran.

*E-mail: mojkhaksar@lums.ac.ir, mojkhaksar@yahoo.com

Abstract

Context: Preparing a suitable substrate for the culture of neural stem cells and their proliferation in neural tissue engineering is of paramount importance.

Aims: To evaluate the effect of the hydroalcoholic Zingiber officinale extract incorporated in the chitosan-alginate scaffold (Chi-Alg-Zo) on nerve tissue.

Methods: The porous scaffolds developed in the present study were investigated in terms of their surface properties, chemical interaction, crystallinity, thermal stability, porosity percentage, pore sizes, degradability, and water absorption properties. To this end, the following tests were performed: Field emission scanning electron microscope (FE-SEM), Fourier-transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD), thermal gravimetric analysis (TGA), porosity based on liquid replacement, Image-J analysis, and water degradation and absorption test. Mouse neural stem/progenitor cells (NS/PCs) were harvested from the embryonic mouse brain. NSCs were seeded on scaffolds incorporated with hydroalcoholic Z. officinale extract. The MTT assay was done for the survival and the proliferation of neural stem/progenitor cells (NS/PCs) on scaffolds.

Results: Results indicated the good capacity of Chi-Alg-Zo for proliferation and differentiation into glial (astrocytes and oligodendrocytes) lineages. A suitable surface, which was provided for cellular interaction, led to the advancement of cell survival, connectivity, proliferation, and separation of NSCs.

Conclusions: The present study evaluated the separation of stem cells on the scaffold, finding that the expression of the glial fibrillary acidic protein (GFAP) and Oligo4 markers was higher in Chi-Alg scaffolds containing hydroalcoholic Z. officinale extract. Chi-Alg-Zo scaffolds could be suitable candidates for neural tissue engineering.

Keywords: neural tissue engineering; neural stem/progenitor cells; chitosan-alginate scaffold; ginger extract.

Resumen

Contexto: La preparación de un sustrato adecuado para el cultivo de las células madre neurales y su proliferación en la ingeniería del tejido neural es de suma importancia.

Objetivos: Evaluar el efecto del extracto hidroalcohólico de Zingiber officinale incorporado al andamio de quitosano-alginato (Chi-Alg-Zo) en el tejido nervioso.

Métodos: Los andamios porosos desarrollados en el presente estudio fueron investigados en cuanto a sus propiedades superficiales, interacción química, cristalinidad, estabilidad térmica, porcentaje de porosidad, tamaño de los poros, degradabilidad y propiedades de absorción de agua. Para ello, se realizaron las siguientes pruebas: Microscopio electrónico de barrido de emisión de campo (FE-SEM), espectroscopia infrarroja por transformada de Fourier (FTIR), difracción de polvo de rayos X (XRD), análisis termo gravimétrico (TGA), porosidad basada en la sustitución de líquidos, análisis Image-J, y ensayo de degradación y absorción de agua. Las células madre/progenitoras neurales de ratón (NSC/PCs) fueron cosechadas del cerebro embrionario de ratón. Las NSC se sembraron en andamios incorporados con extracto hidroalcohólico de Z. officinale. Se realizó el ensayo MTT para la supervivencia y la proliferación de las células madre/progenitoras neurales (NS/PCs) en los andamios.

Resultados: Los resultados indicaron la buena capacidad de Chi-Alg-Zo para la proliferación y diferenciación en linajes gliales (astrocitos y oligodendrocitos). Una superficie adecuada, que se proporcionó para la interacción celular condujo al avance de la supervivencia celular, la conectividad, la proliferación y la separación de las NSC.

Conclusiones: El presente estudio evaluó la separación de las células madre en el andamio, encontrando que la expresión de los marcadores de proteína ácida fibrilar glial (GFAP) y Oligo4 era mayor en los andamios Chi-Alg que contenían extracto hidroalcohólico de Z. officinale. Los andamios Chi-Alg-Zo podrían ser candidatos adecuados para la ingeniería del tejido neural.

Palabras Clave: ingeniería de tejidos neurales; células madre/progenitoras neurales; andamio de quitosano-alginato; extracto de jengibre.

Citation Format: Sohrabian Kafraj H, Alipour M, Shiravi A, Hojati V, Khaksarian M (2022) Chitosan-alginate porous scaffold incorporated with hydroalcoholic Zingiber officinale Roscoe extract for neural tissue engineering. J Pharm Pharmacogn Res 11(2): 229–242. https://doi.org/10.56499/jppres22.1505_11.2.229

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© 2023 Journal of Pharmacy & Pharmacognosy Research

J. Pharm. Pharmacogn. Res., vol. 11, no. 2, pp. 216-228, March-April 2023.

DOI: https://doi.org/10.56499/jppres22.1509_11.2.216

Original Article

Oral supplementation of Ilex paraguariensis extract and eggshell membrane exhibit beneficial effects on the skin of mature male rats

[La suplementación oral de extracto de Ilex paraguariensis y membrana de cáscara de huevo muestran efectos beneficiosos sobre la piel de ratas macho maduras]

Maria R. Ramirez^1,2*, Ignacio Rintoul^2,3, Manuel Leiva¹, José S. Molli^2,3, Juan C. Yori^2,3

¹Instituto Universitario de Ciencias de la Salud, Fundación Barceló, Centeno 710, Santo Tome CP 3340, Argentina.

²Consejo Nacional de Investigaciones Científicas Técnicas (CONICET), Buenos Aires C1033AAJ, Argentina.

³Facultad deIngeniería Química. Universidad Nacional del Litoral, Colectora Ruta Nac, 168, Santa Fe CP 3000, Argentina.

*E-mail: mr.ramirez@conicet.gov.ar

Abstract

Context: Ilex paraguariensis (IP), a South American plant mostly consumed as an infusion, contains several phytocompounds with demonstrated positive effects on skin health and photoprotective properties. Eggshell membrane (ESM), a by-product of the poultry industry, also presents photoprotective properties. Both IP and ESM contain compounds that absorb ultraviolet radiation (UVR) and stop the mechanisms by which UVR damages the skin. The synergistic effects of these natural products on the reparation of skin structure and dermal collagen production deserves to be investigated.

Aims: To determine to what extent the oral supplementation of IP and ESM, administrated individually or in combination, promotes beneficial effects on the skin of mature Wistar rats.

Methods: The chemical composition of IP and ESM and the spectrophotometric solar protection factor (SPF) of the IP extract were characterized. In vitro, antioxidant and anti-inflammatory effects were assessed using erythrocytes. In vivo investigation consisted of macro and microscopic image analysis and diagnosis of the skin of the dorsal region of rats.

Results: The IP extract showed low SPF capacity combined with a protective effect against AAPH-induced erythrocyte haemolysis. IP extract inhibited erythrocyte haemolysis induced by both hypotonic solution and heat. The antioxidant and anti-inflammatory activity of the IP could be explained in terms of its membrane-stabilizing properties. Histologic analysis showed an increase in the collagen content of the skin of supplemented rats. A clear synergistic increase in collagen levels resulted when IP and ESM were administered together.

Conclusions: IP and ESM are beneficial for skin health, present synergistic effects, and could be used as ingredients in oral cosmetics.

Keywords: chemopreventive capacity; membrane-stabilizing property; skin structure.

Resumen

Contexto: El Ilex paraguariensis (IP), planta sudamericana consumida principalmente en infusión, contiene varios fitocompuestos con efectos positivos demostrados sobre la salud de la piel y propiedades fotoprotectoras. La membrana de cáscara de huevo (ESM), un subproducto de la industria avícola, también presenta propiedades fotoprotectoras. Tanto la PI como la ESM contienen compuestos que absorben la radiación ultravioleta (RUV) y detienen los mecanismos por los que la RUV daña la piel. Merece la pena investigar los efectos sinérgicos de estos productos naturales en la reparación de la estructura de la piel y la producción de colágeno dérmico.

Objetivos: Determinar en qué medida la suplementación oral de IP y ESM, administrados individualmente o en combinación, promueve efectos beneficiosos sobre la piel de ratas Wistar maduras.

Métodos: Se caracterizó la composición química de IP y ESM y el factor de protección solar (SPF) espectrofotométrico del extracto de IP. In vitro, se evaluaron los efectos antioxidantes y anti-inflamatorios utilizando eritrocitos. La investigación in vivo consistió en el análisis y diagnóstico por imagen macro y microscópica de la piel de la región dorsal de ratas.

Resultados: El extracto IP mostró una baja capacidad SPF combinada con un efecto protector contra la hemólisis eritrocitaria inducida por AAPH. El extracto IP inhibió la hemólisis eritrocitaria inducida tanto por solución hipotónica como por calor. La actividad antioxidante y anti-inflamatoria de IP podría explicarse por sus propiedades estabilizadoras de la membrana. El análisis histológico mostró un aumento del contenido de colágeno de la piel de las ratas suplementadas. Cuando se administraron conjuntamente IP y ESM se produjo un claro aumento sinérgico de los niveles de colágeno.

Conclusiones: IP y ESM son beneficiosos para la salud de la piel, presentan efectos sinérgicos y podrían utilizarse como ingredientes en cosméticos orales.

Palabras Clave: capacidad quimiopreventiva; propiedad estabilizadora de la membrana; estructura de la piel.

Citation Format: Ramirez MR, Rintoul I, Leiva M, Molli S, Yori JC (2023) Oral supplementation of Ilex paraguariensis extract and eggshell membrane exhibit beneficial effects on the skin of mature male rats. J Pharm Pharmacogn Res 11(2): 216–228. https://doi.org/10.56499/jppres22.1509_11.2.216

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© 2023 Journal of Pharmacy & Pharmacognosy Research

J. Pharm. Pharmacogn. Res., vol. 11, no. 2, pp. 208-215, March-April 2023.

DOI: https://doi.org/10.56499/jppres22.1508_11.2.208

Original Article

Anticancer activity of N-(4-t-butylbenzoyl)-N’-phenylthiourea: Molecular docking, synthesis, and cytotoxic activity in breast and cervical cancer cells

[Actividad anticancerígena de la N-(4-t-butilbenzoil)-N’-feniltiourea: acoplamiento molecular, síntesis y actividad citotóxica en células de cáncer de mama y de cuello uterino]

Dini Kesuma¹, Aguslina Kirtishanti^2*, Citra H.A. Makayasa¹, I Gede A. Sumartha¹

¹Department of Pharmaceutical Chemistry, University of Surabaya, Surabaya, Indonesia.

²Department of Clinical and Community Pharmacy, University of Surabaya, Surabaya, Indonesia.

*E-mail: aguslina@staff.ubaya.ac.id

Abstract

Context: N-(4-t-butylbenzoyl)-N’-phenylthiourea, a derivative compound of N-benzoyl-N’-phenylthiourea, has relatively high lipophilicity with the epidermal growth factor receptor and silent mating type information regulation-1 enzyme as its molecular targets.

Aims: To determine the anticancer activity of N-(4-t-butylbenzoyl)-N’-phenylthiourea as an in silico and in vitro anticancer candidate for the breast and cervical cancer.

Methods: In silico test was performed to predict the cytotoxic activity using AutoDock Vina. This activity was also measured in vitro using the Microculture Tetrazolium Technique assays of three cancer cells (MCF-7, T47D, and HeLa) and normal cells (Vero cells).

Results: In silico test predicted that N-(4-t-butylbenzoyl)-N’-phenylthiourea was more cytotoxic at epidermal growth factor receptor than silent mating type information regulation-1 receptor. In vitro tests showed it exhibited cytotoxic activities against MCF-7, T47D, and HeLa without harming Vero cells.

Conclusions: N-(4-t-butylbenzoyl)-N’-phenylthiourea has the potential as an anticancer candidate for breast and cervical cancers.

Keywords: breast cancer; cervical cancer;EGFR; N-(4-t-butylbenzoyl)-N’-phenylthiourea; SIRT1.

Resumen

Contexto: La N-(4-t-butilbenzoil)-N’-feniltiourea, un compuesto derivado de la N-benzoil-N’-feniltiourea, tiene una lipofilia relativamente alta y tiene como dianas moleculares el receptor del factor de crecimiento epidérmico y la enzima de regulación silenciosa de la información de tipo apareamiento-1.

Objetivos: Determinar la actividad anticancerosa de la N-(4-t-butilbenzoil)-N’-feniltiourea como candidato anticanceroso in silico e in vitro para el cáncer de mama y de cuello uterino.

Métodos: Se realizó un ensayo in silico para predecir la actividad citotóxica utilizando AutoDock Vina. Esta actividad también se midió in vitro mediante ensayos con la técnica de microcultivo de tetrazolio en tres células cancerosas (MCF-7, T47D y HeLa) y células normales (células Vero).

Resultados: La prueba in silico predijo que la N-(4-t-butilbenzoil)-N’-feniltiourea era más citotóxica para el receptor del factor de crecimiento epidérmico que para el receptor de regulación-1 de la información de tipo apareamiento silencioso. Las pruebas in vitro mostraron que presentaba actividades citotóxicas contra las células MCF-7, T47D y HeLa sin dañar las células Vero.

Conclusiones: La N-(4-t-butilbenzoil)-N’-feniltiourea tiene potencial como candidato anticancerígeno para los cánceres de mama y de cuello uterino.

Palabras Clave: cáncer de mama; cáncer de cuello de útero; EGFR; N-(4-t-butilbenzoil)-N’-feniltiourea; SIRT1.

Citation Format: Kesuma D, Kirtishanti A, Makayasa CHA, Sumartha IGA (2023) Anticancer activity of N-(4-t-butylbenzoyl)-N’-phenylthiourea: Molecular docking, synthesis, and cytotoxic activity in breast and cervical cancer cells. J Pharm Pharmacogn Res 11(2): 208–215. https://doi.org/10.56499/jppres22.1508_11.2.208

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© 2023 Journal of Pharmacy & Pharmacognosy Research

J. Pharm. Pharmacogn. Res., vol. 11, no. 1, pp. 198-207, January-February 2023.

DOI: https://doi.org/10.56499/jppres22.1538_11.1.198

Original Article

Advance in transdermal delivery of calcitonin using nanostructured lipid carrier-based emulgel

[Avance en la administración transdérmica de calcitonina mediante un emulgel nanoestructurado basado en un portador lipídico]

Zahrotunisa, Silvia Surini^*

Laboratory of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Indonesia, Depok, West Java, 16424, Indonesia.

*E-mail: silvia@farmasi.ui.ac.id

Abstract

Context: Peptide-protein drugs have a very important role as therapeutic agents for various diseases. However, their therapeutic use has many barriers to delivery, such as large molecular weight, reduced stability during the manufacturing process and storage, and poor absorption when administered orally. One of peptide-protein drugs is calcitonin, a polypeptide of 32 amino acids used to overcome high levels of calcium in the blood, such as hyperparathyroidism. Nevertheless, drug delivery is still challenging to develop.

Aims: To evaluate a calcitonin nanostructured lipid carrier-based emulgel, which could penetrate through the stratum corneum, and meet the stability requirements.

Methods: Four formulas of calcitonin nanostructured lipid carrier (NLC) were prepared by the double emulsion-evaporation method, then all formulas were characterized in terms of particle size, polydispersity index, zeta potential, entrapment efficiency, and particle morphology. Calcitonin NLCs were then formulated into NLC-based emulgel. Further, in vitro penetration and stability of NLC calcitonin emulgel studies were conducted.

Results: The 75:1 ratio of total lipid to the drug (F2) was optimal for calcitonin-loaded NLC with a particle size of 135.6 nm, an index polydispersity of 0.1, the zeta potential of 34.7 mV, and an entrapment efficiency of 99.6%. According to the percutaneous penetration study, the calcitonin NLC-based-emulgel resulted in a fivefold enhancement compared to the non-NLC calcitonin emulgel. Moreover, the stability study illustrated calcitonin levels after six months were 46.09-60.95% and 43.45-68.59% at storage conditions of 5 ± 3ºC and 25 ± 2ºC/RH 60 ±5 %, respectively.

Conclusions: The calcitonin NLC-based-emulgel produced a fivefold enhancement permeation through the stratum corneum.

Keywords: calcitonin; emulgel; nanostructured lipid carrier; peptide-protein drug; transdermal.

Resumen

Contexto: Los fármacos péptido-proteicos desempeñan un papel muy importante como agentes terapéuticos para diversas enfermedades. Sin embargo, su uso terapéutico presenta muchas barreras para su administración, como un gran peso molecular, una estabilidad reducida durante el proceso de fabricación y el almacenamiento, y una absorción deficiente cuando se administran por vía oral. Uno de los fármacos péptido-proteicos es la calcitonina, un polipéptido de 32 aminoácidos que se utiliza para superar los niveles elevados de calcio en sangre, como en el hiperparatiroidismo. Sin embargo, la administración del fármaco sigue siendo difícil de desarrollar.

Objetivos: Evaluar un emulgel nanoestructurado a base de un portador lipídico de calcitonina, que pueda penetrar a través del estrato córneo y cumplir los requisitos de estabilidad.

Métodos: Se prepararon cuatro fórmulas de portador lipídico nanoestructurado (NLC) de calcitonina por el método de doble emulsión-evaporación, y luego se caracterizaron todas las fórmulas en términos de tamaño de partícula, índice de polidispersidad, potencial zeta, eficiencia de atrapamiento y morfología de partícula. A continuación, las NLC de calcitonina se formularon en emulgeles basados en NLC. Además, se realizaron estudios de penetración y estabilidad in vitro del emulgel de NLC de calcitonina.Resultados: La relación 75:1 entre el lípido total y el fármaco (F2) fue óptima para la NLC cargada de calcitonina, con un tamaño de partícula de 135,6 nm, un índice de polidispersidad de 0,1, un potencial zeta de 34,7 mV y una eficiencia de atrapamiento del 99,6%. Según el estudio de penetración percutánea, el emulgel de calcitonina basado en NLC quintuplicó la eficacia del emulgel de calcitonina sin NLC. Además, el estudio de estabilidad ilustró que los niveles de calcitonina después de seis meses eran del 46,09-60,95% y del 43,45-68,59% en condiciones de almacenamiento de 5 ± 3ºC y 25 ± 2ºC/RH 60 ± 5%, respectivamente.

Conclusiones: El emulgel a base de NLC de calcitonina produjo una permeación cinco veces mayor a través del estrato córneo.

Palabras Clave: calcitonina; emulgel; fármaco péptido-proteico; portador lipídico nanoestructurado; transdérmica.

Citation Format: Zahrotunisa, Surini S (2023) Advance in transdermal delivery of calcitonin using nanostructured lipid carrier-based emulgel. J Pharm Pharmacogn Res 11(1): 198–207. https://doi.org/10.56499/jppres22.1538_11.1.198

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© 2023 Journal of Pharmacy & Pharmacognosy Research

J. Pharm. Pharmacogn. Res., vol. 11, no. 1, pp. 191-197, January-February 2023.

DOI: https://doi.org/10.56499/jppres22.1502_11.1.191

Original Article

Anti-leukemic activity of Cyperus rotundus L.on human acute myeloid leukemia HL-60 cells in vitro

[Actividad antileucémica de Cyperus rotundus L. sobre células humanas de leucemia mieloide aguda HL-60 in vitro]

Sulistyo Mulyo Agustini¹, Edi Widjajanto², Muhaimin Rifa’i³, Sofia Mubarika Haryana⁴, Nurdiana⁵, Diana Lyrawati⁵, Usi Sukorini⁶, Noviana Dwi Lestari^7*

¹Department of Pathology, Faculty of Medicine, Muhammadiyah Malang University, Malang, East Java, Indonesia.

²Department of Clinical Pathology, Faculty of Medicine, Brawijaya University, Malang, East Java, Indonesia.

³Department of Biology, Faculty of Mathematics and Natural Sciences, Brawijaya University, Malang, East Java, Indonesia.

⁴Department of Histology and Cell Biology, Faculty of Medicine, Gadjah Mada University, Indonesia.

⁵School of Pharmacy, Faculty of Medicine, Brawijaya University, Malang, Indonesia.

⁶Department of Clinical Pathology, Medical Faculty, Gadjah Mada University, Yogyakarta, Indonesia.

⁷Medical Education Study Program, Faculty of Medicine, Muhammadiyah Malang University, Malang, Indonesia.

*E-mail: novianalestari@umm.ac.id; novianadwi.lestari@yahoo.co.id

Abstract

Context: Acute myeloid leukemia (AML) is the most common form of acute leukemia. Currently, many people use medicinal herbs for the treatment of cancers. Nut grass (Cyperus rotundus L.) is a medicinal plant widely used in conventional medicine due to its role as an anti-cancer.

Aims: To evaluate the effect of Cyperus rotundus tuber (CRT) ethanolic extract on cell proliferation, differentiation, cell cycle, and apoptotic of HL-60 cells.

Methods: HL-60 cells line as a model for AML was cultured under the influence of CRT extract concentrations (35.4, 354, and 3540 µg/mL) for 48 h. Furthermore, the cell was subjected to carboxyfluorescein succinimidyl ester staining for proliferation, using a CD117 marker for differentiation. Annexin V-FITC and PI for cell cycle and apoptosis. The effect of this herb was studied by flow cytometry. The data were statistically analyzed with one-way ANOVA (p≤0.05) and the Tukey test using SPSS version 16 for Windows.

Results: The results showed that the CRT inhibited proliferation activity, differentiation, cell cycle arrest, and apoptosis.

Conclusions: The data clearly showed the potential anti-cancer activity of CRT on HL-60 cells and suggested that it could help develop promising therapeutic agents for AML treatments.

Keywords: acute myeloid leukemia; apoptosis; cell cycle; Cyperus rotundus; HL-60 cells line.

Resumen

Contexto: La leucemia mieloide aguda (LMA) es la forma más común de leucemia aguda. En la actualidad, muchas personas utilizan hierbas medicinales para el tratamiento de los cánceres. La hierba de la nuez (Cyperus rotundus L.) es una planta medicinal ampliamente utilizada en la medicina convencional debido a su papel como anticancerígeno.

Objetivos: Evaluar el efecto del extracto etanólico del tubérculo de Cyperus rotundus (CRT) sobre la proliferación celular, la diferenciación, el ciclo celular y la apoptosis de las células HL-60.

Métodos: Se cultivó la línea celular HL-60 como modelo de LMA bajo la influencia de concentraciones de extracto de CRT (35,4; 354 y 3540 µg/mL) durante 48 h. Además, las células se sometieron a tinción con éster succinimidílico de carboxifluoresceína para la proliferación, y con un marcador CD117 para la diferenciación. Annexin V-FITC y PI para el ciclo celular y la apoptosis. El efecto de este extracto se estudió mediante citometría de flujo. Los datos se analizaron estadísticamente con ANOVA unidireccional (p≤0,05) y la prueba de Tukey utilizando SPSS versión 16 para Windows.

Resultados: Los resultados mostraron que el CRT inhibió la actividad de proliferación, diferenciación, detención del ciclo celular y apoptosis.

Conclusiones: Los datos mostraron claramente la potencial actividad anticancerígena del CRT en células HL-60 y sugirieron que podría ayudar a desarrollar agentes terapéuticos prometedores para tratamientos de LMA.

Palabras Clave: apoptosis; células HL-60; ciclo celular; Cyperus rotundus; leucemia mieloide aguda.

Citation Format: Agustini SM, Widjajanto E, Rifa’i M, Haryana SM, Nurdiana, Lyrawati D, Sukorini U, Lestari ND (2023) Anti-leukemic activity of Cyperus rotundus L. on human acute myeloid leukemia HL-60 cells in vitro. J Pharm Pharmacogn Res 11(1): 191–197. https://doi.org/10.56499/jppres22.1502_11.1.191

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© 2023 Journal of Pharmacy & Pharmacognosy Research

J. Pharm. Pharmacogn. Res., vol. 11, no. 1, pp. 179-190, January-February 2023.

DOI: https://doi.org/10.56499/jppres22.1533_11.1.179

Original Article

Fungistatic effect of Moringa oleifera Lam. on the metabolism changes of Candida albicans

[Efecto fungistático de Moringa oleifera Lam. sobre los cambios en el metabolismo de Candida albicans]

Basri A. Gani^1*, Cut Soraya², Vinna Kurniawati Sugiaman³, Fitri Yunita Batubara⁴, Dharli Syafriza⁵, Silvia Naliani⁶, Sri Rezeki⁷, Subhani Jakfar⁸, Muhammad Nazar⁹, Kemala Hayati¹⁰

¹Department of Oral Biology, Denstistry Faculty, Universitas Syiah Kuala. Jl., Kopelma Darussalam, Kecamatan Syiah Kuala, Kota Banda Aceh, Indonesia.

²Department of Conservative Dentistry, Dentistry Faculty, Universitas Syiah Kuala. Jl. Kopelma Darussalam, Kecamatan Syiah Kuala, Kota Banda Aceh, Indonesia.

³Department of Oral Biology, Dentistry Faculty, Universitas Kristen Maranatha. Jl. Prof. Drg. M.P.H. No. 65, Bandung, Jawa Barat, Indonesia.

⁴Department of Conservative Dentistry, Dentistry Faculty, Universitas Sumatera Utara, Jl. Alumni No.2, Kampus USU, Medan, Sumatera Utara, Indonesia.

⁵Department of Pedodontics, Dentistry Faculty, Universitas Syiah Kuala. Jl., Kopelma Darussalam, Kecamatan Syiah Kuala, Kota Banda Aceh, Indonesia.

⁶Department of Prosthodontics, Dentistry Faculty, Universitas Kristen Maranatha. Jl. Prof. Drg. Surya Sumantri, M.P.H. No. 65, Bandung, Jawa Barat, Indonesia.

⁷Department of Oral Medicine, Dentistry Faculty, Universitas Syiah Kuala. Jl., Kopelma Darussalam, Kecamatan Syiah Kuala, Kota Banda Aceh, Indonesia.

⁸Department of Dental Material, Denstistry Faculty, Universitas Syiah Kuala. Jl., Kopelma Darussalam, Kecamatan Syiah Kuala, Kota Banda Aceh, Indonesia.

⁹Department of Chemistry Education, Faculty of Teacher and Training, Universitas Syiah Kuala.  Jl. Tgk. Hasan Krueng Kalee, Kopelma Darussalam, Kecamatan Syiah Kuala, Kota Banda Aceh, Aceh, Indonesia.

¹⁰Department of Dental Radiology, Dentistry Faculty, Universitas Syiah Kuala. Jl. Kopelma Darussalam, Kecamatan Syiah Kuala, Kota Banda Aceh, Aceh. Indonesia.

*E-mail: basriunoe@unsyiah.ac.id

Abstract

Context: Candida albicans is a pathological agent that triggers oral candidiasis because C. albicans can adapt to changes to increase growth and adhesion through biofilm formation mechanisms. Moringa oleifera Lam. has been reported to have fungistatic properties and increases the metabolism change of C. albicans.

Aims: To evaluate the fungistatic effect of M. oleifera leaves ethanolic extract (MOLE) on the metabolism changes of C. albicans cells associated with growth and biofilm formation.

Methods: The assessment of metabolism changes (stress response and metabolic alterations) of C. albicans by the action of MOLE was performed by mean of FTIR, growth assessment by spectrophotometry, biofilm formation with 1% crystal violet, also read by spectrophotometry, and observation of biofilm mass with a microscope.

Results: MOLE showed substantial absorption values based on topological polar surface area (<140 Å2). Concentrations of 25% and 6.25% of MOLE increased the stress response (metabolism changes) of C. albicans (66-75%), meanwhile 50% and nystatin (100.000 IU/mL)were similar in inducing metabolism changes of C. albicans. All concentrations of M. oleifera could inhibit the growth of C. albicans at all incubation times (24, 48, and 72 h) with an Optical Density (OD) of 0.02-0.05 (<300 CFU/mL) and were able to degrade the biofilm formation of C. albicans on a scale substantial at 24 and 48 h (OD>0.4), and moderate scale at 72 h (OD 0.2-0.39).

Conclusions: The extract of M. oleifera has increased metabolism changes (stress response) of C. albicans cells, which correlate with the ability to inhibit growth and biofilm formation for 24, 48, and 72 h.

Keywords: biofilm; Candida albicans; fungistatic; growth; stress response.

Resumen

Contexto: Candida albicans es un agente patológico que desencadena la candidiasis oral porque C. albicans puede adaptarse a los cambios para aumentar el crecimiento y la adhesión a través de mecanismos de formación de biopelículas. Se ha informado que Moringa oleifera Lam. tiene propiedades fungistáticas y aumenta el cambio de metabolismo de C. albicans.

Objetivos: Evaluar el efecto fungistático del extracto etanólico de hojas de M. oleifera (MOLE) sobre los cambios en el metabolismo de las células de C. albicans asociados con el crecimiento y la formación de biopelículas.

Métodos: La evaluación de los cambios en el metabolismo (respuesta al estrés y alteraciones metabólicas) de C. albicans por acción de MOLE fue realizada mediante FTIR, la evaluación del crecimiento mediante espectrofotometría, la formación de biofilm con cristal violeta al 1%, también leído mediante espectrofotometría, y la observación de la masa del biofilm con un microscopio.

Resultados: MOLE presentó valores de absorción sustanciales basados en el área de superficie polar topológica (<140 Å2). Las concentraciones de 25% y 6,25% de MOLEaumentaron la respuesta de estrés (cambios en el metabolismo) de C. albicans (66-75%), mientras que el 50% y la nistatina (100.000 UI/mL) fueron similares en la inducción de cambios en el metabolismo de C. albicans. Todas las concentraciones de M. oleifera pudieron inhibir el crecimiento de C. albicans en todos los tiempos de incubación (24, 48 y 72 h) con una densidad óptica (DO) de 0,02-0,05 (<300 ufc/mL) y fueron capaces de degradar la formación de biopelículas de C. albicans en una escala sustancial a las 24 y 48 h (DO>0,4), y moderada a las 72 h (DO 0,2-0,39).

Conclusiones: El extracto de M. oleifera ha aumentado los cambios en el metabolismo (respuesta al estrés) de las células de C. albicans, que se correlacionan con la capacidad de inhibir el crecimiento y la formación de biopelículas durante 24, 48 y 72 h.

Palabras Clave: biopelícula; Candida albicans; crecimiento; fungistático; respuesta al estrés.

Citation Format: Gani BA, Soraya C, Sugiaman VK, Batubara FY, Syafriza D, Naliani S, Rezeki S, Jakfar S, Nazar M, Hayati K (2023) Fungistatic effect of Moringa oleifera Lam. on the metabolism changes of Candida albicans. J Pharm Pharmacogn Res 11(1): 179–190. https://doi.org/10.56499/jppres22.1533_11.1.179

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© 2023 Journal of Pharmacy & Pharmacognosy Research

J. Pharm. Pharmacogn. Res., vol. 11, no. 1, pp. 160-178, January-February 2023.

DOI: https://doi.org/10.56499/jppres22.1472_11.1.160

Expert Opinion

Conceptos y aplicaciones de los parámetros farmacocinéticos: Una guía para el salón de clases

[Concepts and applications of pharmacokinetic parameters: A guide for the classroom]

Jorge Duconge-Soler^1*, Víctor Mangas Sanjuan², Gledys Reynaldo Fernández³

¹Departamento de Ciencias Farmacéuticas, Escuela de Farmacia, Universidad de Puerto Rico, PO Box 365067, 00936-5067, San Juan, Puerto Rico.

²Departamento de Farmacia, Tecnología Farmacéutica y Parasitología, Facultad de Farmacia, Universidad de Valencia, 46100 Burjassot, Valencia, España.

³Departamento de Farmacia, Instituto de Farmacia y Alimentos, Universidad de La Habana, Calle 222 y 23 Ave. La Coronela, La Lisa, 13600, Habana, Cuba.

*E-mail: jorge.duconge@upr.edu

Abstract

Context: Pharmacokinetic studies play a fundamental role in making informed decisions during the drug development stage and fulfilling regulatory agencies’ requirements for drug approval. Disposition profiles of plasma drug concentrations over time can be characterized by using non-compartmental analysis, compartmental and physiological-based modeling. These models allow us to determine the pharmacokinetic parameters that best describe the absorption, distribution, metabolism, and excretion (ADME) processes.

Aims: To develop a conceptual and practical guide for the classroom on the most relevant pharmacokinetic parameters and their applications.

Results: The apparent volume of distribution (Vd), systemic drug clearance (CL), bioavailability (F) and elimination half-life (t_1/2) are among the most relevant pharmacokinetic parameters discussed in this article. The Vd describes the relationship at equilibrium between the amount of drug in the body and its plasma concentrations after distribution, used to calculate the initial dose to reach the target drug concentration. The CL describes the relationship between plasma drug concentrations and the rate of elimination from the body, allowing calculation of a maintenance dosing rate to maintain an average target concentration at steady-state. The t_1/2 is the time required to halve the plasma drug concentration, whereas F is critical to understand the biological performance of the drug formulation.

Conclusions: In this teacher’s topic text, we emphasize the importance of these parameters for optimizing strategies of model-informed dose individualization. Indeed, they are crucial for predicting systemic drug exposures and how long the drug will last in the body, as well as time to steady state after multiple-dosing regimens.

Keywords: bioavailability; clearance; elimination half-life; pharmacokinetic parameters; volume of distribution.

Resumen

Contexto: Los estudios farmacocinéticos juegan un papel fundamental en la toma de decisiones informadas durante la etapa de desarrollo de fármacos y para su aprobación final por las agencias reguladoras. Los perfiles de disposición sistémica del fármaco se caracterizan mediante análisis no-compartimental, modelos compartimental y de base fisiológica, permitiendo determinar los parámetros farmacocinéticos que describen la absorción, distribución, metabolismo y excreción (ADME).

Objetivos: Desarrollar una guía conceptual y práctica para el salón de clases sobre los parámetros farmacocinéticos más relevantes y sus aplicaciones.

Resultados: El volumen aparente de distribución (Vd), el aclaramiento sistémico (CL), la biodisponibilidad (F) y el tiempo de vida media de eliminación (t_1/2) están entre los parámetros farmacocinéticos más relevantes discutidos en este artículo. El Vd describe la relación entre la cantidad de fármaco en el cuerpo y sus concentraciones plasmáticas post-equilibrio distributivo y se utiliza para calcular la dosis inicial. El CL describe la relación entre las concentraciones plasmáticas del fármaco y su velocidad de eliminación, lo que permite calcular la dosis para mantener la concentración deseada. El t_1/2 es el tiempo necesario para reducir a la mitad su concentración plasmática, mientras que F es fundamental para comprender el rendimiento biológico de la formulación.

Conclusiones: En este texto educativo, enfatizamos la importancia de estos parámetros para optimizar las estrategias de individualización de dosis asistida por modelación. Estos parámetros son fundamentales para predecir la exposición sistémica al fármaco y cuánto este durará en el cuerpo, así como el tiempo requerido para alcanzar el estado estacionario después de múltiples dosis.

Palabras Clave: aclaramiento; biodisponibilidad; parámetros farmacocinéticos; tiempo de vida media de eliminación; volumen de distribución.

Citation Format: Duconge Soler J, Mangas Sanjuan V, Reynaldo Fernández G (2023) Conceptos y aplicaciones de los parámetros farmacocinéticos: Una guía para el salón de clases [Concepts and applications of pharmacokinetic parameters: A guide for the classroom]. J Pharm Pharmacogn Res 11(1): 160–178. https://doi.org/10.56499/jppres22.1472_11.1.160

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© 2023 Journal of Pharmacy & Pharmacognosy Research

J. Pharm. Pharmacogn. Res., vol. 11, no. 1, pp. 137-159, January-February 2023.

DOI: https://doi.org/10.56499/jppres22.1459_11.1.137

Original Article

Ethnobotanical study of medicinal plants in the Fez-Meknes region of Morocco

[Estudio etnobotánico de plantas medicinales en la región de Fez-Meknes de Marruecos]

Sara Tlemcani^1*, Amal Lahkimi², Noureddine Eloutassi², Ahmed Bendaoud², Anouar Hmamou², Hicham Bekkari¹

¹Laboratory of Biotechnology, Conservation and Valorization of Natural Phytoresources, Faculty of Sciences, University Sidi Mohamed Ben Abdellah, Fez, Morocco.

²Laboratory of Molecular Organometallic Materials Engineering and Environment, Faculty of Sciences, University Sidi Mohamed Ben Abdellah, Fez, Morocco.

*E-mail: sara.tlemcani@usmba.ac.ma

Abstract

Context: The region of Fez-Meknes has a wide variety of aromatic and medicinal plants that can be explored in different ways to draw their virtues and overcome human health problems.

Aims: To identify ethnobotanically the main medicinal plants and collect data about their uses in the region of Fez.

Methods: During each interview, both the personal information and the plants used were collected. The questionnaire revealed the use frequency of each part of the plants (VPP). It also sheds light on the importance of each species (RFC). Furthermore, it showed the relative importance of the families and the method of preparation (FIV).

Results: The results disclosed the richness of the region in terms of medicinal plants. A total of 57 species were identified and grouped into 24 families. The most abundant families were Lamiaceae (FIV = 5.461), Compositae (FIV= 6.085), and Apiaceae (FIV = 6.307). The most cited species were Plantago major L. (RFC = 27.3%), Olea europaea L. (RFC = 31.3 %), and Daphne gnidium L. (RFC = 32.6%). The leaves are the most plant part used (VPP = 0.416). The most used preparation method was decoction (32%). The most declared pathologies were digestive (16%), dermatological (15%), and respiratory affections (13%).

Conclusions: The ethnobotanical study showed the region’s floristic richness and allowed the identification of the different plants involved in many recipes to overcome human health problems

Keywords: aromatic and medicinal plants; ethnobotanical study; Fez-Meknes region; natural remedies.

Resumen

Contexto: La región de Fez-Meknes cuenta con una gran variedad de plantas aromáticas y medicinales que se pueden explorar de diferentes formas para aprovechar sus virtudes y superar los problemas de salud humana.

Objetivos: Identificar etnobotánicamente las principales plantas medicinales y recoger datos sobre sus usos en la región de Fez.

Métodos: Durante cada entrevista se recogió tanto la información personal como las plantas utilizadas. El cuestionario reveló la frecuencia de uso de cada parte de las plantas (VPP), también arrojó luz sobre la importancia de cada especie (RFC). Además, mostró la importancia relativa de las familias y el método de preparación (FIV).

Resultados: : Los resultados dieron a conocer la riqueza de la región en cuanto a plantas medicinales, se identificaron un total de 57 especies, agrupadas en 24 familias. Las familias más abundantes fueron Lamiaceae (FIV = 5,461), Compositae (FIV = 6,085), luego Apiaceae (FIV = 6,307). Las especies más citadas fueron Plantago major L. (RFC = 27,3%), Olea europaea L. (RFC = 31,3%) y Daphne gnidium L. (RFC= 32,6%). Las hojas fueron la parte de la planta más utilizada (VPP = 0,416). El método de preparación más utilizado fue la decocción (32%). Las patologías más declaradas fueron afecciones digestivas (16%), dermatológicas (15%) y respiratorias (13%).

Conclusiones: El estudio etnobotánico mostró la riqueza florística de la región y también permitió identificar las diferentes plantas involucradas en multitud de recetas para superar los problemas de salud humana.

Palabras Clave: estudio etnobotánico; Región de Fez-Meknes; plantas aromáticas y medicinales; remedios naturales.

Citation Format: Tlemcani S, Lahkimi A, Eloutassi N, Bendaoud A, Hmamou A, Bekkari H (2023) Ethnobotanical study of medicinal plants in the Fez-Meknes region of Morocco. J Pharm Pharmacogn Res 1(1): 137–159. https://doi.org/10.56499/jppres22.1459_11.1.137

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© 2023 Journal of Pharmacy & Pharmacognosy Research

J. Pharm. Pharmacogn. Res., vol. 11, no. 1, pp. 129-136, January-February 2023.

DOI: https://doi.org/10.56499/jppres22.1511_11.1.129

Original Article

Metabolite profile and in vitro cholinesterase inhibitory activity of extract and fractions of Aaptos suberitoides

[Perfil de metabolitos y actividad inhibidora de la colinesterasa in vitro del extracto y fracciones de Aaptos suberitoides]

Hanifa R. Putri¹, Rhesi Kristiana²_, I Wayan Mudianta³, Edwin Setiawan⁴, Aty Widyawaruyanti^5,6, Nitra Nuengchamnong⁷, Nungruthai Suphrom⁸, Suciati Suciati^5,6*

¹Master Program in Pharmaceutical Sciences, Faculty of Pharmacy Universitas Airlangga, Surabaya 60115, East Java, Indonesia.

²Indonesian Marine Education & Research Organisation (MERO) Foundation, Desa Tulamben, Karangasem 80853, Bali, Indonesia.

³Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Pendidikan Ganesha, Singaraja 81116, Bali, Indonesia.

⁴Department of Biology, Faculty of Science and Data Analytics, Institut Teknologi Sepuluh Nopember, Surabaya 60115, East Java, Indonesia.

⁵Department of Pharmaceutical Sciences, Faculty of Pharmacy Universitas Airlangga, Surabaya 60115, East Java, Indonesia.

⁶Center for Natural Product Medicine Research and Development, Institute of Tropical Diseases, Universitas Airlangga, Surabaya 60115, East Java, Indonesia.

⁷Science Laboratory Center, Faculty of Science, Naresuan University, Phitsanulok 65000, Thailand.

⁸Department of Chemistry, Faculty of Science and Center of Excellence for Innovation in Chemistry, Naresuan University, Phitsanulok 65000, Thailand.

*E-mail: suciati@ff.unair.ac.id

Abstract

Context: Marine sources such as sponges have shown a significant impact on the drug development from nature. Metabolites isolated from sponges show diversity in terms of structural features and pharmacological properties. Several sponges have been reported to have potency as cholinesterase inhibitors as one of the target therapies for Alzheimer’s disease.

Aims: To investigate the potency of marine sponge Aaptos suberitoides as cholinesterase inhibitors and to explore the chemistry of the sponge.

Methods: The cholinesterase inhibitory assay was carried out against two enzymes, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), based on the modified Ellman’s method. The chemistry of the active fractions was studied by LC-MS/MS method, followed by molecular networking using GNPS.

Results: The results suggested that the extract and fractions inhibited both AChE and BChE enzymes. All samples demonstrated more potent inhibition against AChE compared to BChE enzymes. The n-hexane fraction gave the strongest inhibition against both AChE and BChE, with IC₅₀ values of 4.76 µg/mL and 6.79 µg/mL, respectively. Based on the LC-MS/MS analysis, alkaloids were detected in the n-hexane and ethyl acetate fractions. Four alkaloids were identified in the ethyl acetate fraction, namely demethylaaptamine, aaptamine, isoaaptamine, and 8,9,9-trimethoxy-9H-benzo[de][1,6]naphthyridine at RT 1.52, 1.67, 2.92, and 3.22 mins, respectively. Aaptamine was also identified in the n-hexane fraction together with demethyloxyaaptamine.

Conclusions: The extract, n-hexane, and ethyl acetate fractions of A. suberitoides have shown promising cholinesterase inhibitory properties against both AChE and BChE enzymes. The alkaloids present in the active fractions may be responsible for the bioactivity.

Keywords: Aaptos suberitoides; alkaloid; Alzheimer’s disease; cholinesterase inhibitor.

Resumen

Contexto: Las fuentes marinas como las esponjas han mostrado un impacto significativo en el desarrollo de fármacos a partir de la naturaleza. Los metabolitos aislados a partir de esponjas muestran diversidad en cuanto a características estructurales y propiedades farmacológicas. Se ha informado que varias esponjas tienen potencia como inhibidores de la colinesterasa como una de las terapias diana para la enfermedad de Alzheimer.

Objetivos: Investigar la potencia de la esponja marina Aaptos suberitoides como inhibidor de la colinesterasa y explorar la química de la esponja.

Métodos: El ensayo de inhibición de la colinesterasa se llevó a cabo contra dos enzimas, la acetilcolinesterasa (AChE) y la butirilcolinesterasa (BChE), basándose en el método de Ellman modificado. La química de las fracciones activas se estudió por el método LC-MS/MS, seguido de la creación de redes moleculares mediante GNPS.

Resultados: Los resultados sugirieron que el extracto y las fracciones inhibían las enzimas AChE y BChE. Todas las muestras demostraron una inhibición más potente contra las enzimas AChE en comparación con las BChE. La fracción de n-hexano produjo la mayor inhibición tanto contra la AChE como contra la BChE, con valores de IC₅₀ de 4,76 µg/mL y 6,79 µg/mL, respectivamente. Según el análisis LC-MS/MS, se detectaron alcaloides en las fracciones de n-hexano y acetato de etilo. Se identificaron cuatro alcaloides en la fracción de acetato de etilo, a saber, desmetilaaptamina, aaptamina, isoaaptamina y 8,9,9-trimetoxi-9H-benzo[de][1,6]naftiridina a RT 1,52; 1,67; 2,92 y 3,22 minutos, respectivamente. También se identificó aaptamina en la fracción n-hexano junto con desmetiloxiaaptamina.

Conclusiones: Las fracciones de extracto, n-hexano y acetato de etilo de A. suberitoides han mostrado prometedoras propiedades inhibidoras de la colinesterasa frente a las enzimas AChE y BChE. Los alcaloides presentes en las fracciones activas pueden ser los responsables de la bioactividad.

Palabras Clave: Aaptos suberitoides; alcaloide; enfermedad de Alzheimer; inhibidor de la colinesterasa.

Citation Format: Cane HPCA, Putri HR, Kristiana R, Mudianta IW, Setiawan E, Widyawaruyanti A, Nuengchamnong N, Suphrom N, Suciati S (2023) Metabolite profile and in vitro cholinesterase inhibitory activity of extract and fractions of Aaptos suberitoides. J Pharm Pharmacogn Res 11(1): 129–136. https://doi.org/10.56499/jppres22.1511_11.1.129

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