Table 2.
Immune regulatory activity of Glycyrrhiza polysaccharides.
| Polysaccharides. | Types | Experimental model | Dosage | Administration route | Treatment duration | Toxicity assessment | Physiological/translational relevance | Effect (increase, ↑; decrease, ↓) | Ref |
|---|---|---|---|---|---|---|---|---|---|
| LMW-GP | In vivo | BALB/c mice, | GPL: 100 mg/kg bw; GPH: 200 mg/kg bw | Oral (po) | 14 days | No overt adverse effects described | Doses correspond to ~8–16 mg/kg human equivalent dose (HED), showing moderate translational relevance for intestinal immune modulation | Body weight ↑, food intake ↑, colon length ↑, villus length ↑; goblet cells ↑, mucin ↑; colon CD4+ T ↑, CD8+ T ↑; serum IL-2, IL-10, TGF-β3, IgM, IgG ↑; colon sIgA ↑; colon p38↓, ERK↓, NF-κBp50↓; Proteobacteria ↓; SCFA total ↑ | (75) |
| LP | In vivo | CT-26 colon carcinoma–bearing BALB/c mice | 500 mg/kg bw/day, po, 14 d (CTX positive: 50 mg/kg ip, 10 d) | Oral (po) | 14 days (CTX control: 50 mg/kg ip, 10 d) | Not reported; no overt toxicity at tested dose | 500 mg/kg mouse dose ≈ 40.6 mg/kg HED; high-dose setting limits direct dietary translation | Body weight (no-tumor) ↑; Tumor weight ↓; Spleen ↑, Thymus ↑; Thymus index ↑; CD4+ ↑, CD8+ ↓; Serum IL-2 ↑, IL-6 ↑, IL-7 ↑ (vs Saline), TNFα ↓ | (5) |
| GPS-1 | In vivo | Hy-Line brown chickens | GPS-L: 300 mg/kg bw/day, po; GPS-M: 450 mg/kg; GPS-H: 600 mg/kg; 14 d | Oral (po) | 14 days | Not reported; no overt adverse effects described | Veterinary-relevant dose range; applicability to mammals requires further validation | IL-2 ↑, IL-4 ↑, IFN-γ ↑, IL-17 ↑, CD4+/CD8+ expression ↑ | (5) |
| GPS | In vivo | Hy-Line Brown chickens | GPS-L: 300 mg/kg bw/day, po; GPS-M: 450 mg/kg; GPS-H: 600 mg/kg; 14 d | Oral (po) | 14 days | Not reported; no overt adverse effects described | Veterinary-relevant dose range; mammalian translation not established | IL-2 ↑, IL-4 ↑, IL-1β ↑, IFN-γ ↑, Firmicutes ↓, Bacteroidetes ↑, F/B ↓, Actinobacteria ↑ | (98) |
| NGUP |
In vitro and In vivo |
In vitro: C57BL/6 mice, splenic T co-culture; In vivo: C57BL/6 mice | In vitro: 0.5/5/50 μg/mL; In vivo: NGUPL (low)@OVA: NGUP 50 + OVA 20 μg/dose; NGUPL (high)@OVA: NGUP 200 + OVA 20 μg/dose; AL+OVA: Al 25 μg + OVA 20 μg; 3-dose id | In vitro: cell culture; In vivo: 3-dose immunization | In vitro: 36 h; In vivo: 3-dose prime-boost schedule | Not reported | In vitro concentrations at 0.5–5 μg/mL are physiologically plausible; 50 μg/mL is supraphysiological. In vivo adjuvant doses show preliminary translational relevance | In vitro BMDC: CD80/CD86/MHCII ↑; IL-12p70, TNF-α, IL-6 ↑; SIINFEKL-H2Kb ↑; TLR4/MyD88/TRAF6 mRNA ↑, NF-κB p65 phosphorylation ↑; In vivo: DC ↑, CD69+CD4+/CD8+ ↑, IFN-γ+CD8+ ↑, CD4+ Tmem ↑, CD8+ Tmem ↑ | (105) |
| GUPS |
In vitro and In vivo |
In vitro: human monocyte-derived DCs, murine BM-DCs; In vivo naive: BALB/c mice | In vitro: 1, 5, 10, 20, 50 μg/mL; naive: 100 μg/ip single; CTX model: 20 mg/kg ip ×7 d | In vitro: cell culture; In vivo: intraperitoneal (ip) | In vitro: 24–48 h; In vivo: 7 days (tumor model) | Not reported | In vitro 1–10 μg/mL range is physiologically relevant; 50 μg/mL is supraphysiological. IP route bypasses GI absorption, limiting oral translation | CD86/HLA-DR ↑; CD40, CD80, CD86, MHC-I/II/CCR7 ↑; IL-1β, IL-12p40, TNF-α ↑; FITC-dextran endocytosis ↓; p-ERK, p-JNK, p-p38, p-IKKα/β, p-IκBa, p-NF-κBp65 ↑ | (2) |
| GCP | In vivo | BALB/c mice | 500 mg/kg bw/day | Oral (po) | 14 days | Not reported; no overt toxicity described | 500 mg/kg mouse dose ≈ 40.6 mg/kg HED; high-dose pharmacological effect | Tumor: tumor weight ↓, Ki67+ ↓; Systemic: spleen index ↑; splenic CD3+ ↑, tumor-infiltrating CD3+ ↑; Intestinal γδT (flow): CD3+γδT ↑, NKG2D(high) γδT ↑, CD27(high) γδT ↑, intracellular IFN-γ+ γδT ↑; splenic γδT (IHC) ↑, tumor-infiltrating CD27+ γδT ↑; Serum cytokines: IL-7 ↑, IFN-γ ↑, IL-12 ↑, TNF-α ↑; Gut mucosal cytokines: IL-2 ↑, IL-7 ↑, IL-12 ↑, IL-21 ↑, TNF-α ↑; phyla: Bacteroidetes ↓, Firmicutes ↑, Proteobacteria ↑, Tenericutes ↓, Verrucomicrobia ↑, Epsilonbacteraeota ↓ vs Model; genus: Bacteroides, Alloprevotella, Lachnospiraceae_NK4A136↓, Lactobacillusrecovered, Parabacteroides↑; TLRs/NF-κB (gut mucosa): TLR2, TLR4, TLR6 mRNA ↑; p-IκBα protein ↑, NF-κB p65 ↑ | (17) |
| GPS-1 | In vitro and In vivo | In vivo: ICR mice; In vitro: mouse BM-DC | In vivo: 300/450/600 mg/kg/d po ×14 d; In vitro: 125/250/500 μg/mL, 36 h | In vitro: cell culture; In vivo: Oral (po) | In vitro: 36 h; In vivo: 14 days | Not reported | In vitro concentrations are supraphysiological. In vivo doses (300–600 mg/kg) ≈ 24–49 mg/kg HED, pharmacological dose range | In vivo serum: IFN-γ↑, IL-10↑ dose-dep; histology: duodenum/jejunum/ileum villi↑(GPS-H strongest), spleen germinal center↑(GPS-M/H), thymic cortex↑(GPS-M/H); spleen T: CD3+CD4+ 4.09→5.13%(+25.43%), CD3+CD8+ 2.76→3.92%(+42.03%); In vitro DC: CD80/CD86↑; IFN-γ, TNF-α, IL-1β, IL-10↑ dose-dep; OVA-FITC phagocytosis↑ | (99) |
| GPs | In vivo | Wistar rats | GP-L: 0.52 g/kg/d; GP-H: 2.10 g/kg/d; POS: 40 mg/kg/d; CTX 60 mg/kg ip ×3 d | Oral (po) | 14 days | Not reported; no overt adverse effects described | High doses (0.52–2.10 g/kg) correspond to ~42–170 mg/kg HED; supraphysiological, proof-of-concept only | Body/organ: BW↑; spleen index↑; thymus index↑; Cytokines (serum): IFN-γ↑, IL-6↑, IgG↑, IL-10↑, IL-2↑; Intestinal barrier (ileum IF): ZO-1↑, occludin↑; Genus: Allobaculum, Dubosiella, norank:o_Clostridia_UCG-014, g:norank_o:_RF39↑, Enterococcus↓; SCFA (fecal): propionate, iso-butyrate, 2-methyl-butyrate, iso-valerate ↑; SCFA (serum): propionate, iso-butyrate, butyrate, 2-methyl-butyrate ↑ | (97) |
| LP Fractions A/B/C | In vitro | Mouse intestinal epithelial cells (IEC-6) and mouse colon carcinoma (CT-26) | IEC-6/CT-26: 0.01–0.1 mg/ml screened; ED50 IEC-6 ≈ 100 μg/ml; CT-26 inhibition at ≤50 μg/ml; IL-7 qPCR: 100 μg/ml; T-lymph: supernatant from 100 μg/ml-treated IEC-6, 6 h | Cell culture | 24–48 h | Not reported | Concentrations ≥50 μg/mL are supraphysiological for systemic exposure; may be relevant for luminal intestinal exposure | IEC-6: proliferation ↑; CT-26: proliferation ↓: IL-7: IEC-6 mRNA ↑; T lymphocyte: supernatant ↑ | (6) |
| GPs | In vivo | SPF Kunming mice | GPL: 100; GPM: 200; GPH: 400 mg/kg/d po ×14 d; APS: 200 mg/kg/d po | Oral (po) | 14 days | Not reported; no overt toxicity described | 100–400 mg/kg mouse ≈ 8–32 mg/kg HED; moderate translational relevance for antiviral immune support | Serum cytokines: TNF-α↓, IL-6 ↓, IL-4 ↑, IL-10 ↑; Barrier: serum D-lactate ↓, DAO ↓, intestinal sIgA ↑; ZO-1/Occludin mRNA↑, protein (IF/WB) ↑; Viral load: PRV gE qPCR ↓; Microbiota: α-diversity ↑; Lactobacillus, Bacteroides↑; Prevotella↓ | (74) |
| GPN | In vitro and In vivo | In vitro: Caco-2 cells; In vivo: ICR mice | In vitro DC: 50 μg/mL; In vivo: 100 mg/kg/d po ×7 d | In vitro: cell culture; In vivo: Oral (po) | In vitro: 24–48 h; In vivo: 7 days | Not reported | In vitro 50 μg/mL is supraphysiological. In vivo 100 mg/kg ≈ 8.1 mg/kg HED, more physiologically relevant | BM-DC: CD86↑, CD40↑; IL-12p40↑, TNF-α↑; T, B, NK cells↑ | (100) |
| GRPE-I | In vitro and In vivo | In vitro: murine peritoneal macrophage; In vivo: BALB/c mice | In vitro: 1, 10, 100 μg/mL, 24 h; In vivo: 12.5, 25, 50 mg/kg/d po ×15 d | In vitro: cell culture; In vivo: Oral (po) | In vitro: 24 h; In vivo: 15 days | Not reported | In vitro 1–10 μg/mL is physiologically plausible; 100 μg/mL is supraphysiological. In vivo doses show moderate translational relevance | In vivo clinical: BW loss attenuated dose-dep; Thymus: NC↓; Peritoneal macro: proliferation ↓; phagocytosis ↑ dose-dep; NO↑, IL-6↑; Serum: IgA↑, IgG↑ dose-dep, IL-6↑, TNF-α↑, IFN-γ↑; Spleen tissue: IgA/IgG trend↑, IL-6/TNF-α/IFN-γ ↑ consistent with serum; WB(spleen): p-ERK↓, p-p38↓, IκBa↓; SCFA (fecal + cecum): acetate, propionate, butyrate ↓ | (61) |
| GCP | In vivo | BALB/c mice | 500 mg/kg/d po ×14 d | Oral (po) | 14 days | Not reported | 500 mg/kg ≈ 40.6 mg/kg HED; pharmacological high-dose effect | tumor weight ↓, spleen index ↑, Enterorhabdus↑, Odoribacter↑, Ruminococcaceae_UCG_014↑, Ruminococcaceae_UCG_010↑, Enterococcus↑, Ruminiclostridium_5↑, Parasutterella↓, Clostridium_sensu_stricto_1↓, Blautia↓ | (115) |
| GP-1 | In vivo and In vitro | In vivo: Wistar rats; In vitro: rat fecal fermentation | In vivo: 0.84, 3.36 g/kg/d po ×14 d; In vitro: 2, 10 mg/mL, 12 h | In vitro: fecal culture; In vivo: Oral (po) | In vitro: 12 h; In vivo: 14 days | Not reported | Very high in vivo doses (0.84–3.36 g/kg) ≈ 68–273 mg/kg HED; supraphysiological, proof-of-concept only | In vivo: IL-2↓trend, IL-6↓trend, TNF-α↓, IL-4↑, IgA↑, IgG↑; In vitro: genus Lactobacillus↑, Escherichia-Shigella↓, Dubosiella↑; SCFA: acetate↑, propionate↑, isovalerate↑ | (77) |
| GP1 | In vitro and In vivo | In vitro: RAW 264.7 cell; In vivo: BALB/c mice | In vitro: 5, 10, 25, 50, 100, 200, 500, 1000, 2000, 5000 μg/mL; In vivo: 200, 800 mg/kg/d po ×8 wk | In vitro: cell culture; In vivo: Oral (po) | In vitro: 24–48 h; In vivo: 8 weeks | Not reported | In vitro concentrations ≥25 μg/mL are supraphysiological. In vivo 200 mg/kg ≈ 16.3 mg/kg HED, moderate relevance | In vitro: Macrophage phagocytosis ↑, IL-1β, IL-6, TNF-α ↑; In vivo: liver index ↑, spleen index ↑, splenic T Lymph ↑, splenic macro ↑, colonic T ↑, IFN-γ ↑, TGF-β3 ↑, IgG ↑, IgM ↑, IL-1β ↓, IL-2 ↓, IL-4 ↓, IL-10 ↓, TNF-α ↓, MCP-1↓, MIP-1α↓, Chao1 ↑, Shannon ↑; Bacteroides ↑, Firmicutes ↓, Proteobacteria ↓; genus: Muribaculaceae_unclassified ↑, Muribaculum ↑, Prevotellaceae_UCG-001 ↑, Paramuribaculum↑, Muribaculum_sp_H5 ↑ | (76) |
All entries in this table belong to in vitro, ex vivo, or animal-study categories. Human equivalent dose (HED) estimates are based on standard FDA body surface area conversion (mouse: ÷12.3; rat: ÷6.2) and are provided for reference only.