Abstract
Objective: At present, no proven effective treatment is available for Lung Ischemiareperfusion Injury (LIRI). Natural compounds offer promising prospects for developing new drugs to address various diseases. This study sought to explore the potential of Rebaudioside B (Reb B) as a treatment compound for LIRI, both in vivo and in vitro.
Methods: This study involved utilizing the human pulmonary alveolar cell line A549, consisting of epithelial type II cells, subjected to Oxygen-glucose Deprivation/recovery (OGD/R) for highthroughput in vitro cell viability screening. The aim was to identify the most promising candidate compounds. Additionally, an in vivo rat model of lung ischemia-reperfusion was employed to evaluate the potential protective effects of Reb B.
Results: Through high-throughput screening, Reb B emerged as the most promising natural compound among those tested. In the A549 OGD/R models, Reb B exhibited a capacity to enhance cell viability by mitigating apoptosis. In the in vivo LIRI model, pre-treatment with Reb B notably decreased apoptotic cells, perivascular edema, and neutrophil infiltration within lung tissues. Furthermore, Reb B demonstrated its ability to attenuate lung inflammation associated with LIRI primarily by elevating IL-10 levels while reducing levels of IL-6, IL-8, and TNF-α.
Conclusion: The comprehensive outcomes strongly suggest Reb B's potential as a protective agent against LIRI. This effect is attributed to its inhibition of the mitochondrial apoptotic pathway and its ability to mitigate the inflammatory response.
Keywords: Rebaudioside B, lung ischemia-reperfusion injury, apoptosis, high-throughput screening, oxygen-glucose deprivation/ recovery, A549.
[http://dx.doi.org/10.1186/s12967-020-02467-w] [PMID: 32758258]
[http://dx.doi.org/10.1186/s40064-016-3741-9] [PMID: 27995008]
[http://dx.doi.org/10.3389/fphar.2019.00583] [PMID: 31178737]
[http://dx.doi.org/10.3390/ph13090251] [PMID: 32957668]
[http://dx.doi.org/10.3390/antiox10010072] [PMID: 33429850]
[http://dx.doi.org/10.1038/s41598-018-19622-5] [PMID: 29367749]
[http://dx.doi.org/10.1007/s13197-018-3270-3] [PMID: 30065444]
[http://dx.doi.org/10.1016/j.jtcvs.2018.08.098] [PMID: 30385019]
[http://dx.doi.org/10.1038/s41467-020-18336-5] [PMID: 32908132]
[http://dx.doi.org/10.3892/ol.2021.12593] [PMID: 33692864]
[http://dx.doi.org/10.1093/bioinformatics/btp465] [PMID: 19648136]
[http://dx.doi.org/10.1016/j.stemcr.2021.11.004] [PMID: 34861164]
[http://dx.doi.org/10.1016/j.sjbs.2018.10.009] [PMID: 31762632]
[http://dx.doi.org/10.3390/molecules26134090] [PMID: 34279430]
[http://dx.doi.org/10.1021/jf072681o] [PMID: 18433103]
[http://dx.doi.org/10.1021/jf0523465] [PMID: 16448183]
[http://dx.doi.org/10.3892/mmr.2015.4323] [PMID: 26398332]
[http://dx.doi.org/10.1002/advs.202004588] [PMID: 34026454]
[http://dx.doi.org/10.3892/ol.2015.4037] [PMID: 26893718]
[http://dx.doi.org/10.3389/fimmu.2021.656350] [PMID: 33868301]
[http://dx.doi.org/10.1016/j.omtn.2019.05.009] [PMID: 31604167]
[http://dx.doi.org/10.3390/ijms22094972] [PMID: 34067047]
[http://dx.doi.org/10.1089/hum.2016.070] [PMID: 28052693]