Therapeutic Mechanistic Studies of ShuFengJieDu Capsule in an Acute Lung Injury Animal Model Using Quantitative Proteomics Technology

ShuFengJieDu capsule (SFJDC), a traditional
Chinese medicine (TCM)
that contains eight medicinal herbs, has been extensively utilized
for the treatment of acute lung injury (ALI) and respiratory infections
for more than 30 years in China. SFJDC has also been listed in the
official guidelines of the China Food and Drug Administration (CFDA)
due to its stable clinical manifestations. However, the underlying
mechanism of SFJDC during ALI repair remains unclear. In the present
study, we explored the protective and therapeutic mechanisms of SFJDC
in a rat model by performing qualitative and label-free quantitative
proteomics studies. After establishing lipopolysaccharide (LPS)-induced
ALI rat models, we profiled macrophage cells isolated from freshly
resected rat lung tissues derived from ALI models and ALI rat lung
tissue sections using a high performance liquid chromatography–mass
spectrometry (HPLC–MS/MS) shotgun proteomics approach to identify
changes in the expression levels of proteins of interest. On the basis
of our proteomics results and the results of a protein dysregulation
analysis of ALI rat lung tissues and rat lung macrophages, AKT1 was
selected as a putative key factor that may play an important role
in mediating the effects of SFJDC treatment during ALI progression.
Follow-up validation studies demonstrated that AKT1 expression effectively
regulates various ALI-related molecules, and Gene Ontology analysis
indicated that SFJDC-treated ALI rat macrophages were influenced by
AKT1-based networks. Gain- and loss-of-function analyses following
lentivirus-AKT1 or lentivirus-si-AKT1 infection in macrophages also
indicated that AKT1 was essential for the development of ALI due to
its ability to regulate oxidative stress, apoptosis, or inflammatory
responses. In summary, SFJDC effectively modulated anti-inflammatory
and immunomodulation activity during ALI, potentially due to AKT1
regulation during ALI progression. New insights into SFJDC mechanisms
may facilitate the development of novel pharmaceutical strategies
to control the expression of inflammatory factors.