The Application of Tapak Dara (Catharanthus roseus) Extract Ointment Reducing IL-6 and MMP-1 Production in Photodamaged Rat's Skin

Desiani Putri Ramayanti, Agung Putra, Titiek Sumarawati

Abstract

Tapak dara Catharanthus roseus (L.) Don extract possesses promising properties that could counteract the detrimental effects of UV-B exposure. Its inherent antioxidant and anti-inflammatory capabilities suggest its potential as a therapeutic agent for managing UV-B-induced skin damage. This study aims to analysis the effect of tapak dara extract ointment on IL-6 and MMP-1 levels in photodamaged skin. Twenty-five healthy male Wistar rats were divided into two groups: a healthy control group (n = 5) and a UVB-exposed group (n = 20). The UVB-exposed rats received 1 MED for 8 minutes per day, for 10 sessions over 14 days. Skin tissue was taken on day 15 to observe skin damage and validate collagen loss using the immunohistochemical method. After validation, photodamaged skin rats were divided equally into four experimental groups, namely rats treated with placebo (P2), vitamin E (P3), tapak dara extract 10% (P4) and 20% (P5). The rats were sacrificed at the end of the study, and the skin tissues were analyzed for IL-6 and MMP-1 using ELISA. Based on the analysis results, groups P4 and P5 produced average levels of IL-6 and MMP-1, significantly lower than P2 (p < 0.050). IL-6 and MMP-1 levels in group P5 reached 188.60 ± 40.60 pg/mL and 1,611 ± 344 pg/mL, respectively. This is likely due to the secondary metabolite content of tapak dara, which acts as an antioxidant and anti-inflammatory, so it has the potential to be developed as a photodamaged skin therapy. As many as 20% tapak dara extract cream effectively reduces IL-6 and MMP-1 levels in UV-B-exposed skin tissue. However, this study did not evaluate changes in skin tissue after tapak dara extract treatment. Therefore, further research must be developed to analyze and validate collagen synthesis after tapak dara extract treatment.

Keywords

Collagen loss; IL-6; MMP-1; Tapak dara; UV-B

References

Ahmady, S., Oyen, E. M. M., Jansen, M. H. E., Nelemans, P. J., Kessels, J. P. H. M., Kelleners‐Smeets, N. W. J., & Mosterd, K. (2021). Patient‐reported skin reactions to 5% 5‐fluorouracil in treatment of actinic keratosis. British Journal of Dermatology, 185(5), 1050–1052. https://doi.org/10.1111/bjd.20570.

Ahmed, M., Sahibzada, M. U. K., Rasheed, H. M., Khan, T., Wahid, F., Farooq, U., Khusro, A., Uddin, J., Afzal, S., Khan, A., & Al-Harrasi, A. (2022). Inhibition of inflammation associated corneal neovascularization by Dalbergia sissoo and Catharanthus roseus leaf extracts in an animal model. South African Journal of Botany. https://doi.org/10.1016/j.sajb.2022.03.047.

Bethasari, M., Rahayu, A. P., & Safitri, N. (2025). Flavonoid content and antioxidant activity of Camellia sinensis kombucha ethyl acetate extract and cream formulation. Medical Sains: Jurnal Ilmiah Kefarmasian, 10(4), 401–410. https://doi.org/10.37874/ms.v10i4.1786.

Du, G. L., Chen, W. Y., Li, X. N., He, R., & Feng, P. F. (2017). Induction of MMP-1 and -3 by cyclical mechanical stretch is mediated by IL-6 in cultured fibroblasts of keratoconus. Molecular Medicine Reports. https://doi.org/10.3892/mmr.2017.6433.

Egrilmez, M. Y., Kocturk, S., Aktan, S., Oktay, G., Resmi, H., Keskin, H. S., Akdogan, G. G., & Ozkan, S. (2022). Melatonin prevents UVB-induced skin photoaging by inhibiting oxidative damage and MMP expression through JNK/AP-1 signaling pathway in human dermal fibroblasts. Life, 12(7), 950. https://doi.org/10.3390/life12070950.

Erenel, H., Ozel, A., Oztunc, F., Kizilkilic, O., Comunoglu, N., Uludag, S., & Madazli, R. (2018). Antenatal diagnosis of fetal retinoid syndrome at 20 weeks of gestation: A case report. Fetal and Pediatric Pathology, 37(4), 282–286. https://doi.org/10.1080/15513815.2018.1472354.

Gawade, M., Zaware, Dr. M., Gaikwad, C., Kumbhar, R., & Chavan, T. (2022). Catharanthus roseus L. (Periwinkle): An herb with impressive health benefits and pharmacological therapeutic effects. International Journal of Agriculture and Nutrition, 4(2), 52–57. https://doi.org/10.33545/26646064.2022.v4.i2a.81.

Gracelia, A., & Sudharmono, U. (2019). The effectiveness of rosy periwinkle (Catharanthus roseus) and Cherry (Muntingia calabura L.) decoction on SGOT and SGPT serum in male wistar strain rats of acute hepatitis model. Abstract Proceedings International Scholars Conference. https://doi.org/10.35974/isc.v7i1.2084.

Haruna, A., Ismail, S. I., Omar, D., & Mohamed, M. T. M. (1970). Qualitative analysis of some bioactive components of methanolic leaf extract of M. citrifolia (Noni). Journal of Medicinal Herbs and Ethnomedicine, 38–41. https://doi.org/10.25081/jmhe.2020.v6.6102.

Jamal, Q. M. S., & Ahmad, V. (2024). Identification of metabolites from Catharanthus roseus leaves and stem extract, and in vitro and in silico antibacterial activity against food pathogens. Pharmaceuticals, 17(4), 450. https://doi.org/10.3390/ph17040450.

Kim, D. J., Iwasaki, A., Chien, A. L., & Kang, S. (2022). UVB-mediated DNA damage induces matrix metalloproteinases to promote photoaging in an AhR- and SP1-dependent manner. JCI Insight, 7(9). https://doi.org/10.1172/jci.insight.156344.

Kim, J., Kim, S. young, Noh, E., Song, H., Lee, G., Kwon, K., & Lee, Y. (2018). Reversine inhibits MMP‐1 and MMP‐3 expressions by suppressing of ROS/MAPK/AP‐1 activation in UV‐stimulated human keratinocytes and dermal fibroblasts. Experimental Dermatology, 27(3), 298–301. https://doi.org/10.1111/exd.13494.

Kumar, G., Kumar, R., Gautam, G. K., & Rana, H. (2021). Phytochemical and pharmacological properties of Catharanthus roseus (Vinca). Science Progress and Research. https://doi.org/10.52152/spr/2021.164.

Lakkim, V., Reddy, M. C., Pallavali, R. R., Reddy, K. R., Venkata Reddy, C., Bilgrami, A. L., & Lomada, D. (2020). Green synthesis of silver nanoparticles and evaluation of their antibacterial activity against multidrug-resistant bacteria and wound healing efficacy using a murine model. Antibiotics, 9(12), 902. https://doi.org/10.3390/antibiotics9120902.

Leny, L., Situmorang, T. N. K., Siagian, R., Hafiz, I., & Iskandar, B. (2023). Ointment formulation of tapak dara (Catharanthus roseus (L.) G. Don) flower ethanol extract and its activity in burn-healing. Borneo Journal of Pharmacy. https://doi.org/10.33084/bjop.v6i2.3155.

Liu, F. C., Lee, H. C., Liao, C. C., Chou, A. H., & Yu, H. P. (2023). Role of NADPH oxidase-derived ROS-mediated IL-6/STAT3 and MAPK/NF-κB signaling pathways in protective effect of corilagin against acetaminophen-induced liver injury in mice. Biology. https://doi.org/10.3390/biology12020334.

Magaki, S., Hojat, S. A., Wei, B., So, A., & Yong, W. H. (2019). An introduction to the performance of immunohistochemistry. In J. M. Walker (Ed.), Methods in Molecular Biology (pp. 289–298). https://doi.org/10.1007/978-1-4939-8935-5_25.

Maier, K., He, Y., Wölfle, U., Esser, P. R., Brummer, T., Schempp, C., Bruckner-Tuderman, L., & Has, C. (2016). UV-B-induced cutaneous inflammation and prospects for antioxidant treatment in Kindler syndrome. Human Molecular Genetics. https://doi.org/10.1093/hmg/ddw350.

Maleki, S. J., Crespo, J. F., & Cabanillas, B. (2019). Anti-inflammatory effects of flavonoids. In Food Chemistry. https://doi.org/10.1016/j.foodchem.2019.125124.

Martinez, R. M., Fattori, V., Saito, P., Pinto, I. C., Rodrigues, C. C. A., Melo, C. P. B., Bussmann, A. J. C., Staurengo-Ferrari, L., Bezerra, J. R., Vignoli, J. A., Baracat, M. M., Georgetti, S. R., Verri Jr., W. A., & Casagrande, R. (2020). The lipoxin receptor/FPR2 agonist BML-111 protects mouse skin against ultraviolet B radiation. Molecules, 25(12), 2953. https://doi.org/10.3390/molecules25122953

Mayangsari, E., Mustika, A., Nurdiana, N., & Samad, N. (2024). Comparison of UVA vs UVB photoaging rat models in short-term exposure. Medical Archives, 78(2), 88. https://doi.org/10.5455/medarh.2024.78.88-91.

Moratilla-Rivera, I., Sánchez, M., Valdés-González, J. A., & Gómez-Serranillos, M. P. (2023). Natural products as modulators of NRF2 signaling pathway in neuroprotection. In International Journal of Molecular Sciences. https://doi.org/10.3390/ijms24043748.

Ngibad, K. (2019). Phytochemical screening of sunflower leaf (Helianthus annuus) and anting-anting (Acalypha indica Linn) plant ethanol extract. Borneo Journal of Pharmacy, 2(1), 24–30. https://doi.org/10.33084/bjop.v2i1.689.

Nisr, R. B., Shah, D. S., Ganley, I. G., & Hundal, H. S. (2019). Proinflammatory NFkB signaling promotes mitochondrial dysfunction in skeletal muscle in response to cellular fuel overloading. Cellular and Molecular Life Sciences. https://doi.org/10.1007/s00018-019-03148-8.

Oliveira, M. M., Ratti, B. A., Daré, R. G., Silva, S. O., Truiti, M. da C. T., Ueda-Nakamura, T., Auzély-Velty, R., & Nakamura, C. V. (2019). Dihydrocaffeic acid prevents UVB-induced oxidative stress leading to the inhibition of apoptosis and MMP-1 expression via p38 signaling pathway. Oxidative Medicine and Cellular Longevity, 2019, 1–14. https://doi.org/10.1155/2019/2419096.

Parihar, S., Sharma, D., Chirania, A., & Telrandhe, U. B. (2022). To review on the pharmacology of the leaf extract of Catharanthus roseus. Asian Journal of Pharmaceutical Research and Development. https://doi.org/10.22270/ajprd.v10i1.1075.

Pérez-Cano, F. J., & Castell, M. (2016). Flavonoids, inflammation and immune system. In Nutrients. https://doi.org/10.3390/nu8100659.

Pham, H. N. T., Sakoff, J. A., Vuong, Q. Van, Bowyer, M. C., & Scarlett, C. J. (2019). Phytochemical, antioxidant, anti-proliferative and antimicrobial properties of Catharanthus roseus root extract, saponin-enriched and aqueous fractions. Molecular Biology Reports, 46(3), 3265–3273. https://doi.org/10.1007/s11033-019-04786-8.

Pham, H. N. T., Vuong, Q. Van, Bowyer, M. C., & Scarlett, C. J. (2020). Phytochemicals derived from Catharanthus roseus and their health benefits. Technologies, 8(4), 80. https://doi.org/10.3390/technologies8040080.

Raghu Nataraj, Jagadish MS, Kavitha Raj Varadaraju, & Bindu J. (2023). Isolation, purification and characterization of vindoline from Catharanthus roseus. International Journal of Science and Research Archive, 8(1), 310–319. https://doi.org/10.30574/ijsra.2023.8.1.0047.

Rieppo, L., Janssen, L., Rahunen, K., Lehenkari, P., Finnilä, M. A. J., & Saarakkala, S. (2019). Histochemical quantification of collagen content in articular cartilage. PLOS ONE, 14(11), e0224839. https://doi.org/10.1371/journal.pone.0224839.

Riquelme-Neira, R., Walker-Vergara, R., Fernández-Blanco, J. A., & Vergara, P. (2023). IL-10 modulates the expression and activation of pattern recognition receptors in mast cells. International Journal of Molecular Sciences. https://doi.org/10.3390/ijms24129875.

Ryeom, G. G. M., Bang, W. J., Kim, Y. B., & Lee, G. E. (2018). Gallotannin improves the photoaged-related proteins by extracellular signal-regulated Kinases/c-Jun N-Terminal kinases signaling pathway in human epidermal keratinocyte cells. Journal of Medicinal Food. https://doi.org/10.1089/jmf.2017.4096.

Sadeghipour, A., & Babaheidarian, P. (2019). Making Formalin-Fixed, Paraffin Embedded Blocks (pp. 253–268). https://doi.org/10.1007/978-1-4939-8935-5_22.

Sarkar, S., & Gaddameedhi, S. (2018). UV-B-induced erythema in human skin: The circadian clock is ticking. In Journal of Investigative Dermatology. https://doi.org/10.1016/j.jid.2017.09.002

Searle, T., Al-Niaimi, F., & Ali, F. R. (2021). 5-Fluorouracil in dermatology: The diverse uses beyond malignant and premalignant skin disease. Dermatologic Surgery, 47(3), e66–e70. https://doi.org/10.1097/DSS.0000000000002879.

Shah, K., Minkis, K., Swary, J. H., & Alam, M. (2022). Photoaging. In Cosmetic Dermatology: Products and Procedures. https://doi.org/10.1002/9781119676881.ch2.

Sharma, M. R., Mitrani, R., & Werth, V. P. (2020). Effect of TNFα blockade on UVB-induced inflammatory cell migration and collagen loss in mice. Journal of Photochemistry and Photobiology B: Biology. https://doi.org/10.1016/j.jphotobiol.2020.112072.

Singh, R., & Pandey, S. S. (2021). Efficacy of topical 5% 5-fluorouracil and 0.05% tretinoin and electrosurgery in the treatment of plane warts: A randomized controlled comparative trial. Nepal Journal of Dermatology, Venereology & Leprology, 19(1), 55–59. https://doi.org/10.3126/njdvl.v19i1.28322.

Slaoui, M., Bauchet, A.-L., & Fiette, L. (2017). Tissue sampling and processing for histopathology evaluation. In J.-C. Gautier (Ed.), Drug Safety Evaluation: Methods and Protocols (2nd ed., Vol. 1641, pp. 101–114). Humana Press. https://doi.org/10.1007/978-1-4939-7172-5_4.

Steyn, P. J., Dzobo, K., Smith, R. I., & Myburgh, K. H. (2019). Interleukin-6 induces myogenic differentiation via JAK2-STAT3 signaling in mouse C2C12 myoblast cell line and primary human myoblasts. International Journal of Molecular Sciences. https://doi.org/10.3390/ijms20215273.

Teuscher, A. C., Statzer, C., Pantasis, S., Bordoli, M. R., & Ewald, C. Y. (2019). Assessing Collagen Deposition During Aging in Mammalian Tissue and in Caenorhabditis elegans (pp. 169–188). https://doi.org/10.1007/978-1-4939-9095-5_13.

Tolambiya, P., & Mathur, S. (2016). A study on potential phytopharmaceuticals assets in Catharanthus roseus L. (Alba). International Journal of Life Sciences Biotechnology and Pharma Research. https://doi.org/10.18178/ijlbpr.5.1.1-6.

Ung, T. T., Nguyen, T. T., Lian, S., Li, S., Xia, Y., Kim, N. H., & Jung, Y. Do. (2019). Nicotine stimulates IL-6 expression by activating the AP-1 and STAT-3 pathways in human endothelial EA.hy926 cells. Journal of Cellular Biochemistry. https://doi.org/10.1002/jcb.27837.

Yan, T., Huang, L., Yan, Y., Zhong, Y., Xie, H., & Wang, X. (2023). MAPK/AP-1 signaling pathway is involved in the protection mechanism of bone marrow mesenchymal stem cells-derived exosomes against ultraviolet-induced photoaging in human dermal fibroblasts. Skin Pharmacology and Physiology. https://doi.org/10.1159/000529551.

Yang, J.-W., Fan, G.-B., Tan, F., Kong, H.-M., Liu, Q., Zou, Y., & Tan, Y.-M. (2023). The role and safety of UVA and UVB in UV-induced skin erythema. Frontiers in Medicine, 10. https://doi.org/10.3389/fmed.2023.1163697.

Yang, Y., Wu, R., Sargsyan, D., Yin, R., Kuo, H.-C., Yang, I., Wang, L., Cheng, D., Wang, C., Li, S., Hudlikar, R., Lu, Y., & Kong, A.-N. (2019). UVB drives different stages of epigenome alterations during progression of skin cancer. Cancer Letters, 449, 20–30. https://doi.org/10.1016/j.canlet.2019.02.010.

Yousif, E., Sherif, R., Abeer, A. E.-R., & Safaa, A. (2021). Vinca (Catharanthus roseus) extracts attenuate alloxan-Induced hyperglycemia and oxidative stress in rats. American Journal of Food Science and Technology, 9(4), 161–172. https://doi.org/10.12691/AJFST-9-4-8.

Yuan, C., Pan, Y., & Ning, Y. (2021). Predictive value of IL-6 combined with NLR in inflammation and cancer. Cancer Investigation. https://doi.org/10.1080/07357907.2020.1858852.

Zhang, J., Wang, X., Vikash, V., Ye, Q., Wu, D., Liu, Y., & Dong, W. (2016). ROS and ROS-mediated cellular signaling. Oxidative Medicine and Cellular Longevity, 2016. https://doi.org/10.1155/2016/4350965.

Zhao, H. C., Xiao, T., & Chen, Y. J. (2021). Ultraviolet induced skin inflammation. In International Journal of Dermatology and Venereology. https://doi.org/10.1097/JD9.0000000000000144.

Refbacks

  • There are currently no refbacks.