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Proteomic and mechanistic study of Qingxuan Tongluo formula and curcumin in the treatment of Mycoplasma pneumoniae pneumonia - 19/12/20

Doi : 10.1016/j.biopha.2020.110998 
Lina Wei a, c, 1, Weilong Zhong b, d, 1, Tao Sun c, Huanmin Li a, Ting Sun a, e, Yaowei Han a, Dan Sun a, Xinmin Li a,
a First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300381, China 
b Nankai University, Tianjin 300071, China 
c First Affiliated Hospital to Changchun University of Chinese Medicine, Changchun Jilin 130021, China 
d Tianjin Medical University General Hospital, Tianjin 300052, China 
e Beijing University of Chinese Medicine Affiliated Dongzhimen Hospital, Beijing 100007, China 

Corresponding author.

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Graphical abstract

Qingxuan Tongluo formula and curcumin might play roles in the treatment of MPP by upregulating the expression of glycolytic-related proteins to increase productivity, relieve the oxidative stress of host cells and improve host hypercoagulability. ENO1 and PLG are potential drug targets.




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Highlights

Qingxuan Tongluo formula can reduce the blood hypercoagulability of MPP.
ENO1 and PLG are potential drug targets of the Qingxuan Tongluo formula.
MP infection can inhibit the correct folding of host proteins.
Hsp90aa1/GRP94 can be used as a biomarker for the diagnosis of MPP.

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Abstract

Objective

Mycoplasma pneumoniae (MP) is the only pathogen in the Mycoplasma family that can cause respiratory symptoms, including acute upper respiratory tract infection and bronchitis, which are often attributed to Mycoplasma pneumoniae pneumonia (MPP). MPP is one of the diseases that commonly affects the pediatric respiratory system, but its pathogenesis is unclear. This study investigated the therapeutic effects and mechanisms of Qingxuan Tongluo formula and its main component, curcumin, on MPP.

Methods

A mouse model of MPP was obtained by nasal drip of the MP strain. The effects of Qingxuan Tongluo formula and curcumin on the treatment of MPP were studied. The proteomic profiles of the alveolar lavage fluid of mice in the model group, Qingxuan Tongluo formula group and curcumin group were evaluated by LC–MS/MS. ELISA and immunohistochemistry were used to verify the possible presence of MP infection biomarkers and drug target proteins.

Results

Compared with the mice in the model group, the MPP mice in the Qingxuan Tongluo formula group had significantly reduced fever and cough and prolonged the cough incubation period. Moreover, the pulmonary pathology of the MPP mice was significantly improved, and the lung histopathological score was decreased. After treatment with Qingxuan Tongluo formula and curcumin, the functional and pathway abnormalities caused by MP were mainly inhibited. Levels of HSP90AA1, GRP94, ENO1 and PLG expression were verified by ELISA and immunohistochemistry.

Conclusion

Qingxuan Tongluo formula significantly reduced fevers and cough and prolonged the cough incubation period of MPP mice. Qingxuan Tongluo formula and curcumin significantly improved the pathological changes in lung tissue caused by MP infection. Proteomics analyses indicated that Qingxuan Tongluo formula and curcumin may have therapeutic effects on MPP by regulating energy metabolism, relieving oxidative stress and activating the fibrinolytic system. ENO1 and PLG were found to be potential drug targets.

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Keywords : Qingxuan Tongluo formula, Curcumin, MPP, Proteomics, Drug target


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© 2020  The Authors. Publicado por Elsevier Masson SAS. Todos los derechos reservados.
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