Towards a predicted anti-aging molecular targets of asiaticoside based on bioinformatics analysis
Open accessAbstract
Objectives: Human skin, the largest organ, serves as a critical barrier against environmental damage and microbial invasion.The skin aging process leads to collagen degradation, reduced elasticity, and wrinkle formation, influenced by intrinsic and extrinsic factors.This process has driven significant interest in the anti-aging market, which is expected to grow to $44.5 billion by 2030.Asiaticoside (AS) has exhibited anti-aging properties by promoting collagen synthesis and fibroblast proliferation.Methods: This study employed bioinformatics analyses to identify molecular targets and pathways modulated by AS in skin aging.The gene databases were extracted from PubMed (www.ncbi.nlm.nih.gov),OMIM (www.omim.org),and GeneCards (www.genecards.org).Protein-protein interaction (PPI) networks and CytoHubba algorithms (MCC, DMNC, MNC) identified ten key genes implicated in the skin aging cascade.To validate the results, molecular docking was conducted to assess AS's binding affinity to these targets.Results: This study identified IL-1β, JUN, TGF-β1, CCL-2, MMP-9, STAT-3, MAPK-3, CXCL-8, MMP-2, and KDR as potentially targeted by AS in the skin aging cascade.Molecular docking revealed a strong binding affinity of AS with MMP-9 (-8.16 kcal/mol), indicating its role in inhibiting ECM degradation.Conclusion: This study highlights AS's potential as a promising anti-aging agent by targeting key proteins and pathways, paving the way for further therapeutic exploration.This prediction of molecular pathways should be further verified by in vitro and in vivo experiments.
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Kencana et al. conducted a comprehensive bioinformatics and molecular docking study that predicted asiaticoside exhibits strong binding affinity to key skin-aging mediators such as MMP-9, suggesting it may directly inhibit ECM degradation pathways.
“Kencana et al. [31] conducted a comprehensive bioinformatics and molecular docking study that predicted asiaticoside exhibits strong binding affinity to key skin-aging mediators such as MMP-9, suggesting it may directly inhibit ECM degradation pathways.”
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Khotimah, H., Setiawan, A., Rita, C. I., Mardiyah, M., Ali, A. M., Sukatman, M. P., Retnaningtyas, E., Ismail, D. D. S. L., Widasmara, D., Nurseta, T., et al. (2021) · AIP conference proceedings · doi:10.1063/5.0053016 · Cited by 12 · cited 1× · see citing works
“Previous studies have proven that AS possesses anti-aging properties by inducing collagen synthesis in dermal fibroblasts via the activation of TGF-β signaling pathways [33].”
da Rocha, P., Souza, B. D. S., Andrade, L. M., Marreto, R. N., Lima, E. M., & Taveira, S. F. (2017) · Planta Medica · doi:10.1055/s-0043-113325 · Cited by 10 · cited 1× · see citing works
“Nevertheless, it is commonly used for cosmetic purposes in topical applications [32].”
Unraveling Key Signaling Pathways Altered in Hepatocellular Carcinoma
Shiragannavar, V. D., Karunakara, S. H., Puttahanumantharayappa, L. D., Gowda, N. G. S., & Santhekadur, P. K. (2023) · Gene Expression · doi:10.14218/ge.2022.00009s · Cited by 7 · cited 2× · see citing works
“Subsequently, the activated RAF phosphorylates and triggers mitogen-activated protein kinase kinase (MAPKK) signaling [46].”
Philips, N. E., Ding, X., Kandalai, P., Marte, I., Krawczyk, H., & Richardson, R. (2019) · Cosmetics · doi:10.3390/cosmetics6030046 · Cited by 7 · cited 2× · see citing works
“This leads to the phosphorylation of the AP-1 complex (c-Fos and c-Jun), which translocates into the nucleus to directly regulate MMP-2/9 expression within the extracellular matrix (ECM) network [5, 39, 41, 44].”
Yadav, P. S., Papaioannou, G., Kobelski, M. M., et al. (2023) · iScience · doi:10.1016/j.isci.2023.107548 · Cited by 7
Huang, J., Gong, Y., Liu, K., Chen, J., & Zhou, X. (2023) · Exploratory Research and Hypothesis in Medicine · doi:10.14218/erhm.2023.00037 · Cited by 5 · cited 1× · see citing works
“While Huang and colleagues' study demonstrated that AS targeted apoptosis and inflammation-related signaling pathways [38], our findings suggest that AS targeted both inflammation-related signaling pathways and ECM degradation enzymes.”
Shah, F., Sarheed, O., & Ramesh, K. (2017) · doi:10.4236/jcdsa.2017.73025 · Cited by 5 · cited 1×
“Biologically active compounds with pharmaceutical properties, often referred to as cosmeceuticals, represent the latest advancement in beauty care products aimed at reducing wrinkles [22].”
Pamornpathomkul, B., Rangsimawong, W., Rojanarata, T., et al. (2018) · doi:10.1051/matecconf/201819201016 · Cited by 5 · cited 1×
“In addition, AS, an active main secondary metabolite in Centella asiatica , induces anti-aging properties by promoting collagen levels and encouraging the growth of normal dermal fibroblasts [29–31].”
Hu, W., Jing, Y., Yu, Q., & Huang, N. (2022) · Scientific Reports · doi:10.1038/s41598-022-16314-z · Cited by 4 · cited 4× · see citing works
“These These algorithms measure centrality by predicting and exploring the distance from the direct neighborhood of a vertex [20, 35].”
InfluentialMolecular Cascade of Neolignan as A Natural Anti-Diabetics Agent: A Bioinformatics Approach
Hartini, Y. S., Maharani, B. A., Widyantara, K. A., Saputra, B. W., Setyaningsih, D., & Setiawati, A. (2023) · Tropical Journal of Natural Product Research · doi:10.26538/tjnpr/v7i11.23 · cited 1×
“An interactive Venn diagram tool (www. interactivenn.net) was applied to identify the specific proteins and genes influenced by asiaticoside in relation to skin aging [36].”
Flagged first, then by citations
7 of the 85 references couldn’t be matched to a known paper.
Research works printed but not linked: 8
- Kim M, Park HJ. Molecular mechanisms of skin aging and age- related diseases. InTech 2016;57-74. [CrossRef ] · DOI
- Yulianti L, Mardliyati E, Bramono K, Freisleben HJ. Time-and dose-dependent effects of Centella asiatica ethanolic extract encapsulated into chitosan nanoparticles on collagen III syn- thesis and proliferation in human dermal fibroblasts. J Pharm Biomed Sci 2016;6(5):315-27. [CrossRef ] · DOI
- Jiang H, Zhou X, Chen L. Asiaticoside delays senescence and attenuates the generation of ROS in UV exposure cells through regulation of the TGF β1/Smad pathway. Exp Ther Med 2022;24(5):667. [CrossRef ] · DOI · Paper page
- Kim OT, Jin ML, Lee DY, Jetter R. Characterization of the asi- atic acid glucosyltransferase, UGT73AH1, involved in asiatico- side biosynthesis in centella asiatica (L.) Urban. Int J Mol Sci 2017;18(12):2630. [CrossRef ] · DOI
- Zhou H, Li W, Pan L, Zhu T, Zhou T, Xiao E, et al. Human extra- cellular matrix (ECM)-like collagen and its bioactivity. Regen Biomater 2024;11:1-13. [CrossRef ] · DOI
- Zhang S, Duan E. Fighting against skin aging: The way from bench to bedside. Cell Transplant 2018;27(5):729-38. [CrossRef ] · DOI · Paper page
- Krstic J, Santibanez JF. Transforming growth factor-beta and matrix metalloproteinases: Functional interactions in tu- mor stroma-infiltrating myeloid cells. TSWJ 2014;2014:1-14. [CrossRef ] · DOI
- Boukhedouni N, Martins C, Darrigade AS, Drullion C, Rambert J, Barrault C, et al. Type-1 cytokines regulate MMP-9 produc- tion and E-cadherin disruption to promote melanocyte loss in vitiligo. JCI Insight 2020;5(11):e133772. [CrossRef ] · DOI
Cited by
Sorted by citations
Choi, Y. J., Cho, E.-C., Lim, S., Lee, J., Bae, J., Oh, T. K., Lee, J. K., & Kim, E. J. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms27010204 · Cited by 3 · see citing works
“Kencana et al. [31] conducted a comprehensive bioinformatics and molecular docking study that predicted asiaticoside exhibits strong binding affinity to key skin-aging mediators such as MMP-9, suggesting it may directly inhibit ECM degradation pathways.”
Ratha, J., Padumanonda, T., Yongram, C., et al. (2026) · Plants · doi:10.3390/plants15020187 · Cited by 2 · see citing works
“The X-ray crystal structures of NF-κ B (PDB ID 4KIK), EGFR (PDB ID 1M17), and MMP9 (PDB IDs: and 1GKC) were retrieved from the RCSB protein data bank (https://www.rcsb.org/, accessed on 13 June 2025) [55,66,67].”
- Authors
- Ayu Kencana, M. V. S.
- Venue
- International Journal of Medical Biochemistry
- Publisher
- Kare Publishing
- Published
- 2025
- Pages
- 78-88
- ISSN
- 2587-2362 (ISSN-L)
- OpenAlex
- W4408197867
- Cited by
- 2
- References
- 85
- Citations by year
- 2026: 1 · 2025: 1
- FWCI
- 1.94
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- cc-by-nc
- Locations
- International journal of medical biochemistry/International journal of medical biochemistry : (publishedVersion, cc-by-nc)
- Universitas Sanata Dharma Repository (Universitas Sanata Dharma) (submittedVersion)
- Topics
- Health Sciences › Medicine › Dermatology › Skin Protection and Aging
- Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
- Health Sciences › Medicine › Complementary and alternative medicine › Natural Compounds in Disease Treatment
- Keywords
- asiaticoside, skin aging, anti-aging, molecular targets, protein-protein interaction network, MMP-9, extracellular matrix degradation, collagen synthesis, IL-1β, TGF-β1, STAT3, MAPK signaling, KDR, MCP-1, interleukin-8
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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