(P26-043-25) GOJI Supplements Mitigate LPS-Induced Muscle Dysfunction in Rats Through Modulation of Inflammation, Mitochondrial Function, and Muscle Fiber Composition

Objectives: Chronic fatigue syndrome (CFS) often involves muscle fatigue with limited treatments. We examined GOJI’s effects on CFS-associated muscle functions (muscle endurance, metabolites, and phenotype) and molecular mechanisms in male rats with lipopolysaccharide (LPS) induction.

Methods: Twenty male SD rats were assigned to control (CON, 1x PBS, i.p.), LPS (250 µg/kg i.p., 2x/wk), LPS+GOJI (LPS + 1% Goji diet) for six weeks. Muscle endurance was assessed weekly via rotarod test. Untargeted metabolite analysis of soleus (S-muscle) was performed via ESI positive/negative mass spectrometry, data was analyzed via Kruskal-Wallis test. Gastrocnemius (G-muscle) was analyzed histologically. RNA sequencing (RNA-seq) was performed on S-muscle using differential gene expression analysis via Wald test. G- and S-muscles were harvested for mRNA expression (TNFα, CD68, DRP1, MFN1/2, TFAM, SOD) using qRT-PCR. Rotarod, mRNA expression, and histological results were analyzed with unpaired t-tests. Statistical significance was P ≤ 0.05.

Results: GOJI mitigated LPS-reduced rotarod performance. Metabolite analysis revealed 10 metabolites altered in LPS vs. CON and 12 in LPS+GOJI vs. LPS, with GOJI reversing the LPS-induced decrease in 3-amino-6-chloropyridazine. Initial evaluation of histomorphology showed that GOJI alleviated muscle atrophy induced by LPS. GOJI reversed LPS-induced MyHC-I and MyHC-IIa mRNA reductions in the S-muscle, while reversing MyHC-IIb decreasing in the G-muscle. In the G-muscle, GOJI reduced inflammatory markers (TNFα) but increased proinflammatory marker (CD68), mitochondria homeostasis genes (DRP1, MFN1/2, TFAM) and antioxidant factor (SOD1). GOJI increased TFAM, while it reduced TNFα in the S-muscle. The RNA-seq comparison of LPS vs. CON showed major upregulation of four genes, with 18 upregulated (e.g., Cxcl13 and Hba2) and six downregulated in LPS+GOJI vs. CON (e.g., Col5a3 and Npas2).

Conclusions: GOJI alleviates LPS-induced muscle dysfunction in male CFS rats by improving endurance, reducing atrophy/ inflammation, altering muscle fiber types, enhancing mitochondrial homeostasis, modulating differential RNA expression and regulating non-targeted muscle metabolites.

Funding Sources: Department of Pathology, Texas Tech University Health Sciences Center