Mechanistic Exploration of Yiqi Zengmian in Regulating the Microenvironment as an Immunopotentiator with the Beijing Bio-Institute of Biological Products Coronavirus Vaccine Based on Transcriptomics and Integrated Serum Pharmacochemistry

Zeyue Yu; Yudong Wang; Jianhui Sun; Xiaotong Zheng; Liyu Hao; Yurong Deng; Jianliang Li; Zongyuan Li; Zhongchao Shan; Weidong Li; Yuling Qiao; Ruili Huo; Yibai Xiong; Hairu Huo; Hui Li; Longfei Lin; Hanhui Huang; Guimin Liu; Aoao Wang; Hongmei Li; Luqi Huang

doi:10.3390/ph18060802

Mechanistic Exploration of Yiqi Zengmian in Regulating the Microenvironment as an Immunopotentiator with the Beijing Bio-Institute of Biological Products Coronavirus Vaccine Based on Transcriptomics and Integrated Serum Pharmacochemistry

Pharmaceuticals (Basel). 2025 May 27;18(6):802. doi: 10.3390/ph18060802.

Authors

Zeyue Yu^{1

2}, Yudong Wang², Jianhui Sun², Xiaotong Zheng³, Liyu Hao², Yurong Deng², Jianliang Li², Zongyuan Li², Zhongchao Shan², Weidong Li³, Yuling Qiao³, Ruili Huo⁴, Yibai Xiong⁴, Hairu Huo², Hui Li², Longfei Lin², Hanhui Huang², Guimin Liu², Aoao Wang², Hongmei Li², Luqi Huang¹

Affiliations

¹ National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, No. 16 Nanxiaojie, Dongzhimennei Ave., Beijing 100700, China.
² Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, No. 16 Nanxiaojie, Dongzhimennei Ave., Beijing 100700, China.
³ Beijing Institute of Biological Products Company Limited, No. 9 Boxing Second Road, Beijing 100176, China.
⁴ China Academy of Chinese Medical Sciences, No. 16 Nanxiaojie, Dongzhimennei Ave., Beijing 100700, China.

Abstract

Background: Yiqi Zengmian (YQZM) functions as an immunopotentiator by enhancing both cellular and humoral immunity. However, its pharmacodynamic active constituents, particularly those absorbed into the bloodstream, and mechanism of action remain unclear. This study aimed to investigate the immunopotentiating effects and mechanisms of YQZM in mice immunized with the BBIBP-CorV (Beijing Bio-Institute of Biological Products Coronavirus Vaccine). Methods: Serum pharmacochemistry and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) were employed to identify bioavailable components of YQZM. The mice received the BBIBP-CorV twice on days 1 and 14, while YQZM was orally administered for 28 days. Neutralization assays and ELISA quantified antigen-specific antibodies (abs), flow cytometry (FC) and intracellular cytokine staining (ICS) were used to assess immune cell populations and their cytokines, and an enzyme-linked immunospot assay (ELISpot) quantified memory T and B cells (MBs and MTs). To identify underlying mechanisms, network pharmacology, RNA sequencing (RNA-Seq), molecular docking, Western blotting (WB), and quantitative reverse transcription PCR (RT-qPCR) were performed. Results: YQZM significantly enhanced antigen-specific antibody titers, immune cell proportions, cytokine levels, and memory lymphocyte functions. UPLC-MS/MS analysis identified 31 bioactive compounds in YQZM. KEGG enrichment analysis based on RNA-Seq and network pharmacology implicated the TLR-JAK-STAT signaling pathway in YQZM's immune-enhancing effects. WB and RT-PCR validated that YQZM upregulated the expression of critical nodes in the TLR-JAK-STAT signaling pathway. Furthermore, molecular docking indicated that YQZM's primary active components exhibited strong binding affinity for critical proteins. Conclusions: YQZM effectively enhances vaccine-induced innate and adaptive immunity via a multi-component, multi-target mechanism, among which the TLR-JAK-STAT signaling pathway is a validated molecular target.

Keywords: BBIBP-CorV; Yiqi Zengmian decoction; cellular immunity; humoral immunity; network pharmacology; transcriptome analysis.

Abstract

Grants and funding