Abstract
Wound repair can be disrupted by oxidative stress and enzymatic degradation of extracellular matrix (ECM) proteins, and current synthetic treatments are often limited by side effects. While the leaves and stems of Ipomoea pes-caprae are known for their bioactivity, the flowers remain largely unexplored for their therapeutic potential. This study aims to evaluate the antioxidant activity, enzyme inhibition, and wound healing potential of methanolic extracts from I. pes-caprae flowers (IPFME). Dried flowers were sequentially extracted with hexane, ethyl acetate, and methanol. Extracts were screened for total phenolic content (TPC) and antioxidant capacity (DPPH assay), after which the methanolic extract (IPFME) was further evaluated for anti-elastase and anti-collagenase activity, cytotoxicity (MTT assay), and fibroblast migration (scratch assay). Methanol extraction produced the highest yield (11.6%) and phenolic content (0.38 mg GAE/g ± 0.003) compared to hexane and ethyl acetate extracts. Antioxidant analysis revealed strong radical scavenging activity with IPFME showing an IC₅₀ of 0.06 mg/mL close to gallic acid (0.02 mg/mL). In enzyme inhibition assays, IPFME inhibited collagenase activity by 38.5% and elastase activity by over 90% at 1 mg/mL with inhibition levels comparable to EGCG. Cytotoxicity testing on MRC-5 fibroblast cells revealed an IC₅₀ of 0.05 mg/mL, establishing safe, non-toxic concentrations for subsequent assays. Scratch assays further demonstrated accelerated wound closure, with IPFME-treated fibroblasts achieving 95% closure within 24 h, comparable to ascorbic acid (AA). These findings highlight I. pes-caprae flowers as a promising source of natural antioxidants and enzyme inhibitors with significant wound healing potential. This multifaceted bioactivity — neutralizing free radicals, inhibiting ECM-degrading enzymes, and promoting fibroblast migration positions the flower extract as a strong candidate for natural therapeutics targeting oxidative-stress-impaired wound healing.
References
Adeyemo, O. A., Osibote, E., Adedugba, A., Bhadmus, O. A., Adeoshun, A. A., & Allison, M. O. (2018). Antioxidant activity, total phenolic contents and functional group identification of leaf extracts among lemongrass (Cymbopogon citratus) accessions. NISEB J, 18(2), 83-91.
https://api-ir.unilag.edu.ng/server/api/core/bitstreams/7330eb75-6b27-43e6-9859-a7734e5aa10e/content
Andrade, J. M., Domínguez-Martín, E. M., Nicolai, M., Faustino, C., Rodrigues, L. M., & Rijo, P. (2021). Screening the dermatological potential of plectranthus species components: Antioxidant and inhibitory capacities over elastase, collagenase and tyrosinase. Journal of Enzyme Inhibition and Medicinal Chemistry, 36(1), 258-270.
https://pubmed.ncbi.nlm.nih.gov/33322969/
Akinniyi, G., Lee, J., Kim, H., Lee, J. G., & Yang, I. (2022). A medicinal halophyte Ipomoea pes-caprae (Linn.) R. Br.: A review of its botany, traditional uses, phytochemistry, and bioactivity. Marine Drugs, 20(5), 329.
https://doi.org/10.3390/md20050329
Albahri, G., Badran, A., Hijazi, A., Daou, A., Baydoun, E., Nasser, M., & Merah, O. (2023). The therapeutic wound healing bioactivities of various medicinal plants. Life, 13(2), 317.
https://doi.org/10.3390/life13020317
Alfadda, A. A., & Sallam, R. M. (2012). Reactive oxygen species in health and disease. BioMed Research International, 2012(1), 936486.
https://pubmed.ncbi.nlm.nih.gov/22927725/
Aryal, S., Baniya, M. K., Danekhu, K., Kunwar, P., Gurung, R., & Koirala, N. (2019). Total phenolic content, flavonoid content and antioxidant potential of wild vegetables from Western Nepal. Plants, 8(4), 96.
https://doi.org/10.3390/plants8040096
Assaw, S., Rosli, N. L., Azmi, N. A. M., Mazlan, N. W., & Ismail, N. (2018). Antioxidant and antibacterial activities of polysaccharides and methanolic crude extracts of local edible red seaweed Gracilaria sp. Malaysian Applied Biology, 47(4).
http://www.mabjournal.com/images/47_4_October_2018/47_04_15.pdf
Beheshti, F., Shabani, A. A., Akbari Eidgahi, M. R., Kookhaei, P., Vazirian, M., & Safavi, M. (2021). Anticancer activity of Ipomoea purpurea leaves extracts in monolayer and three‐dimensional cell culture. Evidence‐Based Complementary and Alternative Medicine, 2021(1), 6666567.
https://doi.org/10.1155/2021/6666567
Chan, E. W. C., Baba, S., Chan, H. T., Kainuma, M., & Tangah, J. (2016). Medicinal plants of sandy shores: A short review on Vitex trifolia L. and Ipomoea pes-caprae (L.) R. Br. Indian Journal of Natural Products and Resources (IJNPR) [Formerly Natural Product Radiance (NPR)], 7(2), 107-115.
http://op.niscpr.res.in/index.php/IJNPR/article/view/12710/
Chaudhary, P., Janmeda, P., Docea, A. O., Yeskaliyeva, B., Abdull Razis, A. F., Modu, B., & Sharifi-Rad, J. (2023). Oxidative stress, free radicals and antioxidants: Potential crosstalk in the pathophysiology of human diseases. Frontiers in chemistry, 11, 1158198.
https://doi.org/10.3389/fchem.2023.1158198
Cedillo-Cortezano, M., Martinez-Cuevas, L. R., López, J. A. M., Barrera López, I. L., Escutia-Perez, S., & Petricevich, V. L. (2024). Use of medicinal plants in the process of wound healing: a literature review. Pharmaceuticals, 17(3), 303.
https://doi.org/10.3390/ph17030303
Criollo-Mendoza, M. S., Contreras-Angulo, L. A., Leyva-López, N., Gutiérrez-Grijalva, E. P., Jiménez-Ortega, L. A., & Heredia, J. B. (2023). Wound healing properties of natural products: Mechanisms of action. Molecules, 28(2), 598.
https://doi.org/10.3390/molecules28020598
Diller, R. B., & Tabor, A. J. (2022). The role of the extracellular matrix (ECM) in wound healing: A review. Biomimetics, 7(3), 87.
https://doi.org/10.3390/biomimetics7030087
Freedman, B.R., Hwang, C., Talbot, S.G., Hibler, B., Matoori, S., & Mooney, D.J. (2023). Breakthrough treatments for accelerated wound healing. Science Advances, 9.
https://doi.org/10.1126/sciadv.ade7007
Ghimeray, A. K., Jung, U. S., Lee, H. Y., Kim, Y. H., Ryu, E. K., & Chang, M. S. (2015). In vitro antioxidant, collagenase inhibition, and in vivo anti-wrinkle effects of combined formulation containing Punica granatum, Ginkgo biloba, Ficus carica, and Morus alba fruits extract. Clinical, cosmetic and investigational dermatology, 389-396.
https://doi.org/10.2147/CCID.S80906
Gushiken, L. F. S., Beserra, F. P., Bastos, J. K., Jackson, C. J., & Pellizzon, C. H. (2021). Cutaneous wound healing: An update from physiopathology to current therapies. Life, 11(7), 665.
https://doi.org/10.3390/life11070665
Jakimiuk, K., Gesek, J., Atanasov, A. G., & Tomczyk, M. (2021). Flavonoids as inhibitors of human neutrophil elastase. Journal of Enzyme Inhibition and Medicinal Chemistry, 36(1), 1016-1028.
https://doi.org/10.1080/14756366.2021.1927006
Karbon, M. H., & Alhammer, A. H. (2020). Cytotoxic effect of aqueous-ethanol extract of Typha Domingensis Pers.(pollen) against human breast cancer cells in vitro. Systematic Reviews in Pharmacy, 11(10), 1158-1161.
Karma, N. I., Mellou, F., Pavlou, P., Siamidi, A., & Varvaresou, A. (2024). Compounds of marine origin with possible applications as healing agents. Marine Drugs, 23(1), 5.
https://doi.org/10.3390/md23010005
Kolaczkowska, E., & Kubes, P. (2013). Neutrophil recruitment and function in health and inflammation. Nature Reviews. Immunology, 13(3), 159–175.
https://doi.org/10.1038/nri3399
Kolimi, P., Narala, S., Nyavanandi, D., Youssef, A. a. A., & Dudhipala, N. (2022). Innovative treatment strategies to accelerate wound healing: Trajectory and recent advancements. Cells, 11(15), 2439.
https://doi.org/10.3390/cells11152439
Kumar, A., Paul, S., Kumari, P., Somasundaram, S. T., & Kathiresan, K. (2015). Antioxidant and free radical scavenging activities of Ipomoea pes-caprae (L.) R. Br. Extracts. International Journal of Current Pharmaceutical Review and Research, 5(4), 91-109.
https://impactfactor.org/PDF/IJCPR/5/IJCPR,Vol5,Issue4,Article3.pdf
Kumar, S. S., Badhmapriya, D., & Poornimadevi, C. (2020). A comparative study of bioactive compounds in raw and extract forms of Ipomoea pes-caprae (L.) R. Br.(leaf) detected by FT-IR spectroscopy. Int J Multidisc Res Develop, 7(5), 48-52.
https://www.allsubjectjournal.com/assets/archives/2020/vol7issue5/7-5-13-665.pdf
Kustiawan, P. M., Puthong, S., Arung, E. T., & Chanchao, C. (2014). In vitro cytotoxicity of Indonesian stingless bee products against human cancer cell lines. Asian Pacific journal of tropical biomedicine, 4(7), 549-556.
https://doi.org/10.12980/APJTB.4.2014APJTB-2013-0039
Lin, W. T., Chen, Y. J., Kuo, H. N., Kumar, S., Abomughaid, M. M., & Senthil Kumar, K. J. (2025). Ultraviolet B-induced oxidative damage in human skin keratinocytes is alleviated by Pinus morrisonicola leaf essential oil through activation of the Nrf2-dependent antioxidant defense system. Redox Report, 30(1), 2527427.
https://doi.org/10.1080/13510002.2025.2527427
Mathew-Steiner, S. S., Roy, S., & Sen, C. K. (2021). Collagen in wound healing. Bioengineering, 8(5), 63.
https://doi.org/10.3390/bioengineering8050063
Mehmood, A., Javid, S., Khan, M. F., Ahmad, K. S., & Mustafa, A. (2022). In vitro total phenolics, total flavonoids, antioxidant and antibacterial activities of selected medicinal plants using different solvent systems. BMC Chemistry, 16(1), 64.
https://doi.org/10.1186/s13065-022-00858-2
MyBIS (2025). Malaysia Biodiversity Information System. Ministry of Natural Resources and Environmental Sustainability, Malaysia Biodiversity Centre & Forest Research Institute Malaysia.
https://www.mybis.gov.my/sp/39708
Nagase, H., Visse, R., & Murphy, G. (2006). Structure and function of matrix metalloproteinases and TIMPs. Cardiovascular research, 69(3), 562-573.
https://doi.org/10.1016/j.cardiores.2005.12.002
National Parks Board (NParks). (2025). Ipomoea pes-caprae. Flora of Singapore.
https://www.nparks.gov.sg/florafaunaweb/flora/1/4/1431
Nur, S., Setiawan, H., Hanafi, M., & Elya, B. (2023). Phytochemical composition, antioxidant, in vitro and in silico studies of active compounds of Curculigo latifolia extracts as promising elastase inhibitor. Saudi Journal of Biological Sciences, 30(8), 103716.
https://doi.org/10.1016/j.sjbs.2023.103716
Nuskiya, A., Sibero, M. T., Setyati, W. A., Andriani, C., & Hendryanti, D. N. (2023). Bioprospecting of katang-katang leaves (Ipomoea pes-caprae) from Sumba Island, East Nusa Tenggara: Antimicrobial, antioxidant and secondary metabolites content. In IOP Conference Series: Earth and Environmental Science (Vol. 1260, No. 1, p. 012054). IOP Publishing.
https://doi.org/10.1088/1755-1315/1260/1/012054
Panichakul, T., Ponnikorn, S., Tupchiangmai, W., Haritakun, W., & Srisanga, K. (2022). Skin anti-aging potential of Ipomoea pes-caprae ethanolic extracts on promoting cell proliferation and collagen production in human fibroblasts (CCD-986sk Cells). Pharmaceuticals, 15(8), 969.
https://doi.org/10.3390/ph15080969
Rinnerthaler, M., Bischof, J., Streubel, M. K., Trost, A., & Richter, K. (2015). Oxidative stress in aging human skin. Biomolecules, 5(2), 545-589.
https://doi.org/10.3390/biom5020545
Rodrigues, M., Kosaric, N., Bonham, C. A., & Gurtner, G. C. (2018). Wound healing: A cellular perspective. Physiological reviews.
https://doi.org/10.1152/physrev.00067.2017
Salim, J.M., Lee, G.E., Salam, M.R., Shahimi, S., Pesiu, E., Jani, J.M., Horsali, N.A.I., Shahrudin, R., Nor, S.M.M., Chong, J.L. and Mohamad, F. (2020). A checklist of vascular plants and uses of some species for livelihood-making in Setiu Wetlands, Terengganu, Malaysia. PhytoKeys, 160, 7.
https://doi.org/10.3897/phytokeys.160.52946
Santhanam, R., Karunakaran, T., Sowndhararajan, K., Zulkifli, M. F., Govindan Kothandaraman, M., Aravindhan, V., & Wan Ismail, W. I. (2022). Photoprotective potential, cytotoxicity, and uplc‐qtof/ms analysis on bioactive solvent fractions of Moringa concanensis nimmo bark. Evidence‐Based Complementary and Alternative Medicine, 2022(1), 3781189.
https://doi.org/10.1155/2022/3781189
Sarangthem, V., Singh, T. D., & Dinda, A. K. (2021). Emerging role of elastin-like polypeptides in regenerative medicine. Advances in Wound Care, 10(5), 257–269.
https://doi.org/10.1089/wound.2019.1085
Sheeba, S. N., Ariharan, V. N., Mary, J. V. J., Bai, S. M. M., & Paul, J. V. (2021). Phytochemical and biological screening of organic solvent extracts of Ipomoea pes-caprae flower. Annals of the Romanian Society for Cell Biology, 25(3), 7800-7821.
http://annalsofrscb.ro/index.php/journal/article/view/2323/1943
Sobeh, M., Mahmoud, M.F., Monti, D.M., Criollo-Mendoza, M.S., Contreras-Angulo, L.A., pez, N.L., rrez-Grijalva, E.P., nez-Ortega, L.A., & Heredia, J.B. (2023). Wound healing properties of natural products: Mechanisms of action. Molecules, 28.
https://doi.org/10.3390/molecules28020598
Szewczyk, K., Pietrzak, W., Klimek, K., Miazga-Karska, M., Firlej, A., Flisiński, M., & Grzywa-Celińska, A. (2021). Flavonoid and phenolic acids content and in vitro study of the potential anti-aging properties of Eutrema japonicum (Miq.) Koidz cultivated in Wasabi Farm Poland. International Journal of Molecular Sciences, 22(12), 6219.
https://doi.org/10.3390/ijms22126219
Tamuddin, Y., Utami, H., Husna, S., Lestari, M., Salawali, R., Towolioe, S., Aras, N., Trifany, A., Papriani, N. (2023). Identification of anticancer and antioxidant potentials of katang-katang flower extract (Ipomea pes-caprae Linn) with water solvent. Jurnal Akta Kimia Indonesia (Indonesia Chimica Acta), 38-43.
https://journal.unhas.ac.id/index.php/ica/article/view/25353/10495
Teramachi, F., Koyano, T., Kowithayakorn, T., Hayashi, M., Komiyama, K., & Ishibashi, M. (2005). Collagenase inhibitory quinic acid esters from Ipomoea pes-caprae. Journal of Natural Products, 68(5), 794-796.
https://pubs.acs.org/doi/10.1021/np0500631
Ukaegbu, K., Allen, E., & Svoboda, K. K. (2025). Reactive oxygen species and antioxidants in wound healing: mechanisms and therapeutic potential. International Wound Journal, 22(5), e70330.
https://onlinelibrary.wiley.com/doi/10.1111/iwj.70330
Wang, Z., Hu, W., Wang, W., Xiao, Y., Chen, Y., & Wang, X. (2023). Antibacterial electrospun nanofibrous materials for wound healing. Advanced Fiber Materials, 5(1), 107-129.
https://doi.org/10.1007/s42765-022-00223-x
Wei, M., He, X., Liu, N., & Deng, H. (2024). Role of reactive oxygen species in ultraviolet-induced photodamage of the skin. Cell division, 19(1), 1.
https://doi.org/10.1186/s13008-024-00107-z
Wilkinson, H. N., & Hardman, M. J. (2020). Wound healing: Cellular mechanisms and pathological outcomes. Open biology, 10(9), 200223.
https://doi.org/10.1098/rsob.200223
Xavier-Santos, J.B., Passos, J.G.R., Gomes, J.A.S., Cruz, J.V.C., Alves, J.S.F., Garcia, V.B., da Silva, R.M., Lopes, N.P., Araujo-Junior, R.F., Zucolotto, S.M. and Silva-Junior, A.A. (2022). Topical gel containing phenolic-rich extract from Ipomoea pes-capre leaf (Convolvulaceae) has anti-inflammatory, wound healing, and antiophidic properties. Biomedicine & Pharmacotherapy, 149, 112921.
https://doi.org/10.1016/j.biopha.2022.112921
Xue, M., & Jackson, C. J. (2015). Extracellular matrix reorganization during wound healing and its impact on abnormal scarring. Advances in wound care, 4(3), 119-136.
https://doi.org/10.1089/wound.2013.0485
Yin, Q., Zhang, H., Huang, T., Liu, B., Negm, S., & El-Kott, A. F. (2024). Anti-collagenase, anti-elastase, anti-urease, and anti-cancer potentials of Isokaempferide as natural compound: In vitro and in silico study. Journal of Oleo Science, 73(2), 187-199.

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Copyright (c) 2026 Fatihah Nazar, Farah Anisah Abdul Razak, Dhia Airina Noor Salizam, Dhipan Raj Subramaniam, Khaizuran Shahiran Mohd Izhan, Thirukanthan Chandra Segaran, Suvik Assaw
