Immunomodulatory and locomotor regulations via Diosgenin treatment in lipopolysaccharide-induced chronic fatigue syndrome (CFS)/ depressive despair symptom: an in vivo assessment. — ME/CFS Atlas
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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.
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
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