Protective Effects of Centella Asiatica Leaf Extract Cream on IL-1α Expression and Sunburn Cells in BALB/c Mice Induced by UVB
Abstract
Background/Aim: UVB radiation can induce DNA damage in keratinocyte cells, leading to increased levels of reactive oxygen species (ROS) triggered by the release of proinflammatory cytokine IL-1α and apoptosis (sunburn) of keratinocyte cells. Centella asiatica (C asiatica) leaf extract contains various secondary metabolites such as flavonoids, alkaloids, tannins and saponins, which have been proven to have antioxidant and anti-inflammatory activities. This study aimed to analyse the effect of C asiatica leaf extract cream on the expression of IL-1α and sunburn cells in acute UVB-induced BALB/c mice.
Methods: Experimental research was designed with a post-test control group of 4 groups: normal control group, negative control, 10 % C asiatica leaf extract cream group (P1) and 20 % C asiatica leaf extract cream group (P2). Each mouse was exposed to UV-B light broadband at a dose of 1 minimal erythema dose (MED) or energy 360 mJ/cm² from day 1 to day 5 for 6 minutes with a distance of 30 cm, while the standard group was not exposed to UVB. In P1 and P2, C asiatica leaf extract cream of 10 % and 20 % was applied daily for 5 days, while the negative control received base cream. On day 6, skin tissue samples were taken and analysis was performed for IL-1α expression using immunohistochemistry (IHC) and sunburn cells using haematoxylin and eosin staining.
Results: The expression of IL-1α in the treatment groups decreased with increasing doses, with P2 having IL-1α expression (43.33 ± 7.60), P1 (48.33 ± 8.33), negative control (69.17 ± 9.17) and standard control (50.00 ± 1.91). The number of sunburn cells also decreased in the P1 (1.08 ± 0.15) and P2 (1.20 ± 0.19) groups compared to the negative control group (1.48 ± 0.17).
Conclusion: The administration of C asiatica leaf extract cream can reduce the expression of the IL-1α gene and the number of sunburn cells in the skin tissue of mice induced by acute UVB radiation.
References
Yang CY, Guo Y, Wu WJ, Man MQ, Tu Y, He L. UVB-induced secretion of IL-1 β promotes melanogenesis by upregulating tyr/trp-1 expression in vitro. Biomed Res Int. 2022;2022. doi: 10.1155/2022/8230646.
Wölfle U, Esser PR, Simon-Haarhaus B, Martin SF, Lademann J, Schempp CM. UVB-induced DNA damage, generation of reactive oxygen species, and inflammation are effectively attenuated by the flavonoid luteolin in vitro and in vivo. Free Radic Biol Med. 2011;50(9):1081-93. doi: 10.1016/j.freeradbiomed.2011.01.027.
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(8). doi:10.3390/ijms22083974.
Sollberger G, Strittmatter GE, Grossi S, Garstkiewicz M, Auf dem Keller U, French LE, et al. Caspase-1 activity is required for UVB-induced apoptosis of human keratinocytes. J Invest Dermatol. 2015 May;135(5):1395-404. doi: 10.1038/jid.2014.5515.
Petit-Frère C, Capulas E, Lyon DA, Norbury CJ, Lowe JE, Clingen PH, et al. Apoptosis and cytokine release induced by ionizing or ultraviolet B radiation in primary and immortalized human keratinocytes. Carcinogenesis. 2000 Jun;21(6):1087-95. PMID: 10836995.
Kulms D, Pöppelmann B, Yarosh D, Luger TA, Krutmann J, Schwarz T. Nuclear and cell membrane effects contribute independently to the induction of apoptosis in human cells exposed to UVB radiation. Proc Natl Acad Sci U S A. 1999 Jul 6;96(14):7974-9. doi: 10.1073/pnas.96.14.7974.
Choi MJ, Zheng HM, Kim JM, Lee KW, Park YH, Lee DH. Protective effects of C asiatica leaf extract on dimethylnitrosamine-induced liver injury in rats. Mol Med Rep. 2016;14(5):4521-48. doi: 10.3892/mmr.2016.5809.
Bowers JM, Hamilton JG, Lobel M, Kanetsky PA, Hay JL. Sun exposure, tanning behaviors, and sunburn: examining activities associated with harmful ultraviolet radiation exposures in college students. J Prim Prev. 2021;42(5):425-40. doi: 10.1007/s10935-021-00638-z.
Pamudji R. [Relationship between education level and workers' knowledge in Palembang regarding the use of sunscreen]. Syifa MEDIKA 2017 Sep;8(1):11-4. doi: 10.32502/sm.v8i1.1354. Indonesian.
García-Gavín J, González-Vilas D, Fernández-Redondo V, Toribio J. Pigmented contact dermatitis due to kojic acid. A paradoxical side effect of a skin lightener. Contact Dermatitis. 2010;62(1):63-4. doi: 10.1111/j.1600-0536.2009.01673.x.
Baliña LM, Graupe K. The Treatment of melasma 20 % azelaic acid versus 4 % hydroquinone Cream. Int J Dermatol. 1991;30(12):893-5. doi: 10.1111/j.1365-4362.1991.tb04362.x.
Sarkar R, Bhalla M, Kanwar AJ. A comparative study of 20 % azelaic acid cream monotherapy versus a sequential therapy in the treatment of melasma in dark-skinned patients. Dermatology. 2002;205(2-3):249-54. doi:10.1159/000065851.
Lin P, Shi H yu, Lu Y ying, Lin J. C asiatica alleviates psoriasis through JAK/STAT3-mediated inflammation: An in vitro and in vivo study. J Ethnopharmacol. 2023;317. doi: 10.1016/j.jep.2023.116746.
Sutardi S. [Bioactive compounds in Pegagan plant and its use for increasing immune system]. J Penelitian Pengembangan Pertanian. 2017;35(3):121-30. doi: 10.21082/jp3.v35n3.2016.p121-130.
Sun B, Wu L, Wu Y, Zhang C, Qin L, Hayashi M, et al. Therapeutic potential of Centella asiatica and its triterpenes: a review. Front Pharmacol. 2020 Sep 4;11:568032. doi: 10.3389/fphar.2020.568032.
Hafiz ZZ, Mohd Amin MA, Johari James RM, Teh LK, Salleh MZ, Adenan MI. Inhibitory effects of raw-extract C asiatica (RECA) on acetylcholinesterase, inflammations, and oxidative stress activities via in vitro and in vivo. Molecules. 2020;25(4). doi: 10.3390/molecules25040892.
An IS, An S, Choe TΒ, Kang SΜ, Lee JH, Park IC, et al. Centella asiatica protects against UVB-induced HaCaT keratinocyte damage through microRNA expression changes. Int J Mol Med. 2012 Dec;30(6):1349-56. doi: 10.3892/ijmm.2012.1157.
Amalina ND, Wahyuni S, Harjito. Cytotoxic effects of the synthesized Citrus aurantium peels extract nanoparticles against MDA-MB-231 breast cancer cells. J Phys Conf Ser. 2021;1918(3). doi: 10.1088/1742-6596/1918/3/032006.
Suzery M, Cahyono B, Amalina ND. Antiproliferative and apoptosis effect of hyptolide from Hyptis pectinata (L.) Poit on human breast cancer cells. J Appl Pharm Sci. 2020;10(02):1-6. doi: 10.7324/JAPS.2020.102001.
Wise LM, Stuart GS, Real NC, Fleming SB, Mercer AA. VEGF receptor-2 activation mediated by VEGF-E limits scar tissue formation following cutaneous injury. Adv Wound Care (New Rochelle). 2018;7(8):283-97. doi: 10.1089/wound.2016.0721.
Sayama K, Yuki K, Sugata K, Fukagawa S, Yamamoto T, Ikeda S, et al. Carbon dioxide inhibits UVB-induced inflammatory response by activating the proton-sensing receptor, GPR65, in human keratinocytes. Sci Rep. 2021 Jan 11;11(1):379. doi: 10.1038/s41598-020-79519-0.
Subedi L, Lee TH, Wahedi HM, Baek SH, Kim SY. Resveratrol-enriched rice attenuates UVB-ROS-induced skin aging via downregulation of inflammatory cascades. Oxid Med Cell Longev. 2017;2017. doi: 10.1155/2017/8379539.
Wu PY, Lyu JL, Liu YJ, Chien TY, Hsu HC, Wen KC, et al. Fisetin regulates Nrf2 expression and the inflammation-related signaling pathway to prevent UVB-induced skin damage in hairless mice. Int J Mol Sci. 2017 Oct 10;18(10):2118. doi: 10.3390/ijms18102118.
D’Orazio J, Jarrett S, Amaro-Ortiz A, Scott T. UV radiation and the skin. Int J Mol Sci. 2013;14(6):12222-48. doi: 10.3390/ijms140612222.
Panche AN, Diwan AD, Chandra SR. Flavonoids: An overview. J Nutr Sci. 2016;5. doi: 10.1017/jns.2016.41.
Veeramuthu D, Raja WRT, Al-Dhabi NA, Savarimuthu I. Flavonoids: anticancer properties. In: Justino GC, ed. Flavonoids - from biosynthesis to human health. London: InTech 2017. doi: 10.5772/68095.
Zaidun NH, Thent ZC, Latiff AA. Combating oxidative stress disorders with citrus flavonoid: Naringenin. Life Sci. 2018;208(June):111-22. doi: 10.1016/j.lfs.2018.07.017.
Banjarnahor SDS, Artanti N. Antioxidant properties of flavonoids. Med J Indonesia. 2014;23(4):239-44. doi: 10.13181/mji.v23i4.1015.
Lancellotti P, Oury C. IL-10 targets myofibroblasts and dampens cardiac fibrosis. J Public Health Emerg. 2017;1:83. doi: 10.21037/jphe.2017.10.03.
Jung M, Ma Y, Iyer RP, DeLeon-Pennell KY, Yabluchanskiy A, Garrett MR, et al. IL-10 improves cardiac remodeling after myocardial infarction by stimulating M2 macrophage polarization and fibroblast activation. Basic Res Cardiol. 2017 May;112(3):33. doi: 10.1007/s00395-017-0622-5.
Wang CQF, Akalu YT, Suarez-Farinas M, Gonzalez J, Mitsui H, Lowes MA, et al. IL-17 and TNF synergistically modulate cytokine expression while suppressing melanogenesis: potential relevance to psoriasis. J Invest Dermatol. 2013 Dec;133(12):2741-52. doi: 10.1038/jid.2013.237.
Eichner A, Hänsel M, Domino KB, Hübler M. Mechanisms regulating melanogenesis. Complications and Mishaps in Anesthesia: Cases - Analysis - Preventive Strategies. 2014;9783642454(1):233-42. doi: 10.1007/978-3-642-45407-3_24.
Kim HY, Sah SK, Choi SS, Kim TY. Inhibitory effects of extracellular superoxide dismutase on ultraviolet B-induced melanogenesis in murine skin and melanocytes. Life Sci. 2018;210:201-8. doi: 10.1016/j.lfs.2018.08.056.
An IS, An S, Choe TΒ, Kang SΜ, Lee JH, Park IC, et al. Centella asiatica protects against UVB-induced HaCaT keratinocyte damage through microRNA expression changes. Int J Mol Med. 2012 Dec;30(6):1349-56. doi: 10.3892/ijmm.2012.1157.
Moolsap F, Tanasawet S, Tantisira M, Hutamekalin P, Tipmanee V, Sukketsiri W. Standardized extract of C asiatica ECa 233 inhibits lipopolysaccharide-induced cytokine release in skin keratinocytes by suppressing ERK1/2 pathways. Asian Pac J Trop Biomed. 2020;10(6):273-80. doi: 10.4103/2221-1691.283941.
Gao S, Guo K, Chen Y, Zhao J, Jing R, Wang L, et al. Keratinocyte growth factor 2 ameliorates UVB-induced skin damage via activating the AhR/Nrf2 signaling pathway. Front Pharmacol. 2021 Jun 7;12:655281. doi: 10.3389/fphar.2021.655281.
Jatayu D, Nursyam H, Maizar Suryanto, Hertika A. Antioxidant effect of C asiatica ethanolic extract to superoxide dismutase (SOD) level on Cyprinus carpio liver. Res J Life Sci. 2018;5(3):163-72. doi: 10.21776/ub.rjls.2018.005.03.4.
Kim SS, Kim MJ, Choi YH, Kim BK, Kim KS, Park KJ, et al. Down-regulation of tyrosinase, TRP-1, TRP-2 and MITF expressions by citrus press-cakes in murine B16 F10 melanoma. Asian Pac J Trop Biomed. 2013 Aug;3(8):617-22; discussion 621-2. doi: 10.1016/S2221-1691(13)60125-2.
Holman DM, Ding H, Guy GP, Watson M, Hartman AM, Perna FM. Prevalence of sun protection use and sunburn and association of demographic and behaviorial characteristics with sunburn among US adults. JAMA Dermatol. 2018;154(5):561-8. doi: 10.1001/jamadermatol.2018.0028.
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).