Research Paper Volume 14, Issue 11 pp 4769—4785
ZhenQi FuZheng formula inhibits the growth of colorectal tumors by modulating intestinal microflora-mediated immune function
- 1 Department of Clinical Pharmacy, The First Hospital of Jilin University, Jilin University, Changchun, Jilin, P.R. China
- 2 School of Life Sciences, Jilin University, Changchun, Jilin, P.R. China
- 3 Department of Pharmacy, Changchun University of Chinese Medicine, Changchun, Jilin, P.R. China
- 4 School of Pharmacy and Food Science, Zhuhai College of Science and Technology, Zhuhai, P.R. China
- 5 Engineering Research Center of Chinese Ministry of Education for Edible and Medicinal Fungi, Jilin Agricultural University, Changchun, Jilin, P.R. China
Received: March 9, 2022 Accepted: May 13, 2022 Published: June 8, 2022
https://doi.org/10.18632/aging.204111How to Cite
Copyright: © 2022 Meng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Zhenqi Fuzheng formula (ZQFZ), of which the main ingredients are Astragalus membranaceus and Ligustrum lucidum, has immune system regulatory functions and potential anti-tumor bioactivity. The inhibition of colorectal tumor growth by ZQFZ was analyzed in inflammatory cells and B6/JGpt-Apcem1Cin(MinC)/Gpt (ApcMin/+) mice. ZQFZ exhibited anti-inflammatory activity by decreasing the phosphorylation of nuclear factor-kappa B (NF-κB) pathway-related proteins in lipopolysaccharide-induced RAW264.7 cells. After 56 days of treatment, ZQFZ alleviated the progression of colorectal cancer (CRC) and increased the body weight and thymic index values of the ApcMin/+ mice. An analysis of the intestinal microflora showed that ZQFZ affected the abundance of certain immune-related bacteria, which may explain its immunomodulatory effects. Moreover, the percentages of T cells and NK cells in peripheral blood were significantly increased and 15 immune-related cytokines were regulated in serum or the colon or both. ZQFZ upregulated the levels of CD4 and CD8 in the spleen and colorectal tumors and decreased the expression levels of cytotoxic T-lymphocyte-associated protein 4 and programmed death-ligand 1 in colorectal tumors. ZQFZ promoted an anti-tumor immune response and inhibited the occurrence and development of CRC by regulating the immune system. This study provides the experimental basis for the application of ZQFZ as a therapeutic agent for CRC.
Abbreviations
ZQFZ: Zhenqi Fuzheng formula; ApcMin/+ mice: B6/JGpt-Apcem1Cin(MinC)/Gpt mice; NF-κB: nuclear factor-kappa B; CRC: colorectal cancer; TNF-α: tumor necrosis factor-α; IL-1β: interleukin -1β; TLRs: Toll-like receptors; PBS: phosphate-buffered saline; FBS: fetal bovine serum; DMEM: Dulbecco’s modified Eagle medium; LPS: Lipopolysaccharide; IFN-γ: interferon -γ; FITC: fluorescein isothiocyanate; IκBα: inhibitor of NF-κB α; P-: Phosphorylated-; IKKα/β: nuclear factor kappa-B kinase α/β; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; CTLA4: cytotoxic T-lymphocyte-associated protein 4; PD-L1: programmed death-ligand 1; ASVs: amplicon sequence variants; LDA: linear discriminant analysis; Ig: Immunoglobulin; GM-CSF: granulocyte-macrophage colony-stimulating factor; TREM 2: triggering receptor expressed on myeloid cells 2; Treg: regulatory T cell; PD-1: programmed cell death protein 1.