LIN Hai,YI Jinrong,RAO Yunwei.Inhibitory effects of formononetin on lipopolysaccharide-induced apoptosis and inflammatory response in alveolar epithelial cells[J].ZHONGGUO YAOFANG,2023,34(22):2721-2726.
LIN Hai,YI Jinrong,RAO Yunwei.Inhibitory effects of formononetin on lipopolysaccharide-induced apoptosis and inflammatory response in alveolar epithelial cells[J].ZHONGGUO YAOFANG,2023,34(22):2721-2726. DOI: 10.6039/j.issn.1001-0408.2023.22.06.
Inhibitory effects of formononetin on lipopolysaccharide-induced apoptosis and inflammatory response in alveolar epithelial cells
To investigate the inhibitory effects of formononetin on lipopolysaccharide (LPS)-induced apoptosis and inflammatory response in alveolar epithelial cells through phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway.
METHODS
2
Human lung cancer alveolar basal epithelial cells A549 were cultured
in vitro
and divided into control group (no intervention), model group (1 μg/mL LPS), different concentrations of formononetin groups (1 μg/mL LPS+6.25, 12.5, 25, 50 μmol/L formononetin). The levels of inflammatory factors (interleukin-8, tumor necrosis factor-α) and cell viability were detected in each group. Another A549 cells were divided into control group, model group (1 μg/mL LPS), LPS+25 group (1 μg/mL LPS+25 μmol/L formononetin), inhibitor group (1 μg/mL LPS+20 μmol/L LY294002), formononetin+inhibitor group (1 μg/mL LPS+25 μmol/L formononetin+20 μmol/L LY294002) and formononetin+activator group (1 μg/mL LPS+25 μmol/L formononetin+10 μmol/L SC79). The secretion levels and mRNA expressions of inflammatory factors, cell apoptosis, and expressions of the key proteins of PI3K/Akt signaling pathway were detected in each group.
RESULTS
2
Compared with model group, the levels of inflammatory factors were decreased significantly after the intervention of 25 μmol/L of formononetin, and the cell viability was increased significantly (
P
<0.05). Compared with the control group, the secretion levels and mRNA expressions of inflammatory factors, apoptotic rate, and relative expressions of phosphorylated Akt and phosphorylated PI3K of the model group were increased significantly (
P
<0.05). Compared with the model group, the above indexes of the LPS+25 group and the inhibitor group were decreased significantly (
P
<0.05). Compared with the LPS+25 group, the above indicators of formononetin+inhibitor group were further decreased, while those of formononetin+activator group were increased significantly (
P
<0.05).
CONCLUSIONS
2
Formononetin can inhibit LPS-induced epithelial cell apoptosis and improve inflammatory response, and the mechanism may be related to the inhibition of the PI3K/Akt signaling pathway.
关键词
芒柄花素肺泡上皮细胞脂多糖磷脂酰肌醇3激酶/蛋白激酶B信号通路凋亡炎症反应
Keywords
alveolar epithelial cellslipopolysaccharidephosphoinositide 3-kinase/protein kinase B signaling pathwayapoptosisinflammatory response
references
LONG M E,MALLAMPALLI R K,HOROWITZ J C. Pathogenesis of pneumonia and acute lung injury[J]. Clin Sci,2022,136(10):747-769.
TIAN X,CHANG P,ZHOU Y G,et al. Effect of formononetin on the regulation and proliferation of inflammatory factors in mouse mesangial cells induced by high glucose[J]. Chin Tradit Pat Med,2017,39(5):1052-1056.
MA Z Q,JI W W,FU Q,et al. Formononetin inhibited the inflammation of LPS-induced acute lung injury in mice associated with induction of PPAR gamma expression[J]. Inflammation,2013,36(6):1560-1566.
CHEN Y,WEI D,ZHAO J,et al. Reduction of hyperoxic acute lung injury in mice by formononetin[J]. PLoS One,2021,16(1):e0245050.
SUN X J,CHEN L,HE Z Y. PI3K/Akt-Nrf2 and anti-inflammation effect of macrolides in chronic obstructive pulmonary disease[J]. Curr Drug Metab,2019,20(4):301-304.
LIU Y,TIE L. Apolipoprotein M and sphingosine-1-pho-sphate complex alleviates TNF-α-induced endothelial cell injury and inflammation through PI3K/AKT signaling pathway[J]. BMC Cardiovasc Disord,2019,19(1):279.
SHI J,YU J B,ZHANG Y,et al. PI3K/Akt pathway-mediated HO-1 induction regulates mitochondrial quality control and attenuates endotoxin-induced acute lung injury[J]. Lab Invest,2019,99(12):1795-1809.
SUN F Y,MENG J L,MA Y H,et al. Effects of ligustrazine on inflammation and oxidative stress in rat cardiomyocytes induced by lipopolysaccharide[J]. Chin J Tissue Eng Res,2023,27(20):3253-3258.
SUN T Y,ZHANG J G,DENG B,et al. FOXO1 and FOXO3a sensitize non-small-cell lung cancer cells to cisplatin-induced apoptosis independent of Bim[J]. Acta Biochim Biophys Sin,2020,52(12):1348-1359.
SONG J Z,XU L S,ZHANG C,et al. Mechanism by which SC79,an Akt activator,inhibits dexamethasone-induced apoptosis and programmed necrosis of osteoblasts[J]. Chin J Tissue Eng Res,2022,26(29):4699-4703.
GRIECO D L,MENGA L S,ELEUTERI D,et al. Patient self-inflicted lung injury:implications for acute hypo-xemic respiratory failure and ARDS patients on non-invasive support[J]. Minerva Anestesiol,2019,85(9):1014-1023.
HUANG C Y,DENG J S,HUANG W C,et al. Attenu-ation of lipopolysaccharide-induced acute lung injury by hispolon in mice,through regulating the TLR4/PI3K/Akt/mTOR and Keap1/Nrf2/HO-1 pathways,and suppressing oxidative stress-mediated ER stress-induced apoptosis and autophagy[J]. Nutrients,2020,12(6):1742.
LIANG S,WANG Y,LIU Y. Dexmedetomidine alleviates lung ischemia-reperfusion injury in rats by activating PI3K/Akt pathway[J]. Eur Rev Med Pharmacol Sci,2019,23(1):370-377.
WANG Y P,LIN Y,WANG L H,et al. TREM2 ameliorates neuroinflammatory response and cognitive impairment via PI3K/AKT/FoxO3a signaling pathway in Alzheimer’s disease mice[J]. Aging,2020,12(20):20862-20879.