Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
권호 표지
DOI QR코드

DOI QR Code

Inhibitory Effect of Carnosol on Phthalic Anhydride-Induced Atopic Dermatitis via Inhibition of STAT3

  • Lee, Do Yeon (College of Pharmacy and Medical Research Center) ;
  • Hwang, Chul Ju (College of Pharmacy and Medical Research Center) ;
  • Choi, Ji Yeon (College of Pharmacy and Medical Research Center) ;
  • Park, Mi Hee (College of Pharmacy and Medical Research Center) ;
  • Song, Min Ji (College of Pharmacy and Medical Research Center) ;
  • Oh, Ki Wan (College of Pharmacy and Medical Research Center) ;
  • Son, Dong Ju (College of Pharmacy and Medical Research Center) ;
  • Lee, Seung Hwa (Department of Industrial Cosmetics, Chungbuk National University) ;
  • Han, Sang Bae (College of Pharmacy and Medical Research Center) ;
  • Hong, Jin Tae (College of Pharmacy and Medical Research Center)
  • Received : 2017.01.17
  • Accepted : 2017.05.02
  • Published : 2017.09.01
Download PDF
⟨ Previous Next ⟩

Abstract

Carnosol is a phenolic antioxidant present in rosemary (Rosmarinus officinalis). It is known for anti-inflammatory effects, analgesic activity and anti-cancer effects. However, no study has been dedicated yet to its effect on atopic dermatitis (AD). Here, we show that carnosol effectively inhibited LPS-induced nitric oxide (NO) generation and expression of inflammatory marker proteins (iNOS and COX-2) in RAW 264.7 cells. In addition, carnosol effectively inhibits the phosphorylation of STAT3 and DNA binding activity in RAW 264.7 cells. Pull down assay and docking model analysis showed that carnosol directly binds to the DNA binding domain (DBD) of STAT3. We next examined the anti-atopic activity of carnosol ($0.05{\mu}g/cm^2$) using 5% Phthalic anhydride (PA)-induced AD model in HR1 mice. Carnosol treatment significantly reduced 5% PA-induced AD like skin inflammation in skin tissues compared with control mice. Moreover, carnosol treatment inhibits the expression of iNOS and COX-2 in skin tissue. In addition, the levels of $TNF-{\alpha}$, $IL-1{\beta}$, and Immunoglobulin-E in blood serum was significantly decreased in carnosol treated mice compared with those of 5% PA treated group. Furthermore, the activation of STAT3 in skin tissue was decreased in carnosol treated mice compared with control mice. In conclusion, these findings suggest that carnosol exhibited a potential anti-AD activity by inhibiting pro-inflammatory mediators through suppression of STAT3 activation via direct binding to DBD of STAT3.

Keywords

References

  1. Ahn, S., Siddiqi, M. H., Aceituno, V. C., Simu, S. Y., Zhang, J., Perez, Z. E., Kim, Y. J. and Yang, D. C. (2016) Ginsenoside Rg5:Rk1 attenuates TNF-${\alpha}$/IFN-${\gamma}$-induced production of thymus- and activation-regulated chemokine (TARC/CCL17) and LPS-induced NO production via downregulation of NF-${\kappa}B$/p38 MAPK/STAT1 signaling in human keratinocytes and macrophages. In vitro Cell. Dev. Biol. Anim. 52, 287-295. https://doi.org/10.1007/s11626-015-9983-y
  2. Amano, W., Nakajima, S., Kunugi, H., Numata, Y., Kitoh, A., Egawa, G., Dainichi, T., Honda, T., Otsuka, A., Kimoto, Y., Yamamoto, Y., Tanimoto, A., Matsushita, M., Miyachi, Y. and Kabashima, K. (2015) The Janus kinase inhibitor JTE-052 improves skin barrier function through suppressing signal transducer and activator of transcription 3 signaling. J. Allergy Clin. Immunol. 136, 667-677.e7. https://doi.org/10.1016/j.jaci.2015.03.051
  3. Aries, M. F., Hernandez-Pigeon, H., Vaissiere, C., Delga, H., Caruana, A., Leveque, M., Bourrain, M., Ravard Helffer, K., Chol, B., Nguyen, T., Bessou-Touya, S. and Castex-Rizzi, N. (2016) Anti-inflammatory and immunomodulatory effects of Aquaphilus dolomiae extract on in vitro models. Clin. Cosmet. Investig. Dermatol. 9, 421-434. https://doi.org/10.2147/CCID.S113180
  4. Bao, L., Shi, V. Y. and Chan, L. S. (2012) IL-4 regulates chemokine CCL26 in keratinocytes through the Jak1, 2/Stat6 signal transduction pathway: Implication for atopic dermatitis. Mol. Immunol. 50, 91-97. https://doi.org/10.1016/j.molimm.2011.12.008
  5. Bao, L., Zhang, H. and Chan, L. S. (2013) The involvement of the JAK-STAT signaling pathway in chronic inflammatory skin disease atopic dermatitis. JAKSTAT 2, e24137.
  6. Boos, A. C., Hagl, B., Schlesinger, A., Halm, B. E., Ballenberger, N., Pinarci, M., Heinz, V., Kreilinger, D., Spielberger, B. D., Schimke-Marques, L. F., Sawalle-Belohradsky, J., Belohradsky, B. H., Przybilla, B., Schaub, B., Wollenberg, A. and Renner, E. D. (2014) Atopic dermatitis, STAT3- and DOCK8-hyper-IgE syndromes differ in IgE-based sensitization pattern. Allergy 69, 943-953. https://doi.org/10.1111/all.12416
  7. Cha, H. Y., Ahn, S. H., Cheon, J. H., Park, I. S., Kim, J. T. and Kim, K. (2016) Hataedock treatment has preventive therapeutic effects in atopic dermatitis-induced nc/nga mice under high-fat diet conditions. Evid. Based Complement. Alternat. Med. 2016, 1739760.
  8. Chang, W. A., Hung, J. Y., Jian, S. F., Lin, Y. S., Wu, C. Y., Hsu, Y. L. and Kuo, P. L. (2016) Laricitrin ameliorates lung cancer-mediated dendritic cell suppression by inhibiting signal transducer and activator of transcription 3. Oncotarget 7, 85220-85234.
  9. Choi, E. J., Debnath, T., Tang, Y., Ryu, Y. B., Moon, S. H. and Kim, E. K. (2016) Topical application of Moringa oleifera leaf extract ameliorates experimentally induced atopic dermatitis by the regulation of Th1/Th2/Th17 balance. Biomed. Pharmacother. 84, 870-877. https://doi.org/10.1016/j.biopha.2016.09.085
  10. Drennan, S., D'Avola, A., Gao, Y., Weigel, C., Chrysostomou, E., Steele, A. J., Zenz, T., Plass, C., Johnson, P. W., Williams, A. P., Packham, G., Stevenson, F. K., Oakes, C. C. and Forconi, F. (2017) IL-10 production by CLL cells is enhanced in the anergic IGHV mutated subset and associates with reduced DNA methylation of the IL10 locus. Leukemia 31, 1686-1694. https://doi.org/10.1038/leu.2016.356
  11. Fridman, J. S., Scherle, P. A., Collins, R., Burn, T., Neilan, C. L., Hertel, D., Contel, N., Haley, P., Thomas, B., Shi, J., Collier, P., Rodgers, J. D., Shepard, S., Metcalf, B., Hollis, G., Newton, R. C., Yeleswaram, S., Friedman, S. M. and Vaddi, K. (2011) Preclinical evaluation of local JAK1 and JAK2 inhibition in cutaneous inflammation. J. Invest. Dermatol. 131, 1838-1844. https://doi.org/10.1038/jid.2011.140
  12. He, Y., Sultana, I., Takeda, K. and Reed, J. L. (2017) Cutaneous deficiency of filaggrin and stat3 exacerbates vaccinia disease in vivo. PLoS ONE 12, e0170070. https://doi.org/10.1371/journal.pone.0170070
  13. Holland, S. M., DeLeo, F. R., Elloumi, H. Z., Hsu, A. P., Uzel, G., Brodsky, N., Freeman, A. F., Demidowich, A., Davis, J., Turner, M. L., Anderson, V. L., Darnell, D. N., Welch, P. A., Kuhns, D. B., Frucht, D. M., Malech, H. L., Gallin, J. I., Kobayashi, S. D., Whitney, A. R., Voyich, J. M., Musser, J. M., Woellner, C., Schaffer, A. A., Puck, J. M. and Grimbacher, B. (2007) STAT3 mutations in the hyper-IgE syndrome. N. Engl. J. Med. 357, 1608-1619. https://doi.org/10.1056/NEJMoa073687
  14. Kang, G. J., Kang, N. J., Han, S. C., Koo, D. H., Kang, H. K., Yoo, B. S. and Yoo, E. S. (2012) The chloroform fraction of carpinus tschonoskii leaves inhibits the production of inflammatory mediators in HaCaT keratinocytes and RAW264.7 macrophages. Toxicol. Res. 28, 255-262. https://doi.org/10.5487/TR.2012.28.4.255
  15. Kang, J. S., Lee, C. W., Lee, K., Han, M. H., Lee, H., Youm, J. K., Jeong, S. K., Park, B. D., Han, S. B., Han, G., Park, S. K. and Kim, H. M. (2008) Inhibition of skin inflammation and atopic dermatitis by topical application of a novel ceramide derivative, K112PC-5, in mice. Arch. Pharm. Res. 31, 1004-1009. https://doi.org/10.1007/s12272-001-1260-z
  16. Karuppagounder, V., Arumugam, S., Thandavarayan, R. A., Pitchaimani, V., Sreedhar, R., Afrin, R., Harima, M., Suzuki, H., Nomoto, M., Miyashita, S., Suzuki, K., Nakamura, M. and Watanabe, K. (2015) Modulation of HMGB1 translocation and RAGE/NF${\kappa}B$ cascade by quercetin treatment mitigates atopic dermatitis in NC/Nga transgenic mice. Exp. Dermatol. 24, 418-423. https://doi.org/10.1111/exd.12685
  17. Karuppagounder, V., Arumugam, S., Thandavarayan, R. A., Pitchaimani, V., Sreedhar, R., Afrin, R., Harima, M., Suzuki, H., Nomoto, M., Miyashita, S., Suzuki, K. and Watanabe, K. (2014) Resveratrol attenuates HMGB1 signaling and inflammation in house dust mite-induced atopic dermatitis in mice. Int. Immunopharmacol. 23, 617-623. https://doi.org/10.1016/j.intimp.2014.10.014
  18. Kim, D. C., Lee, H. S., Ko, W., Lee, D. S., Sohn, J. H., Yim, J. H., Kim, Y. C. and Oh, H. (2014) Anti-inflammatory effect of methylpenicinoline from a marine isolate of Penicillium sp. (SF-5995): inhibition of NF-${\kappa}B$ and MAPK pathways in lipopolysaccharide-induced RAW264.7 macrophages and BV2 microglia. Molecules 19, 18073-18089. https://doi.org/10.3390/molecules191118073
  19. Kim, H. S., Park, S. Y., Kim, E. K., Ryu, E. Y., Kim, Y. H., Park, G. and Lee, S. J. (2012) Acanthopanax senticosus has a heme oxygenase-1 signaling-dependent effect on Porphyromonas gingivalis lipopolysaccharide-stimulated macrophages. J. Ethnopharmacol. 142, 819-828. https://doi.org/10.1016/j.jep.2012.06.006
  20. Koppes, S. A., Brans, R., Ljubojevic Hadzavdic, S., Frings-Dresen, M. H., Rustemeyer, T. and Kezic, S. (2016) Stratum corneum tape stripping: monitoring of inflammatory mediators in atopic dermatitis patients using topical therapy. Int. Arch. Allergy Immunol. 170, 187-193. https://doi.org/10.1159/000448400
  21. Kumari, S., Bonnet, M. C., Ulvmar, M. H., Wolk, K., Karagianni, N., Witte, E., Uthoff-Hachenberg, C., Renauld, J. C., Kollias, G., Toftgard, R., Sabat, R., Pasparakis, M. and Haase, I. (2013) Tumor necrosis factor receptor signaling in keratinocytes triggers interleukin-24-dependent psoriasis-like skin inflammation in mice. Immunity 39, 899-911. https://doi.org/10.1016/j.immuni.2013.10.009
  22. Lee, C. H., Hong, C. H., Yu, W. T., Chuang, H. Y., Huang, S. K., Chen, G. S., Yoshioka, T., Sakata, M., Liao, W. T., Ko, Y. C. and Yu, H. S. (2012) Mechanistic correlations between two itch biomarkers, cytokine interleukin-31 and neuropeptide ${\beta}$-endorphin, via STAT3/calcium axis in atopic dermatitis. Br. J. Dermatol. 167, 794-803. https://doi.org/10.1111/j.1365-2133.2012.11047.x
  23. Lee, J. K., Lee, S., Baek, M. C., Lee, B. H., Lee, H. S., Kwon, T. K., Park, P. H., Shin, T. Y., Khang, D. and Kim, S. H. (2017) Association between perfluorooctanoic acid exposure and degranulation of mast cells in allergic inflammation. J. Appl. Toxicol. 37, 554-562. https://doi.org/10.1002/jat.3389
  24. Lee, Y. J., Kim, J. E., Kwak, M. H., Go, J., Kim, D. S., Son, H. J. and Hwang, D. Y. (2014) Quantitative evaluation of the therapeutic effect of fermented soybean products containing a high concentration of GABA on phthalic anhydride-induced atopic dermatitis in IL-4/Luc/CNS-1 Tg mice. Int. J. Mol. Med. 33, 1185-1194. https://doi.org/10.3892/ijmm.2014.1685
  25. Lim, S. J., Kim, M., Randy, A., Nam, E. J. and Nho, C. W. (2016) Effects of Hovenia dulcis Thunb. extract and methyl vanillate on atopic dermatitis-like skin lesions and TNF-${\alpha}$/IFN-${\gamma}$-induced chemokines production in HaCaT cells. J. Pharm. Pharmacol. 68, 1465-1479. https://doi.org/10.1111/jphp.12640
  26. Lyu, Y., Zhu, L., Qi, R., Xu, J., Di, Z., Chen, H. and Gao, X. (2014) Serum levels of suppressor of cytokine signaling 3 and signal transducer and activator of transcription 3 in childhood atopic dermatitis. Chin. Med. J. 127, 2389-2391.
  27. Matsuda, H., Watanabe, N., Geba, G. P., Sperl, J., Tsudzuki, M., Hiroi, J., Matsumoto, M., Ushio, H., Saito, S., Askenase, P. W. and Ra, C. (1997) Development of atopic dermatitis-like skin lesion with IgE hyperproduction in NC/Nga mice. Int Immunol. 9, 461-466. https://doi.org/10.1093/intimm/9.3.461
  28. Mengoni, E. S., Vichera, G., Rigano, L. A., Rodriguez-Puebla, M. L., Galliano, S. R., Cafferata, E. E., Pivetta, O. H., Moreno, S. and Vojnov, A. A. (2011) Suppression of COX-2, IL-1${\beta}$ and TNF-${\alpha}$ expression and leukocyte infiltration in inflamed skin by bioactive compounds from Rosmarinus officinalis L. Fitoterapia 82, 414-421. https://doi.org/10.1016/j.fitote.2010.11.023
  29. Oliveira Gde, A., de Oliveira, A. E., da Conceicao, E. C. and Leles, M. I. (2016) Multiresponse optimization of an extraction procedure of carnosol and rosmarinic and carnosic acids from rosemary. Food Chem. 211, 465-473. https://doi.org/10.1016/j.foodchem.2016.05.042
  30. Orita, K., Hiramoto, K., Kobayashi, H., Ishii, M., Sekiyama, A. and Inoue, M. (2011) Inducible nitric oxide synthase (iNOS) and ${\alpha}$-melanocyte-stimulating hormones of iNOS origin play important roles in the allergic reactions of atopic dermatitis in mice. Exp. Dermatol. 20, 911-914. https://doi.org/10.1111/j.1600-0625.2011.01360.x
  31. Ortuno, J., Serrano, R. and Banon, S. (2015) Antioxidant and antimicrobial effects of dietary supplementation with rosemary diterpenes (carnosic acid and carnosol) vs vitamin E on lamb meat packed under protective atmosphere. Meat Sci. 110, 62-69. https://doi.org/10.1016/j.meatsci.2015.07.011
  32. Park, K. W., Kundu, J., Chae, I. G., Kim, D. H., Yu, M. H., Kundu, J. K. and Chun, K. S. (2014) Carnosol induces apoptosis through generation of ROS and inactivation of STAT3 signaling in human colon cancer HCT116 cells. Int. J. Oncol. 44, 1309-1315. https://doi.org/10.3892/ijo.2014.2281
  33. Riis, J. L., Vestergaard, C., Hjuler, K. F., Iversen, L., Jakobsen, L., Deleuran, M. S. and Olsen, M. (2016) Hospital-diagnosed atopic dermatitis and long-term risk of myocardial infarction: a populationbased follow-up study. BMJ Open 6, e011870. https://doi.org/10.1136/bmjopen-2016-011870
  34. Rocha, J., Eduardo-Figueira, M., Barateiro, A., Fernandes, A., Brites, D., Bronze, R., Duarte, C. M., Serra, A. T., Pinto, R., Freitas, M., Fernandes, E., Silva-Lima, B., Mota-Filipe, H. and Sepodes, B. (2015) Anti-inflammatory effect of rosmarinic acid and an extract of Rosmarinus officinalis in rat models of local and systemic inflammation. Basic Clin. Pharmacol. Toxicol. 116, 398-413. https://doi.org/10.1111/bcpt.12335
  35. Sae-Wong, C., Mizutani, N., Kangsanant, S. and Yoshino, S. (2016) Topical skin treatment with Fab fragments of an allergen-specific IgG1 monoclonal antibody suppresses allergen-induced atopic dermatitis-like skin lesions in mice. Eur. J. Pharmacol. 779, 131-137. https://doi.org/10.1016/j.ejphar.2016.03.020
  36. Sanchez, C., Horcajada, M. N., Membrez Scalfo, F., Ameye, L., Offord, E. and Henrotin, Y. (2015) Carnosol inhibits pro-inflammatory and catabolic mediators of cartilage breakdown in human osteoarthritic chondrocytes and mediates cross-talk between subchondral bone osteoblasts and chondrocytes. PLoS ONE 10, e0136118. https://doi.org/10.1371/journal.pone.0136118
  37. Schwager, J., Richard, N., Fowler, A., Seifert, N. and Raederstorff, D. (2016) Carnosol and related substances modulate chemokine and cytokine production in macrophages and chondrocytes. Molecules 21, 465. https://doi.org/10.3390/molecules21040465
  38. Shershakova, N., Baraboshkina, E., Andreev, S., Purgina, D., Struchkova, I., Kamyshnikov, O., Nikonova, A. and Khaitov, M. (2016) Anti-inflammatory effect of fullerene C60 in a mice model of atopic dermatitis. J. Nanobiotechnology 14, 8. https://doi.org/10.1186/s12951-016-0159-z
  39. Siegel, A. M., Stone, K. D., Cruse, G., Lawrence, M. G., Olivera, A., Jung, M. Y., Barber, J. S., Freeman, A. F., Holland, S. M., O'Brien, M., Jones, N., Nelson, C. G., Wisch, L. B., Kong, H. H., Desai, A., Farber, O., Gilfillan, A. M., Rivera, J. and Milner, J. D. (2013) Diminished allergic disease in patients with STAT3 mutations reveals a role for STAT3 signaling in mast cell degranulation. J. Allergy Clin. Immunol. 132, 1388-1396. https://doi.org/10.1016/j.jaci.2013.08.045
  40. Stempelj, M., Kedinger, M., Augenlicht, L. and Klampfer, L. (2007) Essential role of the JAK/STAT1 signaling pathway in the expression of inducible nitric-oxide synthase in intestinal epithelial cells and its regulation by butyrate. J. Biol. Chem. 282, 9797-9804. https://doi.org/10.1074/jbc.M609426200
  41. Sung, J. E., Kwak, M. H., Kim, J. E., Lee, Y. J., Kim, R. U., Kim, E. A., Lee, G. Y., Kim, D. S. and Hwang, D. Y. (2013) Therapeutic effects of fermented soycrud on phenotypes of atopic dermatitis induced by phthalic anhydride. Lab. Anim. Res. 29, 103-112. https://doi.org/10.5625/lar.2013.29.2.103
  42. Sung, Y. Y., Lee, A. Y. and Kim, H. K. (2016) Forsythia suspensa fruit extracts and the constituent matairesinol confer anti-allergic effects in an allergic dermatitis mouse model. J. Ethnopharmacol. 187, 49-56. https://doi.org/10.1016/j.jep.2016.04.015
  43. Suzuki, H., Makino, Y., Nagata, M., Furuta, J., Enomoto, H., Hirota, T., Tamari, M. and Noguchi, E. (2016) A rare variant in CYP27A1 and its association with atopic dermatitis with high serum total IgE. Allergy 71, 1486-1489. https://doi.org/10.1111/all.12950
  44. Szczepanik, A. M. and Ringheim, G. E. (2003) IL-10 and glucocorticoids inhibit $A{\beta}$(1-42)- and lipopolysaccharide-induced pro-inflammatory cytokine and chemokine induction in the central nervous system. J. Alzheimers Dis. 5, 105-117. https://doi.org/10.3233/JAD-2003-5205
  45. Takeda, K., Clausen, B. E., Kaisho, T., Tsujimura, T., Terada, N., Forster, I. and Akira, S. (1999) Enhanced Th1 activity and development of chronic enterocolitis in mice devoid of Stat3 in macrophages and neutrophils. Immunity 10, 39-49. https://doi.org/10.1016/S1074-7613(00)80005-9
  46. Tsunekawa, T., Banno, R., Mizoguchi, A., Sugiyama, M., Tominaga, T., Onoue, T., Hagiwara, D., Ito, Y., Iwama, S., Goto, M., Suga, H., Sugimura, Y. and Arima, H. (2017) Deficiency of PTP1B attenuates hypothalamic inflammation via activation of the JAK2-STAT3 pathway in microglia. EBioMedicine 16, 172-183. https://doi.org/10.1016/j.ebiom.2017.01.007
  47. Tyagi, A., Agarwal, C., Dwyer-Nield, L. D., Singh, R. P., Malkinson, A. M. and Agarwal, R. (2012) Silibinin modulates TNF-${\alpha}$ and IFN-${\gamma}$ mediated signaling to regulate COX2 and iNOS expression in tumorigenic mouse lung epithelial LM2 cells. Mol. Carcinog. 51, 832-842. https://doi.org/10.1002/mc.20851
  48. Yao, H., Chen, Y., Zhang, L., He, X., He, X., Lian, L., Wu, X. and Lan, P. (2014) Carnosol inhibits cell adhesion molecules and chemokine expression by tumor necrosis factor-${\alpha}$ in human umbilical vein endothelial cells through the nuclear factor-${\kappa}B$ and mitogen-activated protein kinase pathways. Mol. Med. Rep. 9, 476-480. https://doi.org/10.3892/mmr.2013.1839
  49. You, C. E., Moon, S. H., Lee, K. H., Kim, K. H., Park, C. W., Seo, S. J. and Cho, S. H. (2016) Effects of emollient containing bee venom on atopic dermatitis: a double-blinded, randomized, base-controlled, multicenter study of 136 patients. Ann. Dermatol. 28, 593-599. https://doi.org/10.5021/ad.2016.28.5.593
  50. Zhang, L., Tao, L., Shi, T., Zhang, F., Sheng, X., Cao, Y., Zheng, S., Wang, A., Qian, W., Jiang, L. and Lu, Y. (2015) Paeonol inhibits B16F10 melanoma metastasis in vitro and in vivo via disrupting proinflammatory cytokines-mediated NF-${\kappa}B$ and STAT3 pathways. IUBMB Life 67, 778-788. https://doi.org/10.1002/iub.1435

Cited by

  1. Inhibitory effect of Carnosol on UVB-induced inflammation via inhibition of STAT3 pp.1976-3786, 2018, https://doi.org/10.1007/s12272-018-1088-1
  2. Phloxine O, a Cosmetic Colorant, Suppresses the Expression of Thymic Stromal Lymphopoietin and Acute Dermatitis Symptoms in Mice vol.26, pp.5, 2018, https://doi.org/10.4062/biomolther.2017.130
  3. Rosmarinus officinalis L. (rosemary) as therapeutic and prophylactic agent vol.26, pp.1, 2019, https://doi.org/10.1186/s12929-019-0499-8
  4. Signal Transducer and Activator of Transcription Protein 3 (STAT3): An Update on its Direct Inhibitors as Promising Anticancer Agents vol.26, pp.27, 2017, https://doi.org/10.2174/0929867325666180719122729
  5. Anti-inflammatory effect of bee venom in phthalic anhydride-induced atopic dermatitis animal model vol.28, pp.1, 2017, https://doi.org/10.1007/s10787-019-00646-w
  6. Anti-Inflammatory Effects of Bee Venom on Phthalic Anhydride-Induced Atopic Dermatitis vol.37, pp.1, 2017, https://doi.org/10.13045/jar.2019.00087
  7. Rosemary ( Rosmarinus officinalis L., syn Salvia rosmarinus Spenn.) and Its Topical Applications: A Review vol.9, pp.5, 2020, https://doi.org/10.3390/plants9050651
  8. Effect of Bee Venom Pharmacopuncture on Inflammation in Mouse Model of Induced Atopic Dermatitis vol.37, pp.2, 2017, https://doi.org/10.13045/jar.2020.00122
  9. Suppressive Effect of Carnosol on Ovalbumin-Induced Allergic Asthma vol.29, pp.1, 2017, https://doi.org/10.4062/biomolther.2020.050
  10. Rosemary (Rosmarinus officinalis L.): extraction techniques, analytical methods and health-promoting biological effects vol.20, pp.6, 2017, https://doi.org/10.1007/s11101-021-09745-5
  11. Carnosol attenuates bleomycin-induced lung damage via suppressing fibrosis, oxidative stress and inflammation in rats vol.287, pp.None, 2017, https://doi.org/10.1016/j.lfs.2021.120059