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Apigenin protects melanocytes and improve tyrosinase activity in a hydroquinone induced vitiligo mouse model targeting P38 MAP kinase signaling: histopathology and immunohistochemistry analysis

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Abstract

Apigenin (APG) is a plant-based flavonoid that possesses antioxidants, anti-inflammatory, and modulates P38 MAPK as well as tyrosinase. Hydroquinone (HQ), a phenolic compound was used to induce vitiligo in C57BL/6 mice. The present study was performed to check the therapeutic potential of apigenin in HQ-induced vitiligo via targeting P38 MAPK pathway. In the present study, 41 C57BL/6 mice were divided into six groups containing seven animals per group except normal group. (I) normal group, (II) HQ group, (III) to (IV) APG with (1%, 2.5%, 5%), and (VI) tacrolimus (TAC) group. Topical application of HQ was performed from day 1 to day 20 to, (II), (III) to (IV) APG with (1%, 2.5%, 5%), (VI) tacrolimus (TAC) group, and then APG; tacrolimus (TAC) was applied from day 21 to day 60 after removing the hair. In the case of (I) normal group and (II) HQ group, we smeared them with water for 60 days and HQ for 20 days in their individual group. On day 61 after anesthesia, a part of the target skin was peeled and blood serum was taken to check the level of malondialdehyde, cholinesterase, catalase, tyrosinase, pro-inflammatory cytokines, and expression of P38 MAPK, histology of melanin containing hair follicles and depigmentation evaluation. Applying HQ topically had a noticeable impact on depigmentation, inflammatory indicators, oxidative stress, and lowered tyrosinase activity. Further HQ reduced melanin containing hair follicles and increased expression of P38 MAPK was confirmed by histopathology and immunohistochemistry. Furthermore, application of APG and TAC after day 21 to 60 significantly reduced depigmentation, inflammatory markers, oxidative stress, and increased tyrosinase. Furthermore, APG increased melanin containing hair follicles and decreased expression of non-phosphorylated P38 MAPK, as confirmed by histopathology and immunohistochemistry. Our finding demonstrated that APG significantly prevented HQ-induced vitiligo by acting as an anti-inflammatory, increasing tyrosine, and reducing the expression of non-phosphorylated P38 MAPK.

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References

  • Alhawamdeh E, Bulatova NR, Al Motassem FY, AlAbbadi MA, Omer EA (2023) A cross-sectional study of the catalase genetic polymorphism (-262 cytosine/thymine) and blood catalase activity among Jordanian vitiligo patients. Jordan J Pharm Sci 330–344

  • Birbeck MS, Breathnach AS, Everall JD (1961) An electron microscope study of basal melanocytes and high-level clear cells (Langerhans cells) in vitiligo. J Investig Dermatol 37(1):51–64

    Article  Google Scholar 

  • Chang W-L, Ko C-H (2023) The role of oxidative stress in vitiligo: an update on its pathogenesis and therapeutic implications. Cells 12(6):936

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • García BEC, Avila EEEI, Armijos LDCO, Martínez LCL, Quizhpi TCB, Ochoa GFT, ortiz Mora EA (2023) Descriptive overview of vitiligo. EPRA Int J Multidiscip Res (IJMR) 9(6):42-47

  • Gomariz R, Juarranz Y, Abad C, Arranz A, Leceta J, Martinez C (2006) VIP–PACAPsystem in immunity: new insights for multitarget therapy. Ann N Y Acad Sci 1070(1):51-7

  • Han H, Hyun C (2023) Acenocoumarol, an anticoagulant drug, prevents melanogenesis in B16F10 Melanoma Cells. Pharmaceuticals 16(4):604

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Harris JE (2017) Chemical-induced vitiligo. Dermatol Clin 35(2):151–161

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • He S, Xu J, Wu J (2022) The promising role of chemokines in vitiligo: from oxidative stress to the autoimmune response. Oxid Med Cell Longev 2022

  • Huo SX, Liu XM, Ge CH, Gao L, Peng XM, Zhao PP, Yan M (2014) The effects of galangin on a mouse model of vitiligo induced by hydroquinone. Phytother Res 28(10):1533–1538

    Article  PubMed  CAS  Google Scholar 

  • Huo SX, Wang Q, Liu XM, Ge CH, Gao L, Peng XM, Yan M (2017) The effect of butin on the vitiligo mouse model induced by hydroquinone. Phytother Res 31(5):740–746

    Article  PubMed  CAS  Google Scholar 

  • Karagün E, Baysak S (2020) Levels of TNF-α, IL-6, IL-17, IL-37 cytokines in patients with active vitiligo. Aging Male 23(5):1487–1492

    Article  PubMed  Google Scholar 

  • Kaushal J, Mehandia S, Singh G, Raina A, Arya SK (2018) Catalase enzyme: application in bioremediation and food industry. Biocatal Agric Biotechnol 16:192–199

    Article  Google Scholar 

  • Kumari S, Thng STG, Verma NK, Gautam HK (2018) Melanogenesis inhibitors. Acta Derm-Venereol 98(10):924–931

    Article  PubMed  CAS  Google Scholar 

  • Lin M, Lu S-S, Wang A-X, Qi X-Y, Zhao D, Wang Z-H, Man M-Q, Tu C-X (2011) Apigenin attenuates dopamine-induced apoptosis in melanocytes via oxidative stress-related p38, c-Jun NH2-terminal kinase and Akt signaling. J Dermatol Sci 63(1):10–16

    Article  PubMed  CAS  Google Scholar 

  • Luo L, Zhu J, Guo Y, Li C (2023) Mitophagy and immune infiltration in vitiligo: evidence from bioinformatics analysis. Front Immunol 14:1164124

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Papa V, Li Pomi F, Borgia F, Genovese S, Pioggia G, Gangemi S (2023) “Mens Sana in Cute Sana”—a state of the art of mutual etiopathogenetic influence and relevant pathophysiological pathways between skin and mental disorders: an integrated approach to contemporary psychopathological scenarios. Cells 12(14):1828

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Pendlebury GA, Oro P, Ludlow K, Merideth D, Haynes W, Shrivastava V, Ludlow KS (2023) Relevant dermatoses among US military service members: an operational review of management strategies and telemedicine utilization. Cureus 15(1)

  • Rahimi H, Mirnezami M, Yazdabadi A, Hajihashemi A (2023) Evaluation of systemic oxidative stress in patients with melasma. J Cosmet Dermatol

  • Sareen R, Kumar S, Gupta GD (2011) Meloxicam carbopol-based gels: characterization and evaluation. Curr Drug Deliv 8(4):407–415

    Article  PubMed  CAS  Google Scholar 

  • Satooka H, Kubo I (2011) Effects of thymol on mushroom tyrosinase-catalyzed melanin formation. J Agric Food Chem 59(16):8908–8914

    Article  PubMed  CAS  Google Scholar 

  • Song X, Xu A, Pan W, Wallin B, Kivlin R, Lu S, Cao C, Bi Z, Wan Y (2008) Minocycline protects melanocytes against H2O2-inducedcell death via JNK and p38 MAPK pathways. Int J Mol Med 22(1):9–16

    PubMed  Google Scholar 

  • Van Herck H, Baumans V, Brandt C, Boere H, Hesp A, Van Lith H, Schurink M, Beynen A (2001) Blood sampling from the retro-orbital plexus, the saphenous vein and the tail vein in rats: comparative effects on selected behavioural and blood variables. Lab Anim 35(2):131–139

    Article  PubMed  Google Scholar 

  • Wu H, Niu C, Aisa HA (2023) Research progress in small molecules as anti-vitiligo agents. Curr Med Chem

  • Xu Q, Ming Z, Dart AM, Du XJ (2007) Optimizing dosage of ketamine and xylazine in murine echocardiography. Clin Exp Pharmacol Physiol 34(5–6):499–507

    Article  PubMed  CAS  Google Scholar 

  • Yu H-S, Chang K-L, Yu C-L, Li H-F, Wu M-T, Wu C-S, Wu C-S (1997) Alterations in IL-6, IL-8, GM-CSF. TNF-α, and IFN-γ release by peripheral mononuclear cells in patients with active vitiligo. J Invest Dermatol 108(4):527–529

  • Zhu Y, Wang S, Lin F, Li Q, Xu A (2014) The therapeutic effects of EGCG on vitiligo. Fitoterapia 99:243–251

    Article  PubMed  CAS  Google Scholar 

  • Zhu Y, Wang S, Xu A (2013) A mouse model of vitiligo induced by monobenzone. Exp Dermatol 22(7):499–501

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

I would like to express special gratitude to ISF College of Pharmacy for their able support while completion of this article. I would like to thank Professor YK Gupta President AIIMS Bhopal and AIIMS Jammu for his reading and valuable suggestions. I would like to extent my gratitude to all the authors whose papers I had referred.

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Authors and Affiliations

  1. Department of Pharmacology, ISF College of Pharmacy, Moga, 142001, Punjab, India

    Kanupriya Chauhan, Falguni Goel & Shamsher Singh

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  1. Kanupriya Chauhan
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  2. Falguni Goel
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  3. Shamsher Singh
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Contributions

Dr. Shamsher Singh provided the original idea, concept of the manuscript and finalize manuscript, Kanupriya Chauhan wrote the manuscript, collected the data, compile the data and prepared the images, Falguni Goel collected data and review paper. The authors declare that all data were generated in-house and that no paper mill was used.

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Correspondence to Shamsher Singh.

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Ethics approval

The experimental protocol was reviewed and approved by the Institutional Animal Ethics Committee (ISFCP/IAEC/CPCSEA/Meeting no.30/2021/ Protocol no. 497), and all the experiments were conducted in compliance with the guidelines of the Indian National Science Academy (INSA) for the use and care of experimental animals.

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The authors declare no competing interests.

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Chauhan, K., Goel, F. & Singh, S. Apigenin protects melanocytes and improve tyrosinase activity in a hydroquinone induced vitiligo mouse model targeting P38 MAP kinase signaling: histopathology and immunohistochemistry analysis. Naunyn-Schmiedeberg's Arch Pharmacol (2023). https://doi.org/10.1007/s00210-023-02917-4

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