Genkwanin improves inflammatory injury in rats with septic lung injury by regulating NF-κB signaling pathway
Main Article Content
Keywords
sepsis, genkwanin (GKA), acute lung injury (ALI), CLP, apoptosis, NF-κB signaling pathway
Abstract
To assess possible effects of genkwanin (GKA) in septic lung injury and its related mechanisms. An animal model of cecal ligation and puncture (CLP)-induced acute lung injury was constructed. Histological analysis and wet–dry (W/D) ratio of the lung tissue were observed. The cell apoptosis in this model was analyzed by caspase activity detection, protein levels of B-cell lymphoma protein 2 (Bcl-2) and Bcl-2-associated X (Bax), and cell inflammation in CLP model; after GKA treatment, it was analyzed by enzyme-linked-immunosorbent serologic assay (ELISA). The involvement of nuclear factor kappa B (NF-κB) signaling pathway was evaluated by Immunoblot assay. We constructed an animal model of CLP-induced acute lung injury. Our data revealed that GKA reduced lung edema and inflammation in CLP mice. In addition, GKA reduced lung injury and apoptosis in CLP mice. Mechanically, our data in addition confirmed that GKA improved inflammatory injury in CLP mice by regulating NF-κB signaling pathway. Our data therefore confirmed that GKA could serve as a promising drug for the treatment of sepsis-induced acute lung injury.
References
Bao, Y., Sun, Y.W., Ji, J., Gan, L., Zhang, C.F., Wang, C.Z. and Yuan, C.S., 2019. Genkwanin ameliorates adjuvant-induced arthritis in rats through inhibiting JAK/STAT and NF-kappaB signaling pathways. Phytomedicine 63: 153036. 10.1016/j.phymed.2019.153036
Cokluk, E., Doganay, S., Ramazan Sekeroglu, M., Betul Tuncer, F., Cakiroglu, H. and Boz, M., 2021. Investigation of the effect of melatonin administration on inflammatory mediators; MMP-2, TGF-beta and VEGF levels in rats with sepsis. International Journal of Clinical Practice e14832. 10.1111/ijcp.14832
Cottiglia, F., Loy, G., Garau, D., Floris, C., Casu, M., Pompei, R. and Bonsignore, L., 2001. Antimicrobial evaluation of coumarins and flavonoids from the stems of Daphne gnidium L. Phytomedicine 8: 302–305. 10.1078/0944-7113-00036
Gao, Y., Liu, F., Fang, L., Cai, R., Zong, C. and Qi, Y., 2014. Genkwanin inhibits proinflammatory mediators mainly through the regulation of miR-101/MKP-1/MAPK pathway in LPS-activated macrophages. PLoS One. 9: e96741. 10.1371/journal.pone.0096741
Jiang, C.P., He, X., Yang, X.L., Zhang, S.L., Li, H., Song, Z.J., Zhang, C.F., Yang, Z.L. and Li, P., 2014. Intestinal absorptive transport of Genkwanin from Flos genkwa using a single-pass intestinal perfusion rat model. American Journal of Chinese Medicine 42: 349–359. 10.1142/S0192415X14500232
Kalantari, K. and Rosner, M.H., 2021. Recent advances in the pharmacological management of sepsis-associated acute kidney injury. Expert Review of Clinical Pharmacology 1–11. 10.1080/17512433.2021.1978287
Kawano, N., Miura, H. and Matsuishi, E., 1966. The partial demethylation of flavones. I. Preparation of genkwanin. Chemical and Pharmaceutical Bulletin (Tokyo) 14: 299–300. 10.1248/cpb.14.299
Kim, A.R., Zou, Y.N., Park, T.H., Shim, K.H., Kim, M.S., Kim, N.D., Kim, J.D., Bae, S.J., Choi, J.S. and Chung, H.Y., 2004. Active components from Artemisia iwayomogi displaying ONOO(-) scavenging activity. Phytotherapy Research 18: 1–7. 10.1002/ptr.1358
Kraft, C., Jenett-Siems, K., Siems, K., Jakupovic, J., Mavi, S., Bienzle, U. and Eich, E., 2003. In vitro antiplasmodial evaluation of medicinal plants from Zimbabwe. Phytotherapy Research 17: 123–128. 10.1002/ptr.1066
Li, Y., Hong, J., Li, H., Qi, X., Guo, Y., Han, M. and Wang, X., 2017. Genkwanin nanosuspensions: a novel and potential antitumor drug in breast carcinoma therapy. Drug Delivery 24: 1491–1500. 10.1080/10717544.2017.1384519
Liu, J.L., Ma, H.P., Lu, X.L., Sun, S.H., Guo, X. and Li, F.C., 2011. NF-kappa B induces abnormal centrosome amplification by upregulation of CDK2 in laryngeal squamous cell cancer. International Journal of Oncology 39: 915–924. 10.3892/ijo.2011.1125
Ren, C., Yao, R.Q., Wang, L.X., Li, J.C., Chen, K.W., Wu, Y., Dong, N., Feng, Y.W. and Yao, Y.M., 2021. Antagonism of cerebral high mobility group box 1 ameliorates dendritic cell dysfunction in sepsis. Frontiers in Pharmacology 12: 665579. 10.3389/fphar.2021.665579
Shimada, B.K., Boyman, L., Huang, W., Zhu, J., Yang, Y., Chen, F., Kane, M.A., Yadava, N., Zou, L., Lederer, W.J., Polster, B.M. and Chao, W., 2021. Pyruvate-driven oxidative phosphorylation is downregulated in sepsis-induced cardiomyopathy: a study of mitochondrial proteome. Shock. 10.1097/SHK.0000000000001858
van Bockxmeer J.J., Shetty A., Robertson T. and Thomas Y., 2021. Closing the sepsis gap: an exploration of sepsis presentations at a remote north Australian emergency department. Rural Remote Health 21: 5979. 10.22605/RRH5979
Wakana, Y., Takai, S., Nakajima, K., Tani, K., Yamamoto, A., Watson, P., Stephens, D.J., Hauri, H.P. and Tagaya, M., 2008. Bap31 is an itinerant protein that moves between the peripheral endoplasmic reticulum (ER) and a juxtanuclear compartment related to ER-associated Degradation. Molecular Biology of the Cell 19: 1825–1836. 10.1091/mbc.E07-08-0781
Wang, H., Huang, X., Xu, P., Liu, X., Zhou, Z., Wang, F., Li, J., Wang, Y., Xian, X., Liu, G. and Huang, W., 2021. Apolipoprotein C3 aggravates diabetic nephropathy in type 1 diabetes by activating the renal TLR2/NF-kappaB pathway. Metabolism 154740. 10.1016/j.metabol.2021.154740
Wang, X., Song, Z.J., He, X., Zhang, R.Q., Zhang, C.F., Li, F., Wang, C.Z. and Yuan, C.S., 2015. Antitumor and immunomodulatory activity of genkwanin on colorectal cancer in the APC(Min/+) mice. International Immunopharmacology 29: 701–707. 10.1016/j.intimp.2015.09.006
Yang, J., Miao, X., Guan, Y., Chen, C., Chen, S., Zhang, X., Xiao, X., Zhang, Z., Xia, Z., Yin, T., Hei, Z. and Yao, W., 2021. Microbubble functionalization with platelet membrane enables targeting and early detection of sepsis-induced acute kidney injury. Advanced Healthcare Materials e2101628. 10.1002/adhm.202101628
Yang, K., Li, W.F., Yu, J.F., Yi, C. and Huang, W.F., 2017. Diosmetin protects against ischemia/reperfusion-induced acute kidney injury in mice. Journal of Surgical Research 214: 69–78. 10.1016/j.jss.2017.02.067
Yu, G., Wan, R., Yin, G., Xiong, J., Hu, Y., Xing, M., Cang, X., Fan, Y., Xiao, W., Qiu, L., Wang, X. and Hu, G., 2014. Diosmetin ameliorates the severity of cerulein-induced acute pancreatitis in mice by inhibiting the activation of the nuclear factor-kappa B. International Journal of Clinical and Experimental Pathology 7: 2133–2142.
Yuan, S. and Wang, Z., 1995. Influence of processing on contents of genkwanin in flos Genkwa. Zhongguo Zhong Yao Za Zhi 20: 340–342, 382.
Zhang, Q., Xue, T., Guan, J., Wang, W., Shi, J., Lu, J. and Jiang, X., 2021. Irigenin alleviates angiotensin II-induced oxidative stress and apoptosis in HUVEC cells by activating Nrf2 pathway. Drug Development Research 10.1002/ddr.21802
Zhou, H., Wang, J., Zhu, P., Zhu, H., Toan, S., Hu, S., Ren, J. and Chen, Y., 2018. NR4A1 aggravates the cardiac microvascular ischemia reperfusion injury through suppressing FUNDC1-mediated mitophagy and promoting Mff-required mitochondrial fission by CK2alpha. Basic Research in Cardiology 113: 23. 10.1007/s00395-018-0682-1
