Immunomodulatory effects and mechanisms of Qi-Xu-Tiao-Ti formula in Qi-deficiency
constitution: a randomized controlled trial integrated with multi-omics and
network pharmacology analysis
#MMPMID41246353
Cui R
; Fan M
; Yang C
; Chen C
; Xia J
; Liu X
; Zhang G
; Li F
Front Immunol
2025[]; 16
(?): 1675502
PMID41246353
show ga
BACKGROUND: The Qi-deficiency constitution (QDC) is a body constitution type
characterized by weakened immune function and increased susceptibility to
infectious diseases. Emerging evidence indicates that Chinese herbal medicine can
effectively improve immunological competence in individuals with QDC. This study
aims to systematically evaluate the clinical efficacy of the Qi-Xu-Tiao-Ti
Formula (QXTTF) in alleviating QDC and elucidate its underlying pharmacological
mechanisms through transcriptome sequencing and network pharmacology approaches.
METHODS: This single-center randomized controlled trial was performed using QXTTF
to treat the QDC subjects, with Balanced constitution (BC) as the healthy
controls. Primary outcome measures focused on traditional Chinese medicine
constitution assessment of QDC scores, with secondary evaluation parameters
including immune biomarkers (IgA and IgG levels) and adverse events monitoring.
To investigate the molecular mechanisms, we performed transcriptomic profiling to
identify QXTTF-responsive gene targets, followed by integrated network
pharmacology analysis, molecular docking simulations to characterize the
compound-target interactions underlying QXTTF's therapeutic effects, and
ultimately validated at the proteomics level. RESULTS: This study recruited 78
participants, comprising 63 QDC and 15 BC individuals. Comparative analysis
between QDC and BC groups revealed significant differences in immunoglobulin IgA,
IgG levels, and transcriptomic profiles. QXTTF intervention on QDC subjects
significantly reduced the QDC scores (p < 0.05) and enhanced IgA and IgG
production (p < 0.01), indicating QXTTF's dual efficacy in constitution
regulation and potential immunomodulation. Transcriptome sequencing identified
eight putative therapeutic targets: ATP2A1, GOT1, SLC16A8, FTCD, ERBB2, GSS,
VLDLR, and IL2. Functional enrichment analysis revealed significant
overrepresentation of differentially expressed genes in immune-related pathways,
notably "natural killer cell-mediated cytotoxicity", "T cell receptor signaling
pathway", and "B cell receptor signaling pathway". Molecular docking simulations
confirmed stable binding conformations between QXTTF's potential active
components (luteolin, quercetin, naringenin) and key targets ERBB2, GOT1, and
IL2. Proteomic profiling unveiled statistically significant correlations (p <
0.05) between the expression levels of core immune pathway-associated proteins
and putative therapeutic targets. CONCLUSIONS: Our study demonstrates that QXTTF
potentially mitigates QDC via immunomodulatory mechanisms. with therapeutic
targets systematically identified through network pharmacology analysis and
subsequently validated by molecular docking and proteomic profiling. These
insights are crucial in delineating the pharmacological mechanisms of Chinese
herbal formulas that augment the immune function of QDC, thus establishing a
scientific basis for the early prevention and management of immune-related
diseases. CLINICAL TRIAL REGISTRATION: http://www.chictr.org.cn/, identifier
ChiCTR2200063044.
|*Drugs, Chinese Herbal/therapeutic use/pharmacology
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