Tricin attenuates the progression of LPS-induced severe pneumonia in bronchial epithelial cells by regulating AKT and MAPK signaling pathways

Main Article Content

Fan Yang
Wenming Liu


AKT and MAPK pathways, LPS, severe pneumonia, tricin


Background: Pneumonia is a continuous and widespread disease with higher incidence, the effects of it on human life can be fearful. Tricin has been demonstrated to take part in the progression and development of diseases. However, the function of Tricin and its related regulatory pathways remain unclear. This study was planned to investigate the effects of Tricin on severe pneumonia.

Methods: The cell viability was detected through CCK-8 assay. The TNF-α, IL-1β and IL-6 levels were assessed through ELISA and RT-qPCR. The levels of MDA, SOD and GSH were tested through corresponding commercial kits. The protein expressions were examined through western blot.

Results: In our study, the lipopolysaccharide (LPS) was firstly used to stimulate cell model for severe pneumonia. We discovered that Tricin had no toxic effects on BEAS-2B cells and the decreased cell viability induced by LPS was relieved by a dose-dependent Tricin treatment. Additionally, through ELISA and RT-qPCR, it was uncovered that Tricin reduced the LPS-induced inflammation through regulating TNF-α, IL-1β and IL-6. Furthermore, Tricin relieved LPS-induced oxidative stress through reducing MDA level and enhancing SOD and GSH levels. Finally, it was demonstrated that Tricin retarded LPS-activated AKT and MAPK pathways.

Conclusion: Our findings revealed that Tricin attenuated the progression of LPS induced severe pneumonia through modulating AKT and MAPK signaling pathways. This discovery might afford one novel sight for the treatment of severe pneumonia.

Abstract 379 | PDF Downloads 302 HTML Downloads 172 XML Downloads 17


1. Barba T, Mainbourg S, Nasser M, Lega JC, Cottin V. Lung diseases in inflammatory myopathies. Semin Respir Crit Care Med. 2019;40(2):255–70. 10.1055/s-0039-1685187

2. Liu Y, Gao H, Wang X, Zeng Y. Methylation of inflammatory cells in lung diseases. Adv Exp Med Biol. 2020;1255:63–72. 10.1007/978-981-15-4494-1_5

3. Cunha BA. Pneumonia in the elderly. Clin Microbiol Infect. 2001;7(11):581–8. 10.1046/j.1198-743x.2001.00328.x

4. Mizgerd JP. Pathogenesis of severe pneumonia: advances and knowledge gaps. Curr Opin Pulm Med. 2017;23(3):193–7. 10.1097/MCP.0000000000000365

5. Wang J, Song YL. Advances in severe community-acquired pneumonia. Chin Med J. 2019;132(16):1891–3. 10.1097/CM9.0000000000000366

6. Gao W, Yang H. MicroRNA-124-3p attenuates severe community-acquired pneumonia progression in macrophages by targeting tumor necrosis factor receptor-associated factor 6. Int J Mol Med. 2019;43(2):1003–10. 10.3892/ijmm.2018.4011

7. Sun W, Cheng Z, Chen H, Lin G, Chen H. Tetrahydropyrimidines, ZL-5015 alleviated lipopolysaccharide (LPS)-induced acute pneumonia in rats by activating the NRF-2/HO-1 pathway. Med Sci Monit. 2020;26:e924482. 10.12659/MSM.924482

8. Lam PY, Lui ACW, Wang L, et al. Tricin biosynthesis and bioengineering. Front Plant Sci. 2021;12:733198. 10.3389/fpls.2021.733198

9. Jiang B, Song J, Jin Y. A flavonoid monomer tricin in Gramineous plants: metabolism, bio/chemosynthesis, biological properties, and toxicology. Food Chem. 2020;320:126617. 10.1016/j.foodchem.2020.126617

10. Chang CL, Wang GJ, Zhang LJ, et al. Cardiovascular protective flavonolignans and flavonoids from Calamus quiquesetinervius. Phytochemistry. 2010;71(2–3):271–9. 10.1016/j.phytochem.2009.09.025

11. Shalini V, Pushpan CK, Sindhu G, Jayalekshmy A, Helen A. Tricin, flavonoid from Njavara reduces inflammatory responses in hPBMCs by modulating the p38MAPK and PI3K/Akt pathways and prevents inflammation associated endothelial dysfunction in HUVECs. Immunobiology. 2016;221(2):137–44. 10.1016/j.imbio.2015.09.016

12. Kang BM, An BK, Jung WS, et al. Anti-inflammatory effect of tricin isolated from alopecurus aequalis sobol. on the LPS-induced inflammatory response in RAW 264.7 cells. Int J Mol Med. 2016;38(5):1614–20. 10.3892/ijmm.2016.2765

13. Lee JY, Park SH, Jhee KH, Yang SA. Tricin isolated from enzyme-treated Zizania latifolia extract inhibits IgE-mediated allergic reactions in RBL-2H3 cells by targeting the Lyn/Syk pathway. Molecules. 2020;25(9):2084. 10.3390/molecules25092084

14. Lee HJ, Kim KA, Kang KD, et al. The compound isolated from the leaves of Phyllostachys nigra protects oxidative stress-induced retinal ganglion cells death. Food Chem Toxicol. 2010;48(6):1721–7. 10.1016/j.fct.2010.03.052

15. Shalini V, Jayalekshmi A, Helen A. Mechanism of anti-inflammatory effect of tricin, a flavonoid isolated from Njavara rice bran in LPS induced hPBMCs and carrageenan induced rats. Mol Immunol. 2015;66(2):229–39. 10.1016/j.molimm.2015.03.004

16. Li X-X, Chen S-G, Yue GG, et al. Natural flavone tricin exerted anti-inflammatory activity in macrophage via NF-κB pathway and ameliorated acute colitis in mice. Phytomedicine. 2021;90:153625. 10.1016/j.phymed.2021.153625

17. Tian C, Shao Y, Jin Z, et al. The protective effect of rutin against lipopolysaccharide induced acute lung injury in mice based on the pharmacokinetic and pharmacodynamic combination model. J Pharm Biomed Anal. 2021;209:114480. 10.1016/j.jpba.2021.114480

18. Li Z, Yuan X, Wang B, Gao F. Icariin alleviates transforming growth factor-β1-induced epithelial-mesenchymal transition by targeting Smad and MAPK signaling pathways. Am J Transl Res. 2020;12(2):343–60.

19. Cui Y, Xin H, Tao Y, Mei L, Wang Z. Arenaria kansuensis attenuates pulmonary fibrosis in mice via the activation of Nrf2 pathway and the inhibition of NF-kB/TGF-beta1/Smad2/3 pathway. Phytother Res. 2021;35(2):974–86. 10.1002/ptr.6857

20. Chen J, Yuan CB, Yang B, Zhou X. Baicalin inhibits EMT through PDK1/AKT signaling in human nonsmall cell lung cancer. J Oncol. 2021;2021:4391581. 10.1155/2021/4391581

21. Wang QL, Yang L, Peng Y, et al. Ginsenoside Rg1 regulates SIRT1 to ameliorate sepsis-induced lung inflammation and injury via inhibiting endoplasmic reticulum stress and inflammation. Mediat Inflamm. 2019;2019:6453296. 10.1155/2019/6453296

22. Yanling Q, Xiaoning C, Fei B, Liyun F, Huizhong H, Daqing S. Inhibition of NLRP9b attenuates acute lung injury through suppressing inflammation, apoptosis and oxidative stress in murine and cell models. Biochem Biophys Res Commun. 2018;503(2):436–43. 10.1016/j.bbrc.2018.04.079

23. Liu Y, Tong C, Xu Y, et al. CD28 Deficiency ameliorates blast exposure-induced lung inflammation, oxidative stress, apoptosis, and t cell accumulation in the lungs via the PI3K/Akt/FoxO1 signaling pathway. Oxid Med Cell Longev. 2019;2019:4848560. 10.1155/2019/4848560

24. Gungor H, Ekici M, Karayigit MO, Turgut NH, Kara H, Arslanbas E. Zingerone ameliorates oxidative stress and inflammation in bleomycin-induced pulmonary fibrosis: modulation of the expression of TGF-β1 and iNOS. Naunyn Schmiedebergs Arch Pharmacol. 2020;393(9):1659–70. 10.1007/s00210-020-01881-7

25. Yang H, Hua C, Yang X, et al. Pterostilbene prevents LPS-induced early pulmonary fibrosis by suppressing oxidative stress, inflammation and apoptosis in vivo. Food Funct. 2020;11(5):4471–84. 10.1039/C9FO02521A

26. Zhang Q, Ju Y, Ma Y, Wang T. N-acetylcysteine improves oxidative stress and inflammatory response in patients with community acquired pneumonia: a randomized controlled trial. Medicine. 2018;97(45):e13087. 10.1097/MD.0000000000013087

27. Tanaka M, Kishimoto Y, Sasaki M, et al. Terminalia bellirica (Gaertn.) roxb. extract and gallic acid attenuate LPS-induced inflammation and oxidative stress via MAPK/NF-κB and Akt/AMPK/Nrf2 pathways.Oxid Med Cell Longev. 2018;2018:9364364. 10.1155/2018/9364364

28. Jarisarapurin W, Kunchana K, Chularojmontri L, Wattanapitayakul SK. Unripe carica papaya protects methylglyoxal-invoked endothelial cell inflammation and apoptosis via the suppression of oxidative stress and Akt/MAPK/NF-κB signals. Antioxidants. 2021;10(8):1158. 10.3390/antiox10081158

29. Kwon DH, Cha HJ, Choi EO, et al. Schisandrin A suppresses lipopolysaccharide-induced inflammation and oxidative stress in RAW 264.7 macrophages by suppressing the NF-κB, MAPKs and PI3K/Akt pathways and activating Nrf2/HO-1 signaling.Int J Mol Med. 2018;41(1):264–74. 10.3892/ijmm.2017.3209