Crocin Suppresses Inflammatory Response in LPS-Induced Acute Lung Injury (ALI) Via Regulation of HMGB1/TLR4 Inflammation Pathway

Abstract

Keywords

• Acute lung injury
• crocin
• inflammation
• lipopolysaccharide.

Crocin Suppresses Inflammatory Response in LPS-Induced Acute Lung Injury (ALI) Via Regulation of HMGB1/TLR4 Inflammation Pathway

Abstract

Background and Purpose: The most significant pathogen hypothesized to be causing the formation of Acute lung injury (ALI) in sepsis is thought to be lipopolysaccharide (LPS), a key endotoxin component of gram-negative bacteria. The main objective of this study is to determine possible anti-inflammatory effects of crocin (CRO) which has many biological properties such as anti-inflammatory, antioxidant, and anti-apoptotic in LPS-induced ALI. Methods: 40 Wistar albino rats were divided into four groups: Control (no treatment), CRO (given 50 mg/kg crocin for 9 days), LPS (given 30 mg/kg LPS at 9th day), LPS+CRO (given 50 mg/kg crocin for 9 days and 30 mg/kg LPS at 9th day). After experimental, rats were sacrificed and lungs were extracted. Histological examinations were performed in the lung tissue and the changes in the HMGB1 and TLR4 expressions were determined via immunohistochemical staining. Results and Conclusion: Hemorrhage, mononuclear cell infiltration and HMGB1 and TLR4 expressions significantly increased in the LPS group. However, CRO administrations exerted a strong protective effect on the lungs in terms of these parameters in LPS+CRO group. According to our results, we suggest that CRO can be considered as a protective agent against LPS induced ALI via inhibition of HMGB1/TLR4 pathway-mediated inflammatory response.

Keywords

• Acute lung injury
• crocin
• inflammation
• lipopolysaccharide.

References

1. Cinar I, Sirin B, Aydin P, Toktay E, Cadirci E, Halici I, et al. Ameliorative effect of gossypin against acute lung injury in experimental sepsis model of rats. Life Sciences. 2019;221:327-34.
2. Xiao X, Yang M, Sun D, Sun S. Curcumin protects against sepsis-induced acute lung injury in rats. Journal of Surgical Research. 2012;176(1):e31-e9.
3. Ware LB, Matthay M. The acute respiratory distress syndrome. New England Journal of Medicine. 2000;342(18):1334-49.
4. Cai X, Chen Y, Xie X, Yao D, Ding C, Chen M. Astaxanthin prevents against lipopolysaccharide-induced acute lung injury and sepsis via inhibiting activation of MAPK/NF-κB. American Journal of Translational Research. 2019;11(3):1884.
5. Fisher BJ, Seropian IM, Kraskauskas D, Thakkar JN, Voelkel NF, Natarajan R. Ascorbic acid attenuates lipopolysaccharide-induced acute lung injury. Critical Care Medicine. 2011;39(6):1454-60.
6. Mokhtari-Zaer A, Norouzi F, Askari VR, Khazdair MR, Roshan NM, Boskabady M, et al. The protective effect of Nigella sativa extract on lung inflammation and oxidative stress induced by lipopolysaccharide in rats. Journal of Ethnopharmacology. 2020;253:112653.
7. Yang H, Wang H, Czura CJ, Tracey KJ. The cytokine activity of HMGB1. Journal of Leukocyte Biology. 2005;78(1):1-8.
8. Zhong H, Li X, Zhou S, Jiang P, Liu X, Ouyang M, et al. Interplay between RAGE and TLR4 regulates HMGB1-induced inflammation by promoting cell surface expression of RAGE and TLR4. The Journal of Immunology. 2020;205(3):767-75.

9. Ogawa EN, Ishizaka A, Tasaka S, Koh H, Ueno H, Amaya F, et al. Contribution of high-mobility group box-1 to the development of ventilator-induced lung injury. American Journal of Respiratory Critical Care Medicine. 2006;174(4):400-7.
10. Ding N, Wang F, Xiao H, Xu L, She S. Mechanical ventilation enhances HMGB1 expression in an LPS-induced lung injury model. PloS one. 2013;8(9):e74633.
11. Ali I, Nanchal R, Husnain F, Audi S, Konduri GG, Densmore JC, et al. Hypoxia preconditioning increases survival and decreases expression of Toll-like receptor 4 in pulmonary artery endothelial cells exposed to lipopolysaccharide. Pulmonary Circulation. 2013;3(3):578-88.
12. Wu Y, Liu Y, Huang H, Zhu Y, Zhang Y, Lu F, et al. Dexmedetomidine inhibits inflammatory reaction in lung tissues of septic rats by suppressing TLR4/NF-κB pathway. Mediators of Inflammation. 2013;2013.
13. Tang J, Xu L, Zeng Y, Gong F. Effect of gut microbiota on LPS-induced acute lung injury by regulating the TLR4/NF-kB signaling pathway. International Immunopharmacology. 2021;91:107272.
14. Rezaei N, Avan A, Pashirzad M, Rahmani F, Moradi Marjaneh R, Behnam-Rassouli R, et al. Crocin as a novel therapeutic agent against colitis. Drug and Chemical Toxicology. 2020;43(5):514-21.
15. Suh KS, Chon S, Jung W-W, Choi EM. Crocin attenuates methylglyoxal-induced osteoclast dysfunction by regulating glyoxalase, oxidative stress, and mitochondrial function. Food and Chemical Toxicology. 2019;124:367-73.
16. Hashemzaei M, Mamoulakis C, Tsarouhas K, Georgiadis G, Lazopoulos G, Tsatsakis A, et al. Crocin: a fighter against inflammation and pain. Food and Chemical Toxicology. 2020;143:111521.
17. Korani S, Korani M, Sathyapalan T, Sahebkar A. Therapeutic effects of Crocin in autoimmune diseases: A review. BioFactors. 2019;45(6):835-43. 18. Goraca A, Józefowicz-Okonkwo G. Protective effect of an early treatment with lipoic acid in LPS-induced lung injury in rats. Journal of Physiology and Pharmacology. 2007;58(3):541-9.
18. Xie Y, He Q, Chen H, Lin Z, Xu Y, Yang C. Crocin ameliorates chronic obstructive pulmonary disease-induced depression via PI3K/Akt mediated suppression of inflammation. European Journal of Pharmacology. 2019;862:172640.
19. Ceylan T, Karabulut D, Öztürk E, Akin AT, Kaymak E, Yakan B. Histological evaluation of the effects of rapamycin and 3-methyladenine on cisplatin-induced epididymal injury in rats. Cukurova Medical Journal. 2021;46(3):1184-90.
20. Ceylan T, Kaymak E, Akin AT, Yakan B. The ameliorative effects of caffeic acid phenethyl Ester in cisplatin-induced nephrotoxicity: Assessment of the oxidative stress an inflammation. International Journal of Morphology. 2021;39(2).
21. Veale D, Ashcroft T, Marsh C, Gibson G, Harris A. Epidermal growth factor receptors in non-small cell lung cancer. British journal of cancer. 1987;55(5):513-6.
22. Hwang J-S, Kim K-H, Park J, Kim S-M, Cho H, Lee Y, et al. Glucosamine improves survival in a mouse model of sepsis and attenuates sepsis-induced lung injury and inflammation. Journal of Biological Chemistry. 2019;294(2):608-22.
23. Aslani MR, Amani M, Masrori N, Boskabady MH, Ebrahimi HA, Chodari L. Crocin attenuates inflammation of lung tissue in ovalbumin‐sensitized mice by altering the expression of endoplasmic reticulum stress markers. Biofactors. 2022;48(1):204-15.
24. Wang J, Kuai J, Luo Z, Wang W, Wang L, Ke C, et al. Crocin attenuates lipopolysacchride-induced acute lung injury in mice. International Journal of Clinical Experimental Pathology. 2015;8(5):4844.
25. Zhang D, Qi B-y, Zhu W-w, Huang X, Wang X-z. Crocin alleviates lipopolysaccharide-induced acute respiratory distress syndrome by protecting against glycocalyx damage and suppressing inflammatory signaling pathways. Inflammation Research. 2020;69:267-78.
26. Kheiry M, Dianat M, Badavi M, Mard SA, Bayati V. p-Coumaric acid attenuates lipopolysaccharide-induced lung inflammation in rats by scavenging ROS production: An in vivo and in vitro study. Inflammation. 2019;42(6):1939-50.
27. Ye J, Guan M, Lu Y, Zhang D, Li C, Zhou C. Arbutin attenuates LPS-induced lung injury via Sirt1/Nrf2/NF-κBp65 pathway. Pulmonary Pharmacology & Therapeutics. 2019;54:53-9.
28. Lin L, Li J, Song Q, Cheng W, Chen P. The role of HMGB1/RAGE/TLR4 signaling pathways in cigarette smoke‐induced inflammation in chronic obstructive pulmonary disease. Immunity, Inflammation and Disease. 2022;10(11):e711.
29. Tang J, Xu L, Zeng Y, Gong FJII. Effect of gut microbiota on LPS-induced acute lung injury by regulating the TLR4/NF-kB signaling pathway. 2021;91:107272.
30. Lin L, Li J, Song Q, Cheng W, Chen PJI, Inflammation, Disease. The role of HMGB1/RAGE/TLR4 signaling pathways in cigarette smoke‐induced inflammation in chronic obstructive pulmonary disease. 2022;10(11):e711.
31. Ge X, Meng X, Fei D, Kang K, Wang Q, Zhao M. Lycorine attenuates lipopolysaccharide-induced acute lung injury through the HMGB1/TLRs/NF-κB pathway. Biotech. 2020;10(8):1-10.
32. Meng L, Li L, Lu S, Li K, Su Z, Wang Y, et al. The protective effect of dexmedetomidine on LPS-induced acute lung injury through the HMGB1-mediated TLR4/NF-κB and PI3K/Akt/mTOR pathways. Molecular Immunology. 2018;94:7-17.
33. Ding J, Cui X, Liu Q. Emerging role of HMGB1 in lung diseases: friend or foe. Journal of Cellular and Molecular Medicine. 2017;21(6):1046-57.
34. Li L, Zhang H, Jin S, Liu C. Effects of crocin on inflammatory activities in human fibroblast-like synoviocytes and collagen-induced arthritis in mice. Immunologic Research. 2018;66(3):406-13.