Tenebrio molitor Larva Trypsin Hydrolysate Ameliorates Atopic Dermatitis in C57BL/6 Mice by Targeting the TLR-Mediated MyD88-Dependent MAPK Signaling Pathway
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Preparation of Protein Hydrolysates
2.3. Cell Culture and Treatment
2.4. Reverse Transcription-Quantitative Polymerase Chain Reaction (RT-qPCR)
2.5. Animal Model
2.6. Western Blot Analysis
2.7. Skin Histological Analysis of DNCB-Induced Mice
2.8. Determination of Serum IgE and IgG2a Levels in DNCB-Induced Mice
2.9. Immunohistochemistry Analysis of DNCB-Induced Mice Skin
2.10. Statistical Analysis
3. Results
3.1. Effect of TMTH on TNF-α-Stimulated HaCaT Cell
3.2. Effects of TMTH on DNCB-Induced AD-like Lesions in the Skin of C57BL/6 Mice
3.3. Effects of TMTH on Immune Organs of AD Mice
3.4. Effect of TMTH on TLR-Mediated MyD88-Dependent MAPK Signaling Pathway in DNCB-Induced Mice
3.5. Effects of TMTH on Mast Cell Infiltration and Dermal and Epidermal Thickness
3.6. Effects of TMTH on Serum IgE and IgG2a Levels in DNCB-Induced AD Mice
3.7. NF-κB Expression Levels in Dorsal Skin of DNCB-Induced Mice
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Chang, J.; Wang, L.; Zhang, M.; Lai, Z. Glabridin Attenuates Atopic Dermatitis Progression through Downregulating the TLR4/MyD88/NF-ΚB Signaling Pathway. Genes Genom. 2021, 43, 847–855. [Google Scholar] [CrossRef] [PubMed]
- Moon, G.H.; Lee, Y.; Kim, E.K.; Chung, K.H.; Lee, K.J.; An, J.H. Immunomodulatory and Anti-Inflammatory Effects of Asiatic Acid in a Dncb-Induced Atopic Dermatitis Animal Model. Nutrients 2021, 13, 2248. [Google Scholar] [CrossRef]
- Woo, Y.; Moon, S.; Yu, J.; Cho, S. Synergistic Effects of Korean Red Ginseng Extract and the Conventional Systemic Therapeutics of Atopic Dermatitis in a Murine Model. Nutrients 2022, 14, 133. [Google Scholar] [CrossRef] [PubMed]
- Santos-Sierra, S. Targeting Toll-like Receptor (Tlr) Pathways in Inflammatory Arthritis: Two Better than One? Biomolecules 2021, 11, 1291. [Google Scholar] [CrossRef]
- Patel, H.; Shaw, S.G.; Shi-Wen, X.; Abraham, D.; Baker, D.M.; Tsui, J.C.S. Toll-like Receptors in Ischaemia and Its Potential Role in the Pathophysiology of Muscle Damage in Critical Limb Ischaemia. Cardiol. Res. Pract. 2012, 2012, 121237. [Google Scholar] [CrossRef] [PubMed]
- Borremans, A.; Bubler, S.; Tchewonpi Sagu, S.; Rawel, H.; Schluter, O.; Leen, V.C. Effect of Blanching Plus Fermentation on Selected. Foods 2020, 9, 917. [Google Scholar] [CrossRef] [PubMed]
- Zhao, X.; Vázquez-Gutiérrez, J.L.; Johansson, D.P.; Landberg, R.; Langton, M. Yellow Mealworm Protein for Food Purposes—Extraction and Functional Properties. PLoS ONE 2016, 11, e0147791. [Google Scholar] [CrossRef] [Green Version]
- Ryu, H.J.; Song, H.J.; Lee, S.O. Enzymatic Preparation and Antioxidant Activities of Protein Hydrolysates from Allomyrina Dichotoma Larvae. J. Korean Soc. Food Sci. Nutr. 2019, 48, 410–417. [Google Scholar] [CrossRef]
- Eunyoung, O.; Woo-Jae, P.; Yookyung, K. Effects of Tenebrio Molitor Larvae and Its Protein Derivatives on the Antioxidant and Anti- 2 Inflammatory Capacities of Tofu. Food Biosci. 2022, 50, 102105. [Google Scholar]
- Tang, Y.; Debnath, T.; Choi, E.J.; Kim, Y.W.; Ryu, J.P.; Jang, S.; Chung, S.U.; Choi, Y.J.; Kim, E.K. Changes in the Amino Acid Profiles and Free Radical Scavenging Activities of Tenebrio Molitor Larvae Following Enzymatic Hydrolysis. PLoS ONE 2018, 13, e0196218. [Google Scholar] [CrossRef]
- Rivero-Pino, F.; Espejo-Carpio, F.J.; Pérez-Gálvez, R.; Guadix, A.; Guadix, E.M. Effect of Ultrasound Pretreatment and Sequential Hydrolysis on the Production of Tenebrio Molitor Antidiabetic Peptides. Food Bioprod. Process. 2020, 123, 217–224. [Google Scholar] [CrossRef]
- Cho, H.R.; Lee, S.O. Novel Hepatoprotective Peptides Derived from Protein Hydrolysates of Mealworm (Tenebrio Molitor). Food Res. Int. 2020, 133, 109194. [Google Scholar] [CrossRef] [PubMed]
- Bae, S.M.; Fan, M.; Choi, Y.J.; Tang, Y.; Jeong, G.; Myung, K.; Kim, B.G.; Kim, E.K. Exploring the Role of a Novel Peptide from Allomyrina Dichotoma Larvae in Ameliorating Lipid Metabolism in Obesity. Int. J. Mol. Sci. 2020, 21, 8537. [Google Scholar] [CrossRef]
- Fan, M.; Choi, Y.J.; Tang, Y.; Bae, S.M.; Yang, H.P.; Kim, E.K. Efficacy and Mechanism of Polymerized Anthocyanin from Grape-Skin Extract on High-Fat-Diet-Induced Nonalcoholic Fatty Liver Disease. Nutrients 2019, 11, 2586. [Google Scholar] [CrossRef] [Green Version]
- Bonneville, M.; Chavagnac, C.; Vocanson, M.; Rozieres, A.; Benetiere, J.; Pernet, I.; Denis, A.; Nicolas, J.F.; Hennino, A. Skin Contact Irritation Conditions the Development and Severity of Allergic Contact Dermatitis. J. Investig. Dermatol. 2007, 127, 1430–1435. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Liu, W.; Song, W.; Luo, Y.; Dan, H.; Li, L.; Zhang, Z.; Zhou, D.; You, P. Angelica Yinzi Alleviates 1-Chloro-2,4-Dinitrobenzene-Induced Atopic Dermatitis by Inhibiting Activation of NLRP3 Inflammasome and down-Regulating the MAPKs/NF-KB Signaling Pathway. Saudi Pharm. J. 2022, 30, 1426–1434. [Google Scholar] [CrossRef] [PubMed]
- Park, G.; Moon, B.C.; Ryu, S.M.; Kim, W.J.; Lim, H.S. Cicadidae Periostracum Attenuates Atopic Dermatitis Symptoms and Pathology via the Regulation of NLRP3 Inflammasome Activation. Oxid. Med. Cell. Longev. 2021, 2021, 8878153. [Google Scholar] [CrossRef]
- Kordulewska, N.K.; Topa, J.; Stryiński, R.; Jarmołowska, B. Osthole Inhibits Expression of Genes Associated with Toll-like Receptor 2 Signaling Pathway in an Organotypic 3D Skin Model of Human Epidermis with Atopic Dermatitis. Cells 2022, 11, 88. [Google Scholar] [CrossRef] [PubMed]
- He, H.; Gao, X.; Wang, X.; Li, X.; Jiang, X.; Xie, Z.; Ma, K.; Ma, J.; Umezawa, K.; Zhang, Y. Comparison of Anti-Atopic Dermatitis Activities between DHMEQ and Tacrolimus Ointments in Mouse Model without Stratum Corneum. Int. Immunopharmacol. 2019, 71, 43–51. [Google Scholar] [CrossRef]
- Xiong, X.; Huang, C.; Wang, F.; Dong, J.; Zhang, D.; Jiang, J.; Feng, Y.; Wu, B.; Xie, T.; Cheng, L. Qingxue Jiedu Formulation Ameliorated DNFB-Induced Atopic Dermatitis by Inhibiting STAT3/MAPK/NF-ΚB Signaling Pathways. J. Ethnopharmacol. 2021, 270, 113773. [Google Scholar] [CrossRef]
- Wang, Z.; Yi, T.; Long, M.; Gao, Y.; Cao, C.; Huang, C.; Wang, Q.; Yin, N.; Chen, Z. Electro-Acupuncture at Zusanli Acupoint (ST36) Suppresses Inflammation in Allergic Contact Dermatitis Via Triggering Local IL-10 Production and Inhibiting P38 MAPK Activation. Inflammation 2017, 40, 1351–1364. [Google Scholar] [CrossRef]
- Gil, T.Y.; Jin, B.R.; An, H.J. Peucedanum Japonicum Thunberg Alleviates Atopic Dermatitis-like Inflammation via STAT/MAPK Signaling Pathways in Vivo and in Vitro. Mol. Immunol. 2022, 144, 106–116. [Google Scholar] [CrossRef] [PubMed]
- Lim, J.M.; Lee, B.; Min, J.H.; Kim, E.Y.; Kim, J.H.; Hong, S.Y.; Kim, J.J.; Sohn, Y.; Jung, H.S. Effect of Peiminine on DNCB-Induced Atopic Dermatitis by Inhibiting Inflammatory Cytokine Expression in Vivo and in Vitro. Int. Immunopharmacol. 2018, 56, 135–142. [Google Scholar] [CrossRef] [PubMed]
- Kaminska, B. MAPK Signalling Pathways as Molecular Targets for Anti-Inflammatory Therapy—From Molecular Mechanisms to Therapeutic Benefits. Biochim. Biophys. Acta Proteins Proteomics 2005, 1754, 253–262. [Google Scholar] [CrossRef] [PubMed]
- Kim, B.E.; Leung, D.Y.M. Significance of Skin Barrier Dysfunction in Atopic Dermatitis. Allergy Asthma Immunol. Res. 2018, 10, 207–215. [Google Scholar] [CrossRef] [Green Version]
- Werfel, T.; Kapp, A. T Cells in Atopic Dermatitis. Atopic Dermat. 2002, 21, 241–266. [Google Scholar] [CrossRef]
- Lee, Y.; Choi, H.K.; N’deh, K.P.U.; Choi, Y.J.; Fan, M.; Kim, E.K.; Chung, K.H.; An, J.H. Inhibitory Effect of Centella Asiatica Extract on DNCB-Induced Atopic Dermatitis in HaCaT Cells and BALB/c Mice. Nutrients 2020, 12, 411. [Google Scholar] [CrossRef] [Green Version]
- Wang, Y.; Weng, H.; Song, J.F.; Deng, Y.H.; Li, S.; Liu, H.B. Activation of the HMGB1-TLR4-NF-ΚB Pathway May Occur in Patients with Atopic Eczema. Mol. Med. Rep. 2017, 16, 2714–2720. [Google Scholar] [CrossRef] [Green Version]
- Kang, J.; Song, J.; Shen, S.; Li, B.; Yang, X.; Chen, M. Diisononyl Phthalate Aggravates Allergic Dermatitis by Activation of NF-KB. Oncotarget 2016, 7, 85472–85482. [Google Scholar] [CrossRef] [Green Version]
- Liu, F.T.; Goodarzi, H.; Chen, H.Y. IgE, Mast Cells, and Eosinophils in Atopic Dermatitis. Clin. Rev. Allergy Immunol. 2011, 41, 298–310. [Google Scholar] [CrossRef] [PubMed]
- Peng, G.; Mu, Z.; Cui, L.; Liu, P.; Wang, Y.; Wu, W.; Han, X. Anti-IL-33 Antibody Has a Therapeutic Effect in an Atopic Dermatitis Murine Model Induced by 2, 4-Dinitrochlorobenzene. Inflammation 2018, 41, 154–163. [Google Scholar] [CrossRef]
- Mohd Kasim, V.N.K.; Noble, S.M.; Liew, K.Y.; Tan, J.W.; Israf, D.A.; Tham, C.L. Management of AtopicDermatitis Via Oral and Topical Administration of Herbs in Murine Model: A Systematic Review. Front. Pharmacol. 2022, 13, 1–17. [Google Scholar] [CrossRef] [PubMed]
- Zhou, S.; Tan, G.; Huang, F.; Wang, H.; Lin, Y. Sanpao Herbs Inhibit Development of Atopic Dermatitis in Balb/ c Mice. Asian Pac. J. Allergy Immunol. 2014, 32, 140–144. [Google Scholar] [PubMed]
- Lim, H.S.; Ha, H.; Lee, M.Y.; Jin, S.E.; Jeong, S.J.; Jeon, W.Y.; Shin, N.R.; Sok, D.E.; Shin, H.K. Saussurea Lappa Alleviates Inflammatory Chemokine Production in HaCaT Cells and House Dust Mite-Induced Atopic-like Dermatitis in Nc/Nga Mice. Food Chem. Toxicol. 2014, 63, 212–220. [Google Scholar] [CrossRef] [PubMed]
- Park, J.G.; Yi, Y.S.; Han, S.Y.; Hong, Y.H.; Yoo, S.; Kim, E.; Jeong, S.G.; Aravinthan, A.; Baik, K.S.; Choi, S.Y.; et al. TabetriTM (Tabebuia Avellanedae Ethanol Extract) Ameliorates Atopic Dermatitis Symptoms in Mice. Mediators Inflamm. 2018, 2018, 9079527. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lim, H.S.; Ha, H.; Shin, H.K.; Jeong, S.J. The Genome-Wide Expression Profile of Saussurea Lappa Extract on House Dust Mite Induced Atopic Dermatitis in Nc/Nga Mice. Mol. Cells 2015, 38, 765–772. [Google Scholar] [CrossRef]
Gene | Primer | Sequence |
---|---|---|
GAPDH | Forward | 5′-CCCCTGGCCAAGGTCATCCATGACAACTTT-3′ |
Reverse | 5′-GGCCATGAGGTCCACCACCCTGTTGCTGTA-3′ | |
IL-6 | Forward | 5′-AAAGAGGCACTGCCAGAAAA-3′ |
Reverse | 5′-ATCTGAGGTGCCCATGCTAC-3′ | |
IL-8 | Forward | 5′-ACAGCAGAGCACACAAGCTT-3′ |
Reverse | 5′-CTGGCAACCCTACAACAGAC-3′ |
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Fan, M.; Wedamulla, N.E.; Choi, Y.-J.; Zhang, Q.; Bae, S.M.; Kim, E.-K. Tenebrio molitor Larva Trypsin Hydrolysate Ameliorates Atopic Dermatitis in C57BL/6 Mice by Targeting the TLR-Mediated MyD88-Dependent MAPK Signaling Pathway. Nutrients 2023, 15, 93. https://doi.org/10.3390/nu15010093
Fan M, Wedamulla NE, Choi Y-J, Zhang Q, Bae SM, Kim E-K. Tenebrio molitor Larva Trypsin Hydrolysate Ameliorates Atopic Dermatitis in C57BL/6 Mice by Targeting the TLR-Mediated MyD88-Dependent MAPK Signaling Pathway. Nutrients. 2023; 15(1):93. https://doi.org/10.3390/nu15010093
Chicago/Turabian StyleFan, Meiqi, Nishala Erandi Wedamulla, Young-Jin Choi, Qun Zhang, Sung Mun Bae, and Eun-Kyung Kim. 2023. "Tenebrio molitor Larva Trypsin Hydrolysate Ameliorates Atopic Dermatitis in C57BL/6 Mice by Targeting the TLR-Mediated MyD88-Dependent MAPK Signaling Pathway" Nutrients 15, no. 1: 93. https://doi.org/10.3390/nu15010093