Animals – Page 7 – American ME and CFS Society

Effect of acupuncture intervention on learning-memory ability and cerebral superoxide dismutase activity and malonaldehyde concentration in chronic fatigue syndrome rats

Abstract:

OBJECTIVE: To observe the effect of acupuncture intervention on learning-memory ability and cerebral superoxide dismutase (SOD) activity and malonaldehyde (MDA) content in chronic fatigure syndrome (CFS) rats so as to reveal its mechanism underlying improvement of clinical CFS.

METHODS: Thirty-six male SD rats were randomly divided into control group, model group and acupuncture group (n = 12 in each group). CFS model was established by double stress stimulation of suspending (1.0 – 2.5 h increasing gradually) and forced swimming [Morris water maze tasks, 7 min in (10 +/- 1) degrees C water], once daily for 12 days. Manual acupuncture stimulation was applied to “Baihui” (CV 20), bilateral “Zusanli” (ST 36) and “Sanyinjiao” (SP 6), once daily for 21 days (with 3 days’ interval between every two weeks). Learning-memory ability was determined by Morris water maze tests, and SOD activity and MDA concentration in the brain tissues were detected by xanthine oxidase method and thiobarbiturif acid method, respectively.

RESULTS: Compared with the control group, the escape latencies at time-points of day 1, 2, 3, 4 and 5 of Morris water maze tests were significantly longer, the target platform crossing times were markedly fewer and the target platform quadrant staying time obviously shorter, cerebral SOD activity was considerably decreased, and cerebral MDA content remarkably increased in the model group (P < 0.05, P < 0.01). Following acupuncture intervention, the escape latencies at time-points of day 1, 2, 3, 4 and 5 were significantly decreased, both target platform crossing times and staying time, and cerebral SOD activity were apparently increased, as well as cerebral MDA level was markedly lowered in comparison with the model group (P<0.05, P<0.01).

CONCLUSION: Acupuncture intervention can improve the learning-memory ability in CFS rats, which may be related to its effect in regulating metabolism of free radicals in the brain tissues.

Source: Liu CZ, Lei B. Effect of acupuncture intervention on learning-memory ability and cerebral superoxide dismutase activity and malonaldehyde concentration in chronic fatigue syndrome rats.Zhen Ci Yan Jiu. 2013 Dec;38(6):478-81. [Article in Chinese] https://www.ncbi.nlm.nih.gov/pubmed/24588031

The effective mechanism of the polysaccharides from Panax ginseng on chronic fatigue syndrome

Abstract:

Ginseng acidic polysaccharide WGPA isolated from the root of Panax ginseng C. A. Meyer was fractionated into WGPA-A and WGPA-N by anion-exchange chromatography. The antifatigue activity of ginseng acidic polysaccharide WGPA has been reported in our previous research. This present study was designed to identify its active component and elucidate the mechanism for preventing chronic fatigue syndrome (CFS).

WGPA, WGPA-A and WGPA-N were orally administered to mice once daily for 15 days. The effects of these compounds on physiological biomarkers of oxidative stress and on the morphology of the mitochondria in striated skeletal muscle were assessed. The results of forced swimming test-induced indicated that WGPA and WGPA-A could lengthen the swimming time, while WGPA-N could not. In addition, malondialdehyde and lactate dehydrogenase levels in serum were enhanced; while those of superoxide dismutase and glutathione peroxidase were lowered. Interestingly, the structural degeneration of mitochondria were all ameliorated.

These findings suggested that WGPA-A is the active component of WGPA, it might have potential therapeutic effects for CFS and the oxidative stress might be involved in the pathogenesis. Our results also provided essential data for a better understanding of the antifatigue effects of P. ginseng extracts.

Source: Wang J, Sun C, Zheng Y, Pan H, Zhou Y, Fan Y. The effective mechanism of the polysaccharides from Panax ginseng on chronic fatigue syndrome. Arch Pharm Res. 2014 Apr;37(4):530-8. doi: 10.1007/s12272-013-0235-y. Epub 2013 Aug 21. https://www.ncbi.nlm.nih.gov/pubmed/23963977

Shilajit attenuates behavioral symptoms of chronic fatigue syndrome by modulating the hypothalamic-pituitary-adrenal axis and mitochondrial bioenergetics in rats

Abstract:

ETHNOPHARMACOLOGICAL RELEVANCE: Shilajit has been used as a rejuvenator for ages in Indian ancient traditional medicine and has been validated for a number of pharmacological activities.

AIM OF THE STUDY: The effect of processed shilajit which was standardized to dibenzo-α-pyrones (DBPs;0.43% w/w), DBP-chromoproteins (DCPs; 20.45% w/w) and fulvic acids (56.75% w/w) was evaluated in a rat model of chronic fatigue syndrome (CFS). The mitochondrial bioenergetics and the activity of hypothalamus-pituitary-adrenal (HPA) axis were evaluated for the plausible mechanism of action of shilajit.

MATERIALS AND METHODS: CFS was induced by forcing the rats to swim for 15mins for 21 consecutive days. The rats were treated with shilajit (25, 50 and 100mg/kg) for 21 days before exposure to stress procedure. The behavioral consequence of CFS was measured in terms of immobility and the climbing period. The post-CFS anxiety level was assessed by elevated plus maze (EPM) test. Plasma corticosterone and adrenal gland weight were estimated as indices of HPA axis activity. Analysis of mitochondrial complex chain enzymes (Complex I, II, IV and V) and mitochondrial membrane potential (MMP) in prefrontal cortex (PFC) were performed to evaluate the mitochondrial bioenergetics and integrity respectively.

RESULTS: Shilajit reversed the CFS-induced increase in immobility period and decrease in climbing behavior as well as attenuated anxiety in the EPM test. Shilajit reversed CFS-induced decrease in plasma corticosterone level and loss of adrenal gland weight indicating modulation of HPA axis. Shilajit prevented CFS-induced mitochondrial dysfunction by stabilizing the complex enzyme activities and the loss of MMP. Shilajit reversed CFS-induced mitochondrial oxidative stress in terms of NO concentration and, LPO, SOD and catalase activities.

CONCLUSION: The results indicate that shilajit mitigates the effects of CFS in this model possibly through the modulation of HPA axis and preservation of mitochondrial function and integrity. The reversal of CFS-induced behavioral symptoms and mitochondrial bioenergetics by shilajit indicates mitochondria as a potential target for treatment of CFS.

Source: Surapaneni DK, Adapa SR, Preeti K, Teja GR, Veeraragavan M, Krishnamurthy S. Shilajit attenuates behavioral symptoms of chronic fatigue syndrome by modulating the hypothalamic-pituitary-adrenal axis and mitochondrial bioenergetics in rats. J Ethnopharmacol. 2012 Aug 30;143(1):91-9. doi: 10.1016/j.jep.2012.06.002. Epub 2012 Jul 6. https://www.ncbi.nlm.nih.gov/pubmed/22771318

Evaluation of protective effect of Aegle marmelos Corr. in an animal model of chronic fatigue syndrome

Abstract:

OBJECTIVE: To evaluate ethanolic extract of leaves of Aegle marmelos in an experimental animal model of chronic fatigue syndrome for potential therapeutic benefit.

MATERIALS AND METHODS: Age/weight-matched female Wistar albino rats were grouped into five groups. (Group I- V) (n = 8). Group I served as naïve control and II served as stress control. Except for group I animals, other group animals were subjected to forced swimming every day for 15 minutes to induce a state of chronic fatigue and simultaneously treated with ethanolic extract of Aegle marmelos (EEAM) 150 and 250 mg/kg b.w. and Imipramine (20 mg.kg b.w.), respectively. Duration of immobility, anxiety level and locomotor activity were assessed on day 1, 7, 14 and 21 followed by biochemical estimation of oxidative biomarkers at the end of the study.

RESULTS: Treatment with EEAM (150 and 250 mg/kg b.w.) resulted in a statistically significant and dose dependent reduction (P <0.001) in the duration of immobility, reduction in anxiety and increase in locomotor activity. Dose dependent and significant reduction in LPO level and increase in CAT and SOD was observed in extract treated animals.

CONCLUSION: The results are suggestive of potential protective effect of A. marmelos against experimentally induced CFS.

Source: Lalremruta V, Prasanna GS. Evaluation of protective effect of Aegle marmelos Corr. in an animal model of chronic fatigue syndrome. Indian J Pharmacol. 2012 May;44(3):351-6. Doi: 10.4103/0253-7613.96316. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3371458/ (Full article)

Effect of acupuncture on serum malonaldehyde content, superoxide dismutase and glutathione peroxidase activity in chronic fatigue syndrome rats

Abstract:

OBJECTIVE: To study the effect of acupuncture on blood oxygen free radical metabolism in rats with chronic fatigue syndrome (CFS).

METHODS: Thirty male SD rats were randomly divided into control group (n = 10), model group (n = 10) and acupuncture group (n = 10). CFS model was established by repeated suspension (1.0-2.5 h) and forced cold water swimming (7 min), once daily continuously for 12 days. For rats in the acupuncture group, bilateral “Zusanli” (ST 36) and “Sanyinjiao” (SP 6) were stimulated by manipulating the acupuncture needles intermittently for 20 min, once daily, and with 7 days being a treatment course. The treatment was conducted for three courses with an interval of 3 days between two courses. Serum malonaldehyde (MDA) content, superoxide dismutase (SOD) activity, and glutathione peroxidase (GSH-PX) activity were detected by thiobarbituric acid chromatometry (TBA), xanthine oxidase (XOD) and dithio-bis-nitrobenzoic acid (DTNB), respectively.

RESULTS: In comparison with the control group, serum MDA content was up-regulated significantly, while serum SOD activity and GSH-PX activity were decreased considerably in the model group (P < 0.01). Compared with the model group, serum MDA level was down-regulated apparently, and serum SOD activity and GSH-PX activity were up-regulated remarkably in the acupuncture group (P < 0.01).

CONCLUSION: Acupuncture can adjust metabolism of serum oxygen free radicals in CFS rats, which probably contributes to its effect in relieving CFS in clinic.

Source: Liu CZ, Lei B. Effect of acupuncture on serum malonaldehyde content, superoxide dismutase and glutathione peroxidase activity in chronic fatigue syndrome rats. Zhen Ci Yan Jiu. 2012 Feb;37(1):38-40, 58. [Article in Chinese] https://www.ncbi.nlm.nih.gov/pubmed/22574567

Role of Lactobacillus acidophilus loaded floating beads in chronic fatigue syndrome: behavioral and biochemical evidences

Abstract:

BACKGROUND: In recent years the interface between neuropsychiatry and gastroenterology has converged in to a new discipline referred to as enteric neuroscience. Implications of brain-gut communication in the pathogenesis of psychiatric disorders indicate a possible role of suitably packaged/delivered probiotics as newer therapeutic options. In the present study probable role of per-oral administration of free Lactobacillus acidophilus (LAB) and LAB loaded alginate beads in attenuation of the symptoms associated with chronic fatigue syndrome (CFS) were evaluated.

METHODS: Chronic fatigue syndrome following physical fatigue was induced in rats by forcing them to swim (forced swim test; FST) in water till exhaustion, after weighing them down with 10% their body weight, daily for 28 days. Immobility (I) and postswim fatigue time (PSF) were taken as suitable markers. Free LAB and LAB loaded floating beads (FBs) were administered, from 21 to 28 days.

KEY RESULTS: Immobility and PSF were found to increase considerably in FST rats (665 ± 22 s and 196 ± 6 s) as compared with the naïve (32 ± 7 s and 22 ± 2 s) at 20 days, establishing severe fatigue like behavior. FST control group exhibited significant (P < 0.05) hypertrophy of spleen, hypotrophy of thymus, and increased oxido-nitrosative stress in brain and tumor necrosis factor-α (TNF-α) levels in serum. Treatment with LAB and LAB FBs significantly decreased I and PSF and attenuated (P < 0.05) oxido-nitrosative stress and TNF-α levels. Spleen and thymus were also restored to their original size in this group.

CONCLUSIONS & INFERENCES: The findings suggest a valuable therapeutic role of LAB especially when incorporated into alginate beads for the treatment of CFS.

Source: Singh PK, Chopra K, Kuhad A, Kaur IP. Role of Lactobacillus acidophilus loaded floating beads in chronic fatigue syndrome: behavioral and biochemical evidences. Neurogastroenterol Motil. 2012 Apr;24(4):366-e170. doi: 10.1111/j.1365-2982.2011.01861.x. Epub 2012 Feb 1. https://www.ncbi.nlm.nih.gov/pubmed/22296294

Effects of a Chinese traditional formula Kai Xin San (KXS) on chronic fatigue syndrome mice induced by forced wheel running

Abstract:

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional medicine, Kai Xin San (KXS), composed of ginseng (Panax ginseng), hoelen (Wolfiporia cocos), polygala (Polygala tenuifolia) and Acorus gramineus, is famous for the treatment of emotion-thought disease, such as settling fright, quieting the spirit and nourishing the heart.

AIM OF THE STUDY: The present study investigated the effect of KXS on chronic fatigue syndrome (CFS) mice induced by forced wheel running.

MATERIALS AND METHODS: Seventy two healthy adult male Kunming mice were randomly divided into six groups: home cage control group, CFS group, CFS group with Modafinil treatment at 13 mg/kg/d doge, KXS treatment at 175 mg/kg/d, 350 mg/kg/d and 700 mg/kg/d doge. CFS mice were induced by forced wheel running with higher speed for 4 weeks and then taken an exhausted exercise. The biochemical parameters including serum lactate dehydrogenase (LDH), serum urea nitrogen (SUN), serum testosterone (T), liver glycogen (LG), muscle glycogen (MG) and muscle lactic acid (MLA) were determined by using commercially available kits. The splenocytes proliferation from mice was examined by MTT method. The levels of interleukin-2 (IL-2) and interleukin-4 (IL-4) secreted by splenocytes were determined by ELISA.

RESULTS: CFS mice with KXS administration exhibited less electric shock time when compared with CFS group without drug treatment. The effect of KXS has after demonstrated reduction in SUN, LDH and MLA levels and an increase in T, LG and MG levels. CFS mice with KXS could improve the proliferation of splenocytes compared with CFS group without drug treatment. The cultured splenocytes from CFS mice without KXS supplementation produced more interleukin-2 (IL-2) but less interleukin-4 (IL-4) when compared with home cage control mice. The cultured splenocytes of CFS mice with KXS supplementation produced more interleukin-2 (IL-2) but less interleukin-4 (IL-4) when compared with CFS group without drug treatment.

CONCLUSIONS: The results of this preliminary study provide evidence that KXS could ameliorate CFS by affecting the physiological markers for fatigue. This study also supported the use of KXS against CFS by improving the proliferation of splenocytes from CFS mice and modulating the disturbance of cytokines induced by CFS.

Source: Cao Y, Hu Y, Liu P, Zhao HX, Zhou XJ, Wei YM. Effects of a Chinese traditional formula Kai Xin San (KXS) on chronic fatigue syndrome mice induced by forced wheel running. J Ethnopharmacol. 2012 Jan 6;139(1):19-25. doi: 10.1016/j.jep.2011.08.030. Epub 2011 Aug 22. https://www.ncbi.nlm.nih.gov/pubmed/21884774

Epigallocatechin gallate ameliorates behavioral and biochemical deficits in rat model of load-induced chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome is a heterogeneous disorder with unknown pathogenesis and etiology, characterized by tiredness, difficulty in concentration and memory, and concomitant skeletal and muscular pain, thus affecting both mental and physical domains. The pathogenesis of chronic fatigue syndrome is multifactorial and involves increased oxido-nitrosative stress along with generation of pro-inflammatory cytokines such as TNF-α.

In the present study chronic fatigue was produced in rats by plunging a load of 10 ± 2% body weight and subjecting them to forced swim inside a rectangular jar daily for 28 days. Endurance capacity and post-swim fatigue were assessed on 1st, 7th, 14th, 21st and 28th days. EGCG was administered daily by oral gavage 30 min before forced swim session. On the 29th day, after assessment of various behavioral parameters, blood was collected through tail vein, and animals were sacrificed to harvest the brains, spleens and thymus.

Chronic fatigue group exhibited significant behavioral alterations along with enhanced oxido-nitrosative stress and serum TNF-α level as compared to naive group. Chronic treatment with EGCG restored all the behavioral and biochemical alterations associated with chronic fatigue syndrome. The present study signifies the therapeutic potential of EGCG for the treatment of chronic fatigue syndrome.

Source: Sachdeva AK, Kuhad A, Chopra K. Epigallocatechin gallate ameliorates behavioral and biochemical deficits in rat model of load-induced chronic fatigue syndrome. Brain Res Bull. 2011 Oct 10;86(3-4):165-72. doi: 10.1016/j.brainresbull.2011.06.007. Epub 2011 Jul 28. https://www.ncbi.nlm.nih.gov/pubmed/21821105

Nitric oxide modulation in protective role of antidepressants against chronic fatigue syndrome in mice

Abstract:

BACKGROUND AND OBJECTIVE: The present study was designed to elucidate the possible nitric oxide (NO) mechanism in the protective effect of antidepressants using mice model of chronic fatigue syndrome (CFS).

MATERIALS AND METHODS: Male albino laca mice were forced to swim for each 6 min session for 7 days and immobility period was measured on every alternate day (1(st), 3(rd), 5(th), 7(th)). After 7 days various behavioral tests (locomotor, mirror chamber, and plus maze tests for anxiety) were performed and biochemical estimations (lipid peroxidation, nitrite levels, GSH (reduced glutathione), and catalase activity) in mice brain were performed. Animals were pretreated with citalopram (5 and 10 mg/kg) and imipramine (10 and 20 mg/kg) daily for 7 days.

RESULTS: The present study showed that continued forced swimming for 7 days caused chronic fatigue-induced anxiety-like behavior as assessed in mirror chamber, plus maze tests, and impairment in locomotor activity followed by oxidative damage (as evidenced by increased lipid peroxidation, nitrite levels, depleted reduced glutathione, and catalase activity) in animals. Seven days pretreatment with citalopram (5 and 10 mg/kg) and imipramine (10 and 20 mg/kg) significantly improved behavioral and biochemical alterations. Further, L-nitro-arginine methyl ester (L-NAME,5 mg/kg) and methylene blue (MB, 10 mg/kg) pretreatment with citalopram (5 mg/kg) or imipramine (10 mg/kg) potentiated their protective effect. However, l-arginine (100 mg/kg) pretreatment with citalopram (5 mg/kg) or imipramine (10 mg/kg) reversed their protective effect as compared with their effect per se (P < 0.05).

CONCLUSION: The present study suggests that protective effect of citalopram and imipramine might be due to its NO modulation against chronic fatigue induced behavioral and biochemical alterations.

Source: Kumar A, Garg R, Gaur V, Kumar P. Nitric oxide modulation in protective role of antidepressants against chronic fatigue syndrome in mice. Indian J Pharmacol. 2011 May;43(3):324-9. Doi: 10.4103/0253-7613.81506. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3113388/ (Full article)

A Chinese herbal decoction, Danggui Buxue Tang, improves chronic fatigue syndrome induced by food restriction and forced swimming in rats

Abstract:

Danggui Buxue Tang (DBT), a Chinese medicinal decoction that contains Radix Angelicae sinensis (Danggui) and Radix Astragali (Huangqi) at a ratio of 1:5, is used commonly for treating women’s ailments. The present study explored the effects of this preparation on chronic fatigue syndrome (CFS).

Rats were subjected to a combination of food restriction and forced swimming to induce CFS, and rats were gavaged once daily with either 12 or 24 g/kg DBT for 28 days. Body weights, T-cell subset counts, (3) H-TdR incorporation measurements and mRNA levels of IL-1β, TNF-α, NF-кB, p38MAPK and JNK were determined on days 14 and 28. The swimming endurance capacity was measured on day 28.

Rats that received DBT exhibited increased body weight and endurance capacity, corrected T cell subsets counts, increased (3) H-TdR incorporation and decreased mRNA levels of IL-1β, TNF-α, NF-кB, p38MAPK and JNK compared with rats that did not receive DBT. The results indicate that DBT can ameliorate CFS through immune modulation and may act to normalize cytokines and their related signaling pathways.

Source: Liu Y, Zhang HG, Li XH. A Chinese herbal decoction, Danggui Buxue Tang, improves chronic fatigue syndrome induced by food restriction and forced swimming in rats. Phytother Res. 2011 Dec;25(12):1825-32. doi: 10.1002/ptr.3499. Epub 2011 Apr 15. https://www.ncbi.nlm.nih.gov/pubmed/21495102