Morusin attenuates LPS-induced inflammation and oxidative stress in lung epithelial cells by inhibiting NLRP3 inflammasome activation
Main Article Content
Keywords
morusin, LPS, inflammation, oxidative stress, ALI
Abstract
Acute lung injury (ALI) is a pulmonary disorder characterized by severe lung tissue damage and inflammation. Morusin (a flavone, a type of flavonoid; C25H24O6), a flavonoid isolated from mulberry root bark, possesses notable anti-inflammatory and antioxidant properties. However, its regulatory effects on ALI progression remain unclear. This study aimed to investigate whether morusin could mitigate the development of ALI. Morusin was shown to enhance cell viability and reduce apoptosis in lipopolysaccharide (LPS)-stimulated A549 cells. Furthermore, morusin alleviated inflammation by decreasing the levels of interleukin-1β (IL-1β), IL-6, and prostaglandin E2 (PGE2) in LPS-challenged A549 cells. In addition, morusin effectively reduced oxidative stress in these cells. Mechanistically, morusin was found to suppress the activation of NLRP3 (nucleotide-binding domain, leucine rich-containing family, pyrin domain containing 3) inflammasome in LPS-stimulated A549 cells. Finally, this study demonstrated for the first time that morusin ameliorates LPS-induced inflammation and oxidative stress in lung epithelial cells by inhibiting both nuclear factor kappa B signaling pathway and NLRP3 inflammasome activation. However, this project was limited to cell experiments, and no animal experiments or clinical verifications were conducted. Our findings suggest that morusin could serve as a promising therapeutic agent for the treatment of ALI.
References
2 Endo Y, Aoki T, Jafari D, Rolston DM, Hagiwara J, Ito-Hagiwara K, et al. Acute lung injury and post-cardiac arrest syndrome: a narrative review. J Intensive Care. 2024. 12(1):32. 10.1186/s40560-024-00745-z
3 Shen Y, He Y, Pan Y, Liu L, Jia J. Role and mechanisms of autophagy, ferroptosis, and pyroptosis in sepsis-induced acute lung injury. Front Pharmacol. 2024;15:1415145. 10.3389/fphar.2024.1415145
4 Hou L, Zhang J, Liu Y, Fang H, Liao L, Wnag Z, et al. MitoQ alleviates LPS-mediated acute lung injury through regulating Nrf2/Drp1 pathway. Free Radic Biol Med. 2021;165:219–228. 10.1016/j.freeradbiomed.2021.01.045
5 Xie WM Su W, Liu XY, Zhou J, Wang M, Wang W, et al. FTO deficiency alleviates LPS-induced acute lung injury by TXNIP/NLRP3-mediated alveolar epithelial cell pyroptosis. Am J Respir Cell Mol Biol. 2024;70(5):351–363. 10.1165/rcmb.2023-0251OC
6 Chang J, Zhang W. Remifentanil modulates the TLR4-mediated MMP-9/TIMP1 balance and NF-κB/STAT3 signaling in LPS-induced A549 cells. Exp Ther Med. 2023;25(2):79. 10.3892/etm.2022.11778
7 Zeng P, Li J, Chen Y, Zhang L. The structures and biological functions of polysaccharides from traditional Chinese herbs. Prog Mol Biol Transl Sci. 2019;163:423–444. 10.1016/bs.pmbts.2019.03.003
8 Dhanyalakshmi KH, Nataraja KN. Mulberry (Morus spp.) has the features to treat as a potential perennial model system. Plant Signal Behav. 2018;13(8):e1491267. 10.1080/15592324.2018.1491267
9 Jung JW, Park JH, Lee YG, Seo KH, Oh EJ, Lee DY, et al. Three new isoprenylated flavonoids from the root bark of Morus alba. Molecules. 2016;21(9):1112. 10.3390/molecules21091112
10 Choi DW, Cho SW, Lee SG, Choi CY.. The beneficial effects of morusin, an isoprene flavonoid isolated from the root bark of morus. Int J Mol Sci. 2020;21(18):6541. 10.3390/ijms21186541
11 Jin C, Zheng J, Yang Q, Jia Y, Li H, Liu X, et al. Morusin inhibits RANKL-induced osteoclastogenesis and ovariectomized osteoporosis. Comb Chem High Throughput Screen. 2024;27(9):1358–1370. 10.2174/0113862073252310230925062415
12 Zhao R. Zhou Y, Zhang H, Pan J, Yang F, Zhang R, et al. Morusin enhances temozolomide efficiency in GBM by inducing cytoplasmic vacuolization and endoplasmic reticulum stress. J Clin Med. 2022;11(13):3662. 10.3390/jcm11133662
13 Jin SE, Ha H, Shin HK, Seo CS.. Anti-allergic and anti-inflammatory effects of Kuwanon G and Morusin on MC/9 mast cells and HaCaT keratinocytes. Molecules. 2019;24(2):265. 10.3390/molecules24020265
14 Vochyánová Z, Pokorná M, Rotrekl D, Smékal V, Fictum P, Suchý P, et al. Prenylated flavonoid morusin protects against TNBS-induced colitis in rats. PLoS One. 2017;12(8):e0182464. 10.1371/journal.pone.0182464
15 Chen C, Wang J, Chen J, Zhou L, Wang H, Chen J, et al. Morusin alleviates mycoplasma pneumonia via the inhibition of Wnt/β-catenin and NF-κB signaling. Biosci Rep. 2019;39(6):BSR20190190. 10.1042/BSR20190190
16 Wang J, Xue X, Zhao X, Luo L, Liu J, Dai S, et al. Forsythiaside A alleviates acute lung injury by inhibiting inflammation and epithelial barrier damages in lung and colon through PPAR-γ/RXR-α complex. J Adv Res. 2024;60:183–200. 10.1016/j.jare.2023.08.006
17 Zhou J, Peng Z, Wang J. Trelagliptin alleviates lipopolysaccharide (LPS)-induced inflammation and oxidative stress in acute lung injury mice. Inflammation. 2021;44(4):1507–1517. 10.1007/s10753-021-01435-w
18 Woo MS, Cao DL, Kim EJ, Jeong YY, Kang D. Broncho-vaxom attenuates lipopolysaccharide-induced inflammation in a mouse model of acute lung injury. Int J Mol Sci. 2024;25(13):7135. 10.3390/ijms25137135
19 Liu Z, Zheng X, Li N, Wnag Z. Baicalein suppresses inflammation and attenuates acute lung injury by inhibiting glycolysis via HIF-1α signaling. Mol Med Rep. 2025;31(1):18. 10.3892/mmr.2024.13383
20 Pokharel MD, Garcia-Flores A, Marciano D, Franco MC, Fineman JR, Aggarwal S, et al. Mitochondrial network dynamics in pulmonary disease: Bridging the gap between inflammation, oxidative stress, and bioenergetics. Redox Biol. 2024;70:103049. 10.1016/j.redox.2024.103049
21 Ye C, Xu B, Yang J, Liu Y, Zeng Z, Xia L, et al. Mucin1 relieves acute lung injury by inhibiting inflammation and oxidative stress. Eur J Histochem. 2021;65(4):3331. 10.4081/ejh.2021.3331
22 Zhang Y, Cui Y, Feng Y, Jiao F, Jia L. Lentinus edodes polysaccharides alleviate acute lung injury by inhibiting oxidative stress and inflammation. Molecules. 2022;27(21):7328. 10.3390/molecules27217328
23 Dhlamini Q, Wang W, Feng G, Chen A, Lei C, Li X, et al. FGF1 alleviates LPS-induced acute lung injury via suppression of inflammation and oxidative stress. Mol Med. 2022;28(1):73. 10.1186/s10020-022-00502-8
24 Li W, Li M, Chen K, Tang Y, Yin R Lan L, et al. Oxaloacetate acid ameliorates paraquat-induced acute lung injury by alleviating oxidative stress and mitochondrial dysfunction. Front Pharmacol. 2022;13:1029775. 10.3389/fphar.2022.1029775
25 Gu W, Zeng Q, Wang X, Jasem H, Ma L. Acute lung injury and the NLRP3 inflammasome. J Inflamm Res. 2024;17:3801–3813. 10.2147/JIR.S464838
26 Wang S, Hu L, Fu Y, Xu F, Shen Y, Liu H, et al. Inhibition of IRE1α/XBP1 axis alleviates LPS-induced acute lung injury by suppressing TXNIP/NLRP3 inflammasome activation and ERK/p65 signaling pathway. Respir Res. 2024;25(1):417. 10.1186/s12931-024-03044-1
27 Kühl L, Graichen P, Daacke NV, Mende A, Wygrecka M, Potaczek DP, et al. Human lung organoids–A novel experimental and precision medicine approach. Cells. 2023;12(16):2067. 10.3390/cells12162067
28 Mahieu L, Moll LV, Vooght LD, Delputte P, Cos P. In vitro modelling of bacterial pneumonia: a comparative analysis of widely applied complex cell culture models. FEMS Microbiol Rev. 2024;48(2):fuae007. 10.1093/femsre/fuae007
