Iranian Journal of Medical Sciences

The Effects of Apigenin Isolated from Sungkai Leaves (Peronema canescens J.) on Skin Collagen Density in Male White Mice (Mus musculus) in an Ultraviolet B-Induced Aging Model

Document Type : Original Article(s)

Authors

Department of Pharmacology, Faculty of Pharmacy, Universitas Andalas, Padang, Indonesia

10.30476/ijms.2026.109645.4500
Abstract
Background: Skin aging is a multifactorial process driven by intrinsic factors and environmental exposure, particularly ultraviolet radiation, which induces oxidative stress and the degradation of dermal collagen. Given the limited evidence regarding apigenin derived from Peronema canescens, this study aimed to evaluate its protective effects against oxidative stress and collagen degradation in an ultraviolet B (UVB)-induced skin aging model.
Methods: A true experimental study with a post-test-only control group design was conducted from March to August 2025 in Padang, Indonesia. Twenty-five male white mice (Mus musculus) were randomly assigned into five groups (n=5 per group): a negative control, a UVB-exposed positive control, and three UVB-exposed treatment groups receiving apigenin at 25, 50, or 100 mg/Kg body weight (BW) for 30 days. Data were analyzed using SPSS version 27. Normality and homogeneity of variances were assessed using the Shapiro–Wilk and Levene tests, respectively. Malondialdehyde (MDA) levels were analyzed using one-way ANOVA followed by Tukey’s post hoc test, while collagen density scores were analyzed using the Kruskal–Wallis test followed by Dunn’s test with Bonferroni correction.
Results: MDA levels differed significantly among groups (F[4,20]=61.743, P<0.001). The 100 mg/Kg BW group did not differ significantly from the negative control, indicating the restoration of MDA levels to near-normal values. Collagen density also differed significantly among groups (P=0.003), with significant improvement in the 100 mg/Kg BW group compared with the positive control (adjusted P=0.049).
Conclusion: Apigenin derived from P. canescens exhibited dose-dependent antioxidant and dermoprotective effects in a UVB–induced photoaging model.

Highlights

Dwisari Dillasamola (Google Scholar)

Keywords


1.     Nowak-Perlak M, Olszowy M, Wozniak M. The Natural Defense: Anti-Aging Potential of Plant-Derived Substances and Technological Solutions Against Photoaging. Int J Mol Sci. 2025;26. doi: 10.3390/ijms26168061. PubMed PMID: 40869382; PubMed Central PMCID: PMC12386611.
2.     Wei M, He X, Liu N, Deng H. Role of reactive oxygen species in ultraviolet-induced photodamage of the skin. Cell Div. 2024;19:1. doi: 10.1186/s13008-024-00107-z. PubMed PMID: 38217019; PubMed Central PMCID: PMC10787507.
3.     Gromkowska-Kepka KJ, Puscion-Jakubik A, Markiewicz-Zukowska R, Socha K. The impact of ultraviolet radiation on skin photoaging - review of in vitro studies. J Cosmet Dermatol. 2021;20:3427-31. doi: 10.1111/jocd.14033. PubMed PMID: 33655657; PubMed Central PMCID: PMC8597149.
4.     Singh D, Rai V, Agrawal DK. Regulation of Collagen I and Collagen III in Tissue Injury and Regeneration. Cardiol Cardiovasc Med. 2023;7:5-16. doi: 10.26502/fccm.92920302. PubMed PMID: 36776717; PubMed Central PMCID: PMC9912297.
5.     Lee LY, Liu SX. Pathogenesis of photoaging in human dermal fibroblasts. Int J Dermatol Venereol. 2020;3:37-42. doi: 10.1097/JD9.0000000000000068.
6.     Li Pomi F, Gammeri L, Borgia F, Di Gioacchino M, Gangemi S. Oxidative Stress and Skin Diseases: The Role of Lipid Peroxidation. Antioxidants (Basel). 2025;14. doi: 10.3390/antiox14050555. PubMed PMID: 40427437; PubMed Central PMCID: PMC12108378.
7.     Pozo Giraldez A, Bravo Gomez A, Calmarza P, Sienes Bailo P, Dayaldasani Khialani A, Montolio Breva S, et al. Oxidative Stress and Its Role in Vascular Damage and Atherosclerosis. Int J Mol Sci. 2026;27. doi: 10.3390/ijms27021075. PubMed PMID: 41596717; PubMed Central PMCID: PMC12841722.
8.     Ahkam AH, Susilawati Y, Sumiwi SA. Peronema canescens as a Source of Immunomodulatory Agents: A New Opportunity and Perspective. Biology (Basel). 2024;13. doi: 10.3390/biology13090744. PubMed PMID: 39336171; PubMed Central PMCID: PMC11428267.
9.     Tarigan IL, Sutrisno S, Rumaida R, Aini IPS, Latief M. Isolation of a flavone apigenin and a steroid squalene from Peronema canescens Jack leaves with anti-inflammatory activities. Pharmacogn J. 2022;14:744-52. doi: 10.5530/pj.2022.14.162.
10.  Kokom A, Susilawati Y, Sumiwi SA, Putra ON. Pharmacological profile and therapeutic potential of Sungkai plant (Peronema canescens Jack.): an emerging Indonesian herbal medicine. J Sains Farm Klin. 2024;11:95-102. doi: 10.25077/jsfk.11.2.95-102.2024.
11.  Suryani AE, Nisa K, Handayani S, Darsih C, Wuryastuty H, Yanuartono Y. The UHPLC-HRMS profiling, in vitro antioxidant and pancreatic lipase inhibitory activities of Peronema canescens leaves extract and fractions from Indonesia. J Appl Pharm Sci. 2025;15:75-89. doi: 10.7324/JAPS.2025.214965.
12.  Allemailem KS, Almatroudi A, Alharbi HOA, AlSuhaymi N, Alsugoor MH, Aldakheel FM, et al. Apigenin: A Bioflavonoid with a Promising Role in Disease Prevention and Treatment. Biomedicines. 2024;12. doi: 10.3390/biomedicines12061353. PubMed PMID: 38927560; PubMed Central PMCID: PMC11202028.
13.  Dillasamola D, Aldi Y, Fitria N, Oktomalioputri B, Lestari U, Multia R. Isolation of Apigenin from Sungkai ( Peronema canescens) Leaves and Its Immunomodulatory Effects: An In Vivo Study on Granzyme B, Interferon-gamma, and Perforin Expression with Supporting In Silico Analysis. F1000Res. 2025;14:774. doi: 10.12688/f1000research.167153.1. PubMed PMID: 41036318; PubMed Central PMCID: PMC12481153.
14.  Sanchez-Marzo N, Perez-Sanchez A, Ruiz-Torres V, Martinez-Tebar A, Castillo J, Herranz-Lopez M, et al. Antioxidant and Photoprotective Activity of Apigenin and its Potassium Salt Derivative in Human Keratinocytes and Absorption in Caco-2 Cell Monolayers. Int J Mol Sci. 2019;20. doi: 10.3390/ijms20092148. PubMed PMID: 31052292; PubMed Central PMCID: PMC6539602.
15.  Monadi T, Mohajer Z, Soltani A, Khazeei Tabari MA, Manayi A, Azadbakht M. The influence of apigenin on cellular responses to radiation: From protection to sensitization. Biofactors. 2025;51:e2113. doi: 10.1002/biof.2113. PubMed PMID: 39134426.
16.  Kashyap P, Shikha D, Thakur M, Aneja A. Functionality of apigenin as a potent antioxidant with emphasis on bioavailability, metabolism, action mechanism and in vitro and in vivo studies: A review. J Food Biochem. 2022;46:e13950. doi: 10.1111/jfbc.13950. PubMed PMID: 34569073.
17.  Salehi B, Venditti A, Sharifi-Rad M, Kregiel D, Sharifi-Rad J, Durazzo A, et al. The Therapeutic Potential of Apigenin. Int J Mol Sci. 2019;20. doi: 10.3390/ijms20061305. PubMed PMID: 30875872; PubMed Central PMCID: PMC6472148.
18.  Yoon JH, Kim MY, Cho JY. Apigenin: A Therapeutic Agent for Treatment of Skin Inflammatory Diseases and Cancer. Int J Mol Sci. 2023;24. doi: 10.3390/ijms24021498. PubMed PMID: 36675015; PubMed Central PMCID: PMC9861958.
19.  Percie du Sert N, Hurst V, Ahluwalia A, Alam S, Avey MT, Baker M, et al. The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research. PLoS Biol. 2020;18:e3000410. doi: 10.1371/journal.pbio.3000410. PubMed PMID: 32663219; PubMed Central PMCID: PMC7360023.
20.  Aguilar Diaz De Leon J, Borges CR. Evaluation of Oxidative Stress in Biological Samples Using the Thiobarbituric Acid Reactive Substances Assay. J Vis Exp. 2020. doi: 10.3791/61122. PubMed PMID: 32478759; PubMed Central PMCID: PMC9617585.
21.  Dwisari D, Yufri A, Poetti Raihan S, Rativa F. The effect of apigenin isolate from Sungkai leaf (Peronema canescens) on skin collagen density and fibroblast cell count as anti-aging indicators in D-galactose-induced male white mice. Trop J Nat Prod Res. 2026;10. doi: 10.26538/tjnpr/v10i1.73.
22.  Ismawati R, Chodijah C, Sumarawati T, Putra A, Subchan P. Effect of stink bean extract gel on MDA and IL-10 levels in UVB-exposed rat skin tissue: a preclinical investigation. J Exp Lab Med. 2025;2:18-26. doi: 10.5455/JELM.20241029034553.
23.  Ansary TM, Hossain MR, Kamiya K, Komine M, Ohtsuki M. Inflammatory Molecules Associated with Ultraviolet Radiation-Mediated Skin Aging. Int J Mol Sci. 2021;22. doi: 10.3390/ijms22083974. PubMed PMID: 33921444; PubMed Central PMCID: PMC8069861.
24.  Kashyap D, Sharma A, Tuli HS, Sak K, Garg VK, Buttar HS. Apigenin: a natural bioactive flavone-type molecule with promising therapeutic function. J Funct Foods. 2018;48:457-71. doi: 10.1016/j.jff.2018.07.037.
25.  Alghamdi A, Almuqbil M, Alrofaidi MA, Burzangi AS, Alshamrani AA, Alzahrani AR, et al. Potential Antioxidant Activity of Apigenin in the Obviating Stress-Mediated Depressive Symptoms of Experimental Mice. Molecules. 2022;27. doi: 10.3390/molecules27249055. PubMed PMID: 36558188; PubMed Central PMCID: PMC9787100.
26.  Wang D, Yang Y, Zou X, Zhang J, Zheng Z, Wang Z. Antioxidant Apigenin Relieves Age-Related Muscle Atrophy by Inhibiting Oxidative Stress and Hyperactive Mitophagy and Apoptosis in Skeletal Muscle of Mice. J Gerontol A Biol Sci Med Sci. 2020;75:2081-8. doi: 10.1093/gerona/glaa214. PubMed PMID: 32857105; PubMed Central PMCID: PMC7566467.
27.  Chen P, Chen F, Guo Z, Lei J, Zhou B. Recent advancement in bioeffect, metabolism, stability, and delivery systems of apigenin, a natural flavonoid compound: challenges and perspectives. Front Nutr. 2023;10:1221227. doi: 10.3389/fnut.2023.1221227. PubMed PMID: 37565039; PubMed Central PMCID: PMC10410563.
28.  Li J, Mao B, Tang X, Zhang Q, Zhao J, Zhang H, et al. Protective Effects of Naringenin and Apigenin in Ameliorating Skin Damage via Mediating the Nrf2 and NF-kappaB Pathways in Mice. Foods. 2023;12. doi: 10.3390/foods12112120. PubMed PMID: 37297362; PubMed Central PMCID: PMC10252862.
29.  Liu C, Guo X, Chen Y, Zhao M, Shi S, Luo Z, et al. Anti-photoaging effect and mechanism of flexible liposomes co-loaded with apigenin and doxycycline. Biomed Pharmacother. 2023;164:114998. doi: 10.1016/j.biopha.2023.114998. PubMed PMID: 37301137.
30.   Chen F, Lyu L, Xing C, Chen Y, Hu S, Wang M, et al. The pivotal role of TGF-beta/Smad pathway in fibrosis pathogenesis and treatment. Front Oncol. 2025;15:1649179. doi: 10.3389/fonc.2025.1649179. PubMed PMID: 40969268; PubMed Central PMCID: PMC12440922.

Articles InPress, Corrected Proof
Available Online from 20 October 2026


  • Received 11 November 2025
  • Revised 01 May 2026
  • Accepted 15 June 2026