Immunomodulatory and locomotor regulations via Diosgenin treatment in lipopolysaccharide-induced chronic fatigue syndrome (CFS)/ depressive despair symptom: an in vivo assessment. — CFSMEATLAS
Immunomodulatory and locomotor regulations via Diosgenin treatment in lipopolysaccharide-induced chronic fatigue syndrome (CFS)/ depressive despair symptom: an in vivo assessment.
Shirole, Rahul Lotan, Khalane, Mohan Rajendra, Nage, Vijayeta Pralhad et al. · Naunyn-Schmiedeberg's archives of pharmacology · 2026 · DOI
Quick Summary
This study tested a natural compound called diosgenin (found in fenugreek) to see if it could help with fatigue and depression-like symptoms in mice given a substance that triggered an immune response similar to what happens in ME/CFS. Mice treated with diosgenin showed improvements in activity levels, reduced fatigue-like behavior, and their brains had less inflammation and stress. The results suggest diosgenin might be worth investigating further as a potential treatment.
Why It Matters
ME/CFS involves dysregulated immune function and neuroinflammation that current treatments do not effectively address. Identifying compounds that reduce inflammatory markers and improve fatigue-like symptoms in preclinical models may lead to new therapeutic targets. This work contributes to understanding how immune-mediated neuroinflammation drives fatigue symptoms.
Observed Findings
Diosgenin pre-treatment (10-40 mg/kg) significantly reduced immobility duration in forced swim and tail suspension tests compared to LPS-induced controls.
Diosgenin reduced brain lipid peroxidation and nitrite levels, indicating decreased oxidative and nitrosative stress.
Antioxidant enzyme activity (SOD, CAT) and reduced glutathione levels were restored in diosgenin-treated mice.
Tumor necrosis factor-α (TNF-α) levels were significantly elevated in LPS controls and reduced by diosgenin pre-treatment.
Locomotor activity and grip strength improved in diosgenin-treated animals compared to LPS-alone controls.
Inferred Conclusions
Diosgenin exerts protective effects against LPS-induced behavioral abnormalities associated with fatigue and depression-like symptoms.
Diosgenin's benefits are mediated by reduction of neuroinflammation and oxidative/nitrosative stress in brain tissue.
Diosgenin may represent a potential pharmacological treatment option for chronic fatigue syndrome.
Remaining Questions
Does diosgenin show efficacy in chronic (rather than acute) LPS models or other models of ME/CFS pathophysiology?
What are the mechanisms by which diosgenin modulates immune signaling and crosses the blood-brain barrier?
What This Study Does Not Prove
This study does not prove diosgenin will be effective or safe in ME/CFS patients. LPS-induced acute illness in mice is not identical to the complex, chronic pathophysiology of ME/CFS in humans. The study shows correlation between reduced inflammation and improved symptoms in this specific model, but does not establish causation in human disease or translate mechanisms across species.