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Updated: Jul 1, 2026
Isolation, Culture, and Characterization of Primary Dermal Fibroblasts from Human Keloid Tissue
Published on: July 28, 2023
Molecular and bioinformatic mechanism of asiaticoside on macrophage-mediated keloid pathogenesis
Jia Huang1, Yating Yang2, Zhengxin Li3
1Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China; Dermatology Department, Huashan Hospital, Fudan University School of Medicine, Shanghai, 200040, China; Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, Hefei, 230032 Anhui, China.
Background:
Keloid is a fibroproliferative skin disorder driven by dysregulated inflammation and fibrosis, involving complex interactions between keloid fibroblasts (KFs) and immune cells. Although macrophages are implicated in keloid pathogenesis, the exact mechanisms remain poorly defined. Asiaticoside, a natural triterpene molecule, has shown therapeutic potential for pathological scarring, yet its molecular mechanisms warrant further investigation.
Purpose:
This study aims to elucidate the macrophage subtype-specific contributions to keloid progression and to investigate the anti-inflammatory and anti-fibrotic therapeutic efficacy of asiaticoside.
Methods:
In vitro co-culture models were established to assess the interactions between KFs and macrophages. Phenotypic changes, inflammation, fibrogenesis, and macrophage polarization were evaluated. Asiaticoside was tested at various doses for its effects on these pathological phenotypes. Macrophage or human monocyte pre‑treated with asiaticoside were co‑cultured with untreated KFs to determine the indirect inhibitory effect of asiaticoside on KF activation. Proteomic, phosphoproteomic, and molecular docking analyses were conducted to explore underlying mechanisms.
Results:
Both M1 and M2 macrophages exacerbated KFs proliferation, inflammation, and fibrogenesis, while KFs reciprocally promoted M2 macrophage polarization. Asiaticoside dose-dependently suppressed pathological phenotypes of KFs and macrophages and attenuated their pro-inflammatory and pro-fibrogenic cross-activation. Pre-treatment of macrophages or monocytes with asiaticoside inhibited their ability to activate KFs. Proteomic and phosphoproteomic profiling revealed that asiaticoside disrupted multiple keloid-associated pathogenic pathways. Molecular docking further identified high-affinity interactions between asiaticoside and pro-inflammatory factors.
Conclusion:
Asiaticoside exerts a dual therapeutic mechanism by concurrently inhibiting macrophage-driven inflammation and fibroblast-driven fibrogenesis, positioning it as a promising multi-targeting agent for keloid and related fibrotic diseases.
Insights
Asiaticoside treats keloids by reducing inflammation and fibrosis. This natural compound targets both macrophage and fibroblast activity, offering a dual mechanism for scar reduction.
Area of Science:
- Dermatology
- Immunology
- Pharmacology
Background:
- Keloid disorder involves inflammation and fibrosis due to complex fibroblast-immune cell interactions.
- The precise role of macrophages in keloid pathogenesis requires further elucidation.
- Asiaticoside shows promise for scar treatment, but its mechanisms are not fully understood.
Purpose of the Study:
- To clarify the specific roles of macrophage subtypes in keloid progression.
- To investigate the anti-inflammatory and anti-fibrotic effects of asiaticoside in keloids.
Main Methods:
- Co-culture models assessed interactions between keloid fibroblasts (KFs) and macrophages.
- Evaluated phenotypic changes, inflammation, fibrogenesis, and macrophage polarization.
- Utilized proteomic, phosphoproteomic, and molecular docking to explore asiaticoside's mechanisms.
Main Results:
- Both M1 and M2 macrophages worsened KF proliferation, inflammation, and fibrogenesis; KFs promoted M2 polarization.
- Asiaticoside suppressed pathological phenotypes and cross-activation between KFs and macrophages.
- Proteomics revealed asiaticoside disrupted keloid-associated pathogenic pathways, with docking showing interactions with pro-inflammatory factors.
Conclusions:
- Asiaticoside offers a dual therapeutic approach by inhibiting macrophage-driven inflammation and fibroblast-driven fibrogenesis.
- It acts as a multi-targeting agent for keloid treatment and other fibrotic conditions.