图书馆订阅: Guest
Begell Digital Portal Begell 数字图书馆 电子图书 期刊 参考文献及会议录 研究收集
环境病理学,毒理学和肿瘤学期刊
影响因子: 1.625 5年影响因子: 1.63 SJR: 0.402 SNIP: 0.613 CiteScore™: 2.3

ISSN 打印: 0731-8898
ISSN 在线: 2162-6537

环境病理学,毒理学和肿瘤学期刊

DOI: 10.1615/JEnvironPatholToxicolOncol.2020032544
pages 89-99

Tilianin Protects Diabetic Retina through the Modulation of Nrf2/TXNIP/NLRP3 Inflammasome Pathways

Yunda Zhang
Department of Vitreoretinopathy, Shanxi Eye Hospital, Taiyuan, Shanxi, China
Zhao Gao
Department of Vitreoretinopathy, Shanxi Eye Hospital, Taiyuan, Shanxi, China; Department of Ophthalmology, Tianjin Medical University General Hospital, Tianjin, China
Xiaohong Gao
Department of Vitreoretinopathy, Shanxi Eye Hospital, Taiyuan, Shanxi, China
Zhigang Yuan
Department of Vitreoretinopathy, Shanxi Eye Hospital, Taiyuan, Shanxi, China
Tao Ma
Department of Vitreoretinopathy, Shanxi Eye Hospital, Taiyuan, Shanxi, China
Gaiyun Li
Department of Vitreoretinopathy, Shanxi Eye Hospital, Taiyuan, Shanxi, China
Ximei Zhang
Department of Vitreoretinopathy, Shanxi Eye Hospital, Taiyuan, Shanxi, China

ABSTRACT

Oxidative stress and inflammation are regarded as prime reasons for the progression and development of diabetic retinopathy. Currently, nuclear factor erythroid-2-related factor 2 (Nrf2), thioredoxin interacting protein (TXNIP) and NLRP3 inflammasome pathways are under increasing focus in research on oxidative stress and inflammation-related diseases. On the other hand, tilianin (TN) has received much attention because of its various pharmacological properties. Based on results of these studies, this investigation was performed to inspect the therapeutic efficiency of TN on the retina in diabetic rats. Rats were arbitrarily assigned to three groups: control group, diabetic group, and diabetic plus TN (20 mg/ kg body weight for 42 days, orally) group. TN supplementation in diabetic rats, their food intake, fasting blood glucose status, glycosylated hemoglobin (HbA1c) levels were drastically reduced, and there was a marked augmentation in serum insulin status. TN treatment of diabetic rats increased mRNA expression of Nrf2 and its target gene, HO-1, and noticeably decreased the malondialdehyde status. Activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidases (GPX) were increased relative to diabetic rats. Furthermore, administering TN to the diabetic rats resulted in decreased expression of TXNIP, NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), caspase-1, and IL-1β proteins and decreased distribution of TXNIP, NLRP3, ASC, and caspase-1 proteins in retinas. In addition, TN treatment ameliorated morphological and morphometric changes in the retinas of diabetic rats. Together, all of these findings provide clear evidence that TN treatment of diabetic rats attenuated diabetic retinal changes through its hypoglycemic, antioxidant, and anti-inflammatory properties. The antioxidant and anti-inflammatory effects in diabetic retinas occur at least in part through the modulation of Nrf2/TXNIP/NLRP3 inflammasome pathways, which may have remedial benefits in the healing of diabetic retinopathy.

REFERENCES

  1. Lee R, Wong TY, Sabanayagam C. Epidemiology of diabetic retinopathy, diabetic macular edema and related vision loss. Eye Vis (Lond). 2015;2(1):17.

  2. Kawasaki R, Cheung N, Islam FA, Klein R, Klein BE, Cotch MF, Sharrett AR, O'Leary D, Wong TY; Multi-Ethnic Study of Atherosclerosis. Is diabetic retinopathy related to subclinical cardiovascular disease. Ophthalmology. 2011;118(5):860-5.

  3. Kern TS, Antonetti DA, Smith LEH. Pathophysiology of diabetic retinopathy: contribution and limitations of laboratory research. Ophthalmic Res. 2019;62(4):196-202.

  4. Liu Q, Zhang F, Zhang X, Cheng R, Ma JX, Yi J, Li J. Fenofibrate ameliorates diabetic retinopathy by modulating Nrf2 signaling and NLRP3 inflammasome activation. Mol Cell Biochem. 2018;445(1-2):105-15.

  5. Calderon GD, Juarez OH, Hernandez GE, Punzo SM, De la Cruz ZD. Oxidative stress and diabetic retinopathy: development and treatment. Eye (Lond). 2017;31(8):1122-30.

  6. Olvera-Montana C, Castellanos-Gonzalez JA, Navarro-Partida J, Cardona-Munoz EG, Lopez-Contreras AK, Roman-Pinto LM, Robles-Rivera RR, Rodriguez-Carrizalez AD. Oxidative stress as the main target in diabetic retinopathy pathophysiology. J Diabetes Res. 2019;2019:8562408.

  7. Chen W, Zhao M, Zhao S, Lu Q, Ni L, Zou C, Lu L, Xu X, Guan H, Zheng Z, Qiu Q. Activation of the TXNIP/NLRP3 inflammasome pathway contributes to inflammation in diabetic retinopathy: a novel inhibitory effect of minocycline. Inflamm Res. 2017;66(2):157-66.

  8. Perrone L, Devi TS, Hosoya KI, Terasaki T, Singh LP. Thioredoxin interacting protein (TXNIP) induces inflammation through chromatin modification in retinal capillary endothelial cells under diabetic conditions. J Cell Physiol. 2009;221(1):262-72.

  9. Vincent JA, Mohr S. Inhibition of caspase-1/interleukin-1p signaling prevents degeneration of retinal capillaries in diabetes and galactosemia. Diabetes. 2007;56(1):224-30.

  10. Kowluru RA, Odenbach S. Role of interleukin-1p in the pathogenesis of diabetic retinopathy. Br J Ophthalmol. 2004; 88(10):1343-7.

  11. Julius A, Hopper W. A non-invasive, multi-target approach to treat diabetic retinopathy. Biomed Pharmacother. 2019;109:708-15.

  12. Gupta SK, Kumar B, Nag TC, Agrawal SS, Agrawal R, Agrawal P, Saxena R, Srivastava S. Curcumin prevents experimental diabetic retinopathy in rats through its hypoglycemic, antioxidant, and anti-inflammatory mechanisms. J Ocul Pharmacol Ther. 2011;27(2):123-30.

  13. Steigerwalt R, Belcaro G, Cesarone MR, Di Renzo A, Grossi MG, Ricci A, Dugall M, Cacchio M, Schonlau F. Pycnogenol improves microcirculation, retinal edema, and visual acuity in early diabetic retinopathy. J Ocul Pharmacol Ther. 2009;25(6):537-40.

  14. Spadea L, Balestrazzi E. Treatment of vascular retinopathies with Pycnogenol. Phytother Res. 2001;15(3):219-23.

  15. Nakajima M, Cooney MJ, Tu AH, Chang KY, Cao J, Ando A, An GJ, Melia M, de Juan E. Normalization of retinal vascular permeability in experimental diabetes with genistein. Invest Ophthalmol Vis Sci. 2001;42(9):2110-4.

  16. Kumar B, Gupta SK, Nag TC, Srivastava S, Saxena R. Green tea prevents hyperglycemia-induced retinal oxidative stress and inflammation in streptozotocin-induced diabetic rats. Ophthalmic Res. 2012;47(2):103-8.

  17. Kumar VL, Padhy BM. Protective effect of aqueous suspension of dried latex of Calotropis procera against oxidative stress and renal damage in diabetic rats. Biocell. 2011;35(3):63-9.

  18. Chen Y, Li XX, Xing NZ, Cao XG. Quercetin inhibits choroidal and retinal angiogenesis in vitro. Graefes Arch Clin Exp Ophthalmol. 2008;246(3):373-8.

  19. Kim JH, Lee BJ, Yu YS, Kim MY, Kim KW. Rosmarinic acid suppresses retinal neovascularization via cell cycle arrest with increase of p21WAF1 expression. Eur J Pharmacol. 2009;615(1-3):150-4.

  20. Akanda MR, Uddin MN, Kim IS, Ahn D, Tae HJ, Park BY. The biological and pharmacological roles of polyphenol flavonoid tilianin. Eur J Pharmacol. 2019 Jan 5;842:291-7.

  21. Zeng C, Jiang W, Zheng R, He C, Li J, Xing J. Cardioprotection of tilianin ameliorates myocardial ischemia-reper-fusion injury: role of the apoptotic signaling pathway. PLoS One. 2018;13(3):e0193845.

  22. Oh HM, Kang YJ, Lee YS, Park MK, Kim SH, Kim HJ, Seo HG, Lee JH, Chang KC. Protein kinase G-dependent heme oxygenase-1 induction by Agastache rugosa leaf extract protects RAW264.7 cells from hydrogen peroxide-induced injury. J Ethnopharmacol. 2006;103(2):229-35.

  23. Garcia-Diaz JA, Navarrete-Vazquez G, Garcia-Jimenez S, Hidalgo-Figueroa S, Almanza-Perez JC, Alarcon-Aguilar FJ, Gomez-Zamudio J, Cruz M, Ibarra-Barajas M, Estrada-Soto S. Antidiabetic, antihyperlipidemic and anti-inflammatory effects of tilianin in streptozotocin-nicotinamide diabetic rats. Biomed Pharmacother. 2016;83:667-75.

  24. Gong CY, Lu B, Hu QW, Ji LL. Streptozotocin induced diabetic retinopathy in rat and the expression of vascular endothelial growth factor and its receptor. Int J Ophthalmol. 2013;6(5):573-7.

  25. Ahmad U, Ahmad RS. Anti diabetic property of aqueous extract of Stevia rebaudiana Bertoni leaves in streptozotocin-induced diabetes in albino rats. BMC Complement Altern Med. 2018;18(1):179.

  26. Hernandez-Abreu O, Torres-Piedra M, Garcia-Jimenez S, Ibarra-Barajas M, Villalobos-Molina R, Montes S, Rembao D, Estrada-Soto S. Dose-dependent antihypertensive determination and toxicological studies of tilianin isolated from Agastache mexicana. J Ethnopharmacol. 2013;146(1):187-91.

  27. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979 Jun 1;95(2):351-8.

  28. Misra HP, Fridovich I. The role of superoxide anion in the autoxidation of epinephrine and a simple assay for super-oxide dismutase. J Biol Chem. 1972;247(10):3170-5.

  29. Sinha AK. Colorimetric assay of catalase. Anal Biochem. 1972;47(2):389-94.

  30. Chiu DT, Stults FH, Tappel AL. Purification and properties of rat lung soluble glutathione peroxidase. Biochim Biophys Acta. 1976;445(3):558-66.

  31. Lee R, Wong TY, Sabanayagam C. Epidemiology of diabetic retinopathy, diabetic macular edema and related vision loss. Eye Vis (Lond). 2015;2(1):17.

  32. Homme RP, Singh M, Majumder A, George AK, Nair K, Sandhu HS, Tyagi N, Lominadze D, Tyagi SC. Remodeling of retinal architecture in diabetic retinopathy: disruption of ocular physiology and visual functions by inflammatory gene products and pyroptosis. Front Physiol. 2018;9:1268.

  33. Loukovaara S, Piippo N, Kinnunen K, Hytti M, Kaarniranta K, Kauppinen A. NLRP3 inflammasome activation is associated with proliferative diabetic retinopathy. Acta Ophthalmol. 2017;95(8):803-8.

  34. Yang DK, Kang HS. Anti-diabetic effect of cotreatment with quercetin and resveratrol in streptozotocin-induced diabetic rats. Biomol Ther (Seoul). 2018;26(2):130-8.

  35. Ragy MM, Ahmed SM. Protective effects of either C-peptide or L-arginine on pancreatic P-cell function, proliferation, and oxidative stress in streptozotocin-induced diabetic rats. J Cellular Physiol. 2019;234(7):11500-10.

  36. Tian L, Cao W, Yue R, Yuan Y, Guo X, Qin D, Xing J, Wang X. Pretreatment with tilianin improves mitochondrial energy metabolism and oxidative stress in rats with myocardial ischemia/reperfusion injury via AMPK/ SIRT1/PGC-1 alpha signaling pathway. J Pharmacol Sci. 2019;139(4):352-60.

  37. Tkachev VO, Menshchikova EB, Zenkov NK. Mechanism of the Nrf2/Keap1/ARE signaling system. Biochemistry (Mosc). 2011;76(4):407-22.

  38. David JA, Rifkin WJ, Rabbani PS, Ceradini DJ. The Nrf2/Keap1/ARE pathway and oxidative stress as a therapeutic target in type II diabetes mellitus. J Diabetes Res. 2017:4826724. doi: 10.1155/2017/4826724.

  39. Xu Z, Wei Y, Gong J, Cho H, Park JK, Sung ER, Huang H, Wu L, Eberhart C, Handa JT, Du Y, Kern TS, Thimmulappa R, Barber AJ, Biswal S, Duh EJ. NRF2 plays a protective role in diabetic retinopathy in mice. Diabetologia. 2014;57(1):204-13.

  40. Inoue Y, Shimazawa M, Nagano R, Kuse Y, Takahashi K, Tsuruma K, Hayashi M, Ishibashi T, Maoka T, Hara H. Astaxanthin analogs, adonixanthin and lycopene, activate Nrf2 to prevent light-induced photoreceptor degeneration. J Pharmacol Sci. 2017;134(3):147-57.

  41. Sun Y, Xiu C, Liu W, Tao Y, Wang J, Qu YI. Grape seed proanthocyanidin extract protects the retina against early diabetic injury by activating the Nrf2 pathway. Exp Ther Med. 2016;11(4):1253-8.

  42. Oh HM, Kang YJ, Lee YS, Park MK, Kim SH, Kim HJ, Seo HG, Lee JH, Chang KC. Protein kinase G-dependent heme oxygenase-1 induction by Agastache rugosa leaf extract protects RAW264.7 cells from hydrogen peroxide-induced injury. J Ethnopharmacol. 2006;103(2):229-35.

  43. Cao Y, Li X, Shi P, Wang LX, Sui ZG. Effects of L-carnitine on high glucose-induced oxidative stress in retinal ganglion cells. Pharmacology. 2014;94(3-4):123-30.

  44. Perrone L, Devi TS, Hosoya KI, Terasaki T, Singh LP. Inhibition of TXNIP expression in vivo blocks early pathologies of diabetic retinopathy. Cell Death Dis. 2010;1(8):e65.

  45. Devi TS, Hosoya KI, Terasaki T, Singh LP. Critical role of TXNIP in oxidative stress, DNA damage and retinal pericyte apoptosis under high glucose: implications for diabetic retinopathy. Exper Cell Res. 2013;319(7):1001-12.

  46. Yin Y, Chen F, Wang W, Wang H, Zhang X. Resolvin D1 inhibits inflammatory response in STZ-induced diabetic retinopathy rats: possible involvement of NLRP3 inflammasome and NF-KB signaling pathway. Mol Vis. 2017;23:242-50.

  47. Zhang ZH, Chen QZ, Jiang F, Townsend TA, Mao CJ, You CY, Yang WH, Sun ZY, Yu JG, Yan H. Changes in TL1A levels and associated cytokines during pathogenesis of diabetic retinopathy. Mol Med Rep. 2017;15(2):573-80.


Articles with similar content:

Protective Role of Naringenin Against Doxorubicin-Induced Cardiotoxicity in a Rat Model: Histopathology and mRNA Expression Profile Studies
Journal of Environmental Pathology, Toxicology and Oncology, Vol.33, 2014, issue 4
Kumaresan Ganesan, Murugesan Ramachandran, Swathika Subburaman
Protective Role of Curcumin and Flunixin Against Acetic Acid−Induced Inflammatory Bowel Disease via Modulating Inflammatory Mediators and Cytokine Profile in Rats
Journal of Environmental Pathology, Toxicology and Oncology, Vol.34, 2015, issue 4
G BOOBALAN, Matukumalli Usha Rani, C.S.V. Satish Kumar, Alla Gopala Reddy, Rasakatla Dileep, Matham Vijay Kumar
Acute Exposure of Uranyl Nitrate Causes Lipid Peroxidation and Histopathological Damage in Brain and Bone of Wistar Rat
Journal of Environmental Pathology, Toxicology and Oncology, Vol.26, 2007, issue 4
Amit Kumar, Kaushala Prasad Mishra, Badri Narain Pandey, Somnath Ghosh
Influence of Caffeine on Allyl Alcohol-Induced Hepatotoxicity in Rats* I. In Vivo Study
Journal of Environmental Pathology, Toxicology and Oncology, Vol.20, 2001, issue 2
Maria Karas, Saroj K. Chakrabarti
Thyroidal Effects of Di-(2-Ethylhexyl) Phthalate in Rats of Different Selenium Status
Journal of Environmental Pathology, Toxicology and Oncology, Vol.31, 2012, issue 2
Isabelle Hininger-Favier, Anne-Marie Roussel, Murat Kizilgun, Alain Favier, Belma Kocer-Gumusel, Filiz Hincal, Pinar Erkekoglu, Walid Rachidi