Comprehensive Evaluation of the Anti-Inflammatory Activity of Ling-Zhi-8 (LZ-8) In Vitro and a Rheumatoid Arthritis Animal Model.

Rheumatoid arthritis (RA) is an inflammatory disease caused by an autoimmune reaction. Only immunomodulators or related medicines can decrease RA progression. Ling-Zhi-8 (LZ-8) is a small-molecule protein in Ganoderma lucidum that inhibits inflammation. This study aimed to investigate the anti-inflammatory function and immunomodulatory activity of LZ-8 in RA. Rat RA animal and cell models were used to examine the anti-inflammatory efficacy of LZ-8 in inhibiting arthritis. Experimental results indicated that LZ-8 inhibited the production of interleukin (IL)-6 and the over-expression of cyclooxygenase-2 in lipopolysaccharide-stimulated macrophages. This suppressive effect may be associated with the potential inhibitory effect of LZ-8 on the MyD88-mediated Jun N-terminal kinase-mitogen-activated protein kinase signaling pathway. Administration of lower doses (3.125 mg/kg) of LZ-8 injections for 9 days reduced inflammation and swelling in the soles of the feet in the RA animal model. The pathological lesion of the limb digits of rats in the LZ-8 lower doses (3.125 mg/kg) group was relatively milder than those of the medium- and high-dose groups. Comparing the histological lesions, the LZ-8 high-dose group showed reduced synovial hyperplasia, and all three doses of LZ-8 mitigated damage to the articular cartilage. The reduced spleen weight and the distribution of CD4+IL-4+, CD4+IL-17+, CD4+IFN-γ+, and CD4+CD25+FOXP3+ T-cell immune populations were observed. In conclusion, this study demonstrates that LZ-8 attenuates inflammatory and immunological responses in a CFA (complete Freund's adjuvant)- induced arthritis model, supporting its potential as an immunomodulatory agent for arthritis-associated inflammatory conditions.