Razavi Journal of Medicine

Razavi Journal of Medicine

Molecular Effects of Curcumin Nanomicelles on Wharton's Jelly-Derived Mesenchymal Stem Cells: Integrated Analysis of Inflammatory Genes, Regulatory MicroRNAs, and DNA Methylation

Articles in Press

Document Type : Original Article

Authors
Hossein Malekan 1
Ramin Raoufinia 2, 3
Ghazal Alyari 1, 4
Amir Reza Bagheri 5
Reza Mousavi 6
Ayda Yavari Kondori 1
Hamid Reza Rahimi 1, 7
1 Department of Medical Genetics and Molecular Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
2 Noncommunicable Diseases Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran.
3 Workplace Health Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran.
4 Department of Medical Genetics, School of Advanced Technologies in Medicine, Golestan University of Medical Sciences, Gorgan, Iran.
5 Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
6 Molecular Medicine Research Center, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran.
7 Metabolic Syndrome Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran.
10.30483/rjm.2026.254766.1519
Abstract
Background: Mesenchymal stem/stromal cells (MSCs) exert therapeutic effects largely through immunomodulatory and paracrine mechanisms. Pharmacological preconditioning strategies have been proposed to enhance MSC functionality and therapeutic efficacy. Curcumin possesses anti-inflammatory and epigenetic regulatory properties; however, the effects of curcumin nanomicelles on inflammation-associated genes, regulatory microRNAs, and DNA methylation patterns in Wharton's jelly-derived MSCs (WJ-MSCs) remain incompletely understood.

Objectives: This study investigated the molecular effects of curcumin nanomicelles on inflammatory regulatory pathways in WJ-MSCs.

Methods: WJ-MSCs were isolated from human umbilical cords and characterized by flow cytometry and multilineage differentiation assays. Cell viability following exposure to curcumin nanomicelles was assessed using the MTT assay. Cells were treated with 20 μM and 70 μM curcumin nanomicelles for 24 h. Expression levels of IκBα, TGF-β1, miR-21, and miR-146a were evaluated by quantitative real-time PCR. Promoter methylation status of IκBα and TGF-β1 was analyzed using methylation-sensitive high-resolution melting (MS-HRM).

Results: Curcumin nanomicelles induced dose-dependent molecular alterations in WJ-MSCs. Treatment with 70 μM significantly increased IκBα expression and reduced miR-21 expression compared with untreated controls (P < 0.05). TGF-β1 expression was significantly increased following treatment with 20 μM curcumin nanomicelles, whereas no significant change was observed at 70 μM. miR-146a expression was significantly decreased at both tested concentrations. Despite these transcriptional and post-transcriptional changes, no significant alterations in promoter methylation patterns of either IκBα or TGF-β1 were detected after 24 h of treatment.

Conclusion: Curcumin nanomicelles modulated inflammation-associated gene expression and regulatory microRNAs in WJ-MSCs without inducing detectable promoter methylation changes in IκBα or TGF-β1. These findings suggest that the early molecular effects of curcumin nanomicelles are predominantly mediated by transcriptional and post-transcriptional mechanisms. The observed modulation of inflammatory regulatory pathways supports further investigation of curcumin nanomicelles as a potential MSC preconditioning strategy; however, additional protein-level, functional, and disease-model studies are required to determine their translational relevance.
Keywords
Curcumin nanomicelles
Wharton's jelly-derived mesenchymal stem cells
I&kappa
B&alpha
TGF-&beta
1
miR-21
miR-146a
DNA methylation
MSC preconditioning

Acknowledgements: The authors thank Mashhad University of Medical Sciences for its support, which enabled this research.

Funding: None.

Data Availability: Available from the corresponding author upon reasonable request.

Ethical Approval and Consent to Participate: The study was approved by the Ethics Committee of Mashhad University of Medical Sciences (IR.MUMS.REC.1402.189). Written informed consent was obtained from all donors prior to sample collection. he study was conducted in accordance with the ethical principles outlined in the Declaration of Helsinki.

Consent for publication: All authors consent to the publication of the article. 

Conflicts of Interest: None.

Author contributions:H.M. and R.R.: Writing – Original Draft, Writing – Review & Editing. G.A.: Formal Analysis, Methodology, Conceptualization. A.R.B., R.M., and A.Y.K.: Data Curation. H.R.R.: Writing – Review & Editing, Investigation, Supervision, Project Administration. H.M. and R.R. contributed equally to this work. All authors read and approved the final manuscript

Open Access Policy: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. To view a copy of this licence, visit https://creativecommons.org/licenses/by/4.0/

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Articles in Press, Accepted Manuscript
Available Online from 01 July 2026