Topical Centella asiatica cream reduces MMP-1 levels but shows limited effect on TIMP-1 in UVB exposed Wistar rats
Pengaruh Dosis Krim Ekstrak Centella Asiatica Terhadap Kadar Matrix Metalloproteinase-1 dan Tissue Inhibitor Of Metalloproteinase-1
DOI:
https://doi.org/10.22146/inajbcs.v58i1.21815Keywords:
Centella asiatica, MMP-1, TIMP-1,, UVB radiation, topical creamAbstract
UVB-induced photoaging accelerates extracellular matrix (ECM) degradation by increasing MMP-1 and suppressing TIMP-1 expression. Centella asiatica, a traditional medicinal herb with antioxidant and anti-inflammatory properties. However, its effect on the MMP-1/TIMP-1 balance under acute UVB exposure has
not been widely studied. This study aimed to evaluate whether topical C. asiatica extract cream at 5% and 10% concentrations can reduce MMP-1 and increase TIMP-1 in UVB-irradiated Wistar rat. A total of 25 male Wistar rats were randomly assigned to five groups: healthy control, UVB + vehicle, UVB + 5% niacinamide (positive control), UVB + C. asiatica 5%, and UVB + C. asiatica 10%. UVB irradiation (160 mJ/cm²) was administered once daily for five days, with topical application performed 20 minutes before and 4 hours after irradiation. MMP-1 and TIMP-1 levels were measured from skin tissue. UVB exposure significantly increased MMP-1 levels compared to healthy controls (3.100 ± 0.5234 vs. 1.778 ± 0.4081 pg/mL, p < 0.05). The 10% C. asiatica group showed a significant MMP-1 reduction(2.238 ± 0.2705 pg/mL, p < 0.05 vs. UVB + vehicle), comparable to niacinamide. The 5% C. asiatica group showed a non-significant reduction (2.678 ± 0.3148 pg/
mL, p > 0.05). TIMP-1 levels did not differ significantly among groups (p = 0.3432), although the 5% C. asiatica and niacinamide groups showed higher TIMP-1 trends. The 10% Centella group had the lowest TIMP-1 levels among treated animals. We conclude that topical C. asiatica extract, especially at 10%, efficiently reduces UVB-induced increase of MMP-1, while its effects on TIMP-1 are still unclear. These results validate C. asiatica’s promise as a topical anti-photoaging drug, necessitating additional research into the best dosage and ECM regulatory mechanisms.
References
Yan T, Huang L, Yan Y, Zhong Y, Xie H, Wang X. 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 Pharmacol Physiol 2023; 36(2):98-106.
https://doi.org/10.1159/000529551
Rittie L, Fisher GJ. Natural and Sun-Induced Aging of Human Skin. Cold Spring Harb Perspect Med 2015; 5(1):a015370.
https://doi.org/10.1101/cshperspect.a015370
Prakash V, Jaiswal N, Srivastava M. A review on medicinal properties of centella asiatica. Asian Journal of Pharmaceutical and Clinical Research 2017; 10(10):69-74.
https://doi.org/10.22159/ajpcr.2017.v10i10.20760
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; 11:568032.
https://doi.org/10.3389/fphar.2020.568032
Rahmawati YD, Aulanni’am A, Prasetyawan S. Effects of Oral and Topical Application of Centella asiatica Extracts on The UVB-Induced Photoaging of Hairless Rats. The Journal of Pure and Applied Chemistry Research 2019; 8(1):7-14.
https://doi.org/10.21776/ub.jpacr.2019.008.01.430
Purwanti. Pengaruh krim ekstrak daun pegagan (centella asiatica) terhadap inhibisi mmp-1 dan peningkatan kolagen (Studi Eksperimental pada Mencit yang dipapar sinar UVB Akut). Semarang: Unissula; 2024.
Wu F, Bian D, Xia Y, Gong Z, Tan Q, Chen J, et al. Identification of Major Active Ingredients Responsible for Burn Wound Healing of Centella asiatica Herbs. Evid Based Complement Alternat Med 2012; 2012:848093.
https://doi.org/10.1155/2012/848093
Venesia NF, Fachrial E, Lister INE. Effectiveness Test of Centella Asiatica Extract on Improvement of Collagen and Hydration in Female White Rat (Rattus Norwegicus Wistar). American Scientific Research Journal for Engineering Technology, and Sciences 2020; 65(1):98–107.
https://asrjetsjournal.org/American_Scientific_Journal/article/view/5658
Bandopadhyay S, Mandal S, Ghorai M, Jha NK, Kumar M, Radha, et al. Therapeutic properties and pharmacological activities of asiaticoside and madecassoside: A review. J Cell Mol Med 2023; 27(5):593-608.
https://doi.org/10.1111/jcmm.17635
Yokose U, Hachiya A, Sriwiriyanont P, Fujimura T, Visscher MO, Kitzmiller WJ, et al. The endogenous protease inhibitor TIMP-1 mediates protection and recovery from cutaneous photodamage. J Invest Dermatol 2012; 132(12):2800-9.
https://doi.org/10.1038/jid.2012.204
Feng C, Chen X, Yin X, Jiang Y, Zhao C. Matrix Metalloproteinases on Skin Photoaging. J Cosmet Dermatol 2024; 23(12):3847-62.
https://doi.org/10.1111/jocd.16558
Jung H, Lee EH, Lee TH, Cho MH. The Methoxyflavonoid Isosakuranetin Suppresses UV-B-Induced Matrix Metalloproteinase-1 Expression and Collagen Degradation Relevant for Skin Photoaging. Int J Mol Sci 2016; 17(9):1449.
https://doi.org/10.3390/ijms17091449
Karthikeyan R, Kanimozhi G, Prasad NR, Agilan B, Ganesan M, Mohana S, et al. 7-Hydroxycoumarin prevents UVB-induced activation of NF-κB and subsequent overexpression of matrix metalloproteinases and inflammatory markers in human dermal fibroblast cells. J Photochem Photobiol B 2016; 161:170–6.
https://doi.org/10.1016/j.jphotobiol.2016.04.027
Tan SC, Bhattamisra SK, Chellappan DK, Candasamy M. Actions and Therapeutic Potential of Madecassoside and Other Major Constituents of Centella asiatica: A Review. Applied Sciences 2021; 11(18):8475.
https://doi.org/10.3390/app11188475
Mushtaq Z, Imran M, Hussain M, Saeed F, Imran A, Umar M, et al. Asiatic acid: a review on its polypharmacological properties and therapeutic potential against various Maladies. Int J Food Prop 2023; 26(1):1244-63.
https://doi.org/10.1080/10942912.2023.2209702
Porter JF, Shen S, Denhardt DT. Tissue inhibitor of metalloproteinase-1 stimulates proliferation of human cancer cells by inhibiting a metalloproteinase. Br J Cancer 2004; 90(2):463-70.
https://doi.org/10.1038/sj.bjc.6601533
Tiwari S, Saka VP, Singh S, Kumar NGV, Verma D. Pharmaceutical potentials of Centella asiatica (L.) Urb. Medicinal Plants - International Journal of Phytomedicines and Related Industries 2023; 15(2):270-82.
https://doi.org/10.5958/0975-6892.2023.00026.6
Lv J, Sharma A, Zhang T, Wu Y, Ding X. Pharmacological Review on Asiatic Acid and Its Derivatives: A Potential Compound. SLAS Technol 2018; 23(2):111–27.
https://doi.org/10.1177/2472630317751840
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; 11:568032.
https://doi.org/10.3389/fphar.2020.568032
Mustofa A, Nur Sholikah TR, Niari TS, Rahmawati YW. Basal Cell Carcinoma. MAGNA MEDICA Berkala Ilmiah Kedokteran dan Kesehatan 2022; 9(1):62-68.
https://doi.org/10.26714/magnamed.9.1.2022.62-68
Tewari A, Grys K, Kollet J, Sarkany R, Young AR. Upregulation of MMP12 and its activity by UVA1 in human skin: potential implications for photoaging. J Invest Dermatol 2014; 134(10):2598-609.
https://doi.org/10.1038/jid.2014.173
Ryu JY, Na EJ. MMP expression alteration and MMP-1 production control by syringic acid via AP-1 mechanism. Biomedical Dermatology 2018; 2(1):15.
https://doi.org/10.1186/s41702-018-0023-x
Hashim P, Sidek H, Helan MHM, Sabery A, Palanisamy UD, Ilham M. Triterpene composition and bioactivities of Centella asiatica. Molecules 2011; 16(2):1310-22.
https://doi.org/10.3390/molecules16021310
Yuksel Egrilmez M, Kocturk S, Aktan S, Oktay G, Resmi H, Simsek Keskin H, et al. Melatonin Prevents UVB-Induced Skin Photoaging by Inhibiting Oxidative Damage and MMP Expression through JNK/AP-1 Signaling Pathway in Human Dermal Fibroblasts. Life 2022; 12(7):950.
https://doi.org/10.3390/life12070950
Oh JH, Joo YH, Karadeniz F, Ko J, Kong CS. Syringaresinol Inhibits UVA-Induced MMP-1 Expression by Suppression of MAPK/AP-1 Signaling in HaCaT Keratinocytes and Human Dermal Fibroblasts. Int J Mol Sci 2020; 21(11):3981.
https://doi.org/10.3390/ijms21113981
Pedić L, Pondeljak N, Šitum M. Recent information on photoaging mechanisms and the preventive role of topical sunscreen products. Acta Dermatovenerol Alp Pannonica Adriat 2020; 29(4):201-7.
Kim DJ, Iwasaki A, Chien AL, Kang S. UVB-mediated DNA damage induces matrix metalloproteinases to promote photoaging in an AhR- and SP1-dependent manner. JCI Insight 2022; 7(9):e156344.
https://doi.org/10.1172/jci.insight.156344
Myung DB, Han HS, Shin JS, Park JY, Hwang HJ, Kim HJ, et al. Hydrangenol Isolated from the Leaves of Hydrangea serrata Attenuates Wrinkle Formation and Repairs Skin Moisture in UVB-Irradiated Hairless Mice. Nutrients 2019; 11(10):2354.



