Title:The Protective Effects of Modified Dachaihu Decoction against
LPS-induced Acute Lung Injury via Modulating PI3K/Akt Signalling Pathway
Volume: 28
Issue: 5
Author(s): Jincan Li, Jiechun Huang, Gaoxiang Ai, Xiaohong Zheng, Baoyi Chen, Shiting Gong, Xiaowei Lu, Ziren Su, Jiannan Chen, Qingfeng Xie, Yucui Li*Fang Yan*
Affiliation:
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, PR China
- The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, 510006, PR China
- Li Ke and Qi Yu-ru Academic Experience Inheritance Studio, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou,
510006, PR China
- Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, 510006, PR China
Keywords:
Modified Dachaihu decoction, acute lung injury, coronavirus disease 2019, traditional Chinese, medicine, pharmacology network analysis, PI3K/Akt signalling pathway.
Abstract:
Background: Modified Dachaihu decoction (MDD) is a herbal prescription that has
shown promising therapeutic benefits in ameliorating pulmonary diseases in clinical practice.
However, the detailed mechanisms remain unclear.
Objective: This study aimed to elucidate the lung-protective effects of MDD against acute lung
injury (ALI) and the involvement of underlying mechanisms.
Methods: High-performance liquid chromatography (HPLC) was performed to identify the main
active ingredients of MDD. Network pharmacological method was adapted to explore the potential
mechanisms. Mice were orally administered MDD (11.25, 22.5, and 45 g/kg) once daily for
7 days. H&E staining was performed to evaluate histological changes in the lungs. Levels of inflammatory
cytokines and oxidative stress markers were measured to determine the extent of
lung injury. Total protein content in bronchoalveolar lavage fluid (BALF) and lung wet/dry
weight ratio were measured to assess the severity of pulmonary edema. TUNEL staining and
immunohistochemistry analysis were performed to detect apoptosis. RT-qPCR and western blotting
were performed to validate the mechanisms involved.
Results: About 10 main active ingredients of MDD were identified. Notably, treatment with
MDD resulted in a remarkable reduction in total protein content in BALF and lung W/D weight
ratio, as well as substantial mitigation of the inflammatory response and oxidative stress. Mechanistically,
the PI3K/Akt signalling pathway was activated. Moreover, MDD pretreatment
downregulated p53 and caspase-9 mRNA expression and decreased the Bax/Bcl-2 ratio to ameliorate
lung apoptosis.
Conclusions: MDD exhibited pronounced therapeutic effects via attenuating inflammatory response,
oxidative stress, and apoptosis. These therapeutic effects could be attributed to the synergistic
effect of the main active ingredients and are believed to be associated with the activation
of the PI3K/Akt pathway.
