Author(s): Chairul Yahya, Mohammad S. Rohman, Mohammad Hidayat, Alexander P. Nugraha, Fedik A. Rantam


DOI: 10.52711/0974-360X.2022.00385   

Address: Chairul Yahya1,2, Mohammad S. Rohman3*, Mohammad Hidayat4, Alexander P. Nugraha5, Fedik A. Rantam6
1Doctoral Program of Medical Science, Universitas Brawijaya, Malang, Indonesia.
2Blambangan General Hospital, Banyuwangi, Indonesia.
3Department of Clinical Cardiology and Vascular Medicine, Universitas Brawijaya, Malang /Saiful Anwar General Hospital, Malang, Universitas Brawijaya, Malang, Indonesia.
4Department of Orthopedics, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia.
5Departement of Orthodontics, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia.
6Laboratory Virology and Immunology Laboratory, Department of Microbiology, Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya, Indonesia.
*Corresponding Author

Published In:   Volume - 15,      Issue - 5,     Year - 2022

Sirtuin 1 (Sirt-1) - SRY-Box Transcription Factor 2 (sox2) axis maintains the stemness of human MSCs. Resveratrol may maintain stemness of human iliac bone marrow (BM)-MSCs. The aim of this study to investigate resveratrol effect on sox2 to maintain BM-MSCs stemness through an in silico and in vitro study. BM-MSCs was aspirated from orthopedic patients then, cultured in vitro. The study groups were into a control group, resveratrol group at doses of 0.1 µM and 1 µM. The characterization human iliac BM-MSCs was examined by immunocytochemistry analysis cluster of differentiation (CD)73, CD90, CD105 and CD45. The proliferation of human iliac BM-MSCs in each group was analyzed by MTT assay with various dose of resveratrol 0.01 µM; 0.05 µM; 0.1 µM; 0.5 µM; 1 µM respectively. A molecular docking was done to evaluate the interactions between resveratrol, sirt1 and Sox2 in silico. Resveratrol act as Sirt1 activator with high binding affinity between Sirt1 and Sox2 was -883.9 kcal/mol in silico. BM-MSCs at third, fourth, fifth and sixth sub-cultured with administrated resveratrol at dose 1 µM showed more confluent, less apoptosis and less senescence cells than control group. The characterization of human iliac BM-MSCs at third sub-culture showed that positive expression of CD73, CD90 and CD105 but lack of CD45 expression. There was no significant different of BM-MSCs viability percentage after administration of resveratrol with various doses (p>0.05). Resveratrol has an effect to regulate Sox2 expression that can maintain human illiac BM-MSCs proliferation, self-renewal and stemness in silico and in vitro.

Cite this article:
Chairul Yahya, Mohammad S. Rohman, Mohammad Hidayat, Alexander P. Nugraha, Fedik A. Rantam. Resveratrol maintain Human Iliac Bone Marrow Mesenchymal Stem Cells Stemness through Sirtuin 1 Mediated Regulation of SRY-Box Transcription Factor 2: an in vitro and in silico study. Research Journal of Pharmacy and Technology. 2022; 15(5):2313-9. doi: 10.52711/0974-360X.2022.00385

Chairul Yahya, Mohammad S. Rohman, Mohammad Hidayat, Alexander P. Nugraha, Fedik A. Rantam. Resveratrol maintain Human Iliac Bone Marrow Mesenchymal Stem Cells Stemness through Sirtuin 1 Mediated Regulation of SRY-Box Transcription Factor 2: an in vitro and in silico study. Research Journal of Pharmacy and Technology. 2022; 15(5):2313-9. doi: 10.52711/0974-360X.2022.00385   Available on:

1.    Nugraha AP. Rezkita F. Puspitaningrum MS. Luthfimaidah MS. Narmada IB. Prahasanti C. Ernawati DS. Rantam FA. Gingival Mesenchymal Stem Cells and Chitosan Scaffold to Accelerate Alveolar Bone Remodelling in Periodontitis: A Narrative Review. Research J. Pharm. and Tech 2020; 13(5):2502-2506.
2.    Drela K. Stanaszek L. Nowakowski A. Kuczynska Z. Experimental Strategies of Mesenchymal Stem Cell Propagation: Adverse Events and Potential Risk of Func-tional Changes. Stem Cells International 2019;7012692:1-10.
3.    Zomer DH. Vidane SA. Gonçalves NN. Ambrósio EC. Mesenchymal and induced pluripotent stem cells: general insights and clinical perspectives. Stem Cells and Cloning: Advances and Applications 2015;8: 125-131.
4.    Suciadi SP. Nugraha AP. Ernawati DS. Ayuningtyas NF. Narmada IB. Prahasanti C. Dinaryanti A. Ihsan IS. Hendrinto E. Susilowati H. Rantam FA. The Efficacy of Human Dental Pulp Stem Cells in regenerating Submandibular Gland Defects in Diabetic Wistar Rats (Rattus novergicus). Research J. Pharm. and Tech 2019; 12(4):1573-1579.
5.    Tiwari RK. Sharma V. Pandey R. Shukla SS. Stem Cells: Basics and its Prospective uses in Medical field. Research J. Pharm. and Tech 2018; 11(4): 1530-1534.
6.    Ratcliffe E. Current status and perspectives on stem cell based therapies undergoing clinical trials for regenerative medicine: case studies, British Medical Bulletin 2013;108: 73–94.
7.    Timothy CN. Samyuktha PS. Brundha MP. Dental pulp Stem Cells in Regenerative Medicine – A Literature Review. Research J. Pharm. and Tech 2019; 12(8):4052-4056.
8.    Rantam FA. Nugraha AP. Ferdiansyah F. Purwati P. Bumi C. Susilowati H. Hendrianto E. Utomo DN. Suroto H. Sumartono C. Setiawati R. Prakoeswa CR. Indramaya DM. A Potential Differentiation of Adipose and Hair Follicle-derived Mesenchymal Stem Cells to Generate Neurons Induced with EGF, FGF, PDGF and Forskolin. Research J. Pharm. and Tech 2020; 13(1): 275-281.
9.    Kim DS. Lee MW. Lee TH. Sung KW. Koo HH. Yoo KH. Cell culture density affects the stemness gene expression of adipose tis-sue‑derived mesenchymal stem cells. Biomedical Reports 2017;6: 300-306.
10.    Azeem S. Raj S. Kajal K. Thiagarajan P. Umbilical Cord Stem Cells: A Review. Research J. Pharm. and Tech 2018; 11(6): 2709-2714
11.    Patyar DS. Role of Stem Cells in treatment of different Diseases. Research J. Pharm. and Tech 2018; 11(8): 3667-3678.
12.    Balaji S. Umbilical cord blood as a source of stem cells. Research J. Pharm. and Tech. 2015;8(8):1093-1095.
13.    Athanerey A. Verma NR. Bhargava P. Patra PK. Kumar A. Mesenchymal stem cells prove a significant role in Chronic non-healing ulcer progressive healing. Research J. Pharm. and Tech 2021; 14(1):373-377.
14.    Prahasanti C. Nugraha AP. Saskianti T. Suardita K. Riawan W. Ernawati DS. Exfoliated Human Deciduous Tooth Stem Cells Incorporating Carbonate Apatite Scaffold Enhance BMP-2, BMP-7 and Attenuate MMP-8 Expression During Initial Alveolar Bone Remodeling in Wistar Rats (Rattus norvegicus). Clinical, Cosmetic and Investigational Dentistry 2020;12:79–85.
15.    Arnold K. Sarkar A. Yram MA. Polo JM. Bronson R. Sengupta S. Seandel M. Geijsena N. Hochedlinger K. Sox2+ adult stem/progenitor cells are im-portant for tissue regeneration and survival of mice. Cell Stem Cell 2011;9(4): 317–329.
16.    Boiani M. Scholer HR. Regulatory networks in embryo-derived pluripotent stem cells. Nat Rev Mol Cell Biol. 2005;6:872–884.
17.    Boyer AL. Lee IT. Megan FC. Sarah EJ. Core Transcriptional Regulatory Circuitry in Human Embryonic. Journal of Cells 2005;23; 122(6): 947– 956.
18.    Basu-Roy U. Ambrosetti D. Favaro R. The transcription factor Sox2 is required for osteoblast self-renewal. Cell Death Differ. 2010;17:1345–1353.
19.    Niwa H. How is pluripotency determined and maintained? Development 2007;134: 635-646
20.    Yoon DS. Y Choi. JW Lee. Cellular localization of NRF2 determines the self-renewal and osteogenic differentiation potential of human MSCs via the P53–SIRT1 axis. Death and Disease 2016;7: e2093.
21.    Baltus GA. Kowalski MP. Zhai H. Acetylation of sox2 induces its nuclear export in embryonic stem cells. Stem Cells 2009;27:2175–2184.
22.    Kharisma VK. Widyananda MH. Ansori ANM. Nege AS. Naw SW. Nugraha AP. Catechin as antiviral agent via apoptosis agonist and triple inhibitor mechanism against HIV-1 infection: A bioinformatics approach Journal of Pharmacy & Pharmacognosy Research 2021;9 (4):435-445.
23.    Fadholly A. Ansori ANM. Kharisma VD. Rahmahani J. Tacharina MR. Immunobioinformatics of Rabies Virus in Various Countries of Asia: Glycoprotein Gene. Research J. Pharm. and Tech 2021; 14(2):883-886.
24.    Nugraha AP. Rantam FA. Narmada IB. Ernawati DS. Ihsan IS. Gingival-Derived Mesenchymal Stem Cell from Rabbit (Oryctolagus cuniculus): Isolation, Culture, and Characterization. European Journal of Dentistry 2020; 1(1):1.
25.    Nugraha AP. Narmada IB. Ernawati DS. Widodo DWW. Lestari P. Dinaryanti A. Hendrianto E. Ihsan IS.  Susilowati H. Gingival Mesenchymal Stem Cells from Wistar Rat’s Gingiva (Rattus Novergicus) – Isolation and Characterization (In Vitro Study). J Int Dent Med Res 2018;11(2):694-699.
26.    Nugraha AP. Prasetyo EP. Kuntjoro M. Ihsan IS. Dinaryanti A. Susilowati H. Hendrianto E. Narmada IB. Ernawati DS. Nugraha AP. Rantam FA. The Effect of Cobalt (II) Chloride in the Viability Percentage and the Induced Hypoxia Inducible Factor -1α of Human Adipose Mesenchymal Stem Cells (HAMSCs): An In Vitro Study. Sys Rev Pharm 2020;11(6): 308-314.
27.    Hou X. Rooklin D. Fang H. Zhang Y. Resveratrol serves as a protein-substrate interaction stabilizer in human SIRT1 activation. Scientific Reports 2016;6:38186.
28.    Sridhar GR. Nageswara Rao PV. Kaladhar DS, Devi TU, Kumar SV. In Silico Docking of HNF-1a Receptor Ligands. Adv Bioinformatics 2012;2012:705435.
29.    Yang X. Seto E. Lysine acetylation: codified crosstalk with other posttranslational modifications. Mol Cell 2008;31(4): 449–461.
30.    Lakshminarasimhan M. Rau D. Schutkowsk M. Steegbor C. Sirt1 activation by resveratrol is substrate sequence‐selective. Aging 2013;5(3):1.
31.    Borra MT. Smith BC. Denu JM. Mechanism of Human SIRT1 Activation by Resveratrol. J. Biol. Chem. 2005;17187:95.
32.    Wang Y. Peterson SE. Loring JF. Protein post-translational modifications and regulation of pluripotency in human stem cells. Cell Research 2014;24:143-160.  
33.    Wang Z. Efrat O. Nelson B. Razis S. Ivanova N. Distinct Lineage Specification Roles for NANOG, OCT4, and SOX2 in Human Embryonic Stem Cells. Cell Stem Cell 2012;10: 440–454.
34.    Zhao H. Zhang Y. Dai H. Zhang Y. Shen Y. CARM1 Mediates Modulation of Sox2. PLoS ONE 2011;6(10):e27026.    
35.    He S. Nakada D. Morrison SJ. Mechanisms of Stem Cell Self-Renewal. Annu. Rev. Cell Dev. Biol 2009;25:16.1–16,30.    
36.    Gretchen AB. Michael PK. Huili Z. Tutter AV. Douglas Q. Daniel W. Shilpa K. Acetylation of Sox2 Induces Its Nuclear Export in Embryonic Stem Cells. Stem Cells 2009;27:2175–2184.
37.    El-Badawy A. El-Badri N. Regulators of pluripotency and their implications in regenerative medicine. Stem Cells Cloning 2015;21;8:67-80.
38.    Loh Y. Ng J. Ng H. Molecular framework underlying pluripotency. Cell Cycle 2008;7(7): 885-891.    
39.    Kuhn M. Mering C. Campillos M. Jensen LJ. Bork P. STITCH: interaction networks of chemicals and proteins. Nucleic Acids Res 2008;36(Database issue): D684–D688.
40.    Dominici M. Le Blanc K. Mueller I. Slaper-Cortenbach I. Marini F. Krause D. Deans R. Keating A. Prockop Dj. Horwitz E. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 2006;8(4):315-7.
41.    Gazit Z. Mesenchymal Stem Cell, in Essentials of Stem Cell Biology, third ed, Elsevier Inc, China 2014.
42.    Diomede F. Rajan TS. Gatta V D'Aurora M. Merciaro I. Marchisio M. Muttini A. Caputi S. Bramanti P. Mazzon E. Trubiani O. Stemness Maintenance Properties in Human Oral Stem Cells after Long-Term Passage. Stem Cells Int 2017;2017:5651287.

Recomonded Articles:

Research Journal of Pharmacy and Technology (RJPT) is an international, peer-reviewed, multidisciplinary journal.... Read more >>>

RNI: CHHENG00387/33/1/2008-TC                     
DOI: 10.5958/0974-360X 

56th percentile
Powered by  Scopus

SCImago Journal & Country Rank

Recent Articles


Not Available