<i>Ganoderma Lucidum</i> Polysaccharides Ameliorate Symptoms in Rats with Rheumatoid Arthritis by Modulating Macrophage Polarization via the MAPK/NF-κB/IL-6 Pathway

Yun CAO; Rong LIU; Yan WU

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Yun CAO, Rong LIU, Yan WU. Ganoderma Lucidum Polysaccharides Ameliorate Symptoms in Rats with Rheumatoid Arthritis by Modulating Macrophage Polarization via the MAPK/NF-κB/IL-6 Pathway[J]. Journal of Kunming Medical University.

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Yun CAO, Rong LIU, Yan WU. Ganoderma Lucidum Polysaccharides Ameliorate Symptoms in Rats with Rheumatoid Arthritis by Modulating Macrophage Polarization via the MAPK/NF-κB/IL-6 Pathway[J]. Journal of Kunming Medical University.

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Ganoderma Lucidum Polysaccharides Ameliorate Symptoms in Rats with Rheumatoid Arthritis by Modulating Macrophage Polarization via the MAPK/NF-κB/IL-6 Pathway

Department of Pharmacy，Suzhou Hospital of Integrated Traditional Chinese and Western Medicine，Suzhou Jiangsu 215100，China

Received Date: 2026-01-14

Abstract

Abstract

Objective To investigate the ameliorative effects of Ganoderma lucidum polysaccharides （GLP） on Adjuvant-induced arthritis （RA） in rats and to determine whether the mechanism is associated with modulating the MAPK/NF-κB/IL-6 signaling pathway and macrophage polarization. Methods Fifty-five male Sprague-Dawley rats were randomly divided into a control group （CON） of 10 rats, with the remaining 45 rats used to establish a rheumatoid arthritis （RA） model. The 40 successfully modeled rats were randomly divided into four groups: the RA group, the positive control group treated with methotrexate （MTX）, the GLP treatment group （GLP）, and the combined GLP+PDTC group, with 10 rats in each group. Continuous medication was administered for 5 weeks. Arthritis Index （AI） was assessed weekly. Upon completion of the experiment, paw swelling was measured. Micro-CT was used to analyze ankle joint bone microstructure [bone density （BMD）, bone surface area to bone volume ratio （BS/BV）, trabecular thickness （Tb. Th）, and trabecular separation （Tb. Sp）]. Histopathological changes in the joint were assessed using H&E staining and Safranin O/Fast Green staining. Serum levels of pro-inflammatory cytokines （IL-6; TNF-α; IL-1β） and the anti-inflammatory cytokine （IL-10） were measured by Enzyme-linked immunosorbent assay. Immunohistochemistry was performed to detect the expression of the iNOS and CD206 in the synovial tissue. Western Blot analysis was used to evaluate the protein expression of key molecules in macrophage polarization markers （iNOS, CD86, CD206, Arg-1）, the MAPK pathway （p-p38, p38, p-ERK, ERK, p-JNK, JNK）, the NF-κB pathway （p-IκBα, IκBα, p-p65, p65）, and the downstream effector IL-6 in the synovial tissue. Results Compared with the RA group, the GLP group showed significantly reduced Arthritis Index （AI） scores [（6.05±0.71） vs （11.60±0.92）] and paw swelling [（14.95±0.98） mm vs （19.42±1.35） mm] （P < 0.05） in RA rats, with improved joint bone microstructure and alleviated histopathological damage. Serum pro-inflammatory cytokines IL-6, TNF-α, and IL-1β levels were downregulated （P < 0.01）, while the anti-inflammatory cytokine IL-10 level was upregulated （P < 0.01）. Immunohistochemical results demonstrated decreased positive expression of iNOS and increased positive expression of CD206 in the GLP group （P < 0.001）. Western blot analysis revealed reduced expression of M1 macrophage markers iNOS and CD86, and increased expression of M2 macrophage markers CD206 and Arg-1 in the GLP group （P < 0.001）. Phosphorylation levels of key MAPK pathway proteins p-p38/p38, p-ERK/ERK, and p-JNK/JNK were significantly inhibited （P < 0.05）. Phosphorylation levels of key NF-κB pathway proteins p-IκBα/IκBα and p-p65/p65 were significantly suppressed （P < 0.05）, with downstream IL-6 protein expression decreased （P < 0.05）. Compared with the MTX positive control group, the GLP group showed weaker effects in improving all aforementioned indicators with statistically significant differences between groups （P < 0.05）. Compared with the GLP group alone, combined treatment with the NF-κB inhibitor PDTC and GLP demonstrated synergistic enhancement, further strengthening the above effects. Conclusion GLP effectively ameliorate the arthritis symptoms in RA rats, with mechanisms potentially involving inhibition of the excessive activation of the MAPK/NF-κB signaling pathway in synovial tissue, downregulation of pro-inflammatory cytokines such as IL-6, and promotion of macrophage polarization toward M2 type, thereby rebalancing immune inflammatory equilibrium.
- Rheumatoid arthritis,
- Ganoderma lucidum polysaccharides,
- MAPK/NF-κB/IL-6 pathway,
- Macrophage polarization

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References(19)

References

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