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Schisandrae Fructus Ameliorates Topical Particulate Matter 2.5-induced Keratoconjunctivitis Sicca That Are Accompanied by Retinal and Lipid Metabolism Disorders

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Abstract

Particulate matter 2.5 (PM2.5) is the biological toxic substances in the air pollutants, and causes to dry eye disease. To date, studies on the development of treatment for PM2.5-mediated dry eye disease are extremely limited. Schisandrae Fructus (SF), the fruit of Schisandra chinensis Turcz. (Baillon), has been used as traditionally herbal medicine in Northeastern Asia. SF has various pharmacological effects, but its effect on the ocular system have not been well defined. The aim of the present study was to investigate the effect of SF ethanol extract (SFE) on topical PM2.5-mediated dry eye symptoms in rats. SFE ameliorated tear deficiency, corneal epithelium detachment, reduction of conjunctival goblet cell, and inflammation of cornea and lacrimal gland induced by PM2.5 exposure. In addition, SFE markedly suppressed PM2.5-induced changes in the retinal composition, including loss of ganglion cells. Furthermore, oral administration of SFE significantly restrained PM2.5-induced increasing levels of total cholesterol and low low-density lipoprotein cholesterol. In conclusion, oral application of SFE may have protective effects against dry eye disease by PM2.5 exposure that result from restoration of tear film and inhibition of inflammation, and may in part contribute to improvement of retinal disorder and dyslipidemia.

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References

  1. Bo, Y., L.-Y. Chang, C. Guo, C. Lin, A. K. H. Lau, T. Tam, and X. Q. Lao (2021) Reduced ambient PM2.5, better lung function, and decreased risk of chronic obstructive pulmonary disease. Environ. Int. 156: 106706.

    CAS  PubMed  Google Scholar 

  2. Hyun, S.-W., S. J. Song, B. Park, T. G. Lee, and C.-S. Kim (2020) Toxicological effects of urban particulate matter on corneal and conjunctival epithelial cells. Toxicol. Res. 36: 311–318.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Lee, H., H. Hwang-Bo, S. Y. Ji, M. Y. Kim, S. Y. Kim, C. Park, S. H. Hong, G.-Y. Kim, K. S. Song, J. W. Hyun, and Y. H. Choi (2020) Diesel particulate matter2.5 promotes epithelialmesenchymal transition of human retinal pigment epithelial cells via generation of reactive oxygen species. Environ. Pollut. 262: 114301.

    CAS  PubMed  Google Scholar 

  4. Yang, Y., Z. Ruan, X. Wang, Y. Yang, T. G. Mason, H. Lin, and L. Tian (2019) Short-term and long-term exposures to fine particulate matter constituents and health: A systematic review and meta-analysis. Environ. Pollut. 247: 874–882.

    CAS  PubMed  Google Scholar 

  5. Lin, C.-C., C.-C. Chiu, P.-Y. Lee, K.-J. Chen, C.-X. He, S.-K. Hsu, and K.-C. Cheng (2022) The adverse effects of air pollution on the eye: a review. Int. J. Environ. Res. Public Health 19: 1186.

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Jung, S. J., J. S. Mehta, and L. Tong (2018) Effects of environment pollution on the ocular surface. Ocul. Surf. 16: 198–205.

    PubMed  Google Scholar 

  7. Mandell, J. T., M. Idarraga, N. Kumar, and A. Galor (2020) Impact of air pollution and weather on dry eye. J. Clin. Med. 9: 3740.

    PubMed  PubMed Central  Google Scholar 

  8. Yang, Q., K. Li, D. Li, Y. Zhang, X. Liu, and K. Wu (2019) Effects of fine particulate matter on the ocular surface: an in vitro and in vivo study. Biomed. Pharmacother. 117: 109177.

    CAS  PubMed  Google Scholar 

  9. Kashiwagi, K. and Y. Iizuka (2020) Effect and underlying mechanisms of airborne particulate matter 2.5 (PM2.5) on cultured human corneal epithelial cells. Sci. Rep. 10: 19516.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Song, S. J., S.-W. Hyun, T. G. Lee, B. Park, K. Jo, I. S. Lee, and C.-S. Kim (2019) Topical application of Liriope platyphylla extract attenuates dry eye syndrome induced by particulate matter. J. Ophthalmol. 2019: 1429548.

    PubMed  PubMed Central  Google Scholar 

  11. Lee, T. G., S.-W. Hyun, K. Jo, B. Park, I. S. Lee, S. J. Song, and C.-S. Kim (2019) Achyranthis radix extract improves urban particulate matter-induced dry eye disease. Int. J. Environ. Res. Public Health 16: 3229.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Kopustinskiene, D. M. and J. Bernatoniene (2021) Antioxidant effects of Schisandra chinensis fruits and their active constituents. Antioxidants (Basel) 10: 620.

    CAS  PubMed  Google Scholar 

  13. Nowak, A., M. Zakłos-Szyda, J. Błasiak, A. Nowak, Z. Zhang, and B. Zhang (2019) Potential of Schisandra chinensis (Turcz.) Baill. in human health and nutrition: a review of current knowledge and therapeutic perspectives. Nutrients 11: 333.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Chen, X., Y. Zhang, Y. Zu, and L. Yang (2021) Chemical composition and antioxidant activity of the essential oil of Schisandra chinensis fruits. Nat. Prod. Res. 26: 842–849.

    Google Scholar 

  15. Jeong, J.-W., H. H. Lee, E.-O. Choi, K. W. Lee, K. Y. Kim, S. G. Kim, S. H. Hong, G.-Y. Kim, C. Park, H. K. Kim, Y. W. Choi, and Y. H. Choi (2015) Schisandrae fructus inhibits IL-1β-induced matrix metalloproteinases and inflammatory mediators production in SW1353 human chondrocytes by suppressing NF-κB and MAPK activation. Drug Dev. Res. 76: 474–483.

    CAS  PubMed  Google Scholar 

  16. Li, X., M. Li, S. Deng, T. Yu, Y. Ma, H. Yang, J. Zhang, Y. Zheng, and L. Ma (2021) A network pharmacology-integrated metabolomics strategy for clarifying the action mechanisms of Schisandrae chinensis fructus for treating drug-induced liver injury by acetaminophen. Bioorg. Med. Chem. 31: 115992.

    CAS  PubMed  Google Scholar 

  17. Jeong, J.-W., J. Kim, E. O. Choi, D. H. Kwon, G. M. Kong, I.-W. Choi, B. H. Kim, G.-Y. Kim, K. W. Lee, K. Y. Kim, S. G. Kim, Y. W. Choi, S. H. Hong, C. Park, and Y. H. Choi (2017) Schisandrae Fructus ethanol extract ameliorates inflammatory responses and articular cartilage damage in monosodium iodoacetate-induced osteoarthritis in rats. EXCLI J. 16: 265–277.

    PubMed  PubMed Central  Google Scholar 

  18. Zhang L, L. Xiang, Y. Liu, P. Venkatraman, L. Chong, J. Cho, S. Bonilla, Z.-B. Jin, C. P. Pang, K. M. Ko, P. Ma, M. Zhang, and Y. F. Leung (2016) A naturally-derived compound Schisandrin B enhanced light sensation in the pde6c zebrafish model of retinal degeneration. PLoS One 11: e0149663. (Erratum published 2016, PLoS One 11: e0154552)

    PubMed  PubMed Central  Google Scholar 

  19. Lee, H., M. Y. Kim, S. Y. Ji, D. H. Kim, S. Y. Kim, H. Hwangbo, C. Park, S. H. Hong, G.-Y. Kim, and Y. H. Choi (2021) The protective effect of oral application of Corni Fructus on the disorders of the cornea, conjunctiva, lacrimal gland and retina by topical particulate matter 2.5. Nutrients 13: 2986.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Lee, H. S., S. Han, J.-W. Seo, and K.-J. Jeon (2020) Exposure to traffic-related particulate matter 2.5 triggers Th2-dominant ocular immune response in a murine model. Int. J. Environ. Res. Public Health 17: 2965.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Pflugfelder, S. C., W. Farley, L. Luo, L. Z. Chen, C. S. de Paiva, L. C. Olmos, D.-Q. Li, and M. E. Fini (2005) Matrix metalloproteinase-9 knockout confers resistance to corneal epithelial barrier disruption in experimental dry eye. Am. J. Pathol. 166: 61–71.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Ma, X., S. Shimmura, H. Miyashita, S. Yoshida, M. Kubota, T. Kawakita, and K. Tsubota (2009) Long-term culture and growth kinetics of murine corneal epithelial cells expanded from single corneas. Invest. Ophthalmol. Vis. Sci. 50: 2716–2721.

    PubMed  Google Scholar 

  23. Kim, M. Y., Y. W. Choi, and H. S. Hwang (2021) Regulatory effect on skin differentiation by mevastatin in psoriasis model using TNF-α and IL-17-induced HaCaT cells. Biotechnol. Bioprocess Eng. 26: 348–358.

    CAS  Google Scholar 

  24. Kim, M. and A. Moon (2021) A curcumin analog CA-5f inhibits urokinase-type plasminogen activator and invasive phenotype of triple-negative breast cancer cells. Toxicol. Res. 38: 19–26.

    PubMed  PubMed Central  Google Scholar 

  25. Kono, M., T. Okuda, N. Ishihara, H. Hagino, Y. Tani, H. Okochi, C. Tokoro, M. Takaishi, H. Ikeda, and Y. Ishihara (2022) Chemokine expression in human 3-dimensional cultured epidermis exposed to PM2.5 collected by cyclonic separation. Toxicol. Res. 39: 1–13.

    PubMed  Google Scholar 

  26. McGuinn, L. A., A. Schneider, R. W. McGarrah, C. Ward-Caviness, L. M. Neas, Q. Di, J. Schwartz, E. R. Hauser, W. E. Kraus, W. E. Cascio, D. Diaz-Sanchez, and R. B. Devlin (2019) Association of long-term PM2.5 exposure with traditional and novel lipid measures related to cardiovascular disease risk. Environ. Int. 122: 193–200.

    CAS  PubMed  Google Scholar 

  27. Wallwork, R. S., E. Colicino, J. Zhong, I. Kloog, B. A. Coull, P. Vokonas, J. D. Schwartz, and A. A. Baccarelli (2017) Ambient fine particulate matter, outdoor temperature, and risk of metabolic syndrome. Am. J. Epidemiol. 185: 30–39.

    PubMed  Google Scholar 

  28. Shin, W.-Y., J.-H. Kim, G. Lee, S. Choi, S. R. Kim, Y.-C. Hong, and S. M. Park (2020) Exposure to ambient fine particulate matter is associated with changes in fasting glucose and lipid profiles: a nationwide cohort study. BMC Public Health 20: 430.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Mao, S., S. Li, C. Wang, Y. Liu, N. Li, F. Liu, S. Huang, S. Liu, Y. Lu, Z. Mao, W. Huo, G. Chen, H. Xiang, and Y. Guo (2020) Is long-term PM1 exposure associated with blood lipids and dyslipidemias in a Chinese rural population? Environ. Int. 138: 105637.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Park, H. J., H.-J. Kim, S. R. Kim, M.-S. Choi, and U. J. Jung (2017) Omija fruit ethanol extract improves adiposity and related metabolic disturbances in mice fed a high-fat diet. J. Nutr. Biochem. 41: 137–141.

    CAS  PubMed  Google Scholar 

  31. Sun, N., S.-Y. Pan, Y. Zhang, X.-Y. Wang, P.-L. Zhu, Z.-S. Chu, Z.-L. Yu, S.-F. Zhou, and K.-M. Ko (2014) Dietary pulp from Fructus Schisandra Chinensis supplementation reduces serum/ hepatic lipid and hepatic glucose levels in mice fed a normal or high cholesterol/bile salt diet. Lipids Health Dis. 13: 46.

    PubMed  PubMed Central  Google Scholar 

  32. Pan, S.-Y., H. Dong, X.-Y. Zhao, C.-J. Xiang, H.-Y. Fang, W.-F. Fong, Z.-L. Yu, and K.-M. Ko (2008) Schisandrin B from Schisandra chinensis reduces hepatic lipid contents in hypercholesterolaemic mice. J. Pharm. Pharmacol. 60: 399–403.

    CAS  PubMed  Google Scholar 

  33. Lee, S.-E., H. Kim, C.-H. Kim, C. Lim, and S. Cho (2019) Effect of methanol extract of Schisandrae Fructus on high fat diet induced hyperlipidemic mice. J. Tradit. Chin. Med. 39: 818–825.

    Google Scholar 

  34. Pflugfelder, S. C. and C. S. de Paiva (2017) The pathophysiology of dry eye disease: what we know and future directions for research. Ophthalmology 124: S4–S13.

    PubMed  Google Scholar 

  35. Zhou, L. and R. W. Beuerman (2012) Tear analysis in ocular surface diseases. Prog. Retin. Eye Res. 31: 527–550.

    CAS  PubMed  Google Scholar 

  36. Inatomi, T., S. Spurr-Michaud, A. S. Tisdale, Q. Zhan, S. T. Feldman, and I. K. Gipson (1996) Expression of secretory mucin genes by human conjunctival epithelia. Invest. Ophthalmol. Vis. Sci. 37: 1684–1692.

    CAS  PubMed  Google Scholar 

  37. Yang, Q.-C., J. Bao, C. Li, G. Tan, A.-H. Wu, L. Ye, L.-H. Ye, Q. Zhou, and Y. Shao (2018) A murine model of dry eye induced by topical administration of erlotinib eye drops. Int. J. Mol. Med. 41: 1427–1436.

    CAS  PubMed  Google Scholar 

  38. Dana, M. R. and P. Hamrah (2002) Role of immunity and inflammation in corneal and ocular surface disease associated with dry eye. Adv. Exp. Med. Biol. 506: 729–738.

    CAS  PubMed  Google Scholar 

  39. Korn, T., J. Reddy, W. Gao, E. Bettelli, A. Awasthi, T. R. Petersen, B. T. Bäckström, R. A. Sobel, K. W. Wucherpfennig, T. B. Strom, M. Oukka, and V. K. Kuchroo (2007) Myelin-specific regulatory T cells accumulate in the CNS but fail to control autoimmune inflammation. Nat. Med. 13: 423–431.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Ouyang, W., Y. Wu, X. Lin, S. Wang, Y. Yang, L. Tang, Z. Liu, J. Wu, C. Huang, Y. Zhou, X. Zhang, J. Hu, and Z. Liu (2021) Role of CD4+ T helper cells in the development of BAC-induced dry eye syndrome in mice. Invest. Ophthalmol. Vis. Sci. 62: 25.

    CAS  PubMed  PubMed Central  Google Scholar 

  41. McGeachy, M. J. and D. J. Cua (2008) Th17 cell differentiation: the long and winding road. Immunity 28: 445–453.

    CAS  PubMed  Google Scholar 

  42. Cui, Y.-H., Z.-X. Hu, Z.-X. Gao, X.-L. Song, Q.-Y. Feng, G. Yang, Z.-J. Li, and H.-W. Pan (2018) Airborne particulate matter impairs corneal epithelial cells migration via disturbing FAK/RhoA signaling pathway and cytoskeleton organization. Nanotoxicology 12: 312–324.

    CAS  PubMed  Google Scholar 

  43. Niu, L., L. Li, C. Xing, B. Luo, C. Hu, M. Song, J. Niu, Y. Ruan, X. Sun, and Y. Lei (2021) Airborne particulate matter (PM2.5) triggers cornea inflammation and pyroptosis via NLRP3 activation. Ecotoxicol. Environ. Saf. 207: 111306.

    CAS  PubMed  Google Scholar 

  44. Hyun, S.-W., J. Kim, B. Park, K. Jo, T. G. Lee, J. S. Kim, and C.-S. Kim (2019) Apricot kernel extract and amygdalin inhibit urban particulate matter-induced keratoconjunctivitis sicca. Molecules 24: 650.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Lin, X., Y. Wu, L. Tang, W. Ouyang, Y. Yang, Z. Liu, J. Wu, X. Zheng, C. Huang, Y. Zhou, X. Zhang, Y. Chen, W. Li, J. Hu, and Z. Liu (2020) Comparison of treatment effect and tolerance of the topical application of mizoribine and cyclosporine A in a mouse dry eye model. Transl. Vis. Scie. Technol. 9: 22.

    CAS  Google Scholar 

  46. Lee, H., D. H. Kim, H. Hwangbo, S. Y. Kim, S. Y. Ji, M. Y. Kim, J.-H. Shim, S.-H. Leem, J. W. Hyun, G.-Y. Kim, and Y. H. Choi (2021) The protective effect of topical spermidine on dry eye disease with retinal damage induced by diesel particulate matter2.5. Pharmaceutics 13: 1439.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Li, L. H., J. C. Lee, H. H. Leung, W. C. Lam, Z. Fu, and A. C. Y. Lo (2020) Lutein supplementation for eye diseases. Nutrients 12: 1721.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Kim, D. H., J.-H. Kim, H. Hwangbo, S. Y. Kim, S. Y. Ji, M. Y. Kim, H.-J. Cha, C. Park, S. H. Hong, G.-Y. Kim, S.-K. Park, J.-W. Jeong, M.-Y. Kim, Y. H. Choi, and H. Lee (2021) Spermidine attenuates oxidative stress-induced apoptosis via blocking Ca2+ overload in retinal pigment epithelial cells independently of ROS. Int. J. Mol. Sci. 22: 1361.

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Kim, S., H. Park, H. Park, B. Joung, and E. Kim (2016) The acute respiratory exposure by intratracheal instillation of Sprague-Dawley rats with diesel particulate matter induces retinal thickening. Cutan. Ocul. Toxicol. 35: 275–280.

    CAS  PubMed  Google Scholar 

  50. Chua, S. Y. L., A. Warwick, T. Peto, K. Balaskas, A. T. Moore, C. Reisman, P. Desai, A. J. Lotery, B. Dhillon, P. T. Khaw, C. G. Owen, A. P. Khawaja, P. J. Foster, P. J. Patel, and UK Biobank Eye and Vision Consortium (2022) Association of ambient air pollution with age-related macular degeneration and retinal thickness in UK Biobank. Br. J. Ophthalmol. 106: 705–711.

    PubMed  Google Scholar 

  51. Louwies, T., C. Vuegen, L. I. Panis, B. Cox, K. Vrijens, T. S. Nawrot, and P. De Boever (2016) miRNA expression profiles and retinal blood vessel calibers are associated with short-term particulate matter air pollution exposure. Environ. Res. 147: 24–31.

    CAS  PubMed  Google Scholar 

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Acknowledgements

This work was funded by the Basic Science Research Program through the National Research Foundation (grant numbers, 2021R1A2C200954911).

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Authors and Affiliations

  1. Anti-Aging Research Center, Dong-eui University, Busan, 47340, Korea

    Hyesook Lee, Hyun Hwangbo, Da Hye Kim, Min Yeong Kim, Seon Yeong Ji, Su Hyun Hong & Yung Hyun Choi

  2. Department of Biochemistry, Dong-eui University College of Korean Medicine, Busan, 47227, Korea

    Hyesook Lee, Hyun Hwangbo, Min Yeong Kim, Seon Yeong Ji, Su Hyun Hong & Yung Hyun Choi

  3. Department of Convergence Medicine, Pusan National University School of Medicine, Yangsan, 50612, Korea

    Hyesook Lee

  4. Division of Basic Sciences, College of Liberal Studies, Dong-eui University, Busan, 47340, Korea

    Cheol Park

  5. Department of Oriental Neuropsychiatry, Dong-eui University College of Korean Medicine, Busan, 47227, Korea

    Chan-Young Kwon

  6. Department of Biomedical Sciences, College of Natural Sciences, Dong-A University, Busan, 49315, Korea

    Sun-Hee Leem

  7. Department of Health Sciences, Dong-A University, Busan, 49315, Korea

    Sun-Hee Leem

  8. Department of Marine Life Science, Jeju National University, Jeju, 63243, Korea

    Gi-Young Kim

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  1. Hyesook Lee
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Correspondence to Yung Hyun Choi.

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This animal study was reviewed and approved by the Institutional Animal Care and Use Committee of Dong-eui University (Approval No. R2019-005).

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Lee, H., Hwangbo, H., Kim, D.H. et al. Schisandrae Fructus Ameliorates Topical Particulate Matter 2.5-induced Keratoconjunctivitis Sicca That Are Accompanied by Retinal and Lipid Metabolism Disorders. Biotechnol Bioproc E 28, 632–643 (2023). https://doi.org/10.1007/s12257-023-0046-z

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