Tag Archives: medicine

Stachytarpheta jamaicensis antibacterial activity

J. Pharm. Pharmacogn. Res., vol. 10, no. 6, pp. 1087-1102, November-December 2022.

DOI: https://doi.org/10.56499/jppres22.1474_10.6.1087

Original Article

Antibacterial activity of Stachytarpheta jamaicensis (L.) Vahl roots extract on some bacteria proteins: An in silico and in vitro study

[Actividad antibacteriana del extracto de raíces de Stachytarpheta jamaicensis (L.) Vahl sobre algunas proteínas bacterianas: un estudio in silico e in vitro]

Juliyatin Putri Utami1*, Sherli Diana2, Rahmad Arifin3, Irham Taufiqurrahman4, Kholifa Aulia Nugraha5, Milka Widya Sari5, Rizky Yoga Wardana5

1Department of Biomedicine, Faculty of Dentistry, University of Lambung Mangkurat, Banjarmasin, Indonesia.

 2Department of Conservative Dentistry, Faculty of Dentistry, University of Lambung Mangkurat, Banjarmasin, Indonesia.

3Department of Prosthodontic, Faculty of Dentistry, University of Lambung Mangkurat, Banjarmasin, Indonesia.

4Departement of Oral Maxillofacial Surgery, Faculty of Dentistry, University of Lambung Mangkurat, Banjarmasin, Indonesia.

5Undergraduate of Dentistry Program, Faculty of Dentistry, University of Lambung Mangkurat, Banjarmasin, Indonesia.

*E-mail: juliyatin.utami@ulm.ac.id

Abstract

Context: Stachytarpheta jamaicensis (L.) Vahlplant is used for traditional therapy because of its content, including flavonoids, alkaloids, tannins, saponins, terpenoids, and coumarins.

Aims: To determine the antibacterial ability of S. jamaicensis roots extract (SJRE) on some selected mouth bacteria through in vitro and in silico studies.

Methods: Phytochemical analysis and liquid chromatography-high resolution mass spectrometry (LC-HRMS) were done to explore the active compounds on SJRE. Absorption, distribution, metabolism, excretion and toxicity prediction, molecular docking simulation and visualization of luvangetin, and xanthyletin as anti-inflammatory and antibacterial were investigated in silico. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of SJRE against Aggregatibacter actinomycetemcomitans, Enterococcus faecalis, and Actinomyces spp. were calculated.

Results: Luvangetin and xanthyletin are good candidate drug molecules with low toxicity. Xanthyletin has higher binding activity than luvangetin to TNF-α, IL-6, IL-10, peptidoglycan, flagellin, and dectin protein. SJRE exhibited a high antibacterial ability, and MIC. This extract inhibits the growth of A. actinomycetemcomitans, E. faecalis and Actinomyces spp. at various concentrations 2000, 8000, and 8000 µg/mL, respectively, with statistically significant differences (p = 0.0001; p<0.05).

Conclusions: SJRE has an antibacterial ability, and 2000 µg/mL SJRE may act as an antibacterial agent in vitro. In addition, xanthyletin in SJRE has a potential role as an antibacterial and anti-inflammatory in silico.

Keywords: communicable disease; dentistry; infectious disease; medicine; periodontal disease.

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Resumen

Contexto: La planta de Stachytarpheta jamaicensis (L.) Vahl se utiliza para la terapia tradicional por su contenido, que incluye flavonoides, alcaloides, taninos, saponinas, terpenoides y cumarinas.

Objetivos: Determinar la capacidad antibacteriana del extracto de raíces de S. jamaicensis (SJRE) sobre algunas bacterias bucales seleccionadas mediante estudios in vitro e in silico.

Métodos: Se realizaron análisis fitoquímico y cromatografía líquida-espectrometría de masas de alta resolución (LC-HRMS) para explorar los compuestos activos en SJRE. Se investigaron in silico la absorción, la distribución, el metabolismo, la excreción y la predicción de la toxicidad, la simulación de acoplamiento molecular y la visualización de la luvangetina y la xantiletina como antiinflamatorios y antibacterianos. Se calcularon la concentración inhibitoria mínima (MIC) y la concentración bactericida mínima (MBC) de SJRE contra Aggregatibacter actinomycetemcomitans, Enterococcus faecalis y Actinomyces spp.

Resultados: Luvangetin y xanthyletin son buenas moléculas candidatos a fármacos y tienen baja toxicidad. La xantiletina tiene una mayor actividad de unión que la luvangetina a TNF-α, IL-6, IL-10, peptidoglicano, flagelina y proteína dectina. SJRE exhibió una alta capacidad antibacteriana y MIC. Este extracto inhibe el crecimiento de A. actinomycetemcomitans, E. faecalis y Actinomyces spp. a varias concentraciones 2000, 8000 y 8000 µg/mL, respectivamente, con diferencias estadísticamente significativas (p = 0,0001; p<0,05).

Conclusiones: SJRE tiene una capacidad antibacteriana y a 2000 µg/mL SJRE puede actuar como un agente antibacteriano in vitro. Además, la xantiletina en SJRE tiene un papel potencial como antibacteriano y antiinflamatorio in silico.

Palabras Clave: enfermedad infecciosa; enfermedad periodontal; enfermedad transmisible; odontología; medicamento.

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Citation Format: Utami JP, Diana S, Arifin R, Taufiqurrahman I, Nugraha KA, Sari MW, Wardana RY (2022) Antibacterial activity of Stachytarpheta jamaicensis (L.) Vahl roots extract on some bacteria proteins: An in silico and in vitro study. J Pharm Pharmacogn Res 10(6): 1087–1102. https://doi.org/10.56499/jppres22.1474_10.6.1087
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TNF-alpha and NF-kB expressions during OTM post-administration of CAPE

J. Pharm. Pharmacogn. Res., vol. 10, no. 6, pp. 1037-1045, November-December 2022.

DOI: https://doi.org/10.56499/jppres22.1479_10.6.1037

Original Article

Anti-inflammatory effect of caffeic acid phenethyl ester supplementation on TNF-α and NF-κB expressions throughout experimental tooth movement in vivo

[Efecto antiinflamatorio de la suplementación con éster fenetílico de ácido cafeico en las expresiones de TNF-α y NF-κB a través del movimiento dental experimental in vivo]

Kirana Salikha1, Ida Bagus Narmada1*, Alida1, Alexander Patera Nugraha1,2, Annisa Fitria Sari2, Wibi Riawan3, Tengku Natasha Eleena Binti Tengku Ahmad Noor4

1Department of Orthodontics, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia.

2Graduate Student of Dental Health Science, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia.

3Biomolecular Biochemistry, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia.

4Membership of Faculty of Dental Surgery, Royal College of Surgeon, Edinburgh University, United Kingdom.

*E-mail: ida-b-n@fkg.unair.ac.id

Abstract

Context: Orthodontic tooth movement (OTM) changes the periodontal tissue and increases the incidence of root resorption (OIRR). Caffeic acid phenethyl ester (CAPE), an antioxidant and anti-inflammatory chemical generated from honey propolis, might be useful in controlling inflammation during OTM and so reducing the risk of OIRR.

Aims: To evaluate if CAPE supplementation has an anti-inflammatory impact on tumor necrosis factor-α (TNF-α) and nuclear transcription factor κB (NF-κB) during experimental OTM in male Wistar rats (Rattus novergicus).

Methods: Forty-eight healthy male Wistar rats were divided into positive control group (OTM 10 g/mm2 force application) and experimental group (OTM application and CAPE administration). Each groups were observed for 3, 7, 14 days. A nickel-titanium closed coil spring that was 8.0 mm long, thick was inserted between the upper left first molar and upper central incisor in order to move the molar mesially. A 20 mg/kg body weight dose of CAPE was taken orally. Using immunohistochemistry, the expression of TNF-α and NF-κB was examined on the compression side of the OTM. Both the Tukey’s honest significant difference test and the one-way analysis of variance test were applied (p<0.05).

Results: TNF-α and NF-κB expression in the compression side differed considerably across groups (p<0.05). Daily administration of CAPE significantly downregulates TNF-α and NF-κB expression on the compression side.

Conclusions: Administration of CAPE throughout OTM can successfully reduce the number of TNF-α and NF-κB expressions in the compression side in vivo.

Keywords: caffeic acid phenethyl ester; experimental tooth movement; medicine; nuclear transcription factor-κB; tumor necrosis factor-α.

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Resumen

Contexto: El movimiento dental ortodóncico (OTM) cambia el tejido periodontal y aumenta la incidencia de reabsorción radicular (OIRR). El éster fenetílico del ácido cafeico (CAPE), un químico antioxidante y antiinflamatorio generado a partir del propóleo de la miel, podría ser útil para controlar la inflamación durante la OTM y así reducir el riesgo de OIRR.

Objetivos: Evaluar si la suplementación con CAPE tiene un impacto antiinflamatorio sobre el factor de necrosis tumoral-α (TNF-α) y el factor de transcripción nuclear κB (NF-κB) durante OTM experimental en ratas Wistar macho (Rattus novergicus).

Métodos: Cuarenta y ocho ratas Wistar macho sanas se dividieron en un grupo de control positivo (aplicación de fuerza de 10 g/mm2 de OTM) y un grupo experimental (aplicación de OTM y administración de CAPE). Cada grupo se observó durante 3, 7, 14 días. Se insertó un resorte helicoidal cerrado de níquel-titanio de 8,0 mm de largo y espesor entre el primer molar superior izquierdo y el incisivo central superior para mover el molar mesialmente. Se tomó por vía oral una dosis de 20 mg/kg de peso corporal de CAPE. Usando inmunohistoquímica, se examinó la expresión de TNF-α y NF-κB en el lado de compresión del OTM. Se aplicaron tanto la prueba de diferencia significativa honesta de Tukey como la prueba de análisis de varianza de una vía (p<0,05).

Resultados: La expresión de TNF-α y NF-κB en el lado de compresión difirió considerablemente entre los grupos (p<0,05). La administración diaria de CAPE reguló significativamente a la baja la expresión de TNF-α y NF-κB en el lado de la compresión.

Conclusiones: La administración de CAPE a través de OTM puede reducir con éxito las expresiones de TNF-α y NF-κB en el lado de compresión in vivo.

Palabras Clave: éster fenetílico del ácido cafeico; factor de necrosis tumoral-α; factor de transcripción nuclear-κB; medicamento; movimiento dental experimental.

jppres_pdf_free
Citation Format: Salikha K, Narmada IB, Alida, Nugraha AP, Sari AF, Riawan W, Noor TNEBTA (2022) Anti-inflammatory effect of caffeic acid phenethyl ester supplementation on TNF-α and NF-κB expressions throughout experimental tooth movement in vivo. J Pharm Pharmacogn Res 10(6): 1037–1045. https://doi.org/10.56499/jppres22.1479_10.6.1037
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© 2022 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

Co-cultivation of PBMCs microvesicle activated by MSCS and OS-OCs

J. Pharm. Pharmacogn. Res., vol. 10, no. 5, pp. 782-790, September-October 2022.

DOI: https://doi.org/10.56499/jppres22.1414_10.5.782

Original Article

Activation of microvesicle peripheral blood mononuclear cells by mesenchymal stem cells secretome co-cultivated with osteosarcoma stem cell

[Activación de microvesículas de células mononucleares de sangre periférica por secretoma de células madre mesenquimales cocultivadas con células madre de osteosarcoma]

Fachrizal Arfani Prawiragara1,2, Ferdiansyah2*, Mouli Edward2, Dwikora Novembri Utomo2, Mohammad Hardian Basuki2, Alexander Patera Nugraha3, Fedik Abdul Rantam4

1Magister Clinical Medicine Program, Orthopedic and Traumatology Department, General Academic Dr. Soetomo Hospital/Faculty of Medicine, Airlangga, Surabaya, Indonesia.

2Department of Orthopaedic and Traumatology, General Academic Dr. Soetomo Hospital/Teaching Hospital, Faculty of Medicine, Airlangga University, Surabaya, Indonesia.

3Department of Orthodontics, Faculty of Dental Medicine, Airlangga University, Surabaya, Indonesia.

4Stem Cell Research Center and Development, Airlangga University, Surabaya, Indonesia.

*E-mail: ferdiansyah@fk.unair.ac.id

Abstract

Context: Microvesicle is a cell micro molecule that may play a role in the process of osteosarcoma stem cell apoptosis.

Aims: To investigate the activity of peripheral blood mononuclear cells (PBMCs) through the secretion of interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-10 (IL-10), C-X-C Motif Chemokine Ligand 13 (CXCL13) and tissue inhibitor of metalloproteinases-3 (TIMP-3) on co-cultivation of peripheral blood mononuclear cells (PBMCs) sensitized by mesenchymal stem cell secretome (MSCS) co-cultivated with osteosarcoma stem cells (OS-SCs).

Methods: This study was true experimental with a post-test only control group design. This was in vitro study PBMSCs sensitized by MSCS as then samples were divided into 4 treatment groups, respectively: Zero-day treatment (P0) PBMCs were co-cultivated with OS-SCs for 0 hours; First treatment (P1) PBMCs were co-cultivated with OS-SCs for 1 hour; Second treatment (P2) PBMCs were co-cultivated with OS-SCs for 2 days; Third treatment (P3) PBMCs were co-cultivated with OS-SCs for 4 days. The examination method used in this study was flow cytometry and indirect enzyme-linked immunosorbent assay (ELISA). The data were statistically analyzed with analysis of variance (ANOVA) with a p≤0.05 considered a significant difference.

Results: There was a tendency for a significant increase in extravesicular secretion in the secretion of IL-2, IL-6, IL-10, CXCL13, TIMP3, in the microvesicle PBMCs when sensitized by MSCs secretome co-cultivated with OS-SCs environment co-cultivated after the fourth day with significantly different between groups (p≤0.05).

Conclusions: PBMSCs’ microvesicle such as IL-2, IL-6, IL-10, CXCL13, TIMP3 was significantly sensitized by MSCS and co-cultivated with OS-SCs after the fourth day of in vitro.

Keywords: medicine; non-communicable disease; non-infectious disease; osteosarcoma; stem cells.

Resumen

Contexto: La microvesícula es una micromolécula celular que puede desempeñar un papel en el proceso de apoptosis de las células madre del osteosarcoma.

Objetivos: Investigar la actividad de las células mononucleares de sangre periférica (PBMC) a través de la secreción de interleucina-2 (IL-2), interleucina-6 (IL-6), interleucina-10 (IL-10), C-X-C Motif Chemokine Ligand 13 (CXCL13) e inhibidor tisular de metaloproteinasas-3 (TIMP-3) en el cocultivo de células mononucleares de sangre periférica (PBMC) sensibilizadas por secretoma de células madre mesenquimales (MSCS) cocultivadas con células madre de osteosarcoma (OS-SC).

Métodos: Este estudio fue verdaderamente experimental con un diseño de grupo de control solo posterior a la prueba. Este fue un estudio in vitro de PBMSC sensibilizadas por MSCS, ya que luego las muestras se dividieron en 4 grupos de tratamiento, respectivamente: Tratamiento de día cero (P0) Las PBMC se cocultivaron con OS-SC durante 0 horas; Las PBMC del primer tratamiento (P1) se cocultivaron con OS-SC durante 1 hora; Las PBMC del segundo tratamiento (P2) se cocultivaron con OS-SC durante 2 días; Las PBMC del tercer tratamiento (P3) se cocultivaron con OS-SC durante 4 días. El método de examen utilizado en este estudio fue la citometría de flujo y el ensayo inmunoabsorbente ligado a enzimas indirecto (ELISA). Los datos fueron analizados estadísticamente con análisis de varianza (ANOVA) con p≤0.05 considerado como diferencia significativa.

Resultados: Hubo una tendencia a un aumento significativo en la secreción extravesicular en la secreción de IL-2, IL-6, IL-10, CXCL13, TIMP3, en las microvesículas de PBMC cuando se sensibilizan con el secretoma de MSC cocultivado con el entorno de OS-SC. cocultivados después del cuarto día con diferencias significativas entre grupos (p≤0.05).

Conclusiones: Las microvesículas de PBMSC como IL-2, IL-6, IL-10, CXCL13, TIMP3 fueron significativamente sensibilizadas por MSCS y cocultivadas con OS-SC después del cuarto día de in vitro.

Palabras Clave: células madre; enfermedad no transmisible; enfermedad no infecciosa; medicina; osteosarcoma.

Citation Format: Prawiragara FA, Ferdiansyah, Edward M, Utomo DN, Basuki MH, Nugraha AP, Rantam FA (2022) Activation of microvesicle peripheral blood mononuclear cells by mesenchymal stem cells secretome co-cultivated with osteosarcoma stem cell. J Pharm Pharmacogn Res 10(5): 782–790. https://doi.org/10.56499/jppres22.1414_10.5.782
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© 2022 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

Metal ion and cytokines trigger dental metal allergy in silico

J. Pharm. Pharmacogn. Res., vol. 10, no. 4, pp. 687-694, July-August 2022.

DOI: https://doi.org/10.56499/jppres22.1372_10.4.687

Original Article

Computational study of Cu2+, Fe2+, Mn2+, Mn3+, Fe3+, CrO42-, Si4+, and Hg+ binding sites identification on cytokines to predict dental metal allergy: An in silico study

[Estudio computacional de Cu2+, Fe2+, Mn2+, Mn3+, Fe3+, CrO42-, Si4+ y Hg+ e identificación de sitios de unión a citocinas para predecir la alergia dental a metales: Un estudio in silico]

Titiek Berniyanti1, Alexander Patera Nugraha2,3*, Novi Nurul Hidayati2, Viol Dhea Kharisma4, Albertus Putera Nugraha5, Tengku Natasha Eleena Binti Tengku Ahmad Noor6,7

1Dental Public Health Department, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia.

2Graduate Student of Dental Health Science, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia.

3Department of Orthodontics, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia.

4Graduate Student of Biology, Department of Biology, Faculty of Mathematics and Natural Science, Universitas Brawijaya, Malang, Indonesia.

5Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia.

6Membership of Faculty of Dental Surgery, Royal College of Surgeon, Edinburgh University, United Kingdom.

7Malaysian Armed Forces Dental Officer, 609 Armed Forces Dental Clinic, Kem Semenggo, Kuching, Sarawak, Malaysia.

*E-mail: alexander.patera.nugraha@fkg.unair.ac.id

Abstract

Context: Metal allergy is a general term to describe allergic diseases due to the release of metal ion reactions in the body which are mediated by T cells and involve inflammatory cytokines that can cause morbidity and mortality. Molecular docking is an analysis that can be used to assess the interaction of ligand bonds with target proteins that are used to predict metal allergies caused by metal ions that stimulate cytokines.

Aims: To analyze the binding sites of Cu2+, Fe2+, Mn2+, Mn3+, Fe3+, CrO42-, Si4+, and Hg+  ions on cytokines to predict dental metal allergy through a bioinformatics approach, in silico.

Methods: Metal ion particles consisting of Cu2+, Fe2+, Mn2+, Mn3+, Fe3+, CrO42-, Si4+, and Hg+  were predicted to bind tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin (IL) IL-1b, IL-2, IL-4, IL-10, IL-13, IL-17, IL-23, and IL-33 act as target proteins were examined.

Results: The blind docking simulation succeeded in identifying the comparison of the binding activity of metal ion particles on cytokines target proteins. The docking simulation results show that the metal ion with the most negative binding affinity value binds to the IL-17 protein. Conclusions: Metal ion particles consisting of Cu2+, Fe2+, Mn2+, Mn3+, Fe3+, CrO42-, Si4+, and Hg+ have the most negative binding affinity values for binding to IL-17 protein, which can cause allergic reactions predicted by molecular docking, in silico.

Keywords: allergy; dentistry; good health and well-being; medicine; orthodontics.

jppres_pdf_free

Resumen

Contexto: La alergia a los metales es un término general para describir las enfermedades alérgicas debidas a la liberación de reacciones de iones metálicos en el cuerpo que están mediadas por células T e involucran citocinas inflamatorias que pueden causar morbilidad y mortalidad. El acoplamiento molecular es un análisis que se puede utilizar para evaluar la interacción de los enlaces de ligandos con proteínas diana que se utilizan para predecir alergias a metales causadas por iones metálicos que estimulan las citocinas.

Objetivos: Analizar los sitios de unión de los iones Cu2+, Fe2+, Mn2+, Mn3+, Fe3+, CrO42-, Si4+ y Hg+ en citocinas para predecir la alergia dental a metales mediante un enfoque bioinformático, in silico.

Métodos: Partículas de iones metálicos que consisten en Cu2+, Fe2+, Mn2+, Mn3+, Fe3+, CrO42-, Si4+ y Hg+ fueron predichas para unirse al factor de necrosis tumoral-α (TNF-α), interferón-γ (IFN-γ), interleucina (IL) Se examinaron IL-1b, IL-2, IL-4, IL-10, IL-13, IL-17, IL-23 e IL-33 que actúan como proteínas diana.

Resultados: La simulación de acoplamiento ciego logró identificar la comparación de la actividad de unión de las partículas de iones metálicos en las proteínas diana de las citocinas. Los resultados de la simulación de acoplamiento muestran que el ion metálico con el valor de afinidad de unión más negativo se une a la proteína IL-17.Conclusiones: Las partículas de iones metálicos que consisten en Cu2+, Fe2+, Mn2+, Mn3+, Fe3+, CrO42-, Si4+ y Hg+ tienen los valores de afinidad de unión más negativos para unirse a la proteína IL-17, lo que puede causar reacciones alérgicas predichas por acoplamiento molecular, in silico.

Palabras Clave: alergia; buena salud y bienestar; medicamento; odontología; ortodoncia.

jppres_pdf_free

Citation Format: Berniyanti T, Nugraha AP, Hidayati NN, Kharisma VD, Nugraha AP, Tengku NEBTAN (2022) Computational study of Cu2+, Fe2+, Mn2+, Mn3+, Fe3+, CrO42-, Si4+, and Hg+ binding sites identification on cytokines to predict dental metal allergy: An in silico study. J Pharm Pharmacogn Res 10(4): 687–694. https://doi.org/10.56499/jppres22.1372_10.4.687https://doi.org/10.56499/jppres22.1372_10.4.687
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© 2022 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

Molecular docking of polyether ether ketone and nano-hydroxyapatite in orthodontics

J. Pharm. Pharmacogn. Res., vol. 10, no. 4, pp. 676-686, July-August 2022.

DOI: https://doi.org/10.56499/jppres22.1371_10.4.676

Original Article

Molecular docking of polyether ether ketone and nano-hydroxyapatite as biomaterial candidates for orthodontic mini-implant fabrication

[Acoplamiento molecular de poliéter éter cetona y nano-hidroxiapatita como biomateriales candidatos para la fabricación de mini-implantes de ortodoncia]

I Gusti Aju Wahju Ardani1,2, Alexander Patera Nugraha1,2,3*, Monika Nilam Suryani1, Ryan Hafidz Putra Pamungkas1, Devani Githa Vitamamy1, Rizky Alif Susanto1, Riyanarto Sarno4, Aziz Fajar4, Viol Dhea Kharisma5, Albertus Putera Nugraha6, Tengku Natasha Eleena binti Tengku Ahmad Noor7,8

1Orthodontics Department, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia.

2Dental Implant Research Group, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia.

3Graduate Student of Dental Health Science, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia.

4Department of Informatics, Institut Teknologi Sepuluh Nopember, Surabaya, Indonesia.

5Department of Biology, Faculty of Mathematics and Natural Science, Universitas Brawijaya, Malang, Indonesia.

6Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia.

7Membership of Faculty of Dental Surgery, Royal College of Surgeons, Edinburgh University, United Kingdom.

8Malaysian Armed Forces Dental Officer, 609 Armed Forces Dental Clinic, Kem Semenggo, Kuching, Sarawak, Malaysia.

*E-mail: alexander.patera.nugraha@fkg.unair.ac.id

Abstract

Context: Modified polyether ether ketone (PEEK) by adding nano-hydroxyapatite (HA) material on its fixture for mini-implant fabrication may increase resistance force through osseointegration.

Aims: To analyze the binding molecular docking of PEEK incorporated with HA as a biomaterial candidate for orthodontic mini-implant fabrication through a bioinformatic approach, an in silico study.

Methods: 3D ligand structure consisting of HA, PEEK and target proteins consisting of osteopontin, osteocalcin, osteonectin, bone morphogenetic protein 4 (BMP4), bone morphogenetic protein 2 (BMP2), bone morphogenetic protein 7 (BMP7), alkaline phosphatase (ALP),  runt-related transcription factor 2 (RUNX2), Insulin growth factor-1 (IGF-1), osterix, tartrate-resistant acid phosphatase (TRAP), collagen alpha-1 (COL1A1) obtained from RCSB-PDB. It was analyzed the binding affinity of a single HA, PEEK, and HA + PEEK complex to twelve target proteins related to osseointegration. The types of chemical interactions produced by the ligands in the target protein domain consisted of Van der Waals, hydrogen, hydrophobic, pi, and alkyl.

Results: The blind docking simulation succeeded in identifying the most negative binding affinity; it was found in the HA + PEEK molecular complex compared to HA and PEEK in the single condition. The type of chemical interaction formed consisted of hydrogen, van der Waals, pi, and alkyl. HA+PEEK showed the most negative binding affinity with ALP and IGF-1, as much as -8.7 binding affinity.

Conclusions: The molecular docking of PEEK with HA exhibited a prominent binding affinity with osteogenic markers like ALP and IGF-1 in silico, allowing it to have a higher potential than nano-HA or PEEK as a single biomaterial for osseointegration as the fabrication of mini-implants that may support orthodontic treatment.

Keywords: dentistry; good health and well-being; in silico; medicine; temporary anchorage device.

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Resumen

Contexto: La poliéter éter cetona modificada (PEEK) puede aumentar la fuerza de resistencia a través de la osteointegración mediante la adición de material de nanohidroxiapatita (HA) para la fabricación de mini-implantes.

Objetivos: Analizar el acoplamiento molecular de PEEK incorporado con HA como candidato a biomaterial para la fabricación de miniimplantes de ortodoncia a través de un enfoque bioinformático, un estudio in silico.

Métodos: Estructura de ligando 3D que consiste en HA, PEEK y proteínas diana como osteopontina, osteocalcina, osteonectina, proteína morfogenética ósea 4 (BMP4), proteína morfogenética ósea 2 (BMP2), proteína morfogenética ósea 7 (BMP7), fosfatasa alcalina (ALP) , factor de transcripción relacionado con runt 2 (RUNX2), factor de crecimiento de insulina-1 (IGF-1), osterix, fosfatasa ácida tartrato resistente (TRAP), colágeno alfa-1 (COL1A1) obtenido de RCSB-PDB. Fue analizada la afinidad de unión del complejo único HA, PEEK y HA + PEEK a doce proteínas diana relacionadas con la osteointegración. Los tipos de interacciones químicas producidas por los ligandos en el dominio de la proteína objetivo consistieron en Van der Waals, hidrógeno, hidrofóbico, pi y alquilo.

Resultados: La simulación a ciegas de acoplamiento logró identificar la afinidad de unión más negativa. Esta se encontró en el complejo molecular HA + PEEK en comparación con HA y PEEK de forma individual. El tipo de interacción química formada consistió en hidrógeno, van der Waals, pi y alquilo. HA+PEEK mostró la afinidad de unión más negativa con ALP e IGF-1, con una afinidad de unión de -8,7.

Conclusiones: El acoplamiento molecular de PEEK con HA exhibió una afinidad de unión prominente con marcadores osteogénicos como ALP e IGF-1 in silico, lo que le permite tener un mayor potencial que HA o PEEK como biomaterial único para la osteointegración como la fabricación de mini-implantes que puedan soportar el tratamiento de ortodoncia.

Palabras Clave: buena salud y bienestar; dispositivo de anclaje temporal; in silico; odontología; medicina.

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Citation Format: Ardani IGAW, Nugraha AP, Suryani NM, Pamungkas RH, Vitamamy DG, Susanto RA, Sarno R, Fajar A, Kharisma VD, Nugraha AP, Noor TNEBTA (2022) Molecular docking of polyether ether ketone and nano-hydroxyapatite as biomaterial candidates for orthodontic mini-implant fabrication. J Pharm Pharmacogn Res 10(4): 676–686. https://doi.org/10.56499/jppres22.1371_10.4.676
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© 2022 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

Roselle flower for immunomodulatory adjuvant therapy in COVID-19

J. Pharm. Pharmacogn. Res., vol. 10, no. 3, pp. 418-428, May-June 2022

DOI: https://doi.org/10.56499/jppres21.1316_10.3.418

Original Article

Anthocyanin, tartaric acid, ascorbic acid of roselle flower (Hibiscus sabdariffa L.) for immunomodulatory adjuvant therapy in oral manifestation coronavirus disease-19: An immunoinformatic approach

[Antocianina, ácido tartárico, ácido ascórbico de flor de Jamaica (Hibiscus sabdariffa L.) para la terapia adyuvante inmunomoduladora en la manifestación oral de la enfermedad por coronavirus-19: Un enfoque inmunoinformático]

Nastiti Faradilla Ramadhani1, Alexander Patera Nugraha1,2*, Desintya Rahmadhani3, Martining Shoffa Puspitaningrum3, Yuniar Rizqianti3, Viol Dhea Kharisma4, Tengku Natasha Eleena binti Tengku Ahmad Noor5, Rini Devijanti Ridwan6, Diah Savitri Ernawati7, Albertus Putera Nugraha8

1Graduate Student of Dental Health Science, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia.

2Department of Orthodontic, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia.

3Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia.

4Graduate Student of Biology Science, Department of Biology, Faculty of Mathematics and Natural Science, Universitas Brawijaya, Malang, Indonesia

5Military Dental Officer of Royal Medical and Dental Corps, Malaysian Armed Forces, Indonesia.

6Department of Oral Biology, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia.

7Department of Oral Medicine, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia.

8Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia.

*E-mail: alexander.patera.nugraha@fkg.unair.ac.id

Abstract

Context: Oral manifestations that arose from COVID-19 infection often causes morbidity and systemic drug administration is less effective. Roselle flower (Hibiscus sabdariffa) is one of the plants that is often used in infusion as it gives health benefits. Hence, H. sabdariffa may benefit from adjuvant therapy to treat oral manifestation due to COVID-19.

Aims: To investigate the potential of H. sabdariffa anthocyanins, tartaric acid, and ascorbic acid chemical compounds as antiviral, anti-inflammatory, antioxidant, and increasing tissue regeneration in oral manifestation due to COVID-19 infection in silico.

Methods: Chemical compounds consisted of anthocyanins, (+)-tartaric acid, and ascorbic acid beside target proteins consisted of ACE2-spike, Foxp3, IL-10, IL6, IL1β, VEGF, FGF-2, HSP70, TNFR and MDA-ovalbumin were obtained from the database, ligand samples were selected through absorption, distribution, metabolism, excretion and toxicology analysis, then molecular docking simulations, identification of protein-ligand interactions, and 3D visualization were performed.

Results: Anthocyanins, tartaric acid, and ascorbic acid are the active compounds in H. sabdariffa, which act as antioxidants. The activity of anthocyanin compounds is higher than other compounds through value binding affinity, which is more negative and binds to specific domains of target proteins by forming weak binding interactions that play a role in biological responses. Anthocyanins have the most negative binding energy compared to tartaric-acid and ascorbic acid.

Conclusions: Anthocyanins act as antioxidants; this mechanism increases heat shock protein-70 (HSP70), which may play an important role in increasing wound regeneration of oral manifestation in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as documented in silico.

Keywords: COVID-19; dentistry; Hibiscus sabdariffa; infectious disease; medicine.

Resumen

Contexto: Las manifestaciones orales derivadas de la infección por COVID-19 suelen causar morbilidad y la administración sistémica de fármacos es menos efectiva. La flor de Jamaica (Hibiscus sabdariffa) es una de las plantas que se suele utilizar en infusión ya que aporta beneficios para la salud. Por lo tanto, H. sabdariffa puede beneficiarse de la terapia adyuvante para tratar las manifestaciones orales debido a COVID-19.

Objetivos: Investigar el potencial de los compuestos químicos de H. sabdariffa, como antocianinas, ácido tartárico y ácido ascórbico como antivirales, antiinflamatorios, antioxidantes y el aumento de la regeneración de tejidos en la manifestación oral debido a la infección por COVID-19 a través de un enfoque inmunoinformático, un estudio in silico.

Métodos: Antocianinas, ácido tartárico y ácido ascórbico, además de proteínas diana como ACE2-spike, Foxp3, IL-10, IL6, IL1β, VEGF, FGF-2, HSP70, TNFR y MDA-ovoalbúmina, se obtuvieron de la base de datos, las muestras de ligando se seleccionaron mediante análisis de absorción, distribución, metabolismo, excreción y toxicología, luego se realizaron simulaciones de acoplamiento molecular, identificación de interacciones proteína-ligando y visualización 3D.

Resultados: Las antocianinas, el ácido tartárico y el ácido ascórbico son los compuestos activos de H. sabdariffa que actúan como antioxidantes. La actividad de los compuestos de antocianina es mayor que la de otros compuestos a través de una afinidad de unión de valor que es más negativa y se une a dominios específicos de proteínas diana formando interacciones de unión débiles que desempeñan un papel en las respuestas biológicas. Las antocianinas tienen la energía de unión más negativa en comparación con el ácido tartárico y el ácido ascórbico.

Conclusiones: Las antocianinas actúan como antioxidantes; este mecanismo aumenta la proteína de choque térmico-70 (HSP70), que puede desempeñar un papel importante en el aumento de la regeneración de heridas de la manifestación oral en el síndrome respiratorio agudo severo coronavirus 2 (SARS-CoV-2) como se documenta in silico.

Palabras Clave: COVID-19; enfermedad infecciosa; Hibiscus sabdariffa; medicamento; odontología.

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Citation Format: Ramadhani NF, Nugraha AP, Rahmadani D, Puspitaningrum MS, Rizqianti Y, Kharisma VD, Noor TNEBTA, Ridwan RD, Ernawati DS, Nugraha AP (2022) Anthocyanin, tartaric acid, ascorbic acid of roselle flower (Hibiscus sabdariffa L.) for immunomodulatory adjuvant therapy in oral manifestation coronavirus disease-19: An immunoinformatic approach. J Pharm Pharmacogn Res 10(3): 418–428. https://doi.org/10.56499/jppres21.1316_10.3.418
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RANKL and osteoprotegerin in osteoporotic mandibular



J Pharm Pharmacogn Res 9(6): 870-877, 2021.

Original article

Osteoclast activity in osteoporosis mandibular bone based on RANKL and osteoprotegerin ratio

[Actividad de los osteoclastos en el hueso de la mandíbula con osteoporosis basada en la relación RANKL y osteoprotegerina]

Mefina Kuntjoro1,2, Nike Hendrijantini2*, Fedik Abdul Rantam3, Guang Hong4, Sherman Salim2, Muhammad Dimas Aditya Ari2

1Doctoral Program, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia.

2Department of Prosthodontic, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia.

3Laboratory of Virology and Immunology, Department of Microbiology, Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya, Indonesia.

4Liaison Center for Innovative Dentistry, Graduate School of Dentistry, Tohoku University, Aoba-Ku, Sendai, Japan.

*E-mail: nike-h@fkg.unair.ac.id

Abstract

Context: Osteoporosis occurs not only in the lumbar bone, femur, and radius but also occurs in the mandibular bone. Therefore, osteoporosis is a disease that required attention from the dentists.

Aims: To determine the ratio of Receptor Activator of Nuclear Factor kB-Ligand:Osteoprotegerin (RANKL:OPG) expression and the ratio of osteoclasts:osteoblasts number in the mandibular bone of the osteoporosis rat models.

Methods: The research subjects used were 20 Rattus novergicus, which were randomly divided into two groups, namely ovariectomy (OVX) and sham surgery (SHS). Twelve weeks after surgery, the animals were terminated and mandibular bone specimens were taken for histological examination of osteoclasts, osteoblasts, RANKL, and OPG expression. An examination of estrogen levels in the blood of the research subjects was also carried out. All data obtained were tested statistically using a t-test.

Results: There was a decrease in the amount of estrogen in the OVX group rather than SHS (p = 0.005). In the SHS group, the RANKL:OPG expression value ratio was 0.51 ± 0.15, while in the OVX group was 0.86 ± 0.22 (p = 0.001). In the SHS group, the ratio of osteoclasts:osteoblasts number was 0.012 ± 0.004, while in the OVX group was 0.061 ± 0.023 (p = 0.001).

Conclusions: A decrease in estrogen significantly induces the ratio of RANKL:OPG and osteoclast:osteoblasts in the mandibular bone.

Keywords: estrogen; medicine; osteoblast; osteoclast; osteoprotegerin; RANKL.

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Resumen

Contexto: La osteoporosis ocurre no solo en el hueso lumbar, fémur y radio, también ocurre en el hueso mandibular, por lo que la osteoporosis es una enfermedad que requiere atención por parte de los dentistas.

Objetivos: Determinar la proporción de expresión del Receptor Activador del Factor Nuclear kB-Ligando:Osteoprotegerina (RANKL:OPG) y la proporción de osteoclastos:número de osteoblastos en el hueso mandibular de los modelos de rata con osteoporosis.

Métodos: Los sujetos de investigación utilizados fueron 20 Rattus novergicus, que se dividieron aleatoriamente en dos grupos, a saber, ovariectomía (OVX) y cirugía simulada (SHS). Doce semanas después de la cirugía, se sacrificaron los animales y se tomaron muestras de hueso mandibular para el examen histológico de osteoclastos, osteoblastos, expresión de RANKL y OPG. También se llevó a cabo un examen de los niveles de estrógeno en la sangre de los sujetos de investigación. Todos los datos obtenidos se testaron estadísticamente mediante una prueba t.

Resultados: Hubo una disminución en la cantidad de estrógeno en el grupo OVX en lugar de SHS (p = 0,005). En el grupo SHS, la relación de valor de expresión de RANKL:OPG fue de 0,51 ± 0,15, mientras que en el grupo de OVX fue de 0,86 ± 0,22 (p = 0,001). En el grupo de SHS, la relación de osteoclastos:número de osteoblastos fue de 0,012 ± 0,004, mientras que en el grupo de OVX fue de 0,061 ± 0,023 (p = 0,001).

Conclusiones: Una disminución de estrógenos induce significativamente la relación RANKL OPG y osteoclastos:osteoblastos en el hueso mandibular.

Palabras Clave: estrógeno; medicina; osteoblasto; osteoclasto; osteoprotegerina; RANKL.

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Citation Format: Kuntjoro M, Hendrijantini N, Rantam FA, Hong G, Salim S, Ari MDA (2021) Osteoclast activity in osteoporosis mandibular bone based on RANKL and osteoprotegerin ratio. J Pharm Pharmacogn Res 9(6): 870–877.

© 2021 Journal of Pharmacy & Pharmacognosy Research (JPPRes)