antioxidants – Page 3 – American ME and CFS Society

Identification of actin network proteins, talin-1 and filamin-A, in circulating extracellular vesicles as blood biomarkers for human myalgic encephalomyelitis/ chronic fatigue syndrome

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a serious, debilitating disorder with a wide spectrum of symptoms, including pain, depression, and neurocognitive deterioration. Over 17 million people around the world have ME/CFS, predominantly women with peak onset at 30-50 years. Given the wide spectrum of symptoms and unclear etiology, specific biomarkers for diagnosis and stratification of ME/CFS are lacking. Here we show that actin network proteins in circulating extracellular vesicles (EVs) offer specific non-invasive biomarkers for ME/CFS.

We found that circulating EVs were significantly increased in ME/CFS patients correlating to C-reactive protein, as well as biological antioxidant potential. Area under the receiver operating characteristic curve for circulating EVs was 0.80, allowing correct diagnosis in 90-94% of ME/CFS cases. From two independent proteomic analyses using circulating EVs from ME/CFS, healthy controls, idiopathic chronic fatigue, and depression, proteins identified from ME/CFS patients are involved in focal adhesion, actin skeletal regulation, PI3K-Akt signaling pathway, and Epstein-Barr virus infection. In particular, talin-1, filamin-A, and 14-3-3 family proteins were the most abundant proteins, representing highly specific ME/CFS biomarkers.

Our results identified circulating EV number and EV-specific proteins as novel biomarkers for diagnosing ME/CFS, providing important information on the pathogenic mechanisms of ME/CFS.

Source: Eguchi A, Fukuda S, Kuratsune H, Nojima J, Nakatomi Y, Watanabe Y, Feldstein AE. Identification of actin network proteins, talin-1 and filamin-A, in circulating extracellular vesicles as blood biomarkers for human myalgic encephalomyelitis/ chronic fatigue syndrome. Brain Behav Immun. 2019 Nov 20. pii: S0889-1591(19)30762-7. doi: 10.1016/j.bbi.2019.11.015. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/31759091

Antioxidant and immunomodulatory properties of Spilanthes oleracea with potential effect in chronic fatigue syndrome infirmity

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) holds a mystery for researchers due to its multifactorial nature; hence, its diagnosis is still based on symptoms and aetiology remains obscured. Number of scientific evidences regarding the role of oxidative stress, immune dysfunction in CFS and alleviation of symptoms with the help of nutritional supplements guided us to study effect of ethanolic extract of Spilanthes oleracea (SPE) in CFS.

OBJECTIVES: Present study was designed to evaluate antioxidant, immunomodulatory properties of S. oleracea flower to ameliorate CFS infirmity in mice.

MATERIALS AND METHOD: In order to induce fatigue, experimental animals were stressed by chronic water – immersion stress model. Meanwhile, parameters like immobility period and tail withdrawal latency were assessed. On the 21st day, mice blood was collected and they were immediately sacrificed for biochemical estimations.

RESULTS: Biochemical analysis results revealed that CFS elevates lipid peroxidation, nitrite level and diminishes the endogenous antioxidant enzyme like catalase level in stressed animal’s brain homogenate. Stressful condition developed muscle fatigue leading in alteration of lactate dehydrogenase level (LDH), Blood urea nitrogen (BUN) and Triglycerides (TG) levels. Concurrent and chronic treatment of SPE for 21 days restored all these behavioural despairs and associated biochemical adaptation in mice in dose-dependent manner.

CONCLUSION: The outcome of this study indicates ability of SPE in amelioration of CFS by mitigating the oxidative stress and thus provide a powerful combat against CFS which may be due to its antioxidant and immunomodulatory properties.

Source: Nipate SS, Tiwari AH. Antioxidant and immunomodulatory properties of Spilanthes oleracea with potential effect in chronic fatigue syndrome infirmity. J Ayurveda Integr Med. 2018 Nov 16. pii: S0975-9476(17)30116-X. doi: 10.1016/j.jaim.2017.08.008. [Epub ahead of print] https://www.sciencedirect.com/science/article/pii/S097594761730116X?via%3Dihub (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)

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.

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

Does oral coenzyme Q10 plus NADH supplementation improve fatigue and biochemical parameters in chronic fatigue syndrome?

Abstract:

Chronic fatigue syndrome (CFS) is a chronic and extremely debilitating illness characterized by prolonged fatigue and multiple symptoms with unknown cause, diagnostic test, or universally effective treatment. Inflammation, oxidative stress, mitochondrial dysfunction, and CoQ10 deficiency have been well documented in CFS.

We conducted an 8-week, randomized, double-blind placebo-controlled trial to evaluate the benefits of oral CoQ10 (200 mg/day) plus NADH (20 mg/day) supplementation on fatigue and biochemical parameters in 73 Spanish CFS patients. This study was registered in ClinicalTrials.gov (NCT02063126).

A significant improvement of fatigue showing a reduction in fatigue impact scale total score (p<0.05) was reported in treated group versus placebo. In addition, a recovery of the biochemical parameters was also reported. NAD+/NADH (p<0.001), CoQ10 (p<0.05), ATP (p<0.05), and citrate synthase (p<0.05) were significantly higher, and lipoperoxides (p<0.05) were significantly lower in blood mononuclear cells of the treated group. These observations lead to the hypothesis that the oral CoQ10 plus NADH supplementation could confer potential therapeutic benefits on fatigue and biochemical parameters in CFS. Larger sample trials are warranted to confirm these findings.

Source: Castro-Marrero J, Cordero MD, Segundo MJ, Sáez-Francàs N, Calvo N, Román-Malo L, Aliste L, Fernández de Sevilla T, Alegre J. Does oral coenzyme Q10 plus NADH supplementation improve fatigue and biochemical parameters in chronic fatigue syndrome? Antioxid Redox Signal. 2015 Mar 10;22(8):679-85. doi: 10.1089/ars.2014.6181. Epub 2014 Dec 18. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4346380/ (Full article)

A Study of the Protective Effect of Triticum aestivum L. in an Experimental Animal Model of Chronic Fatigue Syndrome

Abstract:

BACKGROUND: Oxidative stress plays a major role in the pathogenesis of chronic fatigue syndrome (CFS). Keeping in view the proven antioxidant activity of Triticum aestivum L., this study has been undertaken to explore the potential therapeutic benefit of this plant in the treatment of CFS.

OBJECTIVE: To study the protective effect of the ethanolic extract of the leaves of Triticum aestivum (EETA) in an experimental mice model of CFS.

MATERIALS AND METHODS: Five groups of albino mice (20-25 g) were selected for the study, with five animals in each group. Group A served as the naïve control and Group B served as the stressed control. Groups C and D received EETA (100 mg/kg and 200 mg/kg b.w.). Group E received imipramine (20 mg/kg b.w.). Except for Group A, mice in each group were forced to swim 6 min each for 7 days to induce a state of chronic fatigue. Duration of immobility was measured on every alternate day. After 7 days, various behavioral tests (mirror chamber and elevated plus maize test for anxiety, open field test for locomotor activity) and biochemical estimations (malondialdehyde [MDA] and catalase activity) in mice brain were performed.

RESULTS: Forced swimming in the stressed group resulted in a significant increase in immobility period, decrease in locomotor activity and elevated anxiety level. The brain homogenate showed significantly increased MDA and decreased catalase levels. The extract-treated groups showed significantly (P < 0.05) improved locomotor activity, decreased anxiety level, elevated catalase levels and reduction of MDA.

CONCLUSION: The study confirms the protective effects of EETA in CFS.

Source: Borah M, Sarma P, Das S. A Study of the Protective Effect of Triticum aestivum L. in an Experimental Animal Model of Chronic Fatigue Syndrome. Pharmacognosy Res. 2014 Oct;6(4):285-91. Doi: 10.4103/0974-8490.138251. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4166815/ (Full article)

Multivitamin mineral supplementation in patients with chronic fatigue syndrome

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is characterized by medically unexplained persistent or reoccurring fatigue lasting at least 6 months. CFS has a multifactorial pathogenesis in which oxidative stress (OS) plays a prominent role. Treatment is with a vitamin and mineral supplement, but this therapeutic option so far has not been properly researched.

MATERIAL AND METHODS: This prospective study included 38 women of reproductive age consecutively diagnosed by CDC definition of CFS and treated with a multivitamin mineral supplement. Before and after the 2-month supplementation, SOD activity was determined and patients self-assessed their improvement in 2 questionnaires: the Fibro Fatigue Scale (FFS) and the Quality of Life Scale (SF36).

Results There was a significant improvement in SOD activity levels; and significant decreases in fatigue (p=0.0009), sleep disorders (p=0.008), autonomic nervous system symptoms (p=0.018), frequency and intensity of headaches (p=0.0001), and subjective feeling of infection (p=0.0002). No positive effect on quality of life was found.

CONCLUSIONS: Treatment with a vitamin and mineral supplement could be a safe and easy way to improve symptoms and quality of life in patients with CFS.

Source: Maric D, Brkic S, Tomic S, Novakov Mikic A, Cebovic T, Turkulov V. Multivitamin mineral supplementation in patients with chronic fatigue syndrome. Med Sci Monit. 2014 Jan 14;20:47-53. doi: 10.12659/MSM.889333. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3907507/ (Full article)

Improved management of primary chronic fatigue syndrome with the supplement French oak wood extract (Robuvit®): a pilot, registry evaluation

Abstract:

AIM: The aim of this supplement study was to evaluate French oak wood extract (Robuvit®, Horphag Research Ltd) used as a supplement in association with a defined management plan for chronic fatigue syndrome (CFS) in healthy subjects with CFS, a condition that has, so far, no specific treatment or management standards.

METHODS: Robuvit® is a new proprietary and exclusive extract of oak wood with important antoxidant actions. The dosage of the supplementation was 200 mg/day for at least 6 months. The CFS questionnaire and the Brief Mood Introspection Scale (BMIS) questionnaire were used to evaluate mood variations associated with CFS patients. The CFS form includes an analogue scale to record the variations of single symptoms with a score range of 0-10. At inclusion into the registry study, at least 5 symptoms were present. All subjects (age range 35-44; BMI range 24-26) with CFS were tested for oxidative stress: 61 out of 91 subjects had an increased value of oxidative stress. The BMIS scale evaluating mood changes in time was also used. The evaluation was repeated at 3 and 6 months.

RESULTS: Out of 91 eligible subjects with CFS, 48 subjects (31 with increased oxidative stress) were accepted as part of the supplement registry study using Robuvit; 43 (30 with increased oxidative stress) were accepted as controls using only the management plan. In the Robuvit® group there were 3 drop outs; also 3 controls were lost. Oxidative stress was increased in 64.58% of subjects that used Robuvit and in 69.7% of controls. The average values of oxidative stress were expressed for the whole group. The average follow up was 199.3;9.2 days in the Robuvit group and 202.2;5.5 in the control group with a minimum of 6 months. Considering variations in oxidative stress, there was no significant average change in controls, but a significant decrease from the initial values was observed in Robuvit subjects after 3 and 6 months. The CFS questionnaire variations in score indicated that there was a significant improvement for most symptoms after 3 and 6 months in the Robuvit group. Positive variations were also present in controls, indicating the positive effect of an increased attention to CFS. The improvement in signs/symptoms was significantly more valuable in subjects using the oak wood extract considering the main 8 symptoms and the accessory symptoms. Considering the BMIS variations, the totals for positive and negative items were significantly more favourable for Robuvit subjects. Overall mood evaluation in the oak wood extract group improved from an inclusion average of -6.93;2.1 to +4.32;2.6 at 6 months; in contrast it changed from -6.5;2.5 to -3.4;1.5 in controls. No side effects were observed during the supplementation with Robuvit. The compliance was optimal with 93% of the capsules correctly used.

CONCLUSION: This promising pilot supplement registry study indicates a new opportunity of management for these difficult and often neglected patients. Correlation between oxidative stress and CFS have to be better explored.

Source: Belcaro G, Cornelli U, Luzzi R, Cesarone MR, Dugall M, Feragalli B, Hu S, Pellegrini L, Ippolito E. Improved management of primary chronic fatigue syndrome with the supplement French oak wood extract (Robuvit®): a pilot, registry evaluation. Panminerva Med. 2014 Mar;56(1):63-72. Epub 2013 Nov 14. http://www.minervamedica.it/en/journals/panminerva-medica/article.php?cod=R41Y2014N01A0063 (Full article available as PDF)

An in vivo proton neurospectroscopy study of cerebral oxidative stress in myalgic encephalomyelitis (chronic fatigue syndrome)

Abstract:

A particularly important family of antioxidant defence enzymes in the body are the glutathione peroxidases, which remove H(2)O(2) by coupling its reduction to H(2)O with oxidation of reduced glutathione (GSH) to oxidised glutathione (GSSG). There are suggestions that GSH in the peripheral blood may be reduced in myalgic encephalomyelitis, which is a highly disabling neurological disease of unknown aetiology.

Since many of the symptoms relate to cerebral functioning, it would seem probable that peripheral blood GSH findings would be reflected in lower cerebral GSH levels. The aim of this study was to carry out the first direct assessment of cerebral GSH levels in myalgic encephalomyelitis; the hypothesis being tested was that cerebral GSH levels would be reduced in myalgic encephalomyelitis.

Cerebral proton neurospectroscopy was carried out at a magnetic field strength of 3T in 26 subjects; spectra were obtained from 20x20x20mm(3) voxels using a point-resolved spectroscopy pulse sequence. The mean cerebral GSH level in the myalgic encephalomyelitis patients was 2.703 (SD 2.311) which did not differ significantly from that in age- and gender-matched normal controls who did not have any history of neurological or other major medical disorder (5.191, SD 8.984; NS). Therefore our study does not suggest that GSH is reduced in the brain in myalgic encephalomyelitis.

At the present time, based on the results of this study, there is no evidence to support the suggestion that, by taking glutathione supplements, an improvement in the brain-related symptomatology of myalgic encephalomyelitis may occur.

Source: Puri BK, Agour M, Gunatilake KD, Fernando KA, Gurusinghe AI, Treasaden IH. An in vivo proton neurospectroscopy study of cerebral oxidative stress in myalgic encephalomyelitis (chronic fatigue syndrome). Prostaglandins Leukot Essent Fatty Acids. 2009 Nov-Dec;81(5-6):303-5. doi: 10.1016/j.plefa.2009.10.002. Epub 2009 Nov 10.https://www.ncbi.nlm.nih.gov/pubmed/19906518

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