Brain atrophy in a murine model of chronic fatigue syndrome and beneficial effect of Hochu-ekki-to (TJ-41)

Abstract:

Brain-derived neurotrophic factor (BDNF) is associated with the main symptoms of chronic fatigue syndrome (CFS) and neuron apoptosis. Nevertheless, no study has been performed directly to explore the relationship between CFS, BDNF and neuron apoptosis.

We induced a CFS model by six injections of killed Brucella abortus antigen in BALB/c mice and treated them with Hochu-ekki-to (TJ-41). Daily running activity, body weight (BW), ratio of cerebral weight to BW (CW/BW) and expression levels of BDNF and Bcl-2 mRNA in the hippocampus were determined. The daily activity and CW/BW decreased significantly in the CFS model. BDNF and Bcl-2 mRNA expression levels in the hippocampus were suppressed in the CFS model and TJ-41 treated mice, while no significant difference was found between them.

We improved a murine model to investigate the relationship between CFS and brain dysfunction. In this model, reduced daily activity might have been associated with decreased hippocampal BDNF mRNA expression, hippocampal apoptosis and brain atrophy. TJ-41 increased the daily running activity of the model, which was independent of brain recovery.

 

Source: Chen R, Moriya J, Yamakawa J, Takahashi T, Li Q, Morimoto S, Iwai K, Sumino H, Yamaguchi N, Kanda T. Brain atrophy in a murine model of chronic fatigue syndrome and beneficial effect of Hochu-ekki-to (TJ-41). Neurochem Res. 2008 Sep;33(9):1759-67. doi: 10.1007/s11064-008-9620-1. Epub 2008 Mar 4. https://www.ncbi.nlm.nih.gov/pubmed/18317925

 

Green tea extract and catechin ameliorate chronic fatigue-induced oxidative stress in mice

Abstract:

Chronic fatigue syndrome (CFS) is an illness characterized by persistent and relapsing fatigue, often accompanied by numerous symptoms involving various body systems. The etiology of CFS remains unclear, but a number of studies have shown that oxidative stress may be involved in its pathogenesis. The present study was designed to investigate the protective effect of green tea extract (GTE) and catechin in the mouse model of CFS.

Animals were subjected to a forced swimming test session of 6 minutes every day for 7 days; a significant increase in immobility time on successive days represented the CFS in mice. Biochemical analysis revealed that the chronic swim test significantly increased lipid peroxidation levels and decreased glutathione levels in mouse whole-brain homogenate.

Treatment with GTE (25 or 50 mg/kg, i.p.) and catechin (50 or 100 mg/kg, i.p.) for 7 days reversed the increase in immobility time. Protection was correlated with the lowered levels of lipid peroxidation and restoration of reduced glutathione levels in the brains of fatigued mice. These findings strongly suggest the pivotal role of oxidative stress in the pathophysiology of CFS and that GTE and catechin could be used as potential agents in the management of CFS and warrant the inclusion of GTE and catechin in the treatment regimen of CFS patients.

 

Source: Singal A, Kaur S, Tirkey N, Chopra K. Green tea extract and catechin ameliorate chronic fatigue-induced oxidative stress in mice. J Med Food. 2005 Spring;8(1):47-52. http://www.ncbi.nlm.nih.gov/pubmed/15857209

 

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)

 

Effect of Kuibitang on lipopolysaccharide-induced cytokine production in peripheral blood mononuclear cells of chronic fatigue syndrome patients

Abstract:

Kuibitang (KBT) is clinically used to treat patients suffering from chronic fatigue syndrome (CFS) in South Korea. However, its effect has not been investigated experimentally. Recent reports have shown that CFS patients display an altered cytokine production. We examined the effect of KBT on lipopolysaccharide (LPS)-induced various cytokines production in peripheral blood mononuclear cells (PBMC) of CFS patients and healthy controls. KBT (1 mg/ml) significantly inhibited LPS-induced tumor necrosis factor-alpha, interleukin-10, and transforming growth factor-beta1 production in PBMC of CFS patients. However, LPS-induced interferon-gamma production was significantly increased by KBT (0.01 mg/ml). These results provide evidence of a novel activity of the KBT that regulate cytokines production related with CFS.

 

Source: Shin HY, An NH, Cha YJ, Shin EJ, Shin TY, Baek SH, Kim CH, Lyu YS, Lee EJ, Kim HM. Effect of Kuibitang on lipopolysaccharide-induced cytokine production in peripheral blood mononuclear cells of chronic fatigue syndrome patients. J Ethnopharmacol. 2004 Feb;90(2-3):253-9. http://www.ncbi.nlm.nih.gov/pubmed/15013189

 

Randomized controlled trial of Siberian ginseng for chronic fatigue

Abstract:

BACKGROUND: Chronic fatigue greatly affects quality of life and is a common reason for consulting a physician. Since conventional therapy is often of limited help, fatigued patients may use herbal treatments. This randomized controlled trial evaluated the effectiveness of Siberian ginseng.

METHOD: Subjects were recruited from advertisements in Iowa (82%) and members of chronic fatigue syndrome support groups (18%). Potential subjects were required to have substantial fatigue > or = 6 months with no identifiable cause. The mean change in a fatigue measure was compared for placebo and Siberian ginseng at 1 and 2 months. Comparisons were for all subjects and for subjects with characteristics previously identified in the literature as important for categorizing chronic fatigue.

RESULTS: Ninety-six subjects were randomized to treatment groups, and 76 provided information at 2 months of follow-up. Fatigue among subjects assigned to either placebo or Siberian ginseng was substantially reduced during the study, but differences between treatment groups were not statistically significant in the full sample. Fatigue severity and duration had a statistically significant interaction with response to Siberian ginseng at the P < 0.05 level. Treatment was effective at 2 months for 45 subjects with less severe fatigue (P = 0.04 unadjusted for multiple comparisons) and for 41 subjects with fatigue for > or = 5 years (P = 0.09 unadjusted for multiple comparisons).

CONCLUSION: Overall efficacy was not demonstrated. However, the findings of possible efficacy for patients with moderate fatigue suggests that further research may be of value.

 

Source: Hartz AJ, Bentler S, Noyes R, Hoehns J, Logemann C, Sinift S, Butani Y, Wang W, Brake K, Ernst M, Kautzman H. Randomized controlled trial of Siberian ginseng for chronic fatigue. Psychol Med. 2004 Jan;34(1):51-61. http://www.ncbi.nlm.nih.gov/pubmed/14971626

 

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

 

Ruscus aculeatus (butcher’s broom) as a potential treatment for orthostatic hypotension, with a case report

Abstract:

CONTEXT: Chronic orthostatic hypotension (OH) is frequently a severely debilitating disease that affects large groups of the population with autonomic insufficiency–the elderly; patients with diabetes, Parkinson’s disease, and chronic fatigue syndrome; and anyone on drugs that affect the autonomic nervous system. Unfortunately, even though more than 60 medications are currently being used to treat OH, none of them is particularly or consistently effective. Ruscus aculeatus, a phytotherapeutic agent that is well known in Europe, may, however, change this. Its vasoconstrictive and venotonic properties make it ideally suited to treat the pooling of blood in the limbs, lack of venous tone, and lack of neurally mediated vasoconstriction that frequently characterize OH. Although it has never been suggested as a treatment for OH, it already has a long, proven record of use in Europe for treating a variety of circulatory disorders.

OBJECTIVE: To provide evidence for what appears to be an effective, safe, inexpensive botanical therapy for OH and encourage further studies on the efficacy of Ruscus for OH patients.

DESIGN: Review of OH and therapies currently available for OH and evaluation of the properties of Ruscus aculeatus, its mechanism of action, and its suitability as a therapeutic agent for treatment of OH.

RESULTS: A review of the many pharmacologic and nonpharmacologic agents for treating OH reveals that all of the drug therapies are disappointing and marginally useful. Although nonpharmacologic management is preferred, in the many cases in which OH becomes debilitating, pharmacologic intervention becomes a last resort. But drug therapy may not always be necessary, because Ruscus aculeatus, a phytotherapeutic agent containing ruscogenins and flavonoids, may prove useful for the treatment of OH if denervation is not so advanced that it has compromised receptor activity at the venous wall. Ruscus aculeatus is an alpha-adrenergic agonist that causes venous constriction by directly activating postjunctional alpha1- and alpha2-receptors, in turn stimulating the release of noradrenaline at the level of the vascular wall. It also possesses venotonic properties: it reduces venous capacity and pooling of blood in the legs and exerts protective effects on capillaries, the vascular endothelium, and smooth muscle. Its flavonoid content strengthens blood vessels, reduces capillary fragility, and helps maintain healthy circulation. Unlike most of the drug therapies used to treat OH, Ruscus aculeatus does not cause supine hypertension. It also appears to do something no other therapy can offer–alleviate the worsening effects of OH in environmentally hot conditions. Finally, it is an extremely safe, inexpensive, over-the-counter botanical medicine.

CONCLUSION: With proven phlebotherapeutic properties, including vasoconstrictive action and venotonic properties, Ruscus aculeatus shows great promise for ameliorating the symptoms of OH and improving the quality of life for large groups in the population. It clearly deserves to be the object of wider research and study as a treatment for OH.

 

Source: Redman DA. Ruscus aculeatus (butcher’s broom) as a potential treatment for orthostatic hypotension, with a case report. J Altern Complement Med. 2000 Dec;6(6):539-49. http://www.ncbi.nlm.nih.gov/pubmed/11152059

 

In vitro effects of echinacea and ginseng on natural killer and antibody-dependent cell cytotoxicity in healthy subjects and chronic fatigue syndrome or acquired immunodeficiency syndrome patients

Abstract:

Extracts of Echinacea purpurea and Panax ginseng were evaluated for their capacity to stimulate cellular immune function by peripheral blood mononuclear cells (PBMC) from normal individuals and patients with either the chronic fatigue syndrome or the acquired immunodeficiency syndrome.

PBMC isolated on a Ficoll-hypaque density gradient were tested in the presence or absence of varying concentrations of each extract for natural killer (NK) cell activity versus K562 cells and antibody-dependent cellular cytotoxicity (ADCC) against human herpesvirus 6 infected H9 cells. Both echinacea and ginseng, at concentrations > or = 0.1 or 10 micrograms/kg, respectively, significantly enhanced NK-function of all groups. Similarly, the addition of either herb significantly increased ADCC of PBMC from all subject groups.

Thus, extracts of Echinacea purpurea and Panax ginseng enhance cellular immune function of PBMC both from normal individuals and patients with depressed cellular immunity.

 

Source: See DM, Broumand N, Sahl L, Tilles JG. In vitro effects of echinacea and ginseng on natural killer and antibody-dependent cell cytotoxicity in healthy subjects and chronic fatigue syndrome or acquired immunodeficiency syndrome patients. Immunopharmacology. 1997 Jan;35(3):229-35. http://www.ncbi.nlm.nih.gov/pubmed/9043936

 

Chronic Fatigue Syndrome: Do herbs or homeopathy help?

Abstract:

To determine the effect of certain herbal and homeopathic preparations on symptoms, lymphocyte markers, and cytotoxic function of the lymphocytes in patients with chronic fatigue syndrome, we studied six outpatients diagnosed with the disease by their family physicians. Patients were given herbal and homeopathic preparations after a 3-week symptom-recording period. After treatment, symptoms were again recorded. Blood samples were taken before and after treatment. None of the values showed any significant change after treatment.

 

Source: Leyton E, Pross H. Chronic Fatigue Syndrome: Do herbs or homeopathy help? Can Fam Physician. 1992 Sep;38:2021-6. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2145466/ (Full article)