Madecassoside suppresses migration of fibroblasts from keloids: involvement of p38 kinase and PI3K signaling pathways
Abstract
Keloid is a specific skin scar that expands beyond the boundaries of the original injury as it heals. The invasive nature of keloid and notable migratory activity of fibroblasts are a hallmark, which distinguishes keloids from other common scars. Madecassoside, a triterpenoid saponin occurring in Centella asiatica herbs, possesses unique pharmacological properties to enhance wound-healing and diminish keloid formation. However, the effects of madecassoside on the formation of keloid scars have been poorly understood. Here, we focused on the potential of madecassoside on the migration of keloid-derived fibroblasts (KFs) and its mechanism. Primary KF, originating from human earlobe keloids, were purified and cultured, and then treated with madecassoside (10, 30, and 100μM). In both transwell migration assays and scratch-wound-closure assays, KF migration was considerably suppressed by madecassoside pretreatment. Furthermore, KFs treated with madecassoside showed decreased F-actin filaments, as revealed by fluorescein isothiocyanate (FITC)-phalloidin staining and confocal microscopy. By Western blot analysis, madecassoside was shown to remarkably attenuate the phosphorylation of cofilin, p38 MAPK and phosphatidylinositol-3-kinase (PI3K)/AKT signaling, but only exhibited a minor effect on MMP-13 and little effect on ERK1/2 phosphorylation. It was concluded that madecassoside could be of great use in the treatment and/or prevention of hypertrophic scars and keloids.
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Madecassoside directly reduces cytoskeletal protein actin expression of KFs.
“Madecassoside can directly reduce the cytoskeletal protein actin expression of KFs”
From Therapeutic Properties and Pharmacological Activities of Asiaticoside and Madecassoside: A Review (2023) · cites this paper as [96]
Madecassoside suppresses migration of keloid-derived fibroblasts (KFs) as observed in madecassoside-treated fibroblasts taken from human earlobe keloids.
“Madecassoside has been seen to suppress the migration of keloid‐derived fibroblasts (KFs) as observed in madecassoside‐treated fibroblasts taken from human earlobe keloids.”
From Therapeutic Properties and Pharmacological Activities of Asiaticoside and Madecassoside: A Review (2023) · cites this paper as [96]
Madecassoside inhibits activity of some intracellular molecules responsible for abnormal keloid migration, including concentration-dependent reduction of phosphorylated Akt, PI3K and p38 of KFs and repression of actin-depolymerization-associated p-cofilin/cofilin.
“its mechanism of action is by inhibiting the activity of some (not all) of the several intracellular molecules that are responsible for abnormal keloid migration, including the significant, concentration‐dependent reduction of phosphorylated Akt, PI3K and p38 of KFs and the repression of actin‐depolymerization‐associated p‐cofilin/cofilin.”
From Therapeutic Properties and Pharmacological Activities of Asiaticoside and Madecassoside: A Review (2023) · cites this paper as [96]
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References 31 · Cited by 50
- Authors
- Song, J., Xu, H., Lu, Q., Xu, Z., Bian, D., Xia, Y., Wei, Z., Gong, Z., & Dai, Y.
- Affiliations
- China Pharmaceutical University (CN)
- Nanjing Normal University (CN)
- Corresponding author
- Dai, Yue
- Venue
- Burns
- Publisher
- Elsevier BV
- Published
- 2012-08
- Volume
- 38
- Issue
- 5
- Pages
- 677-684
- ISSN
- 0305-4179 (ISSN-L)
- OpenAlex
- W2061395332
- Cited by
- 50
- References
- 31
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 6 · 2023: 3 · 2022: 3 · 2021: 2 · 2020: 1 · 2019: 3 · 2018: 4 · 2017: 3 · 2016: 4 · 2015: 7 · 2014: 4 · 2013: 3
- FWCI
- 5.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Burns (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Priority Academic Program Development of Jiangsu Higher Education Institutions
- National Natural Science Foundation of China (30973915)
- Innovative Research Plan for Postgraduate Students of China Pharmaceutical University
- Topics
- Health Sciences › Medicine › Dermatology › Dermatologic Treatments and Research
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Health Sciences › Medicine › Dermatology › Skin Protection and Aging
- Keywords
- madecassoside, keloids, fibroblast migration, p38 MAPK signaling, PI3K/Akt signaling, cofilin phosphorylation, F-actin, Centella asiatica, hypertrophic scars, wound healing, MMP-13, ERK1/2
- MeSH terms
- Analysis of Variance, Cell Movement, Cells, Cultured, Fibroblasts, Humans, Keloid, Actin Cytoskeleton, Plant Extracts, Triterpenes, Wound Healing, Signal Transduction, Phosphatidylinositol 3-Kinases, MAP Kinase Signaling System, p38 Mitogen-Activated Protein Kinases, Cofilin 1, Matrix Metalloproteinase 13
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