# Impact of rice wine-steamed Cistanche deserticola polysaccharides on intestinal flora and immunological modulation in immunosuppressive mice induced by cyclophosphamide

**Authors:** Jing Lian, Yuexin Zhu, Qiushi Hu, Kexu Dong, Zihang Peng, Yurou Feng, Na Ling, Caina Yu, Pengpeng Liu, Xuefei Lei, Ji Shi, Tianzhu Jia

PMC · DOI: 10.3389/fimmu.2026.1732818 · Frontiers in Immunology · 2026-02-05

## TL;DR

This study shows that rice-wine processed Cistanche deserticola polysaccharides improve immunity and gut health in mice with suppressed immune systems.

## Contribution

The study demonstrates that traditional rice-wine processing enhances the immunomodulatory effects of Cistanche polysaccharides.

## Key findings

- Wine-processed polysaccharides improved immune markers like IgA, IgM, IL-2, and IFN-γ in immunosuppressed mice.
- WCP restored gut microbiota balance and increased beneficial bacteria while reducing harmful ones.

## Abstract

Cistanche deserticola, a valued medicinal and food homologous material in traditional Chinese medicine, is renowned for enhancing immunity and protecting the mucosal barrier, with polysaccharides considered its primary active components. Raw material requires processing for optimal efficacy, yet most studies focus on unprocessed polysaccharides (RCP). This study investigates how traditional rice-wine processing alters the polysaccharides (WCP) and their immunomodulatory effects.

The physicochemical properties of RCP and WCP were characterized using SEM, HPGPC, FT-IR, and GC-MS. Immunosuppressed mice induced by cyclophosphamide (CTX) were used as an in vivo model. Immune function was assessed via body weight, organ indices, serum immunoglobulins (IgA, IgM), cytokines (IL-2, IFN-γ), spleen histopathology, and T cell subsets (CD4+/CD8+). Gut microbiota composition was analyzed by 16S rRNA sequencing, and short-chain fatty acid (SCFA) levels were measured.

Wine processing significantly modified the polysaccharides, increasing polysaccharide content, markedly reducing molecular weight, and altering monosaccharide composition in WCP. In CTX-induced mice, WCP administration showed superior immunomodulatory effects: it significantly improved spleen and thymus indices, elevated serum IL-2, IFN-γ, IgA, and IgM levels, and increased the CD4+/CD8+ ratio. Furthermore, WCP restored CTX-disturbed intestinal SCFA levels and positively modulated gut microbiota by increasing Bacteroidetes and beneficial probiotics, lowering the Firmicutes/Bacteroidetes ratio, and suppressing pathogenic bacteria.

Traditional rice-wine processing optimizes the molecular structure of Cistanche polysaccharides and significantly enhances their immunomodulatory efficacy in a cyclophosphamide-induced immunosuppression model. The enhanced activity is associated with marked improvements in gut microbiota composition and systemic immune parameters, suggesting involvement of the gut-immune axis. These findings provide a scientific basis for the traditional processing method and support the further development of processed Cistanche as a potential functional food or therapeutic agent.

## Linked entities

- **Chemicals:** cyclophosphamide (PubChem CID 2907), IgA (PubChem CID 76900), IgM (PubChem CID 71581418), IL-2 (PubChem CID 51397006)

## Full-text entities

- **Genes:** Rab11fip1 (RAB11 family interacting protein 1 (class I)) [NCBI Gene 75767] {aka 2010200K21Rik, 4833414G05Rik, Rcp}, Il2 (interleukin 2) [NCBI Gene 16183] {aka Il-2}, Ighm (immunoglobulin heavy constant mu) [NCBI Gene 16019] {aka Igh-6, Igh-M, Igh6, Igm, TC1460681, muH}, Igha (immunoglobulin heavy constant alpha) [NCBI Gene 238447] {aka IgA, Igh-2}, Ifng (interferon gamma) [NCBI Gene 15978] {aka IFN-g, If2f, Ifg}, Cd4 (CD4 antigen) [NCBI Gene 12504] {aka L3T4, Ly-4}, Apc (APC, WNT signaling pathway regulator) [NCBI Gene 11789] {aka CC1, Min, mAPC}
- **Diseases:** inflammatory bowel illness (MESH:D015212), thymic damage (MESH:D013953), enteritis (MESH:D004751), spleen damage (MESH:D013160), sepsis (MESH:D018805), tissue damage (MESH:D017695), atherosclerotic (MESH:D050197), immunodeficient (MESH:D007153), colitis (MESH:D003092), gastrointestinal damage (MESH:D005767), Immune system disorders (MESH:D007154), infection (MESH:D007239), cytotoxic (MESH:D064420), lethargy (MESH:D053609), weight loss (MESH:D015431), urinary tract infections (MESH:D014552), obesity (MESH:D009765), autoimmune (MESH:D001327), leukopenia (MESH:D007970), weight gain (MESH:D015430), CTX (MESH:D019294), immune-mediated disorders (MESH:C567355), MOD (MESH:D004195), IgA nephropathy (MESH:D005922), hematopoietic toxicity (MESH:D019337), bowel inflammation (MESH:D007249), systemic infection (MESH:D012141), cancer (MESH:D009369), gut dysbiosis (MESH:D064806), atrophy (MESH:D001284)
- **Chemicals:** butyric acid (MESH:D020148), CO2 (MESH:D002245), DSS (MESH:D016264), pantothenic acid (MESH:D010205), Fru (MESH:D005632), Ara (MESH:D001089), paraformaldehyde (MESH:C003043), chloroform (MESH:D002725), H2 (MESH:D006859), alcohol (MESH:D000438), LH (MESH:D007986), PBS (MESH:D007854), acetic acids (MESH:D000085), eosin (MESH:D004801), sulfuric acid (MESH:C033158), reactive oxygen species (MESH:D017382), SCFA (MESH:D005232), Levamisole Hydrochloride (MESH:D007978), inositol (MESH:D007294), D-glucose (MESH:D005947), Valeric acid (MESH:C038780), H&amp;E (MESH:D006371), Hexanoic acid (MESH:C037652), Dextran (MESH:D003911), 1H (-), acetic anhydride (MESH:C031800), borohydride (MESH:D001894), n-butanol (MESH:D020001), hematoxylin (MESH:D006416), penicillin (MESH:D010406), oligosaccharide (MESH:D009844), pyridine (MESH:C023666), thiamine (MESH:D013831), H3PO4 (MESH:C030242), nicotinic acid (MESH:D009525), butyrate (MESH:D002087), Rha (MESH:D012210), Anhydrous sodium sulfate (MESH:C012036), acetone (MESH:D000096), TFA (MESH:D014269), riboflavin (MESH:D012256), vitamin B3 (MESH:D009536), sodium borohydride (MESH:C025364), phenol (MESH:D019800), water (MESH:D014867), CCK-8 (MESH:D012844), propionic acid (MESH:C029658), isoflurane (MESH:D007530), Acetic acid (MESH:D019342), biotin (MESH:D001710), Gal (MESH:D005690), CTX (MESH:D003520), isovaleric acid (MESH:C008216), 4-methylvaleric acid (MESH:C034527), ethanol (MESH:D000431), gold (MESH:D006046), Man (MESH:D008358), methanol (MESH:D000432), paraffin (MESH:D010232), phosphate (MESH:D010710)
- **Species:** Bacillota (clostridial firmicutes, phylum) [taxon 1239], Enterobacteriaceae (enterobacteria, family) [taxon 543], Oryza sativa (Asian cultivated rice, species) [taxon 4530], Rhodiola rosea (rose-root, species) [taxon 203015], Lactobacillaceae (family) [taxon 33958], Bacteroides (genus) [taxon 816], Muribaculum (genus) [taxon 1918540], Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606], Cyanobacteriota (blue-green algae, phylum) [taxon 1117], Pseudomonadota (proteobacteria, phylum) [taxon 1224], Cistanche deserticola (species) [taxon 161395], Pleuropterus multiflorus (fo ti, species) [taxon 76025], Bacteroidaceae (family) [taxon 815], Escherichia coli (E. coli, species) [taxon 562], Mus musculus (house mouse, species) [taxon 10090], Klebsiella pneumoniae (species) [taxon 573]
- **Cell lines:** TM4 — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_4327), RAW264.7 — Mus musculus (Mouse), Mouse leukemia, Cancer cell line (CVCL_0493)

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12916368/full.md

## References

51 references — full list in the complete paper: https://tomesphere.com/paper/PMC12916368/full.md

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Source: https://tomesphere.com/paper/PMC12916368