Jingfang Granule promotes the tricarboxylic acid cycle to improve chronic fatigue syndrome by increasing the expression of Idh1 and Idh2.
Wang, Kun, Shen, Mengmeng, Tang, Hongguang et al. · Journal of ethnopharmacology · 2025 · DOI
Quick Summary
Researchers tested a traditional Chinese medicine called Jingfang Granule (JFG) in mice with chronic fatigue syndrome. The treatment improved fatigue symptoms, helped mice recover weight and exercise capacity, and reduced harmful inflammation and oxidative stress in their bodies. The medicine appeared to work by boosting how efficiently cells produce energy through a key metabolic pathway.
Why It Matters
This research identifies a potential therapeutic mechanism for energy production dysfunction in CFS—a leading hypothesis in the field. By demonstrating that enhancing the TCA cycle reduces both inflammation and fatigue symptoms in an animal model, it provides biological plausibility for metabolic intervention and suggests a testable mechanism that could guide future clinical trials in human ME/CFS patients.
Observed Findings
JFG treatment reversed weight loss and increased exhaustion swimming time and tail suspension time in CFS mice compared to untreated controls.
JFG increased liver glycogen, muscle glycogen, and ATP levels while decreasing serum lactic acid in treated mice.
JFG suppressed serum levels of TNF-α, IL-1β, and IL-6 inflammatory cytokines.
JFG improved mitochondrial morphology on electron microscopy in treated compared to untreated CFS mice.
JFG increased protein expression of Idh1 (P<0.05) and Idh2 (P<0.01), key enzymes in the tricarboxylic acid cycle.
Inferred Conclusions
JFG exerts its protective effects in CFS by promoting the tricarboxylic acid cycle through upregulation of Idh1 and Idh2 expression.
Enhanced TCA cycle activity leads to improved cellular energy production (ATP), reduced lactate accumulation, and decreased inflammation and oxidative stress.
Inhibition of TLR4/NF-κB and NLRP3 inflammasome signaling pathways contributes to JFG's anti-inflammatory mechanism.
JFG may represent a potential pharmaceutical candidate for CFS treatment based on its metabolic and immunomodulatory effects in this animal model.
Remaining Questions
Does JFG or TCA cycle enhancement produce similar metabolic and clinical improvements in human ME/CFS patients, and what is the optimal dosing and duration?
What This Study Does Not Prove
This study does not prove that JFG or TCA cycle enhancement will work in human ME/CFS patients; animal models do not always translate to clinical benefit. It does not establish causation in humans or rule out that improvements resulted from placebo effects or non-specific stress reduction. The study is mechanistic only and cannot yet guide clinical practice decisions.
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 →
Which bioactive compounds within JFG are responsible for Idh1/Idh2 upregulation, and can they be isolated or synthesized for more targeted therapy?
Do improvements in TCA cycle function translate to sustained symptomatic relief in humans, and does post-exertional malaise respond to this intervention?
Are there patient subgroups (based on biomarkers or disease severity) more likely to benefit from TCA cycle-targeted interventions?