Anti-Photoaging Effects of Moisturizer and Serum Containing Andrographis paniculata, Syzygium aromaticum, and Pogostemon cablin: A Network Pharmacology, Molecular Docking, and in vivo Study
Abstract
Ultraviolet-B (UVB)-induced photoaging accelerates collagen degradation, disrupts dermal structure, and compromises epidermal integrity. Natural extracts, such as Andrographis paniculata, Syzygium aromaticum, and Pogostemon cablin demonstrated antioxidant and anti-aging properties to mitigate these damages. This study investigated the protective effects of serum and moisturizer containing A. paniculata extract, S. aromaticum oil, and P. cablin oil on UVB-induced photoaging rats, by integrating network pharmacology and in vivo experiment. Compounds and photoaging-associated targets were retrieved through online databases. Enrichment analyses were performed using Metascape. Protein-protein interaction (PPI) construction and herbs-compounds-targets-pathways disease network were performed using STRING and Cytoscape 3.10.0, respectively, followed by molecular docking. An in vivo study was conducted to evaluate epidermal thickness, collagen density, and dermo-epidermal junction (DEJ) structure. Eleven key phytoconstituents and twelve core targets were identified in anti-photoaging molecular mechanisms using network pharmacology. Molecular docking analysis revealed that 7-O-methylwogonin demonstrated favorable binding against ten photoaging-associated targets. KEGG enrichment analysis showed potential inflammation processes inhibition, including photocarcinogenesis, AGE-RAGE signaling pathway, and TNF-α expression. Furthermore, treatment with serum, moisturizer, or combination of both significantly reduced epidermal thickening and enhanced collagen density compared to the UVB-exposed only group. Although no significant difference was observed in DEJ interdigitation index across groups, treated groups exhibited a trend towards better preservation of DEJ structure relative to the UVB group. In summary, serum and moisturizer containing A. paniculata, S. aromaticum, and P. cablin extracts demonstrated potential anti-photoaging effects by reducing epidermal thickness and preserving collagen density in UVB-exposed rats. These findings support these botanical-based formulations potential as effective anti-aging skincare.
References
Adianingsih, O. R., F. F. Fajrin, and C. K. Johan (2024). Exploring the Mechanism of Glycyrrhiza glabra and Curcuma domestica Against Skin Photoaging Based on Network Pharmacology. Indonesian Journal of Biotechnology, 29(2); 98–110.
Anawalt, B. D. and A. M. Matsumoto (2022). Aging and Androgens: Physiology and Clinical Implications. Reviews in Endocrine and Metabolic Disorders, 23(6); 1123–1137.
Anjum, M. M., D. N. Kumar, S. Bhattacharya, K. K. Patel, M. R. Vijayakumar, A. K. Agrawal, and S. Singh (2023). Topical Delivery of Cyclodextrin Crosslinked Nanosponge of Anacardic Acid for Treatment of UV-B Induced Skin Photoaging: Formulation, Characterization and Biochemical Estimation. Journal of Drug Delivery Science and Technology, 87; 104840.
Benet, L. Z., C. M. Hosey, O. Ursu, and T. I. Oprea (2016). BDDCS, the Rule of 5 and Drugability. Advanced Drug Delivery Reviews, 101; 89–98.
Bosch, R., N. Philips, J. A. Suárez-Pérez, A. Juarranz, A. Devmurari, J. Chalensouk-Khaosaat, and S. González (2015). Mechanisms of Photoaging and Cutaneous Photocarcinogenesis, and Photoprotective Strategies with Phytochemicals. Antioxidants, 4(2); 248–268.
Cavinato, M., B. Waltenberger, G. Baraldo, C. V. C. Grade, H. Stuppner, and P. Jansen-Dürr (2017). Plant Extracts and Natural Compounds Used Against UVB-Induced Photoaging. Biogerontology, 18(4); 499–516.
Chang, K. C. N., Y. Wang, I. G. Oh, S. Jenkins, L. P. Freedman, C. C. Thompson, J. H. Chung, and S. Nagpal (2010). Estrogen Receptor β Is a Novel Therapeutic Target for Photoaging. Molecular Pharmacology, 77(5); 744–750.
Charles-De-Sá, L., N. Gontijo-De-Amorim, A. Sbarbati, D. Benati, P. Bernardi, R. Borojevic, R. B. V. Carias, and G. Rigotti (2020). Photoaging Skin Therapy with PRP and ADSC: A Comparative Study. Stem Cells International.
Chauhan, E. S., K. Sharma, and R. Bist (2019). Andrographis paniculata: A Review of Its Phytochemistry and Pharmacological Activities. Research Journal of Pharmacy and Technology, 12(2); 891–900.
Chen, W., Q. Deng, B. Deng, Y. Li, G. Fan, F. Yang, W. Han, J. Xu, and X. Chen (2024). Comprehensive Analysis of Hibisci mutabilis folium Extract’s Mechanisms in Alleviating UV-Induced Skin Photoaging Through Enhanced Network Pharmacology and Experimental Validation. Frontiers in Pharmacology, 15; 1431391.
Chmielewski, R. and A. Lesiak (2024). Mitigating Glycation and Oxidative Stress in Aesthetic Medicine: Hyaluronic Acid and Trehalose Synergy for Anti-AGEs Action in Skin Aging Treatment. Clinical, Cosmetic and Investigational Dermatology, 17; 2701–2712.
Costa, E. F., W. V. Magalhães, and L. C. Di Stasi (2022). Recent Advances in Herbal-Derived Products with Skin Anti-Aging Properties and Cosmetic Applications. Molecules, 27(21); 7518.
Daina, A., O. Michielin, and V. Zoete (2017). SwissADME: A Free Web Tool to Evaluate Pharmacokinetics, Drug-Likeness and Medicinal Chemistry Friendliness of Small Molecules. Scientific Reports, 7(1); 42717.
Damayanti, C. Prakoeswa, D. Purwanto, A. Endaryanto, M. Listiawan, Y. Wirohadidjoyo, Soetjipto, Siswandono, and B. Utomo (2023). Wistar Rat as Photoaging Mouse Model. Journal of Pakistan Association of Dermatologists, 33(1); 24–29.
Deng, Q., W. Chen, B. Deng, W. Chen, L. Chen, G. Fan, J. Wu, Y. Gao, and X. Chen (2024). Based on Network Pharmacology, Molecular Docking and Experimental Verification to Reveal the Mechanism of Andrographis paniculata Against Solar Dermatitis. Phytomedicine, 135; 156025.
Dibal, N. I., S. H. Garba, and T. W. Jacks (2022). Histological Stains and Their Application in Teaching and Research. Asian Journal of Health Sciences, 8(2); 43–43.
Fardiyah, Q., T. Ersam, Suyanta, A. Slamet, Suprapto, and F. Kurniawan (2020). New Potential and Characterization of Andrographis paniculata L. Ness Plant Extracts as Photoprotective Agent. Arabian Journal of Chemistry, 13(12); 8888–8897.
Feng, C., X. Chen, X. Yin, Y. Jiang, and C. Zhao (2024). Matrix Metalloproteinases on Skin Photoaging. Journal of Cosmetic Dermatology, 23(12); 3847–3862.
Feng, X. X., X. T. Yu, W. J. Li, S. Z. Kong, Y. H. Liu, X. Zhang, Y. F. Xian, X. J. Zhang, Z. R. Su, and Z. X. Lin (2014). Effects of Topical Application of Patchouli Alcohol on the UV-Induced Skin Photoaging in Mice. European Journal of Pharmaceutical Sciences, 63; 113–123.
Ferreira, M. S., M. C. Magalhães, R. Oliveira, J. M. Sousa Lobo, and I. F. Almeida (2021). Trends in the Use of Botanicals in Anti-Aging Cosmetics. Molecules, 26(12).
Freitas-Rodríguez, S., A. R. Folgueras, and C. López-Otín (2017). The Role of Matrix Metalloproteinases in Aging: Tissue Remodeling and Beyond. Biochimica et Biophysica Acta - Molecular Cell Research, 1864(11); 2015–2025.
Fruman, D. A., H. Chiu, B. D. Hopkins, S. Bagrodia, L. C. Cantley, and R. T. Abraham (2017). The PI3K Pathway in Human Disease. Cell, 170(4); 605–635.
Fuller, B. (2019). Role of PGE-2 and Other Inflammatory Mediators in Skin Aging and Their Inhibition by Topical Natural Anti-Inflammatories. Cosmetics, 6(1); 6.
Galovičová, L., P. Borotová, V. Valková, H. Ďúranová, J. Štefániková, N. L. Vukovic, M. Vukic, and M. Kačániová (2022). Biological Activity of Pogostemon cablin Essential Oil and Its Potential Use for Food Preservation. Agronomy, 12(2); 387.
Gao, X., F. Luo, and H. Zhao (2021). Cloves Regulate Na⁺/K⁺-ATPase to Exert Antioxidant Effect and Inhibit UVB Light-Induced Skin Damage in Mice. Oxidative Medicine and Cellular Longevity, 1; 5197919.
Gong, M., P. Zhang, C. Li, X. Ma, and D. Yang (2018). Protective Mechanism of Adipose-Derived Stem Cells in Remodelling of the Skin Stem Cell Niche During Photoaging. Cellular Physiology and Biochemistry, 51(5); 2456–2471.
Han, M., H. Li, D. Ke, L. M. Tian, Y. Hong, C. Zhang, D. Z. Tian, L. Chen, L. R. Zhan, and S. Q. Zong (2022a). Mechanism of Ba Zhen Tang Delaying Skin Photoaging Based on Network Pharmacology and Molecular Docking. Clinical, Cosmetic and Investigational Dermatology, 15; 763–781.
Han, S. H., E. Ballinger, S. Y. Choung, and J. Y. Kwon (2022b). Anti-Photoaging Effect of Hydrolysates from Pacific Whiting Skin via MAPK/AP-1, NF-kB, TGF-β/Smad, and Nrf2/HO-1 Signaling Pathway in UVB-Induced Human Dermal Fibroblasts. Marine Drugs, 20(5); 308.
Hani, R., L. Khayat, A. A. Rahman, and N. Alaaeddine (2023). Effect of Stem Cell Secretome in Skin Rejuvenation: A Narrative Review. Molecular Biology Reports, 50(9); 7745–7758.
Harnelly, E., A. H. Halym, N. Isnaini, K. Khairan, Z. Zulkarnain, A. Syahraini, W. Sari, H. Maghfira, S. Muhammad, R. Idrus, and M. El-Shazly (2025). Protective Effects of Crude and Light Fraction Patchouli Oil Against UVB-Induced Dermal Aging in Mice: In Silico and In Vivo Study. Trends in Sciences, 22(12); 10723.
Hema, K., S. Ahamad, H. K. Joon, R. Pandey, and D. Gupta (2021). Atomic Resolution Homology Models and Molecular Dynamics Simulations of Plasmodium falciparum Tubulins. ACS Omega, 6(27); 17510–17522.
Huang, J., Y. Gong, K. Liu, J. Chen, and X. Zhou (2023). Anti-Photoaging Properties of Asiaticoside in Ultraviolet A-Irradiated Human Dermal Fibroblasts by Activating the PI3K-AKT Pathway and Inhibiting the NF-kB Pathway. Exploratory Research and Hypothesis in Medicine, 000(000); 319337.
Hwang, E., P. Lin, H. T. T. Ngo, and T. H. Yi (2018). Clove Attenuates UVB-Induced Photodamage and Repairs Skin Barrier Function in Hairless Mice. Food and Function, 9(9); 4936–4947.
Intharuksa, A., W. Arunotayanun, W. Yooin, and P. Sirisa-ard (2022). A Comprehensive Review of Andrographis paniculata (Burm. f.) Nees and Its Constituents as Potential Lead Compounds for COVID-19 Drug Discovery. Molecules, 27(14); 4479.
Jain, A. N. and A. Nicholls (2008). Recommendations for Evaluation of Computational Methods. Journal of Computer-Aided Molecular Design, 22(3–4); 133–139.
Jain, R., R. Yadav, S. P. Tiwari, and J. Swarnkar (2023). An Overview of Medicinal Plants Used for Anti-Aging Face Pack Formulation. Journal of Pharmaceutical Negative Results, 14(2); 2023.
Kim, D. E., Y. S. Hwang, B. Y. Chang, D. S. Kim, H. K. Cho, and S. Y. Kim (2019). Effects of the Syzygium aromaticum L. Extract on Antioxidation and Inhibition of Matrix Metalloproteinase in Human Dermal Fibroblast. Asian Pacific Journal of Tropical Biomedicine, 9(2); 53–59.
Kim, D. H., J. H. Auh, J. Oh, S. Hong, S. Choi, E. J. Shin, S. O. Woo, T. G. Lim, and S. Byun (2020). Propolis Suppresses UV-Induced Photoaging in Human Skin Through Directly Targeting Phosphoinositide 3-Kinase. Nutrients, 12(12); 1–12.
Lephart, E. D. and F. Naftolin (2022). Factors Influencing Skin Aging and the Important Role of Estrogens and Selective Estrogen Receptor Modulators (SERMs). Clinical, Cosmetic and Investigational Dermatology, 15; 1695–1709.
Li, W., A. Shih, Y. Freudenberg-Hua, W. Fury, and Y. Yang (2021). Beyond Standard Pipeline and P < 0.05 in Pathway Enrichment Analyses. Computational Biology and Chemistry, 92; 107455.
Li, Y., L. You, E. Nepovimova, V. Adam, Z. Heger, K. Jomova, M. Valko, Q. Wu, and K. Kuca (2024). C-Jun N-Terminal Kinase Signaling in Aging. Frontiers in Aging Neuroscience, 16; 107455.
Liu, H., J. Dong, R. Du, Y. Gao, and P. Zhao (2024). Collagen Study Advances for Photoaging Skin. Photodermatology, Photoimmunology and Photomedicine, 40(1); e12931.
Manosalva, C., P. Alarcón, L. Grassau, C. Cortés, J. L. Hancke, and R. A. Burgos (2025). Andrographolide Mitigates Inflammation and Reverses UVB-Induced Metabolic Reprogramming in HaCaT Cells. International Journal of Molecular Sciences, 26(13); 6508.
Mohiuddin, A. (2019). Skin Aging & Modern Age Anti-Aging Strategies. International Journal of Clinical Dermatology & Research; 209–240.
Muralitharan, R. V., S. F. Masre, D. F. Basri, and A. R. Ghazali (2025). Pterostilbene and Resveratrol: Exploring Their Protective Mechanisms Against Skin Photoaging – A Scoping Review. Biochemistry and Biophysics Reports, 42.
Mutiah, R., M. S. D. Briliana, A. R. A. Ahmad, B. Fauziyah, N. A. Janaloka, and A. Suryadinata (2024). Network Pharmacology and Component Analysis Integrated Study to Uncovers the Molecular Mechanisms of Lansium parasiticum Bark Extract in Colon Cancer Treatment. Science and Technology Indonesia, 9(2); 314–324.
Noh, E. M., J. Park, H. R. Song, J. M. Kim, M. Lee, H. K. Song, O. Y. Hong, P. H. Whang, M. K. Han, K. B. Kwon, J. S. Kim, and Y. R. Lee (2016). Skin Aging-Dependent Activation of the PI3K Signaling Pathway via Downregulation of PTEN Increases Intracellular ROS in Human Dermal Fibroblasts. Oxidative Medicine and Cellular Longevity.
Pandey, V. K., S. Srivastava, Ashish, K. K. Dash, R. Singh, A. H. Dar, T. Singh, A. Farooqui, A. M. Shaikh, and B. Kovacs (2024). Bioactive Properties of Clove (Syzygium aromaticum) Essential Oil Nanoemulsion: A Comprehensive Review. Heliyon, 10(1); e22437.
Pangestuti, R., K. H. Shin, and S. K. Kim (2021). Anti-Photoaging and Potential Skin Health Benefits of Seaweeds. Marine Drugs, 19(3); 172.
Sharma, R. R., A. Deep, and S. T. Abdullah (2022). Herbal Products as Skincare Therapeutic Agents Against Ultraviolet Radiation-Induced Skin Disorders. Journal of Ayurveda and Integrative Medicine, 13(1); 100500.
Tiganescu, A., E. A. Walker, R. S. Hardy, A. E. Mayes, and P. M. Stewart (2011). Localization, Age- and Site-Dependent Expression, and Regulation of 11β-Hydroxysteroid Dehydrogenase Type 1 in Skin. Journal of Investigative Dermatology, 131(1); 30–36.
Urdiales-Gálvez, F., S. Martín-Sánchez, M. Maíz-Jiménez, A. Castellano-Miralla, and L. Lionetti-Leone (2019). Concomitant Use of Hyaluronic Acid and Laser in Facial Rejuvenation. Aesthetic Plastic Surgery, 43(4); 1061–1070.
Wang, M. L., Q. Y. Zhong, B. Q. Lin, Y. H. Liu, Y. F. Huang, Y. Chen, J. Yuan, Z. R. Su, and J. Y. X. Zhan (2020). Andrographolide Sodium Bisulfate Attenuates UV-Induced Photo Damage by Activating the Keap1/Nrf2 Pathway and Downregulating the NF-kB Pathway in HaCaT Keratinocytes. International Journal of Molecular Medicine, 45(2); 343–352.
Wang, X., B. Teferedegne, K. Shatzkes, W. Tu, and H. Murata (2016). Endogenous RNase Inhibitor Contributes to Stability of RNA in Crude Cell Lysates: Applicability to RT-qPCR. Analytical Biochemistry, 513; 21–27.
Wang, Y., Q. Zhang, H. Liao, X. Lu, J. Cong, Z. Liu, Q. Liu, C. Deng, Y. Cheng, P. Shu, and Q. Xiang (2025). Anti-Photoaging Mechanism of a Novel Recombinant Human Fibronectin Peptide (rhFNP) Derived from the Extracellular Matrix. Heliyon, 11(4); e42730.
Whitty, A., M. Zhong, L. Viarengo, D. Beglov, D. R. Hall, and S. Vajda (2016). Quantifying the Chameleonic Properties of Macrocycles and Other High-Molecular-Weight Drugs. Drug Discovery Today, 21(5); 712–717.
Wong, F., A. Krishnan, E. J. Zheng, H. Stärk, A. L. Manson, A. M. Earl, T. Jaakkola, and J. J. Collins (2022). Benchmarking AlphaFold-Enabled Molecular Docking Predictions for Antibiotic Discovery. Molecular Systems Biology, 18(9); e11081.
Xu, D. and M. Zhao (2022). Photoaging Induced by Long-Term Exposure to UV Irradiation and Amelioration by Skipjack Tuna Skin Hydrolysates: Targeting Inhibition of MAPK and NF-kB Signaling Hyperactivation. Journal of Functional Foods, 98; 105281.
Xu, J., G. Wu, X. Yu, Z. Dong, J. Yan, L. Wu, L. Bao, and Q. Liu (2023). Exploring the Mechanism of MPGel Against Skin Photoaging Based on Network Pharmacology, Molecular Docking, and Experimental Validation. Journal of Cosmetic Dermatology, 22(3); 1108–1123.
Zhan, J. Y. X., X. F. Wang, Y. H. Liu, Z. B. Zhang, L. Wang, J. N. Chen, S. Huang, H. F. Zeng, and X. P. Lai (2016). Andrographolide Sodium Bisulfate Prevents UV-Induced Skin Photoaging Through Inhibiting Oxidative Stress and Inflammation. Mediators of Inflammation, 1; 3271451.
Authors

This work is licensed under a Creative Commons Attribution 4.0 International License.