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The Journal of Pharmacy & Pharmacognosy Research (JPPRes) is an international, specialized and peer-reviewed open access journal, which publishes studies in the pharmaceutical and herbal fields concerned with the physical, botanical, chemical, biological, toxicological properties and clinical applications of molecular entities, active pharmaceutical ingredients, devices and delivery systems for drugs, vaccines and biologicals, including their design, manufacture, evaluation and marketing. This journal publishes research papers, reviews, commentaries and letters to the editor as well as special issues and review of pre-and post-graduate thesis from pharmacists or professionals involved in Pharmaceutical Sciences or Pharmacognosy.

Medicinal plants against new-world cutaneous leishmaniasis

J. Pharm. Pharmacogn. Res., vol. 11, no. 6, pp. 975-1001, Nov-Dec 2023.



Medicinal plants with antileishmanial activity on parasites responsible for new-world cutaneous leishmaniasis. A systematic review 2018-2022

[Plantas medicinales con actividad antileishmania sobre parásitos responsables de leishmaniasis cutánea del nuevo mundo. Una revisión sistemática 2018-2022]

Yenny Y. Lozano1, Sara E. Giraldo1, Angela C. Zapata1, Jesús E. Escobar1, Ruth M. Sánchez2*

1Universidad de La Salle, Bogotá, D.C., Colombia.

2Universidad Colegio Mayor de Cundinamarca, Bogotá, D.C., Colombia.



Context: Cutaneous leishmaniasis is a disease of public health importance; treatment is based on the use of pentavalent antimonials with high toxicity and low efficacy; therefore, it´s necessary to search for therapeutic alternatives derived from natural products, based on the study of medicinal plants as a source of molecules with highly effective leishmanicidal potential.

Aims: To carry out a systematic review between 2018 and 2022 on medicinal plants with potential leishmanicidal activity on parasite strains from the New World causing cutaneous leishmaniasis.

Methods: The review study was conducted in four phases following the PRISMA methodology. First, research questions and objectives were formulated to establish the topic areas and construct the search algorithm. Second, a search was performed across different databases, including ScienceDirect, Scopus, PubMed, Web of Science, EBSCO, Taylor and Francis, and Scielo. Third, articles were chosen based on specific inclusion and exclusion criteria. Finally, the relevant information for the review was systematically organized.

Results: The search yielded 163 articles, and 12 of them were selected as the basis for the construction of the review. Ethanolic and aqueous extracts stand out, as well as biocompounds such as terpenes and flavonoids. Antioxidant activity on reactive oxygen species was the most frequently cited.

Conclusions: Promising terpene and flavonoid molecules with high antileishmanial activity (IC50 <2 μM or <10 μg/mL and SI >1) were identified in this study; these findings provide a scientific basis for the traditional use that communities have given to plants as a therapeutic source to treat cutaneous leishmaniasis in the New World.

Keywords: antiprotozoal agents; cutaneous; Leishmania; leishmaniasis; plant extracts.



Contexto: La leishmaniasis cutánea es una enfermedad de importancia en salud pública; su tratamiento se basa en el uso de antimoniales pentavalentes con alta toxicidad y baja eficacia; por tanto, es necesaria la búsqueda de alternativas terapéuticas derivadas de productos naturales, a partir del estudio de plantas medicinales como fuente de moléculas con potencial leishmanicida.

Objetivos: Realizar una revisión sistemática comprendida entre los años 2018-2022 referente a plantas medicinales con potencial actividad leishmanicida sobre cepas parasitarias del nuevo mundo causales de leishmaniasis cutánea.

Métodos: La revisión se realizó en cuatro fases siguiendo la metodología PRISMA. En primer lugar, se formularon las preguntas de investigación y los objetivos para establecer las áreas temáticas y construir el algoritmo de búsqueda. En segundo lugar, se realizó una búsqueda en diferentes bases de datos, como ScienceDirect, Scopus, PubMed, Web of Science, EBSCO, Taylor and Francis y Scielo. En tercer lugar, se seleccionaron los artículos en función de criterios específicos de inclusión y exclusión. Por último, la información relevante se organizó sistemáticamente para la revisión.

Resultados: La búsqueda arrojó 163 artículos, definiendo 12 artículos base para la construcción de la revisión. Sobresalen los extractos etanólicos y acuosos; así como biocompuestos tipo terpenos y flavonoides. La actividad antioxidante sobre especies reactivas de oxígeno fue la más citada.

Conclusiones: Se identificaron moléculas promisorias con alta actividad antileishmania (CI50 <2 μM o <10 μg/mL y con IS >1) tipo terpenos y flavonoides; resultado que brinda una base científica para el uso tradicional que las comunidades le han dado a las plantas como fuente terapéutica para tratar la leishmaniasis cutánea en el nuevo mundo.

Palabras Clave: agentes antiprotozoarios; cutáneo; extractos de plantas; Leishmania; leishmaniasis.

Citation Format: Lozano YY, Giraldo SG, Zapata AC, Escobar JE, Sánchez RM (2023) Medicinal plants with antileishmanial activity on parasites responsible for new-world cutaneous leishmaniasis. A systematic review 2018-2022. J Pharm Pharmacogn Res 11(6): 975–1001.

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Coffee-tea-turmeric work in cardiac-metabolic syndrome

J. Pharm. Pharmacogn. Res., vol. 11, no. 6, pp. 961-974, Nov-Dec 2023.


Original Article

The analysis of coffee-green tea-turmeric combination against cardiac-metabolic syndrome using metabolite profiling, gene expression, and in silico approach

[Análisis de la combinación de café, té verde y cúrcuma contra el síndrome cardiometabólico mediante perfiles de metabolitos, expresión génica y enfoque in silico]

Ermin Rachmawati1,2*, Mohammad S. Rohman1,3*, Nashi Widodo1,4, Mifetika Lukitasari1,5, Dwi A. Nugroho1, Feri E. Hermanto1,6,7, Mukhamad N. Kholis1,2

1Research Center for Cardiovascular, Brawijaya University, Malang, Indonesia.

2Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, UIN Maulana Malik Ibrahim Malang, East Java, Indonesia.

3Department of Cardiology and Vascular Medicine, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia.

4Department of Biology, Faculty of Mathematics and Natural Sciences, Universitas Brawijaya, Malang, Indonesia.

5School of Nursing, Faculty of Health Sciences, Universitas Brawijaya, Malang, Indonesia.

6Faculty of Animal Sciences, Universitas Brawijaya, Malang, Indonesia.

7Bioinformatics Research Center, Indonesian Institute of Bioinformatics, Malang, Indonesia.

*E-mail address:,


Context: The development of functional drinks to inhibit oxidative stress and inflammation as a critical process in inducing heart damage in metabolic syndrome is required. Coffee, tea, and turmeric have all been shown to offer health advantages.

Aims: To investigate the effect of coffee, green tea, turmeric extract (ECGTT) against cardiac-metabolic syndrome (MetS).

Methods: The secondary metabolites from coffee, green tea, and turmeric were identified using LC-HRMS. Male Sprague–Dawley rats were divided into four groups (n = 4) representing normal, MetS, MetS with ECGTT treatment doses: 300/100/150 mg/BW and 300/100/250 mg/BW group. Upon the end of treatment periods, expression of tumor necrosis factor-alpha (TNFα), interleukin-6 (IL-6), nuclear factor kappa B (NF-κB), NADPH oxidase (NOX2), SERCA2a were measured from the heart. A computational approach including network pharmacology, protein-protein interaction (PPI) network, molecular docking, and dynamic was performed to understand the molecular mechanism of ECGTT against cardiac damage in MetS.

Results: Chlorogenic acid (CGA), epigallocatechin gallate (EGCG), and curcumin were identified as the main metabolites in ECGTT. The ECGTT administration decreased the TNFα, IL-6, NF-κB, and NOX2 and increased SERCA2a expression(p<0.05). Moreover, the PPI result suggested that angiotensin II receptor type 1 (AGTR1) was the key regulator of cardiac injury-MetS induced. CGA, EGCG, and curcumin bind to AGTR1 with smaller binding energy than metformin and showed stability of structure and interaction among those metabolites into AGTR1.

Conclusions: Coffee, green tea, and turmeric might prevent heart dysfunction in MetS through modulation of oxidative stress and inflammation.

Keywords: calcium handling; coffee; green tea; inflammation; oxidative stress; turmeric.



Contexto: Se requiere el desarrollo de bebidas funcionales para inhibir el estrés oxidativo y la inflamación como proceso crítico en la inducción del daño cardiaco en el síndrome metabólico. Se ha demostrado que el café, el té y la cúrcuma ofrecen ventajas para la salud.

Objetivos: Investigar el efecto del extracto de café, té verde y cúrcuma (ECGTT) contra el síndrome cardiometabólico (MetS).

Métodos: Se identificaron los metabolitos secundarios del café, el té verde y la cúrcuma mediante LC-HRMS. Las ratas macho Sprague-Dawley se dividieron en cuatro grupos (n = 4) que representaban los grupos normal, MetS, MetS con dosis de tratamiento ECGTT: 300/100/150 mg de peso corporal y 300/100/250 mg de peso corporal. Al final de los periodos de tratamiento, se midió en el corazón la expresión del factor de necrosis tumoral alfa (TNFα), la interleucina-6 (IL-6), el factor nuclear kappa B (NF-κB), la NADPH oxidasa (NOX2) y la SERCA2a. Se realizó un enfoque computacional que incluía farmacología de red, red de interacción proteína-proteína (PPI), acoplamiento molecular y dinámica para comprender el mecanismo molecular de ECGTT contra el daño cardíaco en MetS.

Resultados: El ácido clorogénico (CGA), el galato de epigalocatequina (EGCG) y la curcumina se identificaron como los principales metabolitos en ECGTT. La administración de ECGTT redujo el TNFα, IL-6, NF-κB y NOX2 y aumentó la expresión de SERCA2a (p<0,05). Además, el resultado de la IPP sugirió que el receptor de angiotensina II tipo 1 (AGTR1) era el regulador clave de la lesión cardiaca inducida por MetS. CGA, EGCG y la curcumina se unen a AGTR1 con menor energía de unión que la metformina y mostró la estabilidad de la estructura y la interacción entre los metabolitos en AGTR1.

Conclusiones: El café, el té verde y la cúrcuma podrían prevenir la disfunción cardiaca en MetS a través de la modulación del estrés oxidativo y la inflamación.

Palabras Clave: café; cúrcuma; estrés oxidativo; inflamación; manejo del calcio; té verde.

Citation Format: Rachmawati E, Rohman MS, Widodo N, Lukitasari M, Nugroho DA, Hermanto FE, Kholis MN (2023) The analysis of coffee-green tea-turmeric combination against cardiac-metabolic syndrome using metabolite profiling, gene expression, and in silico approach. J Pharm Pharmacogn Res 11(6): 961–974.

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© 2023 Journal of Pharmacy & Pharmacognosy Research

Molybdenum blue assay for estimating antioxidant activity

J. Pharm. Pharmacogn. Res., vol. 11, no. 6, pp. 953-960, Nov-Dec 2023.


Original Article

Optimization of the molybdenum blue method for estimating the antioxidant activity of natural products

[Optimización del método del azul de molibdeno para estimar la actividad antioxidante de productos naturales]

Enoel Hernández-Barreto1, Vivian Ruz-Sanjuan1*, Venancio Ribalta-Ribalta1, Luis A. Torres-Gómez2

1Department of Pharmacy, Central University “Marta Abreu” of Las Villas (UCLV), Santa Clara, PC 54830, Cuba.

2Institute of Pharmacy and Food (IFAL), University of Havana, Havana, PC 13600, Cuba.



Context: The present experimental conditions of the molybdenum blue spectrophotometric method, used for antioxidant activity estimation, promote the degradation of flavonoids with potential interferences in the above determination.

Aims: To evaluate the effects of physicochemical factors on the formation of the complex for optimizing the total antioxidant activity method to better estimate the antioxidant activity of natural products.

Methods: A 34-1 fractional experimental design was applied. Independent variables were temperature, color development time, type of acid and acidity, and the dependent variable was the absorbance of the complex. The concentration of ammonium molybdate tetrahydrate and sodium hydrogen phosphate remained constant throughout the study. The effects of the reducing agent and its concentration were studied independently. The effect of acidity in a wide range of values, the color development time considering temperature, the influence of co-solvents, and the antioxidant activity of various natural metabolites were also evaluated.

Results: Acid concentration and temperature greatly influenced the complex formation, making the type of acid and incubation time less significant. Ascorbic acid showed a shorter color development time than reference metabolites. Ethanol negatively influenced the amount of complex formed. The proposed conditions for developing this method were: type of acid, HCl or H2SO4; acid concentration 0.01 N; incubation temperature 65°C; and incubation time 40 min. Under these experimental conditions, the ranking order of antioxidant activity was pyrogallol>quercetin>ascorbic acid>gallic acid>rutin.

Conclusions: The new experimental conditions for the molybdenum complex assay give a more reliable determination of the antioxidant activity of natural products.

Keywords: antioxidants; flavonoids; molybdenum blue; research design.



Contexto: Las condiciones experimentales actuales del método espectrofotométrico del azul de molibdeno, utilizado para la estimación de la actividad antioxidante, favorecen la degradación de los flavonoides con potenciales interferencias en la determinación anterior.

Objetivos: Evaluar los efectos de los factores fisicoquímicos en la formación del complejo para optimizar el método de actividad antioxidante total para una mejor estimación de la actividad antioxidante de los productos naturales.

Métodos: Se aplicó un diseño experimental fraccionado 34-1. Las variables independientes fueron la temperatura, el tiempo de desarrollo del color, el tipo de ácido y la acidez, y la variable dependiente fue la absorbancia del complejo. La concentración de molibdato amónico tetrahidratado y de hidrogenofosfato sódico se mantuvo constante durante todo el estudio. Los efectos del agente reductor y su concentración se estudiaron de forma independiente. También se evaluó el efecto de la acidez en un amplio rango de valores, el tiempo de desarrollo del color considerando la temperatura, la influencia de los co-solventes y la actividad antioxidante de varios metabolitos naturales.

Resultados: La concentración de ácido y la temperatura influyeron en gran medida en la formación de complejos, siendo menos significativos el tipo de ácido y el tiempo de incubación. El ácido ascórbico mostró un tiempo de desarrollo del color más corto que los metabolitos de referencia. El etanol influyó negativamente en la cantidad de complejo formado. Las condiciones propuestas para desarrollar este método fueron: tipo de ácido, HCl o H2SO4; concentración de ácido 0,01 N; temperatura de incubación 65°C; y tiempo de incubación 40 min. En estas condiciones experimentales, el orden de clasificación de la actividad antioxidante fue pirogalol>quercetina>ácido ascórbico>ácido gálico>rutina.

Conclusiones: Las nuevas condiciones experimentales para el ensayo del complejo de molibdeno proporcionan una determinación más fiable de la actividad antioxidante de los productos naturales.

Palabras Clave: antioxidantes; azul de molibdeno; diseño experimental; flavonoides.

Citation Format: Hernández-Barreto E, Ruz-Sanjuan V, Ribalta-Ribalta V, Torres-Gómez LA (2023) Optimization of the molybdenum blue method for estimating the antioxidant activity of natural products. J Pharm Pharmacogn Res 11(6): 953–960.

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© 2023 Journal of Pharmacy & Pharmacognosy Research

SLCO1B1/ CYP3A4 associated with adverse reactions to statins

J. Pharm. Pharmacogn. Res., vol. 11, no. 6, pp. 934-952, Nov-Dec 2023.



SLCO1B1 and CYP3A4 allelic variants associated with pharmacokinetic interactions and adverse reactions induced by simvastatin and atorvastatin used in Peru: Clinical implications

[Variantes alélicas de SLCO1B1 y CYP3A4 asociadas a interacciones farmacocinéticas y reacciones adversas inducidas por simvastatina y atorvastatina usadas en el Perú: Implicaciones clínicas]

Angel T. Alvarado1*, Ana María Muñoz2, Roberto O. Ybañez-Julca3, Mario Pineda-Pérez4, Nesquen Tasayco-Yataco5, María R. Bendezú6, Jorge A. García6, Felipe Surco-Laos6, Haydee Chávez6, Doris Laos-Anchante6, Aura Molina-Cabrera6, Carmela Ferreyra-Paredes6, Nelly Vega-Ramos6, Patricia Castillo-Romero6, Javier Chávez-Espinoza6, Juan Panay-Centeno6, Eliades Yarasca-Carlos7

1International Research Unit in Molecular Pharmacology and Genomic Medicine (UNIPHARMAGEM), VRI San Ignacio de Loyola University, La Molina 15024, Lima, Peru.

2Institute of Food Science and Nutrition, ICAN, San Ignacio de Loyola University, La Molina 15024, Lima, Peru.

3Faculty of Pharmacy and Biochemistry, National University of Trujillo, 13006, Trujillo, Peru.

4Pharmacy and Biochemistry, Faculty of Health Sciences, Scientific University of the South, UCSUR, 15067, Lima, Peru.

5Human Medicine, Norbert Wiener University, 15046, Lima, Peru.

6Faculty of Pharmacy and Biochemistry, San Luis Gonzaga National University of Ica, 11004, Ica, Peru.

7Biological Sciences Faculty, San Luis Gonzaga National University of Ica, 11001, Ica, Peru.



Context: Statins reduce the risk of stroke and prevent cardiac events in people with atherosclerosis and diabetes mellitus; and could affect the proliferation, migration, and survival of cancer cells.

Aims: To review the most up-to-date and available scientific evidence on the allelic variants of SLCO1B1 and CYP3A4 associated with pharmacokinetic interactions and adverse reactions induced by simvastatin and atorvastatin used in Peru, and their clinical implications.

Methods: The bibliographic search was carried out in the PubMed/Medline, Google Scholar and Science Direct databases. The keywords were: “statin”, “atorvastatin”, “simvastatin” in combination with “pharmacokinetics”, “pharmacogenetics”, “CYP3A4”, “SLCO1B1” or “drug interactions” considering the eligibility criteria defined by the PRISMA-2020 international statement.

Results: Scientific evidence indicates a significant association between SLCO1B1 rs4149056 c.521T>C (521CC and 521TC) and increased plasma levels, area under the plasma concentration curve (AUC) and maximum plasma concentration (Cmax) of simvastatin, compared to wild-type SLCO1B1*1/*1 521TT (p<0.05). SLCO1B1 521C is not associated with atorvastatin (p>0.05). Patients with SLCO1B1 521CC had a significantly higher risk of myopathy and rhabdomyolysis induced by simvastatin compared to TT (p<0.05). An association was also found between CYP3A4*1/*22/CYP3A4*3/*22 and increased pharmacokinetic parameters of simvastatin compared to CYP3A4*1/*1 (p< 0.05).

Conclusions: Based on the review of the published scientific evidence, it is concluded that individuals carrying the allelic variants SLCO1B1 (c.521T>C), CYP3A4*1/*22 and CYP3A4*3/*22 could be associated with an increase in the pharmacokinetic parameters and with an increased risk of myopathy and rhabdomyolysis induced by simvastatin, and not by atorvastatin.

Keywords: adverse reactions; atorvastatin; CYP3A4; pharmacokinetic interactions; SLCO1B1; simvastatin.



Contexto: Las estatinas reducen el riesgo accidente cerebrovascular y previene los eventos cardíacos en personas con aterosclerosis y diabetes mellitus; y podría afectar la proliferación, migración y supervivencia de las células cancerosas.

Objetivos: Revisar la evidencia científica más actualizada y disponible sobre las variantes alélicas de SLCO1B1 y CYP3A4 asociadas a interacciones farmacocinéticas y reacciones adversas inducidas por la simvastatina y atorvastatina usadas en el Perú, y sus implicaciones clínicas.

Métodos: Se realizó la búsqueda bibliográfica en bases de datos PubMed/Medline, Google Scholar and Science Direct databases. Las palabras clave fueron: “estatina”, “atorvastatina”, “simvastatina” en combinación con “farmacocinética”, “farmacogenética”, “CYP3A4”, “SLCO1B1” o “interacciones con fármacos” teniendo en cuenta los criterios de elegibilidad definidos por la declaración internacional PRISMA-2020.

Resultados: La evidencia científica indica asociación significativa entre SLCO1B1 rs4149056 c.521T>C (521CC y 521TC) y el aumento de los niveles plasmáticos, del área bajo la curva de concentraciones plasmáticas (AUC) y concentración plasmática máxima (Cmax) de simvastatina, respecto al wild-type SLCO1B1*1/*1 521TT (p<0.05). SLCO1B1 521C no está asociado con atorvastatina (p>0.05). Los pacientes con SLCO1B1 521CC presentaron mayor riesgo significativo de miopatía y rabdomiólisis inducida por simvastatina frente a TT (p< 0.05). También se encontró asociación entre CYP3A4*1/*22/CYP3A4*3/*22 y aumento de los parámetros farmacocinéticos de simvastatina en comparación con CYP3A4*1/*1 (p < 0.05).

Conclusiones: Basado en la revisión de la evidencia científica publicada se concluye que los individuos portadores de las variantes alélicas SLCO1B1 (c.521T>C), CYP3A4*1/*22 y CYP3A4*3/*22 podrían estar asociados a un incremento de los parámetros farmacocinéticos y con un mayor riesgo de miopatía y rabdomiólisis inducida por simvastatina, y no por atorvastatina.

Palabras Clave: atorvastatina; CYP3A4; interacciones farmacocinéticas; reacción adversa; SLCO1B1; simvastatina.

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Anti-angiogenic effect of neoadjuvant chemotherapy

J. Pharm. Pharmacogn. Res., vol. 11, no. 6, pp. 926-933, Nov-Dec 2023.


Original Article

Check update pattern of tumorigenic vasculature signature based on MMP9 and CXCR4 expression in locally advanced breast cancer

[Comprobación del patrón de actualización de la señal de vasculatura tumorigénica basada en la expresión de MMP9 y CXCR4 en el cáncer de mama localmente avanzado]

Mochamad Bachtiar Budianto1, Hamzah Sulaiman Lubis2, Muhammad Luqman Fadli3, Wiwit Nurwidyaningtyas4,5*

1Department Oncology of Saiful Anwar General Hospital, Malang 65112, Indonesia.

2Department Oncology of Medan Hajj General Hospital, Sumatera Utara 20371,Indonesia.

3Department Anatomy Pathology of Saiful Anwar General Hospital, Malang 65112, Indonesia.

4Department Molecular and Cellular Biology, Sekolah Tinggi Ilmu Kesehatan Kendedes, Malang, 65126, Indonesia.

5Center for Biomedical Research, Research Organization for Health, National Research and Innovation Agency (BRIN), Genomic Building, Cibinong Science Center, Jl. Raya Bogor No. 490, Cibinong – Bogor Km. 46, Bogor, West Java, Indonesia.



Context: Locally advanced breast cancers (LABC) are the most common women malignant tumors. Appropriate vasculature is required for tumor growth support, formed by involving protein signaling, including matrix metalloprotein 9 (MMP9) and C-X-C chemokine receptor type 4 (CXCR4). Neoadjuvant chemotherapy (NAC) administration to inoperable LABC commonly exhibits a positive response, although recurrences may be encountered in a few cases.

Aims: To evaluate the MMP9 and CXCR4 expression shifting after the NAC procedure to establish evidence of the anti-angiogenic effect of NAC, which encourages knowledge of tumor size reduction pathways in LABC.

Methods: Observational designs were conducted in this study. Tissue specimens before and after NAC were collected from 45 LABC-enrolled subjects. The targeted protein expression was analyzed by immunohistochemistry, and stained sections were classified according to the percentage of nuclear-stained tumor cells. Clinicopathological features of LABC were recorded. Tumor size was measured by Vernier caliper before and after NAC.

Results: The results showed the nuclear expression of MMP9 and CXCR4 protein were observed in all tissue specimens. The expression of MMP9 and CXCR4 tended to decrease after the NAC but was not statistically significant for MMP9. There was a significant correlation between expression levels of CXCR4 and tumor size reduction (p<0.001) but not for MMP9.

Conclusions: The results of this study demonstrate the anti-angiogenic effect of NAC by inhibiting MMP9 and CXCR4, which may be integrated with tumor size reduction in LABC. Further studies are required to highlight the possibility of recurrence following inhibition of MMP9 and CXCR4 by NAC.

Keywords: breast cancers; CXCR4; MMP9; neoadjuvant chemotherapy; positive response.



Contexto: Los cánceres de mama localmente avanzados (LABC) son los tumores malignos femeninos más frecuentes. Se requiere una vasculatura adecuada para el soporte del crecimiento tumoral, formada por la implicación de la señalización de proteínas, incluyendo la metaloproteína de matriz 9 (MMP9) y el receptor de quimioquinas C-X-C tipo 4 (CXCR4). La administración de quimioterapia neoadyuvante (NAC) al LABC inoperable suele mostrar una respuesta positiva, aunque en algunos casos pueden producirse recidivas.

Objetivos: Evaluar el cambio de expresión de MMP9 y CXCR4 tras el procedimiento NAC para establecer evidencias del efecto antiangiogénico de la NAC, lo que favorece el conocimiento de las vías de reducción del tamaño tumoral en el LABC.

Métodos: En este estudio se realizaron diseños observacionales. Se recogieron muestras de tejido antes y después de la NAC de 45 sujetos inscritos en el LABC. La expresión de la proteína diana se analizó mediante inmunohistoquímica, y las secciones teñidas se clasificaron según el porcentaje de células tumorales teñidas nuclearmente. Se registraron las características clinicopatológicas del LABC. El tamaño del tumor se midió con un calibre Vernier antes y después de la NAC.

Resultados: Los resultados mostraron la expresión nuclear de las proteínas MMP9 y CXCR4 en todas las muestras de tejido. La expresión de MMP9 y CXCR4 tendió a disminuir tras la NAC, pero no fue estadísticamente significativa para MMP-9. Se observó una correlación significativa entre los niveles de expresión de CXCR4 y la reducción del tamaño del tumor (p<0,001). Hubo una correlación significativa entre los niveles de expresión de CXCR4 y la reducción del tamaño del tumor (p<0,001), pero no para MMP9.

Conclusiones: os resultados de este estudio demuestran el efecto antiangiogénico de la NAC mediante la inhibición de MMP9 y CXCR4, que puede integrarse con la reducción del tamaño tumoral en el LABC. Se requieren más estudios para poner de relieve la posibilidad de recurrencia tras la inhibición de MMP9 y CXCR4 por NAC.

Palabras Clave: cánceres de mama; CXCR4; MMP9; quimioterapia neoadyuvante; respuesta positiva.

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© 2023 Journal of Pharmacy & Pharmacognosy Research

N-Benzoyl-N’-phenylthiourea derivatives and macrophage migration inhibitory factor

J. Pharm. Pharmacogn. Res., vol. 11, no. 5, pp. 902-925, Sep-Oct 2023.


Original Article

Synthesis and in vitro activity tests of N-benzoyl-N’-phenylthiourea derivatives as macrophage migration inhibitory factor

[Síntesis y pruebas de actividad in vitro de derivados de N-benzoil-N’-feniltiourea como factor inhibidor de la migración de macrófagos]

Dini Kesuma1, Galih S. Putra2*, Tegar A. Yuniarta1,Farida Suhud1, I G.A. Sumartha1, Sawitri Boengas3, Melanny I. Sulistyowaty4, Tjie Kok5

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

2Department of Chemistry, Faculty of Mathematics and Natural Sciences, State University of Malang, Malang Indonesia.

3Faculty of Medicine, University of Surabaya, Surabaya, Indonesia.

4Department of Pharmaceutical Sciences, Faculty of Pharmacy, Universitas Airlangga, Surabaya 60115, Indonesia.

5 Faculty of Biotechnology, University of Surabaya, Surabaya, Indonesia.



Context: The COVID-19 pandemic in 2020 resulted in widespread mortalities due to cytokine storms in the affected patients. Macrophage migration inhibitory factor (MIF) is one of the most interesting targets in developing anti-COVID-19 drugs. Some thiourea compounds have been identified as having potential as MIF inhibitors.

Aims: To investigate MIF inhibitory activity of N-benzoyl-N’-phenylthiourea derivatives.

Methods: The study consists of in-silico activity prediction of designed compounds using a molecular docking approach against MIF protein (PDB ID: 1LJT). Afterwards, the designed compounds were synthesized and tested in vitro using the tautomerase activity approach.

Results: The molecular docking study showed that all designed compounds possess comparable docking scores to the native ligand of the protein. MIF Assay performed on compounds (1) and (2) indicated a decrease in tautomerase activity of the MIF target protein of only 10.1 and 6.2%, respectively, compared to the positive control.

Conclusions: In silico results predicted better bioactivity against MIF protein, but the result does not translate to the in vitro assay, where two of the designed compounds possess only low inhibitory activity.

Keywords: 1LJT; MIF assay; tautomerase activity; thiourea derivatives.



Contexto: La pandemia de COVID-19 en 2020 provocó mortalidades generalizadas debido a las tormentas de citocinas en los pacientes afectados. El factor inhibidor de la migración de macrófagos (MIF) es una de las dianas más interesantes en el desarrollo de fármacos anti-COVID-19. Se han identificado algunos compuestos de tiourea con potencial como inhibidores de MIF.

Objetivos: Investigar la actividad inhibidora de MIF de derivados de N-benzoil-N’-feniltiourea.

Métodos: El estudio consiste en la predicción in silico de la actividad de los compuestos diseñados utilizando un enfoque de acoplamiento molecular frente a la proteína MIF (PDB ID: 1LJT). Posteriormente, los compuestos diseñados se sintetizaron y probaron in vitro mediante el método de actividad tautomerasa.

Resultados: El estudio de acoplamiento molecular mostró que todos los compuestos diseñados poseen puntuaciones de acoplamiento comparables al ligando nativo de la proteína. El ensayo MIF realizado con los compuestos (1) y (2) indicó una disminución de la actividad tautomerasa de la proteína diana MIF de sólo el 10,1 y el 6,2%, respectivamente, en comparación con el control positivo.

Conclusiones: Los resultados in silico predijeron una mejor bioactividad frente a la proteína MIF, pero el resultado no se traslada al ensayo in vitro, donde dos de los compuestos diseñados sólo poseen una baja actividad inhibitoria.

Palabras Clave: actividad tautomerasa; derivados tiourea; ensayo MIF; 1LJT.

Citation Format: Kesuma D, Putra GS, Yuniarta TA, Suhud F, Sumartha IGA, Boengas S, Sulistyowati MI, Kok T (2023) Synthesis and in vitro activity tests of N-benzoyl-N'-phenylthiourea derivatives as macrophage migration inhibitory factor. J Pharm Pharmacogn Res 11(5): 902–925.

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© 2023 Journal of Pharmacy & Pharmacognosy Research

Research trends of studies on oral cancer risk factors

J. Pharm. Pharmacogn. Res., vol. 11, no. 5, pp. 887-901, Sep-Oct 2023.



Risk factors for oral cancer: Thematic trends and research agenda

[Factores de riesgo del cáncer oral: Tendencias temáticas y agenda de investigación]

Orlando Pérez-Delgado1, Pablo Alejandro Millones-Gómez2, Alejandro Valencia-Arias3*, David Yeret Rodríguez-Salazar4

1Laboratorio de Investigación en Ciencias de la Salud, Universidad Señor de Sipán, Chiclayo, 14000, Peru.

2Vicerrectoría de Investigación, Universidad Señor de Sipán, Chiclayo, 14000, Peru.

3School of Industrial Engineering, Faculty of Engineering, Architecture and Urbanism, Universidad Señor de Sipán, Chiclayo 14001, Peru.

4Facultad de Ciencias de la Salud, Universidad Señor de Sipán, Chiclayo, 14000, Peru.



Context: Oral cancer is difficult to define due to several factors. It’s known as oral squamous cell carcinoma (OSCC) and is common in the head and neck. Geographic variations in the impact of OSCC highlight the need for research on risk factors and treatment trends.

Aims: To identify the main research trends of studies on oral cancer risk factors in the scientific literature in the Scopus database and Web of Science.

Methods: This was an exploratory study of the risk factors for oral cancer designed considering the eligibility criteria defined by the PRISMA-2020 international statement, that is, inclusion and exclusion.

Results: A total of 215 documents from Scopus and Web of Science were subjected to bibliometric analysis. The years 2020 and 2021 were the most productive, with 18 and 22 articles, respectively. The leading author in productivity and impact was Johnson N, the leading journal was Oral Oncology, followed by the International Journal of Cancer, and the main contributing countries were the United States, the United Kingdom and India. The main thematic cluster was composed of concepts such as Tobacco and Alcohol as the major risk factors; concepts such as Mortality or Head and Neck were positioned as emerging within the scientific literature.

Conclusions: The main risk factors, i.e., alcohol and tobacco consumption, are relevant in terms of mortality in the consumer population, which is why their role should be determined in future studies.

Keywords: malignancy neoplasms; mortality; mouth neoplasms; oral cancer; risk factors; tobacco.



Contexto: El cáncer oral es difícil de definir debido a varios factores. Se conoce como carcinoma oral de células escamosas (CCEO) y es frecuente en la cabeza y el cuello. Las variaciones geográficas en el impacto del CCEO ponen de manifiesto la necesidad de investigar los factores de riesgo y las tendencias de tratamiento.

Objetivos: Identificar las principales tendencias de investigación de los estudios sobre los factores de riesgo del cáncer oral en la literatura científica de la base de datos Scopus y Web of Science.

Métodos: Se trató de un estudio exploratorio de los factores de riesgo de cáncer oral diseñado considerando los criterios de elegibilidad definidos por la declaración internacional PRISMA-2020, es decir, inclusión y exclusión.

Resultados: Un total de 215 documentos de Scopus y Web of Science fueron sometidos a análisis bibliométrico. Los años 2020 y 2021 fueron los más productivos, con 18 y 22 artículos, respectivamente. El autor líder en productividad e impacto fue Johnson N, la revista líder fue Oral Oncology, seguida de International Journal of Cancer, y los principales países contribuyentes fueron Estados Unidos, Reino Unido e India. El principal cluster temático estuvo compuesto por conceptos como Tabaco y Alcohol como principales factores de riesgo; conceptos como Mortalidad o Cabeza y Cuello se posicionaron como emergentes dentro de la literatura científica.

Conclusiones: Los principales factores de riesgo, es decir, el consumo de alcohol y tabaco, son relevantes en términos de mortalidad en la población consumidora, por lo que su papel debería determinarse en futuros estudios.

Palabras Clave: neoplasias malignas; mortalidad; neoplasias bucales; cáncer oral; factores de riesgo; tabaco.

Citation Format: Pérez-Delgado O, Millones-Gómez PA, Valencia-Arias A, Rodríguez-Salazar DY (2023) Risk factors for oral cancer: Thematic trends and research agenda. J Pharm Pharmacogn Res 11(5): 887–901.

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© 2023 Journal of Pharmacy & Pharmacognosy Research

Vitis gracilis, spermatozoa and maximal exercise

J. Pharm. Pharmacogn. Res., vol. 11, no. 5, pp. 874-886, Sep-Oct 2023.


Original Article

Improvement of spermatozoa concentration due to maximal exercise with Vitis gracilis Wall.

[Mejoría de la concentración de espermatozoides por ejercicio máximo con Vitis gracilis Wall.]

Syafruddin Ilyas1*, Putra Santoso2, Yurnadi Hanafi Midoen3, Putri Cahaya Situmorang1

1Study program of Biology, Faculty of Mathematics and Natural Sciences, Universitas Sumatera Utara, Medan, Indonesia.

2Department of of Biology, Faculty of Mathematics and Natural Sciences, Universitas Andalas, Padang, Indonesia.

3Department of Medical Biology, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.



Context: Swimming is a common form of exercise; however, excessive exercise might reduce sperm count by lowering testosterone levels and increasing the production of free radicals, commonly known as reactive oxygen species (ROS). In Indonesia, Vitis gracilis Wall. is a traditional remedy for increasing stamina.

Aims: To assess the concentration of spermatozoa after vigorous physical activity and V. gracilis administration, as well as the histological and apoptotic changes in testicular histology that occur via caspase-3 expression.

Methods: This study was conducted on six groups of rats: the control group (G+), a group of rats subjected to vigorous swimming then administered 0.2 mg/kg BW vit C (GVitC), and three groups of rats subjected to vigorous swimming then administered 100, 125, or 150 mg/kg BW V. gracilis (G100, G125, and G150). Testicular tissue and blood serum samples were extracted from the rats subjected to vigorous swimming. Testicular tissue was immunohistochemically stained using caspase-3 antibody and TUNEL assays, while blood samples were analysed using ELISA.

Results: V. gracilis administration significantly affected IL-6 and testosterone levels (p<0.00). Testosterone had a greater impact on spermatozoa concentration than IL-6. Caspase-3 expression and the proportion of apoptotic cells were both markedly reduced.

Conclusions: Administering 125 mg/kg BW V. gracilis can help to increase sperm concentration by reducing apoptosis through altering caspase-3 and IL-6 levels, thereby preventing inflammation. This plant might be a viable molecular therapeutic target for staminal medicines.

Keywords: IL-6; overexercise; sperm; testosterone; Vitis gracilis.



Contexto: La natación es una forma común de ejercicio; sin embargo, el ejercicio excesivo podría reducir el recuento de espermatozoides al disminuir los niveles de testosterona y aumentar la producción de radicales libres, comúnmente conocidos como especies reactivas del oxígeno (ROS). En Indonesia, Vitis gracilis Wall. es un remedio tradicional para aumentar la resistencia.

Objetivos: Evaluar la concentración de espermatozoides tras una actividad física vigorosa y la administración de V. gracilis, así como los cambios histológicos y apoptóticos en la histología testicular que se producen a través de la expresión de caspasa-3.

Métodos: Este estudio se llevó a cabo en seis grupos de ratas: el grupo de control (G+), un grupo de ratas sometidas a natación vigorosa y luego administradas 0,2 mg/kg BW vit C (GVitc), y tres grupos de ratas sometidas a natación vigorosa y luego administradas 100, 125 o 150 mg/kg BW V. gracilis (G100, G125 y G150). Se extrajeron muestras de tejido testicular y suero sanguíneo de las ratas sometidas a natación vigorosa. El tejido testicular se tiñó inmunohistoquímicamente con el anticuerpo caspasa-3 y se realizaron ensayos TUNEL, mientras que las muestras de sangre se analizaron mediante ELISA.

Resultados: La administración de V. gracilis afectó significativamente a los niveles de IL-6 y testosterona (p<0,00). La testosterona tuvo un mayor impacto en la concentración de espermatozoides que la IL-6. La expresión de caspasa-3 y la proporción de células apoptóticas se redujeron notablemente.

Conclusiones: La administración de 125 mg/kg BW de V. gracilis puede ayudar a aumentar la concentración de espermatozoides mediante la reducción de la apoptosis a través de la alteración de los niveles de caspasa-3 e IL-6, previniendo así la inflamación. Esta planta podría ser una diana terapéutica molecular viable para medicamentos estaminales.

Palabras Clave: esperma; IL-6; sobreesfuerzo; testosterona; Vitis gracilis.

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© 2023 Journal of Pharmacy & Pharmacognosy Research

Antimalarial and toxicology of Andrographis paniculata tablet

J. Pharm. Pharmacogn. Res., vol. 11, no. 5, pp. 863-873, Sep-Oct 2023.


Original Article

Antimalarial and toxicological assessment of the tablet (AS201-01) ethyl acetate fraction of Andrographis paniculata Nees in animal models

[Evaluación antimalárica y toxicológica de fracción de acetato de etilo del comprimido (AS201-01) de Andrographis paniculata Nees en modelos animales]

Aty Widyawaruyanti1,2*, Hilkatul Ilmi2, Lidya Tumewu2, Dwi Ayu Fitrianingtyas3, Yesinta Kurniawati3, Alfin Laila Najiha3, Hanifah Khairun Nisa2, Che Puteh Osman4,5, Nor Hadiani Ismail4,5, Achmad Fuad Hafid1,2

1Department of Pharmaceutical Sciences, Faculty of Pharmacy, Universitas Airlangga, Surabaya, 60115, Indonesia.

2Center for Natural Product Medicine Research and Development, Institute of Tropical Disease, Universitas Airlangga, Surabaya, 60115, Indonesia.

3Undergraduate Program of Faculty of Pharmacy, Universitas Airlangga, Surabaya, 60115, East Java, Indonesia.

4Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA, Cawangan Selangor, Kampus Puncak Alam, 42300 Bandar Puncak Alam, Selangor Malaysia.

5Faculty of Applied Sciences, Universiti Teknologi MARA, 40450 Shah Alam, Selangor, Malaysia.



Context: Andrographis paniculata has been used as a traditional medicine to treat malaria. The ethyl acetate fraction of A. paniculata containing diterpene lactone compounds was developed into a tablet dosage form, AS201-01.

Aims: To determine the antimalarial activity and toxicity of AS201-01 to guarantee its efficacy and safety.

Methods: Antimalarial assay in male Balb/c mice based on Peter’s four-day suppressive test at a dose of 6.25, 12.5, 25, and 50 mg/kg BW and 10 mg/kg BW of chloroquine as a positive control. In acute toxicity, AS201-01 was administered orally at a dose of 5, 50, 200, and 2,000 mg/kg BW in male rats (Wistar rats) and observed for 14 days to identify signs of toxicity and mortality. Meanwhile, AS201-01 was administered at 50, 327, and 1,000 mg/kg BW per day for 28 days in male and female rats to assess subchronic toxicity.

Results: AS201-01 has antimalarial activity and exhibited the highest suppressive effect at 50 mg/kg BW dose with inhibition of 73.48%. Meanwhile, chloroquine at 10 mg/kg BW has an inhibition of 97.94%. AS201-01 was highly active as an antimalarial with an ED50 value of 5.95 mg/kg BW and increased survival time. Administration of AS201-01 is relatively safe in acute and subchronic toxicity studies. No clinical signs and mortality were observed in either study. The 50% lethal dose (LD50) was above 2,000 mg/kg BW.

Conclusions: AS201-01 is effective as an antimalarial and non-toxic when administered orally at an equivalent therapeutic dose in an animal model.

Keywords: acute toxicity; Andrographis paniculate; antimalarial; subchronic toxicity; medicine.



Contexto: Andrographis paniculata se ha utilizado como medicina tradicional para tratar la malaria. La fracción de acetato de etilo de A. paniculata que contiene compuestos de lactona diterpénica se desarrolló en una forma de dosificación en comprimidos, AS201-01.

Objetivos: Determinar la actividad antimalárica y la toxicidad de AS201-01 para garantizar su eficacia y seguridad.

Métodos: Ensayo antipalúdico en ratones Balb/c macho basado en la prueba supresora de Peter de cuatro días a dosis de 6,25, 12,5, 25 y 50 mg/kg de peso corporal y 10 mg/kg de peso corporal de cloroquina como control positivo. En toxicidad aguda, el AS201-01 se administró por vía oral a dosis de 5, 50, 200 y 2.000 mg/kg de peso corporal en ratas macho (ratas Wistar) y se observó durante 14 días para identificar signos de toxicidad y mortalidad. Mientras tanto, se administró AS201-01 a 50, 327 y 1.000 mg/kg de peso corporal por día durante 28 días en ratas macho y hembra para evaluar la toxicidad subcrónica.

Resultados: AS201-01 tiene actividad antipalúdica y exhibió el mayor efecto supresor con una dosis de 50 mg/kg de peso corporal, con una inhibición del 73,48%. Mientras tanto, la cloroquina a 10 mg/kg de peso corporal tiene una inhibición del 97,94%. AS201-01 fue altamente activo como antimalárico con un valor ED50 de 5,95 mg/kg de peso corporal y aumentó el tiempo de supervivencia. La administración de AS201-01 es relativamente segura en estudios de toxicidad aguda y subcrónica. No se observaron signos clínicos ni mortalidad en ninguno de los dos estudios. La dosis letal al 50% (DL50) fue superior a 2.000 mg/kg de peso corporal.

Conclusiones: AS201-01 es eficaz como antipalúdico y no tóxico cuando se administra por vía oral a una dosis terapéutica equivalente en un modelo animal.

Palabras Clave: Andrographis paniculate; antimalárico; medicamento; toxicidad aguda; toxicidad subcrónica.

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© 2023 Journal of Pharmacy & Pharmacognosy Research

Bioactive compounds of Indonesian plants to inhibit Naegleria fowleri

J. Pharm. Pharmacogn. Res., vol. 11, no. 5, pp. 841-862, Sep-Oct 2023.


Original Article

In silico targeting CYP51 of Naegleria fowleri using bioactive compounds from Indonesian plants

[In silico dirigido a CYP51 de Naegleria fowleri utilizando compuestos bioactivos de plantas de Indonesia]

Nelson Daniel, Fisranda Ferdinand, Parikesit Arli Aditya*

Department of Bioinformatics, School of Life Sciences, Indonesia International Institute for Life-Sciences, Jl. Pulomas Barat Kav. 88, Jakarta, Indonesia.



Context: Given the elusive nature of Primary Amoebic Meningoencephalitis (PAM), caused by Naegleria fowleri, early detection is vital, yet challenging due to limited clinical indicators. This research leverages Indonesia’s rich biodiversity to explore novel sources of traditional medicine.

Aims: To evaluate the potential compounds from Indonesian plants that possess antiamoebic and antifungal properties for inhibiting the N. fowleri CYP51 protein, crucial for cell integrity.

Methods: Initially, 92 compounds were screened, and six were shortlisted following ADMETox evaluation. Subsequent steps encompassed QSAR analysis, molecular docking, and molecular dynamics simulations.

Results: The QSAR analysis verified the activity potential of these six compounds, progressing them to molecular docking analysis. Among these, curcumenol from Curcuma longa emerged as a promising contender, displaying the lowest binding affinity at -9.2 kcal/mol, indicative of superior binding compared to other ligands. Molecular dynamics simulations underscored the stability of all compounds, with root mean square fluctuation (RMSF) values within 1-3 Å.

Conclusions: Consequently, employing a comprehensive approach spanning ADMETox, QSAR, molecular docking, and dynamics simulations, curcumenol emerged as the prime candidate for inhibiting the N. fowleri CYP51 protein, suggesting its potential as a PAM therapeutic agent.

Keywords: bioactive compounds; CYP51; molecular docking; molecular dynamics; molecular simulation; Naegleria fowleri.



Contexto: Dada la naturaleza elusiva de la meningoencefalitis amebiana primaria (MAP), causada por Naegleria fowleri, la detección precoz es vital, aunque difícil debido a los limitados indicadores clínicos. Esta investigación aprovecha la rica biodiversidad de Indonesia para explorar nuevas fuentes de medicina tradicional.

Objetivos: Evaluar los posibles compuestos de plantas indonesias que poseen propiedades antiamebianas y antifúngicas para inhibir la proteína CYP51 de N. fowleri, crucial para la integridad celular.

Métodos: Inicialmente, se examinaron 92 compuestos y se preseleccionaron seis tras la evaluación ADMETox. Los pasos siguientes incluyeron análisis QSAR, acoplamiento molecular y simulaciones de dinámica molecular.

Resultados: El análisis QSAR verificó el potencial de actividad de estos seis compuestos, que pasaron al análisis de acoplamiento molecular. Entre ellos, el curcumenol de Curcuma longa resultó ser un candidato prometedor, mostrando la menor afinidad de unión con -9,2 kcal/mol, lo que indica una unión superior a la de otros ligandos. Las simulaciones de dinámica molecular subrayaron la estabilidad de todos los compuestos, con valores de fluctuación cuadrática media (RMSF) dentro de 1-3 Å.

Conclusiones: En consecuencia, empleando un enfoque exhaustivo que abarca ADMETox, QSAR, acoplamiento molecular y simulaciones dinámicas, el curcumenol surgió como el principal candidato para inhibir la proteína CYP51 de N. fowleri, lo que sugiere su potencial como un agente terapéutico para la MAP.

Palabras Clave: acoplamiento molecular; compuestos bioactivos; CYP51; dinámica molecular; Naegleria fowleri; simulación molecular.

Citation Format: Nelson D, Fisranda F, Parikesit AA (2023) In silico targeting CYP51 of Naegleria fowleri using bioactive compounds from Indonesian plants. J Pharm Pharmacogn Res 11(5): 841–862.

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