Tag: mouse model

Polysaccharide of radix pseudostellariae improves chronic fatigue syndrome induced by poly I:C in mice

Abstract:

Radix Pseudostellariae is used as a tonic drug in traditional Chinese medicine with immunomodulating and anti-fatigue activities, and the polysaccharide is considered as the main active component. The purpose of this study is to examine the effect of the polysaccharide isolated from Radix Pseudostellariae (PRP) on mouse chronic fatigue syndrome (CFS) induced by intraperitoneal injection of polyriboinosinic:polyribocytidylic acid (poly I:C), a double-stranded synthetic RNA.

It has shown that the fatigue symptom of mice lasted at least 1 week as evaluated by forced swimming time. PRP (100, 200, 400 mg kg(-1)), orally administered 3 days before poly I:C injection, showed dose-dependent anti-fatigue effects.

In addition, poly I:C led to evident alterations in neuroendocrine and immune systems of mice, such as reduced spontaneous activity and learning ability, declined serum level of corticosterone, increased weight indexes and T lymphocyte numbers in thymuses and spleens, and increased CD4(+)/CD8(+) ratio but decreased proliferation ability of T lymphocytes in spleens. PRP alleviated the abnormalities caused by poly I:C, and restored the function of hosts to normal conditions.

The findings suggest that PRP is beneficial to CFS, and the underlying mechanisms of action involve neuroendocrine and immune systems.

 

Source: Sheng R, Xu X, Tang Q, Bian D, Li Y, Qian C, He X, Gao X, Pan R, Wang C, Luo Y, Xia Y, Dai Y. Polysaccharide of radix pseudostellariae improves chronic fatigue syndrome induced by poly I:C in mice. Evid Based Complement Alternat Med. 2011;2011:840516. doi: 10.1093/ecam/nep208. Epub 2011 Jun 23. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3137695/ (Full article)

 

Epigallocatechin gallate ameliorates chronic fatigue syndrome in mice: behavioral and biochemical evidence

Abstract:

Three decades after the coining of the term chronic fatigue syndrome, the diagnosis of this illness is still symptom based and the aetiology remains elusive. Chronic fatigue syndrome pathogenesis seems to be multifactorial and the possible involvement of immune system is supported. The present study was designed to evaluate the effects of the epigallocatechin gallate in a mouse model of immunologically induced chronic fatigue.

On 19th day, after lipopolysaccharide/Brucella abortus administration, the mice showed significant increase in immobility period, post swim fatigue and thermal hyperalgesia. Behavioral deficits were coupled with enhanced oxidative-nitrosative stress as evident by increased lipid peroxidation, nitrite levels and decreased endogenous antioxidant enzymes (superoxide dismutase, reduced glutathione and catalase) and inflammation (increased levels of tumor necrosis factor-alpha and tissue growth factor-beta).

Chronic treatment with epigallocatechin gallate restored these behavioral and biochemical alterations in mice. The present study points out towards the beneficial effect of epigallocatechin gallate in the amelioration of chronic fatigue syndrome and thus may provide a new, effective and powerful strategy to treat chronic fatigue syndrome.

 

Source: Sachdeva AK, Kuhad A, Tiwari V, Chopra K. Epigallocatechin gallate ameliorates chronic fatigue syndrome in mice: behavioral and biochemical evidence. Behav Brain Res. 2009 Dec 28;205(2):414-20. doi: 10.1016/j.bbr.2009.07.020. Epub 2009 Jul 28. https://www.ncbi.nlm.nih.gov/pubmed/19643148

 

Modulation of antigen-induced chronic fatigue in mouse model of water immersion stress by naringin, a polyphenolic antioxidant

Abstract:

It is believed that physical stress, infection and oxidative stress are involved in the development of chronic fatigue syndrome. There is little evidence stating the beneficial role of nutritional supplements in chronic fatigue syndrome. Based on this, this study was designed to evaluate the effect of naringin, a natural polyphenol, in a mouse model of immunologically-induced fatigue, wherein purified lipopolysaccharide (LPS) as well as Brucella abortus (BA) antigen was used as immunogens.

The assessment of chronic fatigue syndrome was based on chronic water-immersion stress test for 10 mins as well as measurement of hyperalgesia for 19 days. Immobility time and tail withdrawal latency as well as oxidative stress were taken as the markers of fatigue. Mice challenged with LPS or BA for 19 days showed significant increase in the immobility time, hyperalgesia and oxidative stress on 19th day. Serum tumor necrosis factor-alpha (TNF-alpha) levels markedly increased with LPS or BA challenge.

Concurrent treatment with naringin resulted in the significant decrease in the immobility time as well as hyperalgesia. There was significant attenuation of oxidative stress as well as in TNF-alpha levels. Present findings strongly suggest the role of oxidative stress and immunological activation in the pathophysiology of chronic fatigue syndrome, and treatment with naringin can be a valuable option in chronic fatigue syndrome.

 

Source: Vij G, Gupta A, Chopra K. Modulation of antigen-induced chronic fatigue in mouse model of water immersion stress by naringin, a polyphenolic antioxidant. Fundam Clin Pharmacol. 2009 Jun;23(3):331-7. doi: 10.1111/j.1472-8206.2009.00675.x. Epub 2009 Mar 11. https://www.ncbi.nlm.nih.gov/pubmed/19469804

 

Protective effects of antidepressants against chronic fatigue syndrome-induced behavioral changes and biochemical alterations

Abstract:

Chronic fatigue syndrome (CFS) is characterized by profound fatigue, which substantially interferes with daily activities. The aim of this study was to explore the protective effects of antidepressants in an animal model of CFS in mice. Male albino mice were forced to swim individually for a period of 6-min session each for 7 days. Imipramine (10 and 20 mg/kg), desipramine (10 and 20 mg/kg) and citalopram (5 and 10 mg/kg) were administered 30 min before forced swimming test on each day.

Various behavior tests (immobility time, locomotor activity, anxiety-like behavior by plus maze and mirror chamber) followed by biochemical parameters (lipid peroxidation, reduced glutathione, catalase and nitrite level) were assessed in chronic stressed mice. Chronic forced swimming for 7 days significantly caused increase in immobility period, impairment in locomotor activity, anxiety-like behavior, and oxidative stress (raised lipid peroxidation, nitrite activity and reduced glutathione and catalase activity) as compared with naïve mice (P < 0.05).

Seven days of pretreatment with imipramine (10 and 20 mg/kg), desipramine (10 and 20 mg/kg), and citalopram (5 and 10 mg/kg) significantly reduced immobility time, improved locomotor activity and anti-anxiety effect (in both plus maze and mirror chamber test), and attenuated oxidative stress in chronic stressed mice as compared with control (chronic fatigues) (P < 0.05). These results suggested that these drugs have protective effect and could be used in the management of chronic fatigue like conditions.

 

Source: Kumar A, Garg R. Protective effects of antidepressants against chronic fatigue syndrome-induced behavioral changes and biochemical alterations. Fundam Clin Pharmacol. 2009 Feb;23(1):89-95. doi: 10.1111/j.1472-8206.2008.00638.x. Epub 2009 Jan 10. https://www.ncbi.nlm.nih.gov/pubmed/19207541

 

Curcumin, a polyphenolic antioxidant, attenuates chronic fatigue syndrome in murine water immersion stress model

Abstract:

Chronic fatigue syndrome, infection and oxidative stress are interrelated in epidemiological case studies. However, data demonstrating scientific validation of epidemiological claims regarding effectiveness of nutritional supplements for chronic fatigue syndrome are lacking. This study is designed to evaluate the effect of natural polyphenol, curcumin, in a mouse model of immunologically induced fatigue, where purified lipopolysaccharide (LPS) and Brucella abortus (BA) antigens were used as immunogens.

The assessment of chronic fatigue syndrome was based on chronic water-immersion stress test for 10 min daily for 19 days and the immobility time was taken as the marker of fatigue. Mice challenged with LPS or BA for 19 days showed significant increase in the immobility time and hyperalgesia on day 19, as well as marked increase in serum tumor necrosis factor-alpha (TNF-alpha) levels. Concurrent treatment with curcumin resulted in significantly decreased immobility time as well as hyperalgesia. There was significant attenuation of oxidative stress as well as TNF-alpha levels.

These findings strongly suggest that during immunological activation, there is significant increase in oxidative stress and curcumin can be a valuable option in the treatment of chronic fatigue syndrome.

 

Source: Gupta A, Vij G, Sharma S, Tirkey N, Rishi P, Chopra K. Curcumin, a polyphenolic antioxidant, attenuates chronic fatigue syndrome in murine water immersion stress model. Immunobiology. 2009;214(1):33-9. doi: 10.1016/j.imbio.2008.04.003. Epub 2008 Jun 17. https://www.ncbi.nlm.nih.gov/pubmed/19159825

 

Nitric oxide modulation mediates the protective effect of trazodone in a mouse model of chronic fatigue syndrome

Abstract:

The present study was conducted with the aim of elucidating the possible role of nitric oxide (NO) in the neuroprotective effects of trazodone used to treat chronic fatigue syndrome (CFS) in mice.

Male albino mice were forced to swim for a six minute session each day for 7 days and the immobility period was recorded every other day. Trazodone (5 mg/kg and 10 mg/kg) was administered each day 30 min before the forced swim test. In addition, L-arginine (100 mg/kg) and L-NAME (5 mg/kg) were administered 15 min before administration of trazodone (5 mg/kg).

Various behavioral tests, including locomotor (actophotometer) and anxiety (mirror chamber and plus maze) tests, as well as biochemical parameters (lipid peroxidation, reduced glutathione, catalase, and nitrites) were evaluated on the 8th day.

Forced swimming for 7 days caused a chronic fatigue-like condition, anxiety-like behavior, impairments in locomotor activity, and oxidative damage (increased lipid peroxidation and nitrite levels, and depletions in the reduced forms of glutathione and catalase activity) in animals. Pretreatment with L-NAME (5 mg/kg) potentiated the antioxidant effect of trazodone (5 mg/kg). However, L-arginine (100 mg/kg) pretreatment reversed the protective effect of trazodone (5 mg/kg) (p<0.05). The present study suggests the possible involvement of NO signaling in the protective effect of trazodone.

 

Source: Kumar A, Garg R, Kumar P. Nitric oxide modulation mediates the protective effect of trazodone in a mouse model of chronic fatigue syndrome. Pharmacol Rep. 2008 Sep-Oct;60(5):664-72. http://www.if-pan.krakow.pl/pjp/pdf/2008/5_664.pdf (Full article)

 

Hochu-ekki-to combined with interferon-gamma moderately enhances daily activity of chronic fatigue syndrome mice by increasing NK cell activity, but not neuroprotection

Abstract:

The purpose of this study was to evaluate the beneficial effect of Hochu-ekki-to (TJ-41) combined with interferon-gamma (IFN gamma) on daily activity, immunological and neurological alternation in a mouse model of chronic fatigue syndrome (CFS).

CFS was induced by 6 times of repeated injection of Brucella abortus antigen every 2 weeks. Both single TJ-41 and TJ-41 combined with IFN gamma increased running activity and thymus weight of CFS mice, while thicker thymic cortex together with elevation of natural killer cell activity was only found in the combined treatment group. No significant improvement was observed in the atrophic brain and decreased expression level of brain-derived neurotrophic factor and Bcl-2 mRNA in hippocampus in both treatment groups.

Our results suggest that TJ-41 combined with IFN gamma might have a protective effect on the marked reduction in the activity in a model of CFS via normalization of host immune responses, but not neuroprotection.

 

Source: Chen R, Moriya J, Luo X, Yamakawa J, Takahashi T, Sasaki K, Yoshizaki F. Hochu-ekki-to combined with interferon-gamma moderately enhances daily activity of chronic fatigue syndrome mice by increasing NK cell activity, but not neuroprotection. Immunopharmacol Immunotoxicol. 2009 Jun;31(2):238-45. doi: 10.1080/08923970802391525.https://www.ncbi.nlm.nih.gov/pubmed/18791913

 

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

 

Beneficial effect of brewers’ yeast extract on daily activity in a murine model of chronic fatigue syndrome

Abstract:

The aim of this study was to assess the effect of Brewers’ yeast extract (BYE) on daily activity in a mouse model of chronic fatigue syndrome (CFS). CFS was induced by repeated injection of Brucella abortus (BA) antigen every 2 weeks. BYE was orally administered to mice in a dose of 2 g per kg per day for 2 weeks before injecting BA and for 4 weeks thereafter. We evaluated daily running activity in mice receiving BYE as compared with that in untreated mice.

Weekly variation of body weight (BW) and survival in both groups was monitored during the observation period. Spleen weight (SW), SW/BW ratio, percent splenic follicular area and expression levels of interferon-gamma (IFN-gamma) and interleukin-10 (IL-10) mRNA in spleen were determined in both groups at the time of sacrifice. The daily activity during 2 weeks after the second BA injection was significantly higher in the treated group than in the control. There was no difference in BW between both groups through the experimental course. Two mice in the control died 2 and 7 days after the second injection, whereas no mice in the treated group died. Significantly decreased SW and SW/BW ratio were observed in the treated mice together with elevation of splenic follicular area.

There were suppressed IFN-gamma and IL-10 mRNA levels in spleens from the treated mice. Our results suggest that BYE might have a protective effect on the marked reduction in activity following repeated BA injection via normalization of host immune responses.

 

Source: Takahashi T, Yu F, Zhu SJ, Moriya J, Sumino H, Morimoto S, Yamaguchi N, Kanda T. Beneficial effect of brewers’ yeast extract on daily activity in a murine model of chronic fatigue syndrome. Evid Based Complement Alternat Med. 2006 Mar;3(1):109-15. Epub 2006 Jan 23. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1375235/ (Full article)

 

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