journal article·2026-06-01Open access

Gingerol Enhances Osteogenic/Odontogenic Differentiation of Dental Pulp Stem Cells Impaired by Oxidative Stress via the Wnt/β-Catenin Pathway

Abdullah Alqarni, Jagadish Hosmani, Naif Abdulrhman Al Fadhil, Nasser Zafer Abdullah AlHamid, Hassan Ahmed Assiri, Rayan Mohammedfarooq Meer, Bandar Yahya Alshehri

Abstract

Background and Objectives: Dental pulp stem cells (DPSCs) possess significant regenerative potential; however, oxidative stress impairs their viability and osteogenic differentiation. Gingerol, the principal bioactive component of ginger, exhibits antioxidant and cytoprotective properties. This study evaluated the protective effects of gingerol on DPSCs exposed to H2O2-induced oxidative stress. Materials and Methods: DPSCs isolated from extracted human teeth following Institutional Review Board approval and informed consent were exposed to H2O2-induced oxidative stress and treated with varying concentrations of gingerol. Cell viability, migration, osteogenic activity, mineralization, intracellular ROS accumulation, and Wnt/β-catenin signaling-related gene expression were evaluated using MTT, scratch wound healing assay, Alizarin Red S staining, ROS staining, ELISA, and real-time PCR. Results: Gingerol improved DPSC viability, migration, and mineralization under oxidative stress conditions. Increased ALP and BSP expression indicated enhanced osteogenic activity, while reduced ROS accumulation suggested attenuation of oxidative injury. Gingerol also modulated MMP-2 and MMP-9 expression and normalized oxidative stress-associated alterations in inflammatory and Wnt/β-catenin signaling-related gene expression. Conclusions: Gingerol demonstrated protective effects against oxidative stress-induced dysfunction in DPSCs and supported osteogenic differentiation. These findings suggest that gingerol may serve as a supportive bioactive candidate for regenerative dental applications; however, further mechanistic and in vivo studies are required to confirm its therapeutic potential.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Ginger and Zingiberaceae research · Mesenchymal stem cell research · Wound Healing and Treatments

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Oral Diagnosis, Oral Biology & Periodontology, College of Dentistry, King Khalid University, Abha 61421, Saudi Arabia

Intern Clinic, College of Dentistry, King Khalid University, Abha 61421, Saudi Arabia

Department of Preventive Dental Sciences, College of Dentistry, Taibah University, Madinah 42353, Saudi Arabia

Department of Pediatric Dentistry and Orthodontic Sciences, College of Dentistry, King Khalid University, Abha 61421, Saudi Arabia

Funding

Deanship of Research and Graduate Studies at King Khalid University, KSA

References (46)

Show source-provided references
1. Abulhamael, A.M., Bhandi, S., Albar, N.H., Shaiban, A.S., Bavabeedu, S.S., Alzahrani, K.J., Alzahrani, F.M., Halawani, I.F., and Patil, S. (2023). Effects of bacterial metabolites on the Wnt4 protein in dental-pulp-stem-cells-based endodontic pulpitis treatment. Microorganisms, 11.10.3390/microorganisms11071764 ↗
2. Human dental pulp stem/stromal cells in clinical practice10.4252/wjsc.v16.i2.54 ↗
3. Abdalla, M.M., Lung, C.Y.K., Bijle, M.N., and Yiu, C.K.Y. (2022). Physicochemical properties and inductive effect of calcium strontium silicate on the differentiation of human dental pulp stem cells for vital pulp therapies: An in vitro study. Materials, 15.10.3390/ma15175854 ↗
4. Role of hypoxia in mesenchymal stem cells from dental pulp: Influence, mechanism and application10.1007/s12013-024-01274-0 ↗
5. Dental pulp stem cells response on the nanotopography of scaffold to regenerate dentin–pulp complex tissue10.1016/j.reth.2020.09.007 ↗
6. Effect of age and extrinsic microenvironment on proliferation and osteogenic differentiation of rat dental pulp stem cells10.1016/j.joen.2009.07.016 ↗
7. FGF-2 suppresses cellular senescence of human mesenchymal stem cells by down-regulation of TGF-β210.1016/j.bbrc.2007.05.067 ↗
8. Cell-penetrating superoxide dismutase attenuates oxidative stress-induced senescence by regulating the p53–p21Cip1 pathway and restores osteoblastic differentiation in human dental pulp stem cells
9. Human dental pulp stem cells mitigate the neuropathology and cognitive decline via AKT–GSK3β–Nrf2 pathways in Alzheimer’s disease10.1038/s41368-024-00300-4 ↗
10. A ROS-responsive hydrogel incorporated with dental follicle stem cell-derived small extracellular vesicles promotes dental pulp repair by ameliorating oxidative stress
11. Abuarqoub, D., Mahmoud, N., Alshaer, W., Mohammad, M., Ibrahim, A.A., Al-Mrahleh, M., Alnatour, M., Alqudah, D.A., Esawi, E., and Awidi, A. (2023). Biological performance of primary dental pulp stem cells treated with gold nanoparticles. Biomedicines, 11.10.3390/biomedicines11092490 ↗
12. Effectiveness of calcium hydroxide and gingerols mixture as a novel obturation material for infected root in primary teeth10.1155/2024/5528260 ↗
13. Ghasemzadeh, A., Jaafar, H.Z.E., and Rahmat, A. (2015). Optimization protocol for the extraction of 6-gingerol and 6-shogaol from Zingiber officinale var. Rubrum and improving antioxidant and anticancer activity. BMC Complement. Altern. Med., 15.10.1186/s12906-015-0718-0 ↗
14. Clinical aspects and health benefits of ginger (Zingiber officinale)
15. Yu, W., Peng, Y., Peng, X., Li, Z., Liu, C., Yang, L., Gao, Y., Liang, S., Yuan, B., and Chen, C. (2023). 6-Gingerol improves in vitro porcine embryo development by reducing oxidative stress. Animals, 13.10.3390/ani13081315 ↗
16. Axin2-expressing cells differentiate into reparative odontoblasts via autocrine Wnt/β-catenin signaling in response to tooth damage10.1038/s41598-017-03145-6 ↗
17. Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo10.1073/pnas.240309797 ↗
18. Wnt-responsive odontoblasts secrete new dentin after superficial injury
19. Wnt/β-catenin signaling in oral tissue development and disease10.1177/0022034510363373 ↗
20. Treated dentin matrix induces odontogenic differentiation of dental pulp stem cells via regulation of Wnt/β-catenin signaling
21. Expression of Axin2 indicates a role for canonical Wnt signaling in crown and root development10.1002/dvdy.22047 ↗
22. β-Catenin is required in odontoblasts for tooth root formation10.1177/0022034512470137 ↗
23. Baicalin enhances odonto/osteogenic differentiation of inflammatory dental pulp stem cells by inhibiting NF-κB and β-catenin/Wnt signaling pathways10.1007/s11033-023-08398-1 ↗
24. Stem cell signaling: An integral program for tissue renewal and regeneration—Wnt signaling and stem cell control10.1126/science.1248012 ↗
25. Chaussain, C., Boukpessi, T., Khaddam, M., Tjäderhane, L., George, A., and Menashi, S. (2013). Dentin matrix degradation by host matrix metalloproteinases: Inhibition and clinical perspectives toward regeneration. Front. Physiol., 4.10.3389/fphys.2013.00308 ↗
26. Effects of matrix metalloproteinases on the fate of mesenchymal stem cells10.1186/s13287-016-0393-1 ↗
27. Matrix metalloproteinases in bone development and pathology: Current knowledge and potential clinical utility
28. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays10.1016/0022-1759(83)90303-4 ↗
29. An Alizarin Red-based assay of mineralization by adherent cells in culture: Comparison with cetylpyridinium chloride extraction10.1016/j.ab.2004.02.002 ↗
30. In vitro scratch assay: A convenient and inexpensive method for analysis of cell migration in vitro10.1038/nprot.2007.30 ↗
31. Quantifying cellular oxidative stress by dichlorofluorescein assay using microplate reader10.1016/S0891-5849(99)00107-0 ↗
32. Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method10.1006/meth.2001.1262 ↗
33. Naringenin stimulates osteogenic/odontogenic differentiation and migration of human dental pulp stem cells10.1016/j.jds.2022.08.029 ↗
34. Isolation, characterization and comparative differentiation of human dental pulp stem cells derived from permanent teeth by using two different methods
35. Therapeutic potential of melatonin-pretreated human dental pulp stem cells in an animal model of spinal cord injury10.1038/s41598-024-78077-z ↗
36. Kim, Y., Park, H.J., Kim, M.K., Kim, H.J., Kim, Y.I., Bae, S.K., and Bae, M.K. (2024). Effects of hispidulin on the osteo/odontogenic and endothelial differentiation of dental pulp stem cells. Pharmaceuticals, 17.10.3390/ph17121740 ↗
37. Effects of 6-gingerol, an antioxidant from ginger, on inducing apoptosis in human leukemic HL-60 cells
38. Preciado-Ortiz, M.E., Martínez-López, E., Pedraza-Chaverri, J., Medina-Campos, O.N., Rodríguez-Echevarría, R., Reyes-Pérez, S.D., and Rivera-Valdés, J.J. (2024). 10-Gingerol increases antioxidant enzymes and attenuates lipopolysaccharide-induced inflammation by modulating adipokines. Antioxidants, 13.10.3390/antiox13091093 ↗
39. 6-Gingerol protects nucleus pulposus-derived mesenchymal stem cells from oxidative injury by activating autophagy10.4252/wjsc.v12.i12.1603 ↗
40. 6-Gingerol suppresses oral cancer cell growth by inducing AMPK activation and suppressing AKT/mTOR signaling pathway10.21873/invivo.12614 ↗
41. The effects of 6-gingerol on proliferation, differentiation, and maturation of osteoblast-like MG-63 cells10.1590/1414-431x20154494 ↗
42. Akermanite bioceramics promote osteogenesis, angiogenesis and suppress osteoclastogenesis for osteoporotic bone regeneration10.1038/srep22005 ↗
43. Bao, S., Li, S., and Sun, Y. (2024). Hederagenin regulates the migration and invasion of hepatocellular carcinoma cells through FOXO signaling pathway. PLoS ONE, 19.10.1371/journal.pone.0310930 ↗
44. Wnt/β-catenin signaling pathway: Proteins’ roles in osteoporosis and cancer diseases and the regulatory effects of natural compounds on osteoporosis10.1186/s10020-024-00957-x ↗
45. Wnt modulation in bone healing10.1016/j.bone.2020.115491 ↗
46. Wnt family members regulating osteogenesis and their origins10.1007/s00774-024-01554-y ↗