Polygonum aviculare L. extract reduces fatigue by inhibiting neuroinflammation in restraint-stressed mice

Phytomedicine. 2018 Mar 15:42:180-189. doi: 10.1016/j.phymed.2018.03.042. Epub 2018 Mar 19.


Background: Chronic fatigue patients experience various neuropsychological symptoms, including fatigue behaviors, chronic pain, and depression. They also display immune system dysregulation. Polygonum aviculare L. extract (PAE) is a traditional herbal medicine used to treat inflammatory diseases by reportedly decreasing pro-inflammatory cytokine production.

Hypothesis/purpose: We hypothesized that the anti-inflammatory properties of PAE would attenuate fatigue symptoms in a mouse model of restraint stress.

Study design: We evaluated the effects of PAE on fatigue using three experimental groups: unstressed, vehicle-treated stressed, and PAE-treated stressed mice. This restraint stress paradigm, comprised of restraint for 3 h daily for 15 days, was used to model chronic fatigue.

Methods: We compared lethargy-like behavior between our experimental groups using forced-swim, sucrose preference, and open-field tests once per week on days 7 and 14 of restraint stress. We also used histology and western blotting to evaluate pro-inflammatory cytokine expression in the brain and serum, and microglial activation in the brain. Finally, we used liquid chromatography/mass spectroscopy (LC/MS) to identify individual components of PAE, and applied cell culture techniques to test the effects of these components on neuronal cells in vitro.

Results: In restraint-stressed mice, PAE treatment decreased lethargy-like behavior relative to vehicle-treated animals. PAE treatment also reduced expression of fatigue-related factors such as corticosterone, serotonin, and catecholamines (adrenaline and noradrenaline) in the brain and serum, and decreased expression of CD68, Ibal-1, and the inflammatory cytokines TNF-α, IL-6, and IL-1β in the brain. Together, these data indicate that PAE reduced fatigue and is anti-inflammatory. Furthermore, histopathological analyses indicated that PAE treatment recovered atrophic volumes and hepatic injuries. Finally, LC/MS analysis of PAE identified four individual chemicals: myricitrin, isoquercitrin, avicularin, and quercitrin. In neuronal cell cultures, treatment with these PAE components inhibited TNF-α production, confirming that PAE treatment reduces neuroinflammation.

Conclusions: PAE treatment may reduce fatigue by suppressing neuroinflammation and the expression of fatigue-related hormones.

Keywords: Fatigue; Mibyeong; Polygonum aviculare L.; Restraint stress; Stress.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Brain / drug effects
  • Brain / metabolism
  • Brain / pathology
  • Corticosterone / blood
  • Cytokines / metabolism
  • Disease Models, Animal
  • Drugs, Chinese Herbal / pharmacology
  • Fatigue / drug therapy*
  • Fatigue / physiopathology
  • Flavonoids / analysis
  • Inflammation / drug therapy*
  • Male
  • Mice, Inbred C57BL
  • Plant Extracts / pharmacology*
  • Polygonum / chemistry*
  • Serotonin / metabolism
  • Stress, Physiological / drug effects


  • Anti-Inflammatory Agents, Non-Steroidal
  • Cytokines
  • Drugs, Chinese Herbal
  • Flavonoids
  • Plant Extracts
  • Serotonin
  • avicularin
  • myricitrin
  • Corticosterone