Effect of Hochu-ekki-to (TJ-41), a Japanese Herbal Medicine, on Daily Activity in a Murine Model of Chronic Fatigue Syndrome

Abstract:

We aimed to evaluate the effect of a Japanese herbal medicine, Hochu-ekki-to (TJ-41), on daily activity in a murine model of chronic fatigue syndrome (CFS).

CFS was induced by repeated injection of Brucella abortus (BA) antigen every 2 weeks. TJ-41 was orally administered to mice in a dose of 500 mg/kg/day for 1 week before injecting BA and for 4 weeks thereafter. We evaluated daily running activity in mice receiving TJ-41 as compared with that in untreated mice. Survival of both mouse groups was also monitored during the observation period. Body weight (BW), spleen weight (SW), SW/ BW ratio and expression levels of interleukin-10 (IL-10) mRNA in spleen were determined in both groups at the time of sacrifice.

The daily activity was significantly higher in the treated group than in the control. Two mice in the untreated group died 2 days after the second injection of BA, whereas no mice in the group treated with TJ-41 died. The SW and SW/BW ratio were significantly lower in the treated mice than in the control. Suppressed IL-10 mRNA levels were observed in the spleens of the mice treated with TJ-41. Our data suggest that Hochu-ekki-to might possess an inhibitory effect on the marked decrease in running activity following BA injection.

 

Source: Wang XQ, Takahashi T, Zhu SJ, Moriya J, Saegusa S, Yamakawa J, Kusaka K, Itoh T, Kanda T. Effect of Hochu-ekki-to (TJ-41), a Japanese Herbal Medicine, on Daily Activity in a Murine Model of Chronic Fatigue Syndrome. Evid Based Complement Alternat Med. 2004 Sep 1;1(2):203-206. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC516453/ (Full article)

 

Role of antioxidants in chronic fatigue syndrome in mice

Abstract:

The present study was carried out using mice model of chronic fatigue syndrome (CFS) in which mice were forced to swim everyday for 7 days for a 6 min session. There was a significant increase in despair behavior (immobility period) in saline treated mice on successive days.

Treatment with potent antioxidants carvedilol (5 mg/kg, i.p.) and melatonin (10 mg/kg, i.p.) produced a significant reduction in immobility period. Similar results were observed with herbal products St. John’s Wort (Hypericum perforatum L) (10 mg/kg, p.o.) and GS-02 (20 mg/kg, p.o.). Fluoxetine, a selective serotonin reuptake inhibitor produced a significant effect only on first and second day of its treatment.

Biochemical analysis revealed that chronic swim test significantly increased lipid peroxidation and catalase levels in whole brains of mice. There was a decrease in the levels of super oxide dismutase (SOD) and glutathione reductase (GSH) in the brain.

Administration of carvedilol, melatonin, GS-02 and St. John’s Wort restored the levels of lipid peroxidation and glutathione. The enzymes SOD and catalase were also restored. Fluoxetine affected the biochemical variables not to the same extent as other treatments. The findings of the present study suggest that oxidative stress might play a significant role in the pathophysiology of CFS. Thus antioxidants and herbal products like St. Johns wort and GS-02 could be useful in the treatment of CFS.

 

Source: Singh A, Garg V, Gupta S, Kulkarni SK. Role of antioxidants in chronic fatigue syndrome in mice. Indian J Exp Biol. 2002 Nov;40(11):1240-4. http://www.ncbi.nlm.nih.gov/pubmed/13677625

 

Mouse running activity is lowered by Brucella abortus treatment: a potential model to study chronic fatigue

Abstract:

Chronic fatigue syndrome, which can occur after acute infection and last for years, is characterized by severe and persistent fatigue. Others have reported decreases in mouse running activity following infection and have suggested this may provide an animal model for studying chronic fatigue.

Voluntary running is a highly motivated activity in mice, which will often run 5-7 mi/day in our laboratory. Following 2 weeks of acclimation to running wheels with food and water available ad lib, female BALB/c mice received 0.2-mL tail vein injections of killed Brucella abortus (BA) or saline vehicle. Subsequently the effects on voluntary running and grooming behavior were determined.

Injection of BA caused an immediate large decrease in running and a lack of grooming. Vehicle injections produced no changes in behavior. After the first several days of reduced running behavior, levels of running and grooming slowly returned back to normal over the next 2-4 weeks, with substantial individual differences in the rate of recovery.

The pattern of running during recovery was intriguing in that BA mice first ran at normal levels just after the lights went out, but they stopped after only 1-2 h. As recovery proceeded, they gradually increased the duration of the running bout during the night. Because this model uses voluntary exertion and the ability to run for longer periods of time characterizes recovery, the model may be a good one for studying the biologic underpinnings of chronic fatigue.

 

Source: Ottenweller JE, Natelson BH, Gause WC, Carroll KK, Beldowicz D, Zhou XD, LaManca JJ. Mouse running activity is lowered by Brucella abortus treatment: a potential model to study chronic fatigue. Physiol Behav. 1998 Mar;63(5):795-801. http://www.ncbi.nlm.nih.gov/pubmed/9618001