Category: Animals

Characterization of a protein-bound polysaccharide from Herba Epimedii and its metabolic mechanism in chronic fatigue syndrome

Abstract:

OBJECTIVES: Herba Epimedii is one of the famous Traditional Chinese Medicines used to treat the chronic fatigue syndrome (CFS). The polysaccharides are the main active components in Herba Epimedii. The aim of this study is to discover the therapeutic effect and metabolic mechanism of Herba Epimedii polysaccharides against CFS.

METHODS: The polysaccharide conjugates named HEP2-a were isolated from the leaves of Herba Epimedii using a water extraction method, and the general physicochemical properties of HEP2-a were analysed. In addition, a CFS rat model was established, and then, urinary metabonomic studies were performed using gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) in combination with multivariate statistical analysis.

RESULTS: The physicochemical properties revealed that HEP2-a had an average molecular weight of 13.6×104 Da and consisted of mannose (4.41%), rhamnose (5.43%), glucose (31.26%), galactose (27.07%), arabinose (23.43%), and galacturonic acid (8.40%). The amino acids in HEP2-a include glutamate, cysteine, leucine, tyrosine, lysine, and histidine. Molecular morphology studies revealed many highly curled spherical particles with diameters of 5-10µm in solids and 100-200nm for particles in water. Five metabolites in the HEP2-a group were oppositely and significantly changed compared to the CFS model group.

CONCLUSION: Two metabolic pathways were identified as significant metabolic pathways involved with HEP2-a. The therapeutic effects of HEP2-a on CFS were partially due to the restoration of these disturbed pathways.

Copyright © 2017. Published by Elsevier B.V.

 

Source: Chi A, Shen Z, Zhu W, Sun Y, Kang Y, Guo F. Characterization of a protein-bound polysaccharide from Herba Epimedii and its metabolic mechanism in chronic fatigue syndrome. J Ethnopharmacol. 2017 Mar 27. pii: S0378-8741(16)31138-2. doi: 10.1016/j.jep.2017.03.041. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/28359851

 

Metabolic mechanism of a polysaccharide from Schisandra chinensis to relieve chronic fatigue syndrome

Abstract:

Schisandra chinensis fruits are a famous traditional Chinese medicine to treat all kinds of fatigue. This study aimed to investigate the therapeutic effect and metabolic mechanism of a polysaccharide (SCP) from Schisandra chinensis fruits on chronic fatigue syndrome (CFS). SCP was isolated and the physicochemical properties were analyzed.

A CFS model of rats was established and the urinary metabonomic studies were performed using gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) in combination with multivariate statistical analysis. The results showed that SCP is a protein-bound polysaccharide. The amino acid composition of SCP consisted of 12 amino acids.

The growth and the behaviors of the rats in the CFS model group were worse than those in the control group and improved after SCP treatment. Analysis of the GC-TOF-MS revealed that twelve metabolites were significantly changed, and six metabolites were oppositely and significantly changed after the SCP treatment. The TCA cycle metabolic pathways and the alanine, aspartate and glutamate metabolism were identified as significant metabolic pathways involved with SCP. The therapeutic mechanism of SCP against CFS was partially due to the restoration of these disturbed pathways.

Copyright © 2016 Elsevier B.V. All rights reserved.

 

Source: Chi A, Zhang Y, Kang Y, Shen Z. Metabolic mechanism of a polysaccharide from Schisandra chinensis to relieve chronic fatigue syndrome. Int J Biol Macromol. 2016 Dec;93(Pt A):322-332. doi: 10.1016/j.ijbiomac.2016.08.042. Epub 2016 Aug 18. https://www.ncbi.nlm.nih.gov/pubmed/27545408

 

Investigation of the effects of vanilloids in chronic fatigue syndrome

Abstract:

AIM OF THE STUDY: To assess the effectiveness of TRPV1 modulators in animal model of Chronic fatigue syndrome (CFS). To assess central and peripheral behavioral activity of TRPV1 modulators.

MATERIAL AND METHODS: CFS was induced by forcing the rats to swim for 10min for 21 consecutive days. The rats were treated with capsaicin (TRPV1 agonist, 2.5mg/kg) and n-tert-butylcyclohexanol (TRPV1 antagonist, 10mg/kg) for 21days 30min before the exposure to stress procedure. The behavioral consequence of CFS was measured in terms of immobility time, grip strength, locomotor activity, and anxiety level using Rota rod, Actophotometer, and Elevated plus maze model respectively. The other parameters include Plasma corticosterone, adrenal gland and spleen weight, complete blood count, blood urea niterogen (BUN), Lactate dehydrogenase (LDH), Lipid peroxidation, catalase and reduced glutathione (GSH).

RESULTS AND DISCUSSION: TRPV1 modulators reversed (p<0.05) the increase in immobility period, anxiety, spleen weight, BUN and LDH levels, and MDA levels along with decrease in grip strength, locomotor activity, plasma corticosterone, adrenal gland weight, catalase, and GSH. There was also significant increase in total WBC count when compared with the disease control group. The reversal was attributed to modulation of HPA axis, oxidative stress, anaerobic respiration product, muscle degradation product.

CONCLUSION: The present study reveals the effectiveness of n-tert-butylcyclohexanol and capsaicin against chronic fatigue syndrome. The mechanism of action can be attributed to inhibition of TRPV1 channel and thereby modulating pain perception, neuroendocrine function, oxidative stress and immune function.

Copyright © 2016 Elsevier Inc. All rights reserved.

 

Source: Sarvaiya K, Goswami S. Investigation of the effects of vanilloids in chronic fatigue syndrome. Brain Res Bull. 2016 Oct;127:187-194. doi: 10.1016/j.brainresbull.2016.09.015. Epub 2016 Sep 28. https://www.ncbi.nlm.nih.gov/pubmed/27693335

 

Activation of the NLRP3 inflammasome in lipopolysaccharide-induced mouse fatigue and its relevance to chronic fatigue syndrome

Abstract:

BACKGROUND: The NLRP3 inflammasome (NOD-like receptor family, pyrin domain containing 3) is an intracellular protein complex that plays an important role in innate immune sensing. Its activation leads to the maturation of caspase-1 and regulates the cleavage of interleukin (IL)-1β and IL-18. Various studies have shown that activation of the immune system plays a pivotal role in the development of fatigue. However, the mechanisms underlying the association between immune activation and fatigue remained elusive, and few reports have described the involvement of NLRP3 inflammasome activation in fatigue.

METHODS: We established a mouse fatigue model with lipopolysaccharide (LPS, 3 mg/kg) challenge combined with swim stress. Both behavioural and biochemical parameters were measured to illustrate the characteristics of this model. We also assessed NLRP3 inflammasome activation in the mouse diencephalon, which is the brain region that has been suggested to be responsible for fatigue sensation. To further identify the role of NLRP3 inflammasome activation in the pathogenesis of chronic fatigue syndrome (CFS), NLRP3 KO mice were also subjected to LPS treatment and swim stress, and the same parameters were evaluated.

RESULTS: Mice challenged with LPS and subjected to the swim stress test showed decreased locomotor activity, decreased fall-off time in a rota-rod test and increased serum levels of IL-1β and IL-6 compared with untreated mice. Serum levels of lactic acid and malondialdehyde (MDA) were not significantly altered in the treated mice. We demonstrated increased NLRP3 expression, IL-1β production and caspase-1 activation in the diencephalons of the treated mice. In NLRP3 KO mice, we found remarkably increased locomotor activity with longer fall-off times and decreased serum IL-1β levels compared with those of wild-type (WT) mice after LPS challenge and the swim stress test. IL-1β levels in the diencephalon were also significantly decreased in the NLRP3 KO mice. By contrast, IL-6 levels were not significantly altered.

CONCLUSIONS: These findings suggest that LPS-induced fatigue is an IL-1β-dependent process and that the NLRP3/caspase-1 pathway is involved in the mechanisms of LPS-induced fatigue behaviours. NLRP3/caspase-1 inhibition may be a promising therapy for fatigue treatment.

 

Source: Zhang ZT, Du XM, Ma XJ, Zong Y, Chen JK, Yu CL, Liu YG, Chen YC, Zhao LJ, Lu GC. Activation of the NLRP3 inflammasome in lipopolysaccharide-induced mouse fatigue and its relevance to chronic fatigue syndrome. J Neuroinflammation. 2016 Apr 5;13(1):71. doi: 10.1186/s12974-016-0539-1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4822300/ (Full article)

 

Evaluation of the effect of ethanolic extract of fruit pulp of Cassia fistula Linn. on forced swimming induced chronic fatigue syndrome in mice

Abstract:

The fruit of Cassia fistula Linn. is a legume, has antioxidant and lots of other medicinal properties. As oxidants are involved in the pathogenesis of chronic fatigue syndrome, the present study was done to evaluate the effect of ethanolic extract of fruit pulp of C. fistula Linn. (EECF) on forced swimming induced chronic fatigue syndrome (CFS).

Albino mice of 25-40 grams were grouped into five groups (n=5). Group A served as naive control and group B served as stress control. Group C received EECF 200 mg/kg and group D received EECF 400 mg/kg respectively. Group E received imipramine 20 mg/kg (standard). All animals were treated with their respective agent orally daily for 7 days. Except for group A, animals in other groups were subjected to force swimming 6 min daily for 7 days to induce a state of chronic fatigue. Duration of immobility was assessed on day 1(st), 3(rd), 5(th) and 7(th). Anxiety level (by elevated plus maze and mirrored chamber) and loco-motor activity (by open field test) were assessed 24 h after last force swimming followed by biochemical estimations of oxidative biomarkers in brain homogenate at the end of study.

Treatment with EECF resulted in significant reduction in the duration of immobility, reduced anxiety and increased loco-motor activity. Malondialdehyde level was also reduced and catalase level was increased in the extract treated group and standard group compared to stress control group. The study indicates that EECF has protective effect against experimentally induced CFS.

 

Source: Sarma P, Borah M, Das S. Evaluation of the effect of ethanolic extract of fruit pulp of Cassia fistula Linn. on forced swimming induced chronic fatigue syndrome in mice. Res Pharm Sci. 2015 May-Jun;10(3):206-13. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4621627/ (Full article)

 

Induction Murine Models of Chronic Fatigue Syndrome by Brucella abortus Antigen Injections: Is Anemia Induced or Not?

Abstract:

To investigate whether Brucella abortus (BA) antigen injections lead to anemia, and to establish an appropriate Chronic Fatigue Syndrome (CFS) animal model by BA injections, 6 repeated injections of BA antigen were fulfilled every 2 weeks. At a high dose of 1∗10(10) particles/mouse, anemia was induced within 2 weeks and then recovered a lot at the end of the research, while at a moderate dose of 1∗10(8) (3 injections) shifting to 1∗10(9)/mouse (3 injections) anemia was absent. In both groups running wheel activity remained very low even 6 weeks after the last injection.

 

Source: Moriya J, He Q, Uenishi H, Akazawa S, Yamakawa J, Kobayashi J, Ishigaki Y. Induction Murine Models of Chronic Fatigue Syndrome by Brucella abortus Antigen Injections: Is Anemia Induced or Not? Biomed Res Int. 2015;2015:191489. doi: 10.1155/2015/191489. Epub 2015 Jun 11. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4480237/ (Full article)

 

Immunomodulating and antioxidant effects of polysaccharide conjugates from the fruits of Ziziphus Jujube on Chronic Fatigue Syndrome rats

Abstract:

To detect the treatment effect of the fruits of Ziziphus Jujube in Chronic Fatigue Syndrome (CFS). Jujube polysaccharide conjugates (JPC) were isolated from the fruits of Z. Jujube. General physicochemical properties of JPC were analyzed.

A four-week rats CFS model was established and JPC were orally administrated, the behavior experiments were conducted after CFS. The activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and the levels of malondialdehyde (MDA) in serum were elevated and T lymphocyte proliferation, CD4(+)/CD8(+) ratio and natural killer (NK) cells activity were analyzed.

JPC markedly improved behaviors of CFS rats, also decreased MDA levels in serum, and elevated T lymphocyte proliferation, CD4(+)/CD8(+) ratio and natural killer (NK) cells activities. This suggests that JPC can improve the immune system and antioxidant activity of CFS rats and might be regarded as a biological response modifier.

Copyright © 2015 Elsevier Ltd. All rights reserved.

 

Source: Chi A, Kang C, Zhang Y, Tang L, Guo H, Li H, Zhang K. Immunomodulating and antioxidant effects of polysaccharide conjugates from the fruits of Ziziphus Jujube on Chronic Fatigue Syndrome rats. Carbohydr Polym. 2015 May 20;122:189-96. doi: 10.1016/j.carbpol.2014.12.082. Epub 2015 Jan 14. https://www.ncbi.nlm.nih.gov/pubmed/25817658

 

Effect of manual acupuncture stimulation of “Baihui” (GV 20), etc. on serum IFN-gamma and IL-4 contents in rats with chronic fatigue syndrome

Abstract:

OBJECTIVE: To observe the effect of manual acupuncture stimulation of “Baihui” (GV 20), etc. on serum IFN- gamma and IL-4 contents in rats with chronic fatigue syndrome (CFS).

METHODS: A total of 24 male SD rats were equally randomized into control group, model group and acupuncture group. CFS model was established by bounding and forced swimming in cold water once daily for 14 days. Rats in the acupuncture group were treated by manual acupuncture stimulation of bilateral “Zusanli” (ST 36), “Baihui” (GV 20), and “Guanyuan” (CV 4), once daily for 14 days. Serum IFN-gamma and IL-4 contents were detected by ELISA.

RESULTS: Compared with the control group, the contention of serum IFN-gamma and ratio of IFN-gamma/IL-4 were significant decreased in the model group (P<0.01). While in comparison with the model group, the contention of IFN-gamma and ratio of IFN-gamma/IL-4 were obviously increased in the acupuncture group (P<0.05). No significant differences were found among the three groups in serum IL-4 levels (P>0.05).

CONCLUSION: Manual acupuncture can inhibit CFS induced reduction of serum IFN-gamma level and the ratio of IFN-gamma/IL-4 in CFS rats, suggesting a favorable adjustment of acupuncture intervention for CFS by balancing the ratio of IFN-gamma/IL-4.

 

Source: Wang C, Xie WJ, Liu M, Yan J, Zhang JL, Liu Z, Guo LN. Effect of manual acupuncture stimulation of “Baihui” (GV 20), etc. on serum IFN-gamma and IL-4 contents in rats with chronic fatigue syndrome. Zhen Ci Yan Jiu. 2014 Oct;39(5):387-9. [Article in Chinese] https://www.ncbi.nlm.nih.gov/pubmed/25518113

 

Isoflavones inhibit poly(I:C)-induced serum, brain, and skin inflammatory mediators – relevance to chronic fatigue syndrome

Abstract:

BACKGROUND: Chronic Fatigue Syndrome (CFS) is a neuroimmunoendocrine disease affecting about 1% of the US population, mostly women. It is characterized by debilitating fatigue for six or more months in the absence of cancer or other systemic diseases. Many CFS patients also have fibromyalgia and skin hypersensitivity that worsen with stress. Corticotropin-releasing hormone (CRH) and neurotensin (NT), secreted under stress, activate mast cells (MC) necessary for allergic reactions to release inflammatory mediators that could contribute to CFS symptoms.

OBJECTIVE: To investigate the effect of isoflavones on the action of polyinosinic:polycytidylic acid (poly(I:C)), with or without swim stress, on mouse locomotor activity and inflammatory mediator expression, as well as on human MC activation.

METHODS: Female C57BL/6 mice were randomly divided into four groups: (a) control/no-swim, (b) control/swim, (c) polyinosinic:polycytidylic acid (poly(I:C))/no swim, and (d) polyinosinic:polycytidylic acid (poly(I:C))/swim. Mice were provided with chow low or high in isoflavones for 2 weeks prior to ip injection with 20 mg/kg poly(I:C) followed or not by swim stress for 15 minutes. Locomotor activity was monitored overnight and animals were sacrificed the following day. Brain and skin gene expression, as well as serum levels, of inflammatory mediators were measured. Data were analyzed using the non-parametric Mann-Whitney U-test.

RESULTS: Poly(I:C)-treated mice had decreased locomotor activity over 24 hours, and increased serum levels of TNF-α, IL-6, KC (IL-8/CXCL8 murine homolog), CCL2,3,4,5, CXCL10, as well as brain and skin gene expression of TNF, IL-6, KC (Cxcl1, IL8 murine homolog), CCL2, CCL4, CCL5 and CXCL10. Histidine decarboxylase (HDC) and NT expression were also increased, but only in the skin, over the same period. High isoflavone diet reversed these effects.

CONCLUSION: Poly(I:C) treatment decreased mouse locomotor activity and increased serum levels and brain and skin gene expression of inflammatory mediators. These effects were inhibited by isoflavones that may prove useful in CFS.

 

Source: Vasiadi M, Newman J, Theoharides TC. Isoflavones inhibit poly(I:C)-induced serum, brain, and skin inflammatory mediators – relevance to chronic fatigue syndrome. J Neuroinflammation. 2014 Oct 31;11:168. doi: 10.1186/s12974-014-0168-5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4236420/ (Full article)

 

Behavioral perturbation and sleep in healthy and virus-infected inbred mice

Abstract:

Murine gammaherpesvirus (MuGHV) is a natural pathogen of wild rodents that has been studied extensively in terms of host immune responses to herpesviruses during acute infection, latency, and reactivation from latency. Although herpesvirus infections in people can be associated with fatigue and excessive sleepiness during both acute and latent infection, MuGHV has not been assessed extensively as a model for studying the behavioral consequences of chronic latent herpesvirus infections.

To assess MuGHV infection as a model for evaluating fatigue and assessing potential mechanisms that underlie the exacerbation of fatigue during chronic viral disease, we evaluated sleep, temperature, and activity after exposure of healthy and latently MuGHV-infected mice to sleep fragmentation and social interaction. Neither treatment nor infection significantly affected temperature. However, at some time points, latently infected mice that underwent sleep fragmentation had less locomotor activity and more slow-wave sleep than did mice exposed to social interaction. In addition, delta-wave amplitude during slow-wave sleep was lower in infected mice exposed to sleep fragmentation compared with uninfected mice exposed to the same treatment.

Both reduced locomotor activity and increased time asleep could indicate fatigue in infected mice after sleep fragmentation; reduced delta-wave amplitude during slow-wave sleep indicates a light plane of sleep from which subjects would be aroused easily. Identifying the mechanisms that underlie sleep responses of mice with chronic latent MuGHV infection may increase our understanding of fatigue during infections and eventually contribute to improving the quality of life for people with chronic viral infections.

 

Source: Trammell RA, Toth LA. Behavioral perturbation and sleep in healthy and virus-infected inbred mice. Comp Med. 2014 Aug;64(4):283-92. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4170093/ (Full article)