Therapeutic effect of Formononetin on Mycoplasma pneumoniae pneumonia in mice based on the MAPK/NF-κB signaling pathway
10.13431/j.cnki.immunol.j.20250077
- VernacularTitle:基于MAPK/NF-κB信号通路探讨芒柄花素对肺炎支原体肺炎小鼠的治疗作用
- Author:
Shuang ZHANG
1
;
Ran TAO
;
Xiaojian CUI
;
Leilei SHI
Author Information
1. 天津市儿童医院中医科,天津 300134
- Publication Type:Journal Article
- Keywords:
Mycoplasma pneumoniae pneumonia;
mouse;
MAPK/NF-κB signaling pathway;
Formononetin;
frequency of coughing;
oxygenation index;
interleukin-10;
apoptosis
- From:
Immunological Journal
2025;41(8):535-540
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the therapeutic effect of Formononetin on mice with Mycoplasma pneumoniae pneumonia(MPP)by regulating the mitogen-activated protein kinase(MAPK)/nuclear factor κB(NF-κB)signaling pathway.Methods Six-week-old SPF-grade male BALB/c mice were selected.The MPP mouse model was established as the model group by instillating Mycoplasma pneumoniae bacterial solution through the nose.On the second day after successful modeling,mice were intraperitoneally injected with 15,30,and 60 mg/kg of Formononetin and 60 mg/kg of Formononetin+20 mg/kg of Anisomycin respectively as the low-dose,medium-dose,and high-dose Formononetin groups and the high-dose Formononetin+Anisomycin group,with 12 mice in each group.Another 12 mice were intraperitoneally injected with the same amount of 0.9％sodium chloride injection as the control group.The cough frequency of mice in each group was detected through the cough induction test.The partial pressure of carbon dioxide(PCO2)and partial pressure of oxygen(PO2)in each group of mice were detected by a blood gas analyzer,and the oxygenation index(OI)was calculated.The levels of inflammatory factors in each group were detected by ELISA,and the apoptosis of lung tissue cells in each group of mice was detected by TUNEL.HE staining was performed to observe the pathological changes of lung tissues in each group.The expression of MAPK/NF-κB pathway-related proteins in the lung tissues of mice in each group was detected by Western blot method.Results The lung tissue morphology of the mice in the control group was normal.The alveolar ducts and alveolar structures of mice in the model group were damaged,the alveolar septa thickened,and there was a large amount of inflammatory cell infiltration.Compared with the model group,the lung tissue morphology was improved in the low-dose,medium-dose and high-dose Formononetin groups.The lung tissue injury in the high-dose Formononetin+Anisamycin group was more severe compared with the high-dose Formononetin group.Compared with the control group,the cough latency period in the model group was shortened,and PO2,OI,and interleukin-10(IL-10)were decreased,while the frequency of coughing,PCO2,interleukin-18(IL-18),tumor necrosis factor-α(TNF-α),apoptosis rate,and the ratios of p-P38 MAPK/P38 MAPK,p-NF-κB p65/NF-κB p65,p-extracellular signal-regulated kinase 1/2(ERK1/2)/ERK1/2,and p-C-jun N-terminal kinase(p-JNK)/JNK increased(P＜0.05).Compared with the model group,the low-,medium-and high-dose Formononetin groups had improved lung tissue morphology,prolonged cough latency,increased PO2,OI and IL-10,and reduced cough frequency.The PCO2,IL-18,TNF-α,apoptosis rate,and the ratios of p-p38 MAPK/P38 MAPK,p-NF-κB p65/NF-κB p65,ERK1/2/ERK1/2,and p-JNK/JNK decreased(P＜0.05).In the low-,medium-,and high-dose Formononetin groups,with the increase of Formononetin dose,the cough latency gradually prolonged,the cough frequency gradually decreased,and the PO2,oxygenation index,and IL-10 gradually increased.The PCO2,IL-18,TNF-α,apoptosis rate and the ratios of p-p38 MAPK/P38 MAPK,p-NF-κB p65/NF-κB p65,p-ERK1/2/ERK1/2,and p-JNK/JNK gradually decreased(P＜0.05).Compared with the high-dose Formononetin group,the high-dose Formononetin+Anisamycin group had shorter cough latency,lower PO2,OI and IL-10.The frequency of coughing,PCO2,IL-18,TNF-α,apoptosis rate,and the ratios of p-p38 MAPK/P38 MAPK,p-NF-κB p65/NF-κB p65,p-ERK1/2/ERK1/2,and p-JNK/JNK increased(P＜0.05).Conclusion Formononetin may improve lung injury in MPP mice by inhibiting the MAPK/NF-κB signaling pathway.
