Immunomodulatory effects and multi-omics analysis of Codonopsis Pilosula Extract in septic rats

Codonopsis Pilosula (CP), as a well-known traditional Chinese medicine (TCM) with medicinal and edible herb, is one of the most representative tonic Chinese herbal medicine. It has been widely used for regulating immune function with hardly any adverse effects in clinical practice.

This study aimed to elucidate the immunomodulatory effect and to explore probable mechanism of Codonopsis Pilosula Extract (CPE) in septic rats.

The model of septic rat was established by cecal ligation and perforation (CLP). The thymus index, spleen index and cerebral index were calculated. Histological changes were observed by Hematoxylin-eosin (HE). The positive expression of CD4⁺ T cells was determined in the thymus and spleen by immunohistochemical (IHC). The expression level of 24 h CD4 was corroborated by real-time quantitative polymerase chain reaction (RT-QPCR). Infectious factors, immune factors and inflammatory factors were determined by enzyme-linked immunosorbent assay (ELISA). Blood cells were detected by automatic biochemical analyzer. The metabolite changes and gene expression levels, the potential targets and pathways of CPE in regulating immune function of thymus were analyzed by integrative analysis of transcriptomic and metabolomic methods.

High dose of CPE increased the thymus index and spleen index of septic rats at different stages, and the brain index at different stages could be increased at medium dose and high dose. Medium and high doses of CPE reduced the pathological changes of thymus, spleen and brain tissue. CPE promoted the expression levels of CD4 in the thymus and spleen. CPE improved the levels of red blood cells (RBC), lymphocytes (LYM) and hemoglobin (HGB), and decreased the levels of neutrophils (NEUT), NLR (NEUT/LYM) and PLR (PLT/LYM). CPE dynamically regulated the levels of white blood cells (WBC) and PLT (platelet). CPE dynamically regulated the expression levels of infectious factors, immune factors, and inflammatory factors related to disease severity.

CPE has the ability to dynamically modulate the expression levels of infectious factors, immune factors, and inflammatory factors related to disease severity, and alleviate the damages of immune organs. The research has provided a global view of the integration of metabolomics and transcriptomics to elucidate the immunomodulatory effects and mechanisms of CPE. CPE could affect a series of biological processes in glycerophospholipid metabolism by interfering with the B cell receptor (BCR) signaling pathway in the thymus, to maintain immune homeostasis of septic rats on the whole, especially humoral immunity.