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Current Molecular Medicine

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ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

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Research Article

Tanshinone Alleviates UVA-induced Melanogenesis in Melanocytes via the Nrf2-regulated Antioxidant Defense Signaling Pathway

Author(s): Jiaoquan Chen, Zonghao Yin, Nanji Yu, Shanshan Ou, Xue Wang, Huaping Li and Huilan Zhu*

Volume 24, Issue 12, 2024

Published on: 30 October, 2023

Page: [1529 - 1539] Pages: 11

DOI: 10.2174/0115665240263196230920161019

Price: $65

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Abstract

Background: As a complex of natural plant compounds, tanshinone is renowned for its remarkable antioxidant properties. However, the potential impact of tanshinone on melanocyte pigmentation regulation has yet to be elucidated. This study aimed to explore the protective effects of tanshinone I (T-I) and dihydrotanshinone (DHT) on melanogenesis by modulating nuclear factor E2-related factor 2 (Nrf2) signaling and antioxidant defenses in human epidermal melanocyte (HEM) cells.

Methods: HEM cells and Nrf2 knockdown HEM cells were subjected to ultraviolet A (UVA) and treated with T-I and/or DHT. Then, the anti-melanogenic properties of T-I and DHT were examined by assessing tyrosinase activity, melanogenesis-related proteins, and melanin content in UVA-irradiated HEM cells. Furthermore, the antioxidant activities of T-I and DHT were evaluated by assessing oxidant formation and modulation of Nrf2-related antioxidant defenses, including reactive oxygen species (ROS), glutathione (GSH) content, and the activity and expression of antioxidant enzymes, such as catalase (CAT), heme oxygenase-1 (HO-1), and superoxide dismutase (SOD).

Results: Our findings revealed that T-I and DHT diminished melanogenesis in UVAirradiated HEM cells, activated Nrf2-antioxidant response element signaling, and enhanced antioxidant defenses in the irradiated cells. Furthermore, Nrf2 knockdown by shRNA abolished the anti-melanogenesis effects of T-I and DHT on HEM cells against oxidative damage.

Conclusion: These results suggest that T-I and DHT inhibit UVA-induced melanogenesis in HEM cells, possibly through redox mechanisms involving Nrf2 signaling activation and increased antioxidant defenses. This indicates that T-I and DHT have potential as whitening agents in cosmetics and medical treatments for hyperpigmentation disorders.

Keywords: UVA, melanogenesis, tanshinone I, dihydrotanshinone, Nrf2, antioxidant defense mechanism.

« Previous Next »
[1]
D’Mello S, Finlay G, Baguley B, Askarian-Amiri M. Signaling pathways in melanogenesis. Int J Mol Sci 2016; 17(7): 1144.
[http://dx.doi.org/10.3390/ijms17071144] [PMID: 27428965]
[2]
Rachmin I, Ostrowski SM, Weng QY, Fisher DE. Topical treatment strategies to manipulate human skin pigmentation. Adv Drug Deliv Rev 2020; 153: 65-71.
[http://dx.doi.org/10.1016/j.addr.2020.02.002] [PMID: 32092380]
[3]
Nguyen NT, Fisher DE. MITF and UV responses in skin: From pigmentation to addiction. Pigment Cell Melanoma Res 2019; 32(2): 224-36.
[http://dx.doi.org/10.1111/pcmr.12726] [PMID: 30019545]
[4]
Pillaiyar T, Manickam M, Jung SH. Recent development of signaling pathways inhibitors of melanogenesis. Cell Signal 2017; 40: 99-115.
[http://dx.doi.org/10.1016/j.cellsig.2017.09.004] [PMID: 28911859]
[5]
Shain AH, Bastian BC. From melanocytes to melanomas. Nat Rev Cancer 2016; 16(6): 345-58.
[http://dx.doi.org/10.1038/nrc.2016.37] [PMID: 27125352]
[6]
Panich U, Kongtaphan K, Onkoksoong T, et al. Modulation of antioxidant defense by Alpinia galanga and Curcuma aromatica extracts correlates with their inhibition of UVA-induced melanogenesis. Cell Biol Toxicol 2010; 26(2): 103-16.
[http://dx.doi.org/10.1007/s10565-009-9121-2] [PMID: 19288216]
[7]
Panich U, Pluemsamran T. Protective effect of AVS073, a polyherbal formula, against UVA-induced melanogenesis through a redox mechanism involving glutathione-related antioxidant defense. BMC Complement Altern Med 2013; 13: 159.
[8]
Kowalska J, Banach K, Beberok A, Rok J, Rzepka Z, Wrześniok D. The biochemical and molecular analysis of changes in melanogenesis induced by uva-activated fluoroquinolones—in vitro study on human normal melanocytes. Cells 2021; 10(11): 2900.
[http://dx.doi.org/10.3390/cells10112900] [PMID: 34831123]
[9]
Hseu YC, Chen XZ, Vudhya Gowrisankar Y, Yen HR, Chuang JY, Yang HL. The skin-whitening effects of ectoine via the suppression of α-msh-stimulated melanogenesis and the activation of antioxidant Nrf2 pathways in UVA-irradiated keratinocytes. Antioxidants 2020; 9(1): 63.
[http://dx.doi.org/10.3390/antiox9010063] [PMID: 31936771]
[10]
Forrester SJ, Kikuchi DS, Hernandes MS, Xu Q, Griendling KK. Reactive oxygen species in metabolic and inflammatory signaling. Circ Res 2018; 122(6): 877-902.
[http://dx.doi.org/10.1161/CIRCRESAHA.117.311401] [PMID: 29700084]
[11]
Wang M, Charareh P, Lei X, Zhong JL. Autophagy: Multiple mechanisms to protect skin from ultraviolet radiation-driven photoaging. Oxid Med Cell Longev 2019; 2019: 1-14.
[http://dx.doi.org/10.1155/2019/8135985] [PMID: 31915514]
[12]
de Jager TL, Cockrell AE, Du Plessis SS. Ultraviolet light induced generation of reactive oxygen species. Adv Exp Med Biol 2017; 996: 15-23.
[http://dx.doi.org/10.1007/978-3-319-56017-5_2] [PMID: 29124687]
[13]
Pourzand C, Albieri-Borges A, Raczek NN. Shedding a new light on skin aging, iron- and redox-homeostasis and emerging natural antioxidants. Antioxidants 2022; 11(3): 471.
[http://dx.doi.org/10.3390/antiox11030471] [PMID: 35326121]
[14]
Pugliese PT. The skin’s antioxidant systems. Dermatol Nurs 1998; 10(6): 401-16.
[PMID: 10670316]
[15]
He Li, Li Tang, Li Xiong. Natural components in sunscreens: Topical formulations with sun protection factor (SPF). Biomed Pharmacother 2021; 134111161.
[http://dx.doi.org/10.1016/j.biopha.2020.111161] [PMID: 33360043]
[16]
Oresajo C, Pillai S, Manco M, Yatskayer M, McDaniel D. Antioxidants and the skin: Understanding formulation and efficacy. Dermatol Ther 2012; 25(3): 252-9.
[http://dx.doi.org/10.1111/j.1529-8019.2012.01505.x] [PMID: 22913443]
[17]
Pisoschi AM, Pop A. The role of antioxidants in the chemistry of oxidative stress: A review. Eur J Med Chem 2015; 97: 55-74.
[http://dx.doi.org/10.1016/j.ejmech.2015.04.040] [PMID: 25942353]
[18]
Babbush K, Babbush R, Khachemoune A. The therapeutic use of antioxidants for melasma. J Drugs Dermatol 2020; 19(8): 788-92.
[http://dx.doi.org/10.36849/JDD.2020.5079] [PMID: 32845595]
[19]
Flieger J, Flieger W, Baj J, Maciejewski R. Antioxidants: Classification, natural sources, activity/capacity measurements, and usefulness for the synthesis of nanoparticles. Materials (Basel) 2021; 14(15): 4135.
[http://dx.doi.org/10.3390/ma14154135] [PMID: 34361329]
[20]
Kim J, Kim K, Yu B. Optimization of antioxidant and skin-whitening compounds extraction condition from tenebrio molitor Larvae (Mealworm). Molecules 2018; 23(9): 2340.
[http://dx.doi.org/10.3390/molecules23092340] [PMID: 30216986]
[21]
Mendonça JS, Guimarães RCA, Zorgetto-Pinheiro VA, et al. Natural antioxidant evaluation: A review of detection methods. Molecules 2022; 27(11): 3563.
[http://dx.doi.org/10.3390/molecules27113563] [PMID: 35684500]
[22]
Boo YC. Natural Nrf2 modulators for skin protection. Antioxidants 2020; 9(9): 812.
[http://dx.doi.org/10.3390/antiox9090812] [PMID: 32882952]
[23]
Chaiprasongsuk A, Panich U. Role of phytochemicals in skin photoprotection via regulation of Nrf2. Front Pharmacol 2022; 13823881.
[http://dx.doi.org/10.3389/fphar.2022.823881] [PMID: 35645796]
[24]
Edamitsu T, Taguchi K, Okuyama R, Yamamoto M. AHR and NRF2 in skin homeostasis and atopic dermatitis. Antioxidants 2022; 11(2): 227.
[http://dx.doi.org/10.3390/antiox11020227] [PMID: 35204110]
[25]
Ikehata H, Yamamoto M. Roles of the KEAP1-NRF2 system in mammalian skin exposed to UV radiation. Toxicol Appl Pharmacol 2018; 360: 69-77.
[http://dx.doi.org/10.1016/j.taap.2018.09.038] [PMID: 30268578]
[26]
Chaiprasongsuk A, Onkoksoong T, Pluemsamran T, Limsaengurai S, Panich U. Photoprotection by dietary phenolics against melanogenesis induced by UVA through Nrf2-dependent antioxidant responses. Redox Biol 2016; 8: 79-90.
[http://dx.doi.org/10.1016/j.redox.2015.12.006] [PMID: 26765101]
[27]
Gęgotek A, Skrzydlewska E. The role of transcription factor Nrf2 in skin cells metabolism. Arch Dermatol Res 2015; 307(5): 385-96.
[http://dx.doi.org/10.1007/s00403-015-1554-2] [PMID: 25708189]
[28]
Li Z, Zou J, Cao D, Ma X. Pharmacological basis of tanshinone and new insights into tanshinone as a multitarget natural product for multifaceted diseases. Biomed Pharmacother 2020; 130110599.
[http://dx.doi.org/10.1016/j.biopha.2020.110599] [PMID: 33236719]
[29]
Wang X, Yang Y, Liu X, Gao X. Pharmacological properties of tanshinones, the natural products from Salvia miltiorrhiza. Adv Pharmacol 2020; 87: 43-70.
[http://dx.doi.org/10.1016/bs.apha.2019.10.001] [PMID: 32089238]
[30]
Li Z, Xu S, Liu P. Salvia miltiorrhizaBurge (Danshen): a golden herbal medicine in cardiovascular therapeutics. Acta Pharmacol Sin 2018; 39(5): 802-24.
[http://dx.doi.org/10.1038/aps.2017.193] [PMID: 29698387]
[31]
Wu M, Yang F, Huang D, et al. Tanshinone I attenuates fibrosis in fibrotic kidneys through down-regulation of inhibin beta-A. BMC Complement Med Ther 2022; 22(1): 110.
[32]
Xu L, Zhang Y, Ji N, et al. Tanshinone IIA regulates the TGF β1/Smad signaling pathway to ameliorate non alcoholic steatohepatitis related fibrosis. Exp Ther Med 2022; 24(1): 486.
[http://dx.doi.org/10.3892/etm.2022.11413] [PMID: 35761808]
[33]
Zhang P, Zhang Q, Liu X, et al. Tanshinone protects against spinal cord ischemia-reperfusion injury by inhibiting JNK Activity. Comput Intell Neurosci 2022; 2022: 1-6.
[http://dx.doi.org/10.1155/2022/7619797] [PMID: 35602615]
[34]
Li Y, Wu H, Wang Z, Tang H, Yang L. Tanshinone IIA, a melanogenic ingredient basis of Salvia miltiorrhiza Bunge. Zhonghua Pifuke Yixue Zazhi 2021; 39(1): 33-40.
[http://dx.doi.org/10.4103/ds.ds_1_21]
[35]
Zhong H, An X, Li Y, et al. Sodium tanshinone IIA silate increases melanin synthesis by activating the MAPK and PKA pathways and protects melanocytes from H 2 O 2 -induced oxidative stress. RSC Advances 2019; 9(33): 18747-57.
[http://dx.doi.org/10.1039/C8RA09786K] [PMID: 35516905]
[36]
Tao S, Justiniano R, Zhang DD, Wondrak GT. The Nrf2-inducers tanshinone I and dihydrotanshinone protect human skin cells and reconstructed human skin against solar simulated UV. Redox Biol 2013; 1(1): 532-41.
[http://dx.doi.org/10.1016/j.redox.2013.10.004] [PMID: 24273736]
[37]
Liang B, Peng L, Li R, et al. Lycium barbarum polysaccharide protects HSF cells against ultraviolet-induced damage through the activation of Nrf2. Cell Mol Biol Lett 2018; 23(1): 18.
[http://dx.doi.org/10.1186/s11658-018-0084-2] [PMID: 29743894]
[38]
Dunaway S, Odin R, Zhou L, Ji L, Zhang Y, Kadekaro AL. Natural antioxidants: Multiple mechanisms to protect skin from solar radiation. Front Pharmacol 2018; 9: 392.
[http://dx.doi.org/10.3389/fphar.2018.00392] [PMID: 29740318]
[39]
Lee CH, Wu SB, Hong CH, Yu HS, Wei YH. Molecular mechanisms of UV-induced apoptosis and its effects on skin residential cells: The implication in UV-Based Phototherapy. Int J Mol Sci 2013; 14(3): 6414-35.
[http://dx.doi.org/10.3390/ijms14036414] [PMID: 23519108]
[40]
Salama SA, Arab HH, Omar HA, et al. L-carnitine mitigates UVA-induced skin tissue injury in rats through downregulation of oxidative stress, p38/c-Fos signaling, and the proinflammatory cytokines. Chem Biol Interact 2018; 285: 40-7.
[http://dx.doi.org/10.1016/j.cbi.2018.02.034] [PMID: 29499191]
[41]
Tsuchida K, Sakiyama N, Ogura Y, Kobayashi M. Skin lightness affects ultraviolet A‐induced oxidative stress: Evaluation using ultraweak photon emission measurement. Exp Dermatol 2023; 32(2): 146-53.
[http://dx.doi.org/10.1111/exd.14690] [PMID: 36256509]
[42]
Kiyoi T, Liu S, Takemasa E, Hato N, Mogi M. Intermittent environmental exposure to hydrogen prevents skin photoaging through reduction of oxidative stress. Geriatr Gerontol Int 2023; 23(4): 304-12.
[http://dx.doi.org/10.1111/ggi.14562] [PMID: 36807963]
[43]
Park S, Choi E, Kim S, et al. Oxidative stress-protective and anti-melanogenic effects of loliolide and ethanol extract from fresh water green algae, Prasiola japonica. Int J Mol Sci 2018; 19(9): 2825.
[http://dx.doi.org/10.3390/ijms19092825] [PMID: 30231594]
[44]
Alekhya Sita GJ, Gowthami M, Srikanth G, et al. Protective role of luteolin against bisphenol A induced renal toxicity through suppressing oxidative stress, inflammation, and upregulating Nrf2/ARE/ HO 1 pathway. IUBMB Life 2019; 71(7): iub.2066.
[http://dx.doi.org/10.1002/iub.2066] [PMID: 31091348]
[45]
Li H, Zhang Q, Li W, et al. Role of Nrf2 in the antioxidation and oxidative stress induced developmental toxicity of honokiol in zebrafish. Toxicol Appl Pharmacol 2019; 373: 48-61.
[http://dx.doi.org/10.1016/j.taap.2019.04.016] [PMID: 31022495]
[46]
Ma Q. Role of nrf2 in oxidative stress and toxicity. Annu Rev Pharmacol Toxicol 2013; 53(1): 401-26.
[http://dx.doi.org/10.1146/annurev-pharmtox-011112-140320] [PMID: 23294312]
[47]
Ullah S, Park C, Ikram M, et al. Tyrosinase inhibition and anti-melanin generation effect of cinnamamide analogues. Bioorg Chem 2019; 87: 43-55.
[http://dx.doi.org/10.1016/j.bioorg.2019.03.001] [PMID: 30856375]
[48]
Hu ZM, Zhou Q, Lei TC, Ding SF, Xu SZ. Effects of hydroquinone and its glucoside derivatives on melanogenesis and antioxidation: Biosafety as skin whitening agents. J Dermatol Sci 2009; 55(3): 179-84.
[http://dx.doi.org/10.1016/j.jdermsci.2009.06.003] [PMID: 19574027]
[49]
Panich U. Inhibition of UVA-mediated melanogenesis by ascorbic acid through modulation of antioxidant defense and nitric oxide system. Arch Pharm Res 2011; 34(5): 811-20.
[50]
Liu C, Vojnovic D, Kochevar IE, Jurkunas UV. UV-A irradiation activates Nrf2-regulated antioxidant defense and induces p53/caspase3-dependent apoptosis in corneal endothelial cells. Invest Ophthalmol Vis Sci 2016; 57(4): 2319-27.
[http://dx.doi.org/10.1167/iovs.16-19097] [PMID: 27127932]
[51]
Durchdewald M, Beyer TA, Johnson DA, Johnson JA, Werner S, auf dem Keller U. Electrophilic chemicals but not UV irradiation or reactive oxygen species activate Nrf2 in keratinocytes in vitro and in vivo. J Invest Dermatol 2007; 127(3): 646-53.
[http://dx.doi.org/10.1038/sj.jid.5700585] [PMID: 17008872]
[52]
Chen WJ, Wu C, Xu Z, Kuse Y, Hara H, Duh EJ. Nrf2 protects photoreceptor cells from photo-oxidative stress induced by blue light. Exp Eye Res 2017; 154: 151-8.
[http://dx.doi.org/10.1016/j.exer.2016.12.001] [PMID: 27923559]
[53]
Park DJ, Sekhon SS, Yoon J, Kim YH, Min J. Color reduction of melanin by lysosomal and peroxisomal enzymes isolated from mammalian cells. Mol Cell Biochem 2016; 413(1-2): 119-25.
[http://dx.doi.org/10.1007/s11010-015-2645-2] [PMID: 26738491]
[54]
Kasraee B, Nikolic DS, Salomon D, et al. Ebselen is a new skin depigmenting agent that inhibits melanin biosynthesis and melanosomal transfer. Exp Dermatol 2012; 21(1): 19-24.
[http://dx.doi.org/10.1111/j.1600-0625.2011.01394.x] [PMID: 22082249]
[55]
Onkoksoong T, Jeayeng S, Poungvarin N, et al. Thai herbal antipyretic 22 formula (APF22) inhibits UVA-mediated melanogenesis through activation of Nrf2-regulated antioxidant defense. Phytother Res 2018; 32(8): 1546-54.
[http://dx.doi.org/10.1002/ptr.6083] [PMID: 29672960]
[56]
Sharath Babu GR, Anand T, Ilaiyaraja N, Khanum F, Gopalan N. Pelargonidin modulates Keap1/Nrf2 pathway gene expression and ameliorates citrinin-induced oxidative stress in HepG2 cells. Front Pharmacol 2017; 8: 868.
[http://dx.doi.org/10.3389/fphar.2017.00868] [PMID: 29230174]
[57]
Dai C, Liu Y, Dong Z. Tanshinone I alleviates motor and cognitive impairments via suppressing oxidative stress in the neonatal rats after hypoxic-ischemic brain damage. Mol Brain 2017; 10(1): 52.
[http://dx.doi.org/10.1186/s13041-017-0332-9] [PMID: 29137683]
[58]
Cuadrado A, Rojo AI, Wells G, et al. Therapeutic targeting of the NRF2 and KEAP1 partnership in chronic diseases. Nat Rev Drug Discov 2019; 18(4): 295-317.
[http://dx.doi.org/10.1038/s41573-018-0008-x] [PMID: 30610225]

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