大黄酸通过抑制p38 MAPK磷酸化减轻UVB诱导的皮肤光老化损伤

doi:10.3969/j.issn.2097-2806.2024.07.011

摘要/Abstract

摘要：

揭示大黄酸（rhein）对紫外线B（UVB）诱导的皮肤光老化损伤的影响及机制。将大鼠分为6组，分别为正常对照组（NC）、UVB组、低剂量Rhein组（L-Rhein）、中剂量Rhein组（M-Rhein）、高剂量Rhein组（H-Rhein）和高剂量Rhein+p38 MAPK激动剂Anisomycin组（H-Rhein+Anisomycin）。NC组大鼠仅剃毛，不照射，其他组进行UVB照射。大黄酸的给药途径为口服。大鼠共治疗8周。治疗结束后，分别测定各组大鼠的体重、表皮含水量、皮肤组织中氧化应激指标水平，并对皮肤组织进行HE染色和Masson三色染色，计算胶原体积分数（CVF）。通过RT-qPCR检测皮肤组织中TNF-α、IL-1β、IL-6、MMP-1、MMP-3和CollagenⅠmRNA水平。通过Western blotting检测皮肤组织中p-p38 MAPK和p38 MAPK蛋白水平。结果显示，与UVB组比较，L-Rhein组、M-Rhein组和H-Rhein组大鼠皮肤p38 MAPK磷酸化水平降低，表皮含水量升高，皮肤损伤减轻，CVF升高，皮肤MMP-1和MMP-3 mRNA相对表达量降低，CollagenⅠmRNA相对表达量升高，皮肤SOD、CAT和GSH-Px水平升高，MDA水平降低，皮肤TNF-α、IL-1β和IL-6 mRNA相对表达量降低（P<0.05）。Anisomycin减弱了大黄酸的皮肤保护作用（P<0.05）。说明大黄酸通过抑制p38 MAPK磷酸化减轻UVB诱导的皮肤光老化损伤。因此，大黄酸可能是一种防治皮肤光老化的候选天然药物。

关键词: 大黄酸, 紫外线B, 皮肤光老化, p38 MAPK, 抗氧化, 抗炎

Abstract:

The study aimed to reveal the effect and mechanism of rhein on skin photoaging injury induced by ultraviolet B （UVB）. Rats were divided into 6 groups: normal control group （NC）, UVB group, low dose Rhein group （L-Rhein）, medium dose Rhein group （M-Rhein）, high dose Rhein group （H-Rhein） and high dose Rhein+p38 MAPK agonist Anisomycin group （H-Rhein+Anisomycin）. Rats in the NC group were shaved without irradiation, while the other groups were irradiated with UVB. In this study, the administration route of rhein was oral administration. Rats were treated for 8 weeks. After treatment, the body weight, water content of epidermis and the levels of oxidative stress indexes （SOD, CAT, GSH-Px and MDA） in skin tissue were measured, and the skin tissue was stained with HE staining and Masson trichrome staining, and the volume fraction of collagen （CVF） was calculated. The levels of TNF-α, IL-1β, IL-6, MMP-1, MMP-3 and Collagen Ⅰ mRNA in skin tissue were detected by RT-qPCR. The protein levels of p-p38 MAPK and p38 MAPK in skin tissue were detected by Western blotting. The results show that compared with UVB group, the phosphorylation level of p38 MAPK in L-Rhein group, M-Rhein group and H-Rhein group decreases, the water content of epidermis increases, the skin injury is alleviated, CVF increases, the relative expression of MMP-1 and MMP-3 mRNA decreases, the relative expression of Collagen Ⅰ mRNA increases, the level of SOD, CAT and GSH-Px increassd, the level of MDA decreases, and the relative expression of TNF-α, IL-1β and IL-6 mRNA decreases in the skin （P<0.05）. Anisomycin attenuates the skin protective effect of rhein （P<0.05）. This study shows that rhein attenuates UVB-induced skin photoaging injury by inhibiting p38 MAPK phosphorylation. Therefore, Rhein may be a candidate natural drug for the prevention and treatment of skin photoaging.

Key words: rhein, ultraviolet B, skin photoaging, P38 MAPK, antioxidation, anti-inflammation

中图分类号:

TQ658

邵冠儒, 张坤阳. 大黄酸通过抑制p38 MAPK磷酸化减轻UVB诱导的皮肤光老化损伤[J]. 日用化学工业（中英文）, 2024, 54(7): 836-843.

Guanru Shao, Kunyang Zhang. Rhein attenuates UVB-induced skin photoaging injury by inhibiting p38 MAPK phosphorylation[J]. China Surfactant Detergent & Cosmetics, 2024, 54(7): 836-843.

图/表 7

图1

图2

图3

图4

图5

图6

图7

参考文献 27

[1]	Uitto J. The role of elastin and collagen in cutaneous aging: intrinsic aging versus photoexposure[J]. J. Drugs Dermatol., 2008, 7(2 Suppl) : 12-16. pmid: 18404866
[2]	Yang L L, Guo H, Li D, et al. The application of Rheum palmatum L. in the treatment of skin diseases[J]. Journal of Sichuan of Traditional Chinese Medicine, 2008, 26 (5) : 32-33
[3]	Sun H, Luo G, Chen D, et al. A comprehensive and system review for the pharmacological mechanism of action of rhein, an active anthraquinone ingredient[J]. Front Pharmacol, 2016, 7: 247. doi: 10.3389/fphar.2016.00247 pmid: 27582705
[4]	Xu N, Chen Y, Guo D, et al. Rhein promotes the proliferation of keratinocytes by targeting oestrogen receptors for skin ulcer treatment[J]. BMC Complement Med. Ther., 2022, 22 (1) : 209.
[5]	Yin C, Han X, Lu Q, et al. Rhein incorporated silk fibroin hydrogels with antibacterial and anti-inflammatory efficacy to promote healing of bacteria-infected burn wounds[J]. Int. J. Biol. Macromol., 2022, 201: 14-19. doi: 10.1016/j.ijbiomac.2021.12.156 pmid: 34995653
[6]	Whitmarsh A J, Davis R J. Transcription factor AP-1 regulation by mitogen-activated protein kinase signal transduction pathways[J]. J. Mol. Med. (Berl), 1996, 74 (10) : 589-607.
[7]	Kim A L, Labasi J M, Zhu Y, et al. Role of p38 MAPK in UVB-induced inflammatory responses in the skin of SKH-1 hairless mice[J]. J. Invest. Dermatol., 2005, 124 (6) : 1318-1325. doi: 10.1111/j.0022-202X.2005.23747.x pmid: 15955110
[8]	Malterud K E, Farbrot T L, Huse A E, et al. Antioxidant and radical scavenging effects of anthraquinones and anthrones[J]. Pharmacology, 1993, 47(Suppl) 1: 77-85.
[9]	Wang Q W, Su Y, Sheng J T, et al. Anti-influenza A virus activity of rhein through regulating oxidative stress, TLR4, Akt, MAPK, and NF-κB signal pathways[J]. PLoS One, 2018, 13 (1) : e0191793.
[10]	Zhuang S, Zhong J, Bian Y, et al. Rhein ameliorates lipopolysaccharide-induced intestinal barrier injury via modulation of Nrf2 and MAPKs[J]. Life Sci., 2019, 216: 168-175. doi: S0024-3205(18)30769-0 pmid: 30471284
[11]	Li R J, Xu J J, Zhang Z H, et al. Rhein ameliorates transverse aortic constriction-induced cardiac hypertrophy via regulating STAT3 and p38 MAPK signaling pathways[J]. Front. Pharmacol., 2022, 13: 940574.
[12]	Wang X M, Feng L, Ding M H, et al. Percutaneous penetration effects of caryophylli flos volatile oil on rhein in shenhuang gel ointment[J]. Chinese Traditional Patent Medicine, 2019, 41 (2) : 245-249.
[13]	Chen Y, Liu X, Lei X, et al. Premna microphylla Turcz pectin protected UVB-induced skin aging in BALB/c-nu mice via Nrf2 pathway[J]. Int. J. Biol. Macromol., 2022, 215: 12-22. doi: 10.1016/j.ijbiomac.2022.06.076 pmid: 35718142
[14]	Zhang L, Zhang S, Song H, et al. Ingestion of collagen hydrolysates alleviates skin chronological aging in an aged mouse model by increasing collagen synthesis[J]. Food Funct., 2020, 11 (6) : 5573-5580. doi: 10.1039/d0fo00153h pmid: 32520042
[15]	Bae J Y, Choi J S, Choi Y J, et al. (-)Epigallocatechin gallate hampers collagen destruction and collagenase activation in ultraviolet-B-irradiated human dermal fibroblasts: involvement of mitogen-activated protein kinase[J]. Food Chem. Toxicol., 2008, 46 (4) : 1298-1307.
[16]	Hwang E, Park S Y, Lee H J, et al. Gallic acid regulates skin photoaging in UVB-exposed fibroblast and hairless mice[J]. Phytother. Res., 2014, 28 (12) : 1778-1788. doi: 10.1002/ptr.5198 pmid: 25131997
[17]	Fineschi S, Cozzi F, Burger D, et al. Anti-fibroblast antibodies detected by cell-based ELISA in systemic sclerosis enhance the collagenolytic activity and matrix metalloproteinase-1 production in dermal fibroblasts[J]. Rheumatology (Oxford), 2007, 46 (12) : 1779-1785. pmid: 17982166
[18]	Afnan Q, Kaiser P J, Rafiq R A, et al. Glycyrrhizic acid prevents ultraviolet-B-induced photodamage: a role for mitogen-activated protein kinases, nuclear factor kappa B and mitochondrial apoptotic pathway[J]. Exp. Dermatol., 2016, 25 (6) : 440-446. doi: 10.1111/exd.12964 pmid: 26836460
[19]	Hwang E, Lee D G, Park S H, et al. Coriander leaf extract exerts antioxidant activity and protects against UVB-induced photoaging of skin by regulation of procollagen type I and MMP-1 expression[J]. J. Med. Food, 2014, 17 (9) : 985-995. doi: 10.1089/jmf.2013.2999 pmid: 25019675
[20]	Dodd T, Jadhav R, Wiggins L, et al. MMPs 2 and 9 are essential for coronary collateral growth and are prominently regulated by p38 MAPK[J]. J. Mol. Cell. Cardiol., 2011, 51 (6) : 1015-1025. doi: 10.1016/j.yjmcc.2011.08.012 pmid: 21884701
[21]	Gomes L R, Terra L F, Wailemann R A, et al. TGF-β1 modulates the homeostasis between MMPs and MMP inhibitors through p38 MAPK and ERK1/2 in highly invasive breast cancer cells[J]. BMC Cancer, 2012, 12: 26. doi: 10.1186/1471-2407-12-26 pmid: 22260435
[22]	Mohania D, Chandel S, Kumar P, et al. Ultraviolet radiations: skin defense-damage mechanism[J]. Adv. Exp. Med. Biol., 2017, 996: 71-87. doi: 10.1007/978-3-319-56017-5_7 pmid: 29124692
[23]	Peus D, Vasa R A, Beyerle A, et al. UVB activates ERK1/2 and p38 signaling pathways via reactive oxygen species in cultured keratinocytes[J]. J. Invest. Dermatol., 1999, 112 (5) : 751-756. pmid: 10233767
[24]	Wang Z, Zhao G, Zibrila A I, et al. Acetylcholine ameliorated hypoxia-induced oxidative stress and apoptosis in trophoblast cells via p38 MAPK/NF-κB pathway[J]. Mol. Hum. Reprod., 2021, 27 (8) : gaab045.
[25]	Zhang H, Yuan B, Huang H, et al. Gastrodin induced HO-1 and Nrf2 up-regulation to alleviate H₂O₂-induced oxidative stress in mouse liver sinusoidal endothelial cells through p38 MAPK phosphorylation[J]. Braz. J. Med. Biol. Res., 2018, 51 (10) : e7439.
[26]	Ma X, Yan W, He N. Lidocaine attenuates hypoxia/reoxygenation-induced inflammation, apoptosis and ferroptosis in lung epithelial cells by regulating the p38 MAPK pathway[J]. Mol. Med. Rep., 2022, 25 (5) : 150.
[27]	Yong H Y, Koh M S, Moon A. The p38 MAPK inhibitors for the treatment of inflammatory diseases and cancer[J]. Expert Opin. Investig. Drugs, 2009, 18 (12) : 1893-1905.