Tag Archives: medicine

Metal ion and cytokines trigger dental metal allergy in silico

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

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.
References

Agnihotri R, Gaur S, Albin S (2020) Nanometals in dentistry: Applications and toxicological implications-a systematic review. Biol Trace Elem Res 197(1): 70–88.

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.

Ashraf T, Taneez M, Kalsoom S, Irfan T, Shafique MA (2021) Experimental calculations of metals content in skin-whitening creams and theoretical investigation for their biological effect against tyrosinase enzyme. Biol Trace Elem Res 199(9): 3562–3569.

Bonaventura P, Lamboux A, Albarède F, Miossec P (2017) Regulatory effects of zinc on cadmium-induced cytotoxicity in chronic inflammation. PLoS One 12(7): e0180879.

Chandu GS, Hema BS, Mahajan H, Mishra S (2014) Dental metal allergy: An update. J Res Adv Dent 3(3): 156–163

Christensen TJ, Samant SA, Shin AY (2017) Making sense of metal allergy and hypersensitivity to metallic implants in relation to hand surgery. J Hand Surg Am 42(9): 737–746.

Dundu MAJ, Aditya G (2017) The effect of 50% betel leaf extract (Piper betle L.) on the release of metal ions (Ni, Cr and Fe) in orthodontic brackets. Odonto Dent J 4(1): 32–37.

FDA – Food and Drug Administration (2019) Biological Responses to Metal Implants: Clinical Response to Metal Implants.  

Haddad SF, Helm MM, Meath B, Adams C, Packianathan N, Uhl R (2019) Exploring the incidence, implications, and relevance of metal allergy to orthopaedic surgeons. J Am Acad Orthop Surg Glob Res Rev 3(4): e023.

Her M, Kavanaugh A (2016) Alterations in immune function with biologic therapies for autoimmune disease. J Allergy Clin Immunol 137(1): 19–27.

Hosoki M, Nishigawa K, Tajima T,  Ueda M, Matsuka Y (2018) Cross-sectional observational study exploring clinical risk of titanium allergy caused by dental implants. J Prosthodont Res  62(4): 426–431.

Itoh E, Furumura M, Furue M (2020) Rate of actual metal allergy prior to dental treatment in subjects complaining of possible metal allergy. Asian Pac J Allergy Immunol 38(3): 186–189.

Jukka (2018) Dental Materials (Priciples And Applications): Dental Amalgam 3rd Ed. Paramount Books (Pvt.) Ltd.

Kharisma VD, Ansori ANM,  Nugraha AP (2020) Computational study of ginger (Zingiber officinale) as E6 inhibitor in human papillomavirus type 16 (HPV-16) infection. Biochem Cell Arch 20(1): 3155–3159.

Kharisma VD, Widyananda MH, Ansori ANM, Nege AS, Naw SW, Nugraha AP (2021) Tea catechin as antiviral agent via apoptosis agonist and triple inhibitor mechanism against HIV-1 infection: A bioinformatics approach. J Pharm Pharmacogn Res 9(4): 435–445.

Kitagawa M, Murakami S, Akashi Y, Oka H, Shintani T, Ogawa I,  Inoue T, Kurihara H (2019) Current status of dental metal allergy in Japan. J Prosthodont Res 63(3): 309–312.

Liu J, Wang Y, Zhao H, Mu M, Guo M, Nie X, Sun Y, Xing M (2020) Arsenic (III) or/and copper (II) exposure induce immunotoxicity through trigger oxidative stress, inflammation and immune imbalance in the bursa of chicken. Ecotoxicol Environ Saf  190: 110127.

Maeno M, Tamagawa-Mineoka R, Arakawa Y, Masuda K, Adachi T, Katoh N (2021) Metal patch testing in patients with oral symptoms. J Dermatol 48(1): 85–87.

Nakasone Y, Kumagai K, Matsubara R, Shigematsu H, Kitaura K, Suzuki S, Satoh M, Hamada, Suzuki R RS (2018) Characterization of T cell receptors in a novel murine model of nickel-induced intraoral metal contact allergy. Plos One 13(12): e0209248.

Nugraha AP, Rahmadhani D,  Puspitaningrum MS, Rizqianti Y,  Kharisma VD, Ernawati DS (2021) Molecular docking of anthocyanins and ternatin in Clitoria ternatea as coronavirus disease oral manifestation therapy. J Adv Pharm Technol Res 12(4): 362.

Pazzini C, Pereira L, Peconick A,  Marques LS, Paiva SM (2016) Nickel allergy: Blood and periodontal evaluation after orthodontic treatment. Acta Odontol Latinoam 29(1): 42–48.

Prahasanti C, Nugraha AP,  Kharisma VD, Ansori ANM, Ridwan RD, Putri TPS, Ramadhani NF, Narmada IB, Ardani IGAW, Ramadhani NF, Noor TNEBA (2021) A bioinformatic approach of hydroxyapatite and polymethylmethacrylate composite exploration as dental implant biomaterial. J Pharm Pharmacogn Res 9(5): 746–754.

Ramadhani NF, Nugraha AP, Rahmadhani 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.

Rantam FA, Kharisma VD, Sumartono C, Nugraha J, Wijaya AY, Susilowati H, Kuncorojakti S, Nugraha AP (2021) Molecular docking and dynamic simulation of conserved B cell epitope of SARS-CoV-2 glycoprotein Indonesian isolates: An immunoinformatic approach. F1000Res 10: 813.

Rose PW, Prlić A, Altunkaya A, Bi C,  Bradley AR, Christie CH, Costanzo LD, Duarte JM, Dutta S, Feng Z, Green RK, Goodsell DS, Hudson B, Kalro T, Lowe R, Peisach E, Randle C, Rose AS, Shao C, Tao YP, Valasatava Y, Voigt M, Westbrook JD, Woo J, Yang H, Young JY, Zardecki C, Berman HM, Burley SK (2017) The RCSB protein data bank: integrative view of protein, gene and 3D structural information. Nucleic Acids Res 45(D1): D271–D281.

Saito M, Arakaki R, Yamada A, Tsunematsu T, Kudo Y, Ishimaru N (2016) Molecular mechanisms of nickel allergy. Int J Mol Sci 17(2): 202.

Sakaguchi R, Ferracane JPJ (2019) Craig’s Restorative Dental Materials. 14th Ed. Elsevier.

Sitalaksmi RM, Ito K, Ogasawara K, Suto Y, Itabashi M, Ueda K, Hirasawa N, Narushima T, Hendrijantini N, Kresnoadi U, Sasaki K (2019) COX-2 induces T cell accumulation and IFN-γ production during the development of chromium allergy. Autoimmunity 52(5–6): 228–234.

Susanto H, Kharisma V, Listyorini D, Taufiq A, Sunaryono, Aulanni’am (2018) Effectivity of black tea polyphenol in adipogenesis related IGF-1 and its receptor pathway through in silico based study. J Phys Conf Ser 1093(1): 012037.

Takaoka Y, Akiba Y, Nagasawa M,  Ito A, Masui Y, Akiba N, Eguchi K, Miyazawa H, Tabeta K, Uoshima K (2021) The relationship between dental metal allergy, periodontitis, and palmoplantar pustulosis: An observational study. J Prosthodont Res. doi: 10.2186/jpr.JPR_D_20_00307

Teo Wendy ZW, Schalock PC (2016) Hypersensitivity reactions to implanted metal devices: Facts and fictions.  J Investig Allergol Clin Immunol 26(5): 279–294.

Younas, Khan A, Shehzad O, Seo EK, Onder A, Khan S (2021) Anti-allergic activities of umbelliferone against histamine- and picryl chloride-induced ear edema by targeting Nrf2/iNOS signaling in mice. BMC Complement Med Ther 21(1): 215.

© 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.

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.

This image has an empty alt attribute; its file name is jppres_pdf_free.png

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.

This image has an empty alt attribute; its file name is jppres_pdf_free.png

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.
References

Albrektsson T, Johansson C (2001) Osteoinduction, osteoconduction and osseointegration. Eur Spine J 10: S96–S101.

Alqahtani AR, Gufran K, Silva F, Rocha MG, Chang J (2021) A clinical case report of a potential acute allergic reaction with titanium dental implant. Case Rep Dent 2021: 5592934.

Antolis M, Anggani HS, Marshadianti D, Ayu D (2021) Mini implant orthodontic as an anchorage in skeletal class II malocclusion treatment with severe dental protrusion [Indonesian]. J Ked Gi Unpad 33(1):71–78.

Ardani IG, Rahmawati D, Narmada IB, Nugraha AP, Taftazani H, Kusumawardani MK (2020) Surface Electromyography unveil the relationship between masticatory muscle tone and maloclusion class I & II in Javanese ethnic patient. J Int Dent Med Res 13(4): 1447–1454.

Barkarmo S, Wennerberg A, Hoffman M, Kjellin P, Breding K, Handa P, Stenport V (2013) Nano-hydroxyapatite-coated PEEK implants: A pilot study in rabbit bone. J Biomed Mater Res Part A 101A(2): 465–471.

Cheng Z, Guo C, Dong W, He FM, Zhao SF, Yang GL (2012) Effect of thin nano-hydroxyapatite coating on implant osseointegration in ovariectomized rats. Oral Surg Oral Med Oral Pathol Oral Radiol 113(3): e48-e53.

Choi JW, Shin S, Lee CY, Lee J, Seo HH, Lim S, Lee S, Kim IK, Lee HB, Kim SW, Hwang KC (2017) Rapid induction of osteogenic markers in mesenchymal stem cells by adipose-derived stromal vascular fraction cells. Cell Physiol Biochem 44(1): 53–65.

de Oliveira PGFP, de Melo Soares MS, Silveira E Souza AMM (2021) Influence of nano-hydroxyapatite coating implants on gene expression of osteogenic markers and micro-CT parameters. An in vivo study in diabetic rats. J Biomed Mater Res A 109(5): 682–694.

Elias CN, Oliveira Ruellas AC, Fernandes DJ (2012) Orthodontic implants: Concepts for the orthodontic practitioner. Int J Dent 2012: 549761.

Geng YM, Ren DN, Li SY, Li ZY, Shen XQ, Yuan YY (2020) Hydroxyapatite-incorporation improves bone formation on endosseous PEEK implant in canine tibia. J Appl Biomater Funct Mater 18: 2280800020975172.

Gromolak S, Krawczenko A, Antończyk A, Buczak K, Kiełbowicz Z, Klimczak A (2020) Biological characteristics and osteogenic differentiation of ovine bone marrow derived mesenchymal stem cells stimulated with FGF-2 and BMP-2. Int J Mol Sci 21(24): 9726.

Guo T, Kang W, Xiao D, Duan R, Zhi W, Weng J (2013) Molecular docking characterization of a four-domain segment of human fibronectin encompassing the RGD loop with hydroxyapatite. Molecules 19(1): 149–158.

Gupitasari A, Putri LS (2018) The prevalence of bad habits as the etiology of angle’s class I malocclusion in orthodontic clinic dental hospital Jember in 2015-2016 [Indonesian]. Pus Kes 6(2): 365–370.

Hayman AR (2008) Tartrate-resistant acid phosphatase (TRAP) and the osteoclast/immune cell dichotomy. Autoimmunity 41(3):218-223.

Henry JP, Bordoni B (2021) Histology, Osteoblasts. In: StatPearls. Treasure Island (FL): StatPearls Publishing; Update May 10, 2021.

Herwanda H, Arifin R, Lindawati L (2016) Knowledge of adolescents age 15-17 at SMAN 4 Banda Aceh City on the side effects of using fixed orthodontic appliances  [Indonesian]. J Syiah Kuala Dent Soc 1(1): 79–84.

Jubhari EH, Dammar I, Launardo V, Goan Y (2020) Implant coating materials to increase osseointegration of dental implant: A systematic review. Sys Rev Pharm 11(12): 35–41.

Kazimierczak P, Przekora A (2020) Osteoconductive and osteoinductive surface modifications of biomaterials for bone regeneration: A concise review. Coatings 10(10): 971.

Kharisma VD, Ansori AN, Nugraha AP (2020) Computational study of ginger (Zingiber officinale) as E6 Inhibitor in human papillomavirus type 16 (HPV-16) infection. Biochem Cell Arch 20: 3155–3159.

Khotib J, Lasandara CSC, Samirah S, Budiatin AS (2019) Acceleration of bone fracture healing through the use of natural bovine hydroxyapatite implant on bone defect animal model. Fol Med Indones 55(33): 176-187.

Kim S, Thiessen PA, Bolton EE, Chen J, Fu G, Gindulyte A, Han L, He J, He S, Shoemaker BA, Wang J (2016) PubChem Substance and Compound databases. Nucleic Acids Res 44(D1): D1202–D1213.

Levingstone TJ, Ardhaoui M, Benyounis K, Looney L, Stokes JT (2015) Plasma sprayed hydroxyapatite coatings: Understanding process relationships using design of experiment analysis. Surf Coat Technol 283: 29–36.

Loblobly M, Anindita PS, Leman MA (2015) Gambaran Maloklusi Berdasarkan Indeks Handicapping Malocclusion Assessment Record (HMAR) Pada Siswa SMAN 9 Manado [Indonesian]. e-GiGi 3(2): 625­–633.

Luqman A, Kharisma VD, Ruiz RA, Götz F (2020) In silico and in vitro study of trace amines (TA) and dopamine (DOP) interaction with human alpha 1-adrenergic receptor and the bacterial adrenergic receptor QseC. Cell Physiol Biochem 54(5): 888–898.

Ma Z, Zhao X, Zhao J, Zhao Z, Wang Q, Zhang C (2020) Biologically modified polyether ether ketone as dental implant material. Front Bioeng Biotechnol 8: 620537.

Megat Badarul Hisham PN, Narmada IB, Alida A, Rahmawati D, Nugraha A,  Putranti N (2019) Effects of vitamin D in alveolar bone remodeling on osteoblast numbers and bone alkaline phosphatase expression in pregnant rats during orthodontic tooth movement. J Orofac Sci 11(2): 79–83.

Mešić E, Muratović E, Redžepagić-Vražalica L, Pervan N, Muminović AJ, Delić M, Glušac M (2021) Experimental & fem analysis of orthodontic mini-implant design on primary stability. Appl Sci 11(12): 5461.

Najeeb S, Bds ZK, Bds SZ, Bds MS (2016) Bioactivity and osseointegration of PEEK are inferior to those of titanium: A systematic review. J Oral Implantol 42(6):512–516.

Naini A, Rubianto M, Latief FDE, Gunadi A, Kristiana D, Hendrijantini N (2020) Inflammatory and immunogenic response of the tissue after application of freeze-dried hydroxyapatite gypsum puger scaffold compared to freeze-dried hydroxyapatite bovine scaffold. Contemp Clin Dent 11(4): 371–375.

Nayak UK, Malviya N (2011) Role of mini-implants in orthodontics. Int J Oral Implantol Clin Res 2(3): 126–134.

Ntolou P, Tagkli A, Pepelassi E (2018) Factors related to the clinical application of orthodontic mini-implants. J Int Oral Health 10(3): 110.

Oka S, Li X, Zhang F (2020) MicroRNA-21 facilitates osteoblast activity. Biochem Biophys Rep 25: 100894.

Papathanasiou I, Kamposiora P, Papavasiliou G, Ferrari M (2020) The use of PEEK in digital prosthodontics: A narrative review. BMC Oral Health 20(1): 217.

Peng XB, Zhang Y, Wang YQ, He Q, Yu Q (2019) IGF-1 and BMP-7 synergistically stimulate articular cartilage repairing in the rabbit knees by improving chondrogenic differentiation of bone-marrow mesenchymal stem cells. J Cell Biochem 120(4): 5570–5582.

Prahasanti C, Nugraha AP, Kharisma VD, Ansori AN, Devijanti R, Ridwan TP, Ramadhani NF, Narmada IB, Ardani IG, Noor TN (2021) A bioinformatic approach of hydroxyapatite and polymethylmethacrylate composite exploration as dental implant biomaterial. J Pharm Pharmacogn Res 9(5): 746–754.

Prahasanti C, Nugraha AP, Saskianti T, Suardita K, Riawan W, Ernawat DS (2020) Exfoliated human deciduous tooth stem cells incorporating carbonate apatite scaffold enhance BMP-2, BMP-7 and attenuate MMP-8 expression duringinitial alveolar bone remodeling in Wistar rats (Rattus norvegicus). Clin Cosmet Investig Dent 12: 79–85.

Purnama YHC, Mastutik G, Putra ST (2018) Increased activity of mature osteoblast from rat bone marrow mesenchymal stem cells in osteogenic medium exposed to melatonin. Fol Med Indones 54(4): 282–288.

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.

Rose PW, Prlić A, Altunkaya A, Bi C, Bradley AR, Christie CH, Costanzo LD, Duarte JM, Dutta S, Feng Z, Green RK (2017) The RCSB protein data bank: Integrative view of protein, gene and 3D structural information. Nucleic Acids Res 45(D1): D271–D281.

Samirah, Budiatin AS, Mahyudin F, Khotib J (2021) Fabrication and characterization of bovine hydroxyapatite-gelatin-alendronate scaffold cross-linked by glutaraldehyde for bone regeneration. J Basic Clin Physiol Pharmacol 32(4): 555–560.

Sheoran L, Kumar P, Kumar S, Ulla ST, Hussain F (2021) Implants in orthodontics: A brief review. IP Indian J Orthod Dentofacial Res 7(1): 45–48.

Simangunsong S, Muttaqin Z, Tampubolon IA (2018) Description of malocclusion in Batak students based on dental aesthetic index [Indonesian]. Prima JODS 1(1): 40–48.

Sitasari PI, Narmada IB, Hamid T, Triwardhani A, Nugraha AP, Rahmawati D (2020) East Java green tea methanolic extractcan enhance RUNX2 and osterixexpression during orthodontic tooth movement in vivo. J Pharm Pharmacogn Res 8(4): 290–298.

Syada AN, Kurniawan FK, Wibowo D (2017) Comparison of severity levels and levels of orthodontic treatment needs using the malalignment index overview in junior high schools that have school health units and junior high schools that do not have UKS [Indonesian]. Jur Ked Gigi 2(1): 78–83.

Wang X, Mei L, Jiang X, Jin M, Xu Y, Li J, Li X, Meng Z, Zhu J, Wu F (2021) Hydroxyapatite-coated titanium by micro-arc oxidation and steam-hydrothermal treatment promotes osseointegration. Front Bioeng Biotechnol 9: 625877.

Valenti MT, Dalle Carbonare L, Mottes M (2016) Osteogenic differentiation in healthy and pathological conditions. Int J Mol Sci 18(1): 41.

Vieira-Andrade RG, Paiva S, Marques LS (2015) Impact of malocclusions on quality of life from childhood to adulthood. Iss Contemp Orthod 3: 39–55.

Zhou M, Geng YM, Li SY, Yang XB, Che YJ, Pathak JL, Wu G (2019) Nanocrystalline hydroxyapatite-based scaffold adsorbs and gives sustained release of osteoinductive growth factor and facilitates bone regeneration in mice ectopic model. Journal of Nanomaterials 2019: 1202159.

Zogheib T, Walter-Solana A, De la Iglesia F, Espinar E, Gil J, Puigdollers A (2021) Do titanium mini-implants have the same quality of finishing and degree of contamination before and after different manipulations? An in vitro study. Metals 11(2): 245.

© 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

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.

This image has an empty alt attribute; its file name is jppres_pdf_free.png
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.
References

Al-Snafi AE (2016) Pharmacological importance of Clitoria ternatea–A review. IOSR J Pharm 6(3): 68–83.

Amorim Dos Santos J, Normando AGC, Carvalho da Silva RL, De Paula RM, Cembranel AC, Santos-Silva AR, Guerra ENS (2020) Oral mucosal lesions in a COVID-19 patient: New signs or secondary manifestations? Int J Infect Dis 97: 326–328.

Arrigoni O, De Tullio MC (2002) Ascorbic acid: Much more than just an antioxidant. Biochim Biophys Acta 1569(1-3): 1–9.

Atiqi S, Hooijberg F, Loeff FC, Rispens T, Wolbink GJ (2020) Immunogenicity of TNF-inhibitors. Front Immunol 11: 312.

Babich O, Sukhikh S, Prosekov A, Asyakina L, Ivanova S (2020) Medicinal plants to strengthen immunity during a pandemic. Pharmaceuticals 13(10): 313.

Bell LCK, Meydan C, Kim J, Foox J, Butler D, Mason CE, Shapira SD, Noursadeghi M, Pollara G (2021) Transcriptional response modules characterize IL-1β and IL-6 activity in COVID-19. iScience 24(1): 101896.

Carvajal-Zarrabal O, Barradas-Dermitz DM, Orta-Flores Z, Hayward-Jones PM, Nolasco-Hipólito C, Aguilar-Uscanga MG, Miranda-Medina A, Bujang KB (2012) Hibiscus sabdariffa L, roselle calyx, from ethnobotany to pharmacology. J Exp Pharmacol 4: 25–39.

Coomes EA, Haghbayan H (2020) Interleukin-6 in Covid-19: A systematic review and meta-analysis. Rev Med Virol 30(6): 1–9.

Danladi J, Sabir H (2021) Innate immunity, inflammation activation and heat-shock protein in COVID-19 pathogenesis. J Neuroimmunol 358: 577632.

Dewi AMC, Dagradi EM, Wibowo P (2021) The effect of high dose vitamin C (ascorbic acid) on pro-inflammatory cytokines in COVID-19. Med Health Sci J 5(1): 46–50.

Díaz Rodríguez M, Jimenez Romera A, Villarroel M (2020) Oral manifestations associated with COVID‐19. Oral Dis DOI: 10.1111/odi.13555

Diomede F, Marconi GD, Fonticoli L, Pizzicanella J, Merciaro I, Bramanti P, Mazzon E, Trubiani O (2020) Functional relationship between osteogenesis and angiogenesis in tissue regeneration. Int J Mol Sci 21(9): 3242.

Fakeye T (2008) Toxicity and immunomodulatory activity of fractions of Hibiscus sabdariffa Linn (family Malvaceae) in animal models. Afr J Tradit Complement Altern Med 5(4): 394–398.

Galvan-Pena S, Leon J, Chowdhary K, Michelson DA, Vijaykumar B, Yang L, Magnuson A, Manickas-Hill Z, Piechocka-Trocha A, Worrall DP, Hall KE, Ghebremichael M, Walker BD, Li JZ, Yu XG, Mathis D, Benoist C (2020) Profound Treg perturbations correlate with COVID-19 severity. bioRxiv [Preprint]. 12(11): 416180.

Gani MA, Nurhan AD, Maulana S, Siswodihardjo S, Shinta DW, Khotib J (2021) Structure-based virtual screening of bioactive compounds from Indonesian medical plants against severe acute respiratory syndrome coronavirus-2. J Adv Pharm Technol Res 12: 120–126.

Gollen B, Mehla J, Gupta P (2018) Clitoria ternatea Linn: A herb with potential pharmacological activities: Future prospects as therapeutic herbal medicine. J Pharma Reports 3(1): 1000141.

Haider T, Simader E, Glück O, Ankersmit HJ, Heinz T, Hajdu S, Negrin LL (2019) Systemic release of heat-shock protein 27 and 70 following severe trauma. Sci Rep 9(1): 9595.

Heck TG, Ludwig MS, Frizzo MN, Rasia-Filho AA, Homem de Bittencourt PI (2020) Suppressed anti-inflammatory heat shock response in high-risk COVID-19 patients: Lessons from basic research (inclusive bats), light on conceivable therapies. Clin Sci (Lond) 134(15): 1991–2017.

Iranmanesh B, Khalili M, Amiri R, Zartab H, Aflatoonian M (2021) Oral manifestations of COVID‐19 disease: A review article. Dermatol Ther 34(1): e14578.

Izquierdo-Vega JA, Arteaga-Badillo DA, Sánchez-Gutiérrez M, Morales-González JA, Vargas-Mendoza N, Gómez-Aldapa CA, Castro-Rosas J, Delgado-Olivares L, Madrigal-Bujaidar E, Madrigal-Santillán E (2020) Organic acids from roselle (Hibiscus sabdariffa L.)—A brief review of its pharmacological effects. Biomedicines 8(5): 100.

Jiang XW, Zhang Y, Zhang H, Lu K, Yang SK, Sun GL (2013) Double-blind, randomized, controlled clinical trial of the effects of diosmectite and basic fibroblast growth factor paste on the treatment of minor recurrent aphthous stomatitis. Oral Surg Oral Med Oral Pathol Oral Radiol 116(5): 570–575.

Khandia R, Munjal AK, Iqbal HMN, Dhama K (2017) Heat shock proteins: Therapeutic perspectives in inflammatory disorders. Recent Pat Inflamm Allergy Drug Discov 10(2): 94–104.

Kharisma VD, Ansori ANM, Widyananda MH, Utami SL, Nugraha AP (2020) Molecular simulation: The potency of conserved region on E6 HPV-16 as a binding target of black tea compounds against cervical cancer. Biochem Cell Arch 20(Suppl 1): 2795–2802.

Kharisma VD, Widyananda MH, Ansori ANM, Nege A, Naw SW, Nugraha AP (2021) Tea catechin as antiviral agent via apoptosis agonist and triple inhibitor mechanism against HIV-1 infection: A bioinformatics approach. J Pharm Pharmacogn Res 9(4): 435–445.

Li S, Zhang Y, Guan Z, Li H, Ye M, Chen X, Shen J, Zhou Y, Shi ZL, Zhou P, Peng K (2020) SARS-CoV-2 triggers inflammatory responses and cell death through caspase-8 activation. Signal Transduct Target Ther 5(1): 235.

López-Collazo E, Avendaño-Ortiz J, Martín-Quirós A, Aguirre LA (2020) Immune response and COVID-19: A mirror image of sepsis. Int J Biol Sci 16(14): 2479–2489.

Luo XH, Zhu Y, Mao J, Du RC (2021) T cell immunobiology and cytokine storm of COVID-19. Scand J Immunol 93(3): e12989.

Luqman A, Kharisma VD, Ruiz RA, Götz F (2020) In silico and in vitro study of trace amines (TA) and dopamine (DOP) interaction with human alpha1-adrenergic receptor and the bacterial adrenergic receptor QseC. Cell Physiol Biochem 54: 888–898.

Marpaung A (2020) Tinjauan manfaat bunga telang (Clitoria ternatea L.) bagi kesehatan manusia. J Funct Food Nutraceutical 1(2): 47–69.

Mehri F, Rahbar AH, Ghane ET, Souri B, Esfahani M (2021) Changes in oxidative markers in COVID-19 patients. Arch Med Res 52(8): 843–849.

Mishra N, Tandon VL, Gupta R (2012) Immunomodulation by Hibiscus rosa-sinensis: Effect on the humoral and cellular immune response of Mus musculus. Pak J Biol Sci 15(6): 277–283.

Plum SM, Vu HA, Mercer B, Fogler WE, Fortier AH (2004) Generation of a specific immunological response to FGF-2 does not affect wound healing or reproduction. Immunopharmacol Immunotoxicol 26(1): 29–41.

Putra WE, Kharisma VD, Susanto H (2020) The exploration of medicinal plants’ phytochemical compounds as potential inhibitor against human α-3 nicotinic acetylcholine receptors: The insight from computational study. AIP Conf Proc 2231(1): 040078.

Reang J, Sharma PC, Thakur VK, Majeed J (2021) Understanding the therapeutic potential of ascorbic acid in the battle to overcome cancer. Biomolecules 11(8): 1130.

Sari F, Nurkhasanah, Bachri MS (2016) Acute toxicity test of rosella (Hibiscus sabdariffa L.) calyx ethanolic extract on Sprague Dawley rats. Trad Med J 21: 12–18.

Shruthi VH, Ramachandra CT, Nidoni U, Hiregoudar S, Naik N, Kurubar AR (2016) Roselle (Hibiscus sabdariffa L.) as a source of natural colour: A review. Plant Arch 16(2): 515–522.

Smadja DM, Philippe A, Bory O, Gendron N, Beauvais A, Gruest M, Peron N, Khider L, Guerin CL, Goudot G, Levavasseur F, Duchemin J, Pene F, Cheurfa C, Szwebel TA, Sourdeau E, Planquette B, Hauw-Berlemont C, Hermann B, Gaussem P, Samama CM, Mirault T, Terrier B, Sanchez O, Rance B, Fontenay M, Diehl JL, Chocron R (2021) Placental growth factor level in plasma predicts COVID-19 severity and in-hospital mortality. J Thromb Haemost 19(7): 1823–1830.

Sokol CL, Luster AD (2015) The chemokine system in innate immunity. Cold Spring Harb Perspect Biol 7(5): a016303.

Susanto H, Kharisma VD, Listyorini D, Taufiq A (2018) Effectivity of black tea polyphenol in adipogenesis related IGF-1 and its receptor pathway through in silico based study. J Phys Conf Ser 1093 (1): 012037.

Syahrana NA, Akrom A, Darmawan E (2017) Efek serbuk bunga rosella merah (Hibiscus sabdariffa L.) terhadap ekspresi IL-10 pada sukarelawan sehat. Indones J Pharm Pharm Sci 4(1): 1–5.

Umeoguaju FU, Ephraim-Emmanuel BC, Uba JO, Bekibele GE, Chigozie N, Orisakwe OE (2021) Immunomodulatory and mechanistic considerations of Hibiscus sabdariffa (HS) in dysfunctional immune responses: A systematic review. Front Immunol 12: 550670.

Velavan TP, Meyer CG (2020) The COVID‐19 epidemic. Trop Med Int Health 25(3): 278.

Vieira AR (2021) Oral manifestations in coronavirus disease 2019 (COVID-19). Oral Dis 27(3): 770.

Widyananda MH, Pratama SK, Samoedra RS, Sari FN, Kharisma VD, Ansori ANM, Yulanda A (2021) Molecular docking study of sea urchin (Arbacia lixula) peptides as multi-target inhibitor for non-small cell lung cancer (NSCLC) associated proteins. J Pharm Pharmacogn Res 9(4): 484–496

WHO (2021) World Health Organization. https://covid19.who.int/table [Accessed online on: 19 March 2021]

Yalçin B, Arda N, Tezel GG, Erman M, Alli N (2006) Expressions of vascular endothelial growth factor and CD34 in oral aphthous lesions of Behçet’s disease. Anal Quant Cytol Histol 28(6): 303–306.

Zhang JM, An J (2007) Cytokines, inflammation, and pain. Int Anesthesiol Clin 45(2): 27–37.

© 2022 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

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.

This image has an empty alt attribute; its file name is jppres_pdf_free.png
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.

This image has an empty alt attribute; its file name is jppres_pdf_free.png
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)