Article

Therapeutic Potential of Indian Medicinal Herbs and Current Therapeutic Approach used to Mitigate the Symptoms of Chronic Fatigue Syndrome: A Review

Bentham Science
Current Traditional Medicine
Authors:
  • Amar Shaheed Baba Ajit Singh Jujhar Singh Memorial, College of Pharmacy BELA
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Abstract

Chronic fatigue syndrome (CFS) is a complex condition marked by severe exhaustion that lasts at least 6 months. The global prevalence of CFS ranging between 0.4% and 2.5% is growing. Women are affected by CFS more often than men. It is considered a common condition in developed countries. There is no approved treatment for CFS but symptoms can be managed and controlled persistent exhaustion causes significant impairment in daily routine activities. Lowered ATP synthesis, mitochondrial impairment, decreased oxidative phosphorylation, disruption of the hypothalamic–pituitary–adrenal (HPA) axis, and an imbalance of brain neurotransmitters play a major role in the pathophysiology of CFS. The purpose of the present study is to figure out the several plants that are used as a source of medication in chronic fatigue syndrome (CFS) and its current therapeutic approach. The Indian medicinal herbs described in this article are very efficacious in the management of chronic fatigue syndrome symptoms due to the presence of phytochemicals. This review article also covers the current therapeutic approach for chronic fatigue syndrome in a concise form that comprises CBT (Cognitive based therapy), GET (Graded exercise therapy), usage of immunoglobins, psychodynamic counseling, and yoga therapy that includes isometric yoga and yoga nidra are very beneficial in alleviating the symptoms of chronic fatigue syndrome. Antidepressants, immunomodulatory agents, and corticosteroids come under conventional medication for CFS. This article explores different Indian medicinal herbs, their pharmacological properties, and their potential role and current treatments for reducing the severity of symptoms of chronic fatigue syndrome.

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Background: Chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME) is a serious disorder characterised by persistent postexertional fatigue and substantial symptoms related to cognitive, immune and autonomous dysfunction. There is no specific diagnostic test, therefore diagnostic criteria are used to diagnose CFS. The prevalence of CFS varies by type of diagnostic criteria used. Existing treatment strategies primarily aim to relieve symptoms and improve function. One treatment option is exercise therapy. Objectives: The objective of this review was to determine the effects of exercise therapy for adults with CFS compared with any other intervention or control on fatigue, adverse outcomes, pain, physical functioning, quality of life, mood disorders, sleep, self-perceived changes in overall health, health service resources use and dropout. Search methods: We searched the Cochrane Common Mental Disorders Group controlled trials register, CENTRAL, and SPORTDiscus up to May 2014, using a comprehensive list of free-text terms for CFS and exercise. We located unpublished and ongoing studies through the World Health Organization International Clinical Trials Registry Platform up to May 2014. We screened reference lists of retrieved articles and contacted experts in the field for additional studies. Selection criteria: We included randomised controlled trials (RCTs) about adults with a primary diagnosis of CFS, from all diagnostic criteria, who were able to participate in exercise therapy. Data collection and analysis: Two review authors independently performed study selection, 'Risk of bias' assessments and data extraction. We combined continuous measures of outcomes using mean differences (MDs) or standardised mean differences (SMDs). To facilitate interpretation of SMDs, we re-expressed SMD estimates as MDs on more common measurement scales. We combined dichotomous outcomes using risk ratios (RRs). We assessed the certainty of evidence using GRADE. Main results: We included eight RCTs with data from 1518 participants.Exercise therapy lasted from 12 weeks to 26 weeks. The studies measured effect at the end of the treatment and at long-term follow-up, after 50 weeks or 72 weeks.Seven studies used aerobic exercise therapies such as walking, swimming, cycling or dancing, provided at mixed levels in terms of intensity of the aerobic exercise from very low to quite rigorous, and one study used anaerobic exercise. Control groups consisted of passive control, including treatment as usual, relaxation or flexibility (eight studies); cognitive behavioural therapy (CBT) (two studies); cognitive therapy (one study); supportive listening (one study); pacing (one study); pharmacological treatment (one study) and combination treatment (one study).Most studies had a low risk of selection bias. All had a high risk of performance and detection bias.Exercise therapy compared with 'passive' controlExercise therapy probably reduces fatigue at end of treatment (SMD -0.66, 95% CI -1.01 to -0.31; 7 studies, 840 participants; moderate-certainty evidence; re-expressed MD -3.4, 95% CI -5.3 to -1.6; scale 0 to 33). We are uncertain if fatigue is reduced in the long term because the certainty of the evidence is very low (SMD -0.62, 95 % CI -1.32 to 0.07; 4 studies, 670 participants; re-expressed MD -3.2, 95% CI -6.9 to 0.4; scale 0 to 33).We are uncertain about the risk of serious adverse reactions because the certainty of the evidence is very low (RR 0.99, 95% CI 0.14 to 6.97; 1 study, 319 participants).Exercise therapy may moderately improve physical functioning at end of treatment, but the long-term effect is uncertain because the certainty of the evidence is very low. Exercise therapy may also slightly improve sleep at end of treatment and at long term. The effect of exercise therapy on pain, quality of life and depression is uncertain because evidence is missing or of very low certainty.Exercise therapy compared with CBTExercise therapy may make little or no difference to fatigue at end of treatment (MD 0.20, 95% CI -1.49 to 1.89; 1 study, 298 participants; low-certainty evidence), or at long-term follow-up (SMD 0.07, 95% CI -0.13 to 0.28; 2 studies, 351 participants; moderate-certainty evidence).We are uncertain about the risk of serious adverse reactions because the certainty of the evidence is very low (RR 0.67, 95% CI 0.11 to 3.96; 1 study, 321 participants).The available evidence suggests that there may be little or no difference between exercise therapy and CBT in physical functioning or sleep (low-certainty evidence) and probably little or no difference in the effect on depression (moderate-certainty evidence). We are uncertain if exercise therapy compared to CBT improves quality of life or reduces pain because the evidence is of very low certainty.Exercise therapy compared with adaptive pacingExercise therapy may slightly reduce fatigue at end of treatment (MD -2.00, 95% CI -3.57 to -0.43; scale 0 to 33; 1 study, 305 participants; low-certainty evidence) and at long-term follow-up (MD -2.50, 95% CI -4.16 to -0.84; scale 0 to 33; 1 study, 307 participants; low-certainty evidence).We are uncertain about the risk of serious adverse reactions (RR 0.99, 95% CI 0.14 to 6.97; 1 study, 319 participants; very low-certainty evidence).The available evidence suggests that exercise therapy may slightly improve physical functioning, depression and sleep compared to adaptive pacing (low-certainty evidence). No studies reported quality of life or pain.Exercise therapy compared with antidepressantsWe are uncertain if exercise therapy, alone or in combination with antidepressants, reduces fatigue and depression more than antidepressant alone, as the certainty of the evidence is very low. The one included study did not report on adverse reactions, pain, physical functioning, quality of life, sleep or long-term results. Authors' conclusions: Exercise therapy probably has a positive effect on fatigue in adults with CFS compared to usual care or passive therapies. The evidence regarding adverse effects is uncertain. Due to limited evidence it is difficult to draw conclusions about the comparative effectiveness of CBT, adaptive pacing or other interventions. All studies were conducted with outpatients diagnosed with 1994 criteria of the Centers for Disease Control and Prevention or the Oxford criteria, or both. Patients diagnosed using other criteria may experience different effects.
Article
Objectives: Fatigue is a common problem in modern-day life. The aim of this study was to evaluate the effect of Delphinium denudatum (Jadwar) on fatigue. Methods: This study was a randomized double-blind placebo-controlled clinical trial between healthy normal university students. In each group, participants were given one capsule of either WEACURE® (containing 500 milligrams of Jadwar root powder) or placebo for 15 consecutive days. Multidimensional Fatigue Inventory (MFI) questionnaire was used before and after the intervention to evaluate different aspects of fatigue. Results: A total number of 64 participants completed the study. Data analysis showed decrease in the scores of all five domains of fatigue in Jadwar group (13.31±3.05 to 7.75±2.66, 12.31±3.55 to 7.63±2.62, 12.22±4.26 to 6.97±2.06, 11.56±4.21 to 7.28±2.37, 12.91±3.09 to 7.34±2.13 in general fatigue, physical fatigue, reduced activity, reduced motivation, and mental fatigue domains, respectively) which was statistically significant (P value<0.0001). This situation was significantly superior to the placebo group. Prescribed dosage of WEACURE® capsule was well tolerated. Conclusion: As a complementary tonic agent, Jadwar have a potential to reduce fatigue in normal population. However, objective evaluation of its anti-fatigue effect should be further evaluated.
Article
Context Current research suggests that dark cocoa may reduce fatigue; however, the effect on fatigue in people with MS (pwMS) has never been established. The objective of this feasibility study was to explore the acute effect of high flavonoid cocoa on measures of fatigue and glycaemic response. Methods This was a randomised crossover participant blind exploratory study in 12 participants (2 male and 10 female) with MS-related fatigue (>4 on the Fatigue Severity Scale; FSS). After fasting overnight, participants consumed the high flavonoid cocoa drink (350 mg gallic acid equivalents {GAE}/g) or a low flavonoid cocoa control (120 mg GAE/g), consuming the alternative drink on the next visit. Fatigue was self-reported on a 100 mm visual analogue scale at 30-min time intervals for 2 h post cocoa consumption and every 2 h for the rest of the day. Fatigability was monitored using a 6 min walk test (6MWT) at the end of the visit (2 h), and activity monitors worn for 24 h commencing at 12 noon on the day of testing. The feasibility of performing the trial including outcome measures was documented. Results A moderate effect was found in self-reported fatigue throughout the day in favour of the high flavonoid group (Cohen's d 0.32, 95% non-central t CI −0.57 to 1.20). Fatigability measures did not change. Participants consumed and enjoyed the cocoa, all participants completed the study and outcome measures were accepted. Conclusion The results of this study support further trials to investigate the feasibility and efficacy of pure cocoa as a dietary supplement for fatigue in pwMS.
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Exercise therapy for chronic fatigue syndrome - Volume 23 Issue 3 - Lillebeth Larun, Kjetil G. Brurberg, Jan Odgaard-Jensen, Jonathan R. Price
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This comprehensive review explores the current evidence on benefits and harms of therapeutic interventions in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) and makes recommendations. CFS/ME is a complex, multi-system, chronic medical condition whose pathophysiology remains unknown. No established diagnostic tests exist; nor are any FDA-approved drugs available for treatment. Because of the range of symptoms of CFS/ME, treatment approaches vary widely. Studies undertaken have heterogeneous designs and are limited by sample size, length of follow-up, applicability and methodological quality. The use of rintatolimod and rituximab as well as counselling, behavioural and rehabilitation therapy programs may be of benefit for CFS/ME, but the evidence of their effectiveness is still limited. Similarly, adaptive pacing appears to offer some benefits, but the results are debatable: so is the use of nutritional supplements, which may be of value to CFS/ME patients with lab-proven deficiencies. To summarize, then, the recommended treatment strategies should include proper administration of nutritional supplements in CFS/ME patients with demonstrated deficiencies and personalized pacing programs to relieve symptoms and improve performance of daily activities, but a larger RCT evaluation is required to confirm these preliminary observations. At present no firm conclusions can be drawn because the few RCTs undertaken to date have been small-scale, with a high risk of bias, and have used different case definitions. Further RCTs are now urgently needed with rigorous experimental designs and appropriate data analysis, focusing particularly on the comparison of outcomes measures according to clinical presentation, patient characteristics, case criteria and degree of disability (i.e., severely ill ME cases or bedridden). This article is protected by copyright. All rights reserved.
Article
Myalgic encephalomyelits/chronic fatigue syndrome (ME/CFS) has been both a medical mystery and a source of controversy in Western medicine for over 50 years. This article reviews the major historical developments over this period, describes the clinical pattern and spectrum of severity, and then explores the current major controversies surrounding the subject.
Article
Many of the epiphytic orchid sare used as traditional medicine. Chemical components and pharmacology have been studied in recent 15 years. Medicinal orchids, in general, are not subjected to detailed pharmacological studies. A wide range of chemical compounds are presented including alkaloids, bibenzyl derivatives, flavonoids, phenanthrenes and terpenoids which have been isolated recently from this species. Extracts and metabolites of these plants, particularly those from flowers and leaves, possess useful pharmacological activities. Particular attention has been given to diuretic, antirheumatic, anti-inflammatory, anti-carcinogenic, hypoglycemic activities, antimicrobial, anticonvulsive, relaxation, neuroprotective, and antivirus, activities. A comprehensive account of chemical constituents and biological activities is presented and a critical appraisal of the ethnopharmacological issues is included in view of the many recent findings of importance of these orchids. A large number of orchids have been empirically used for treatment of different diseases, thus, several studies have been undertaken to provide scientific proof to justify the medicinal use of various plants in treatment of diseases. The aim of this review is to up-date and to present a comprehensive analysis of traditional and folklore uses, pharmacological reports and phyto-constituents isolated from the orchids family.
Article
This editorial reviews the literature regarding psychological studies that are designed to address the question of not just whether, psychological interventions effect change, but how. The practicalities and implications of assessing mechanisms of treatments are considered with examples from the fields of Cognitive Behavioural Therapy (CBT) and Mindfulness. The potential for elucidating theoretical mechanisms, developing new theoretical models and modifying treatment approaches are described. In addition an overview of different types of statistical methods available to researchers for assessing mediation is given. Structural Equation Modelling (SEM) is a recommended approach. The review concludes with a summary of optimum study conditions adopted by researchers for establishing mediating effects.
Article
Ocimum sanctum (O. sanctum) has gained special attention due to its biological properties, however, little is known about its immunomodulatory effects. The purpose of this study was to investigate effect of O. sanctum on inflammation and immune response and its effect on Th1/Th2 cytokine production by spleen cells of myelosuppressed mice model. Female Swiss albino mice were challenged with SRBC and then were grouped and treated with either O. sanctum methanolic extract 850 mg kg-1 or Prednisolone 5 mg kg-1 body weight for 15 days. Blood was collected on 16th day from retro orbital plexus to perform hematological and immunological tests. Bone marrow cellularity was determined and supernatants of splenocytes cultures were analyzed for Th1/Th2 cytokines by ELISA. Antioxidant activity of O. sanctum was evaluated by DPPH (2,2'-diphenyl-1- picrylhydrazyl) assay. Treatment with O. sanctum showed significant increase in bone marrow cellularity (p<0.01), total WBC count (p<0.01) and hemoglobin concentration (p<0.01). In addition, there was a significant increase in SRBC antibody titer (1:1024) compared to the control group (1:256). O. sanctum increased the production of TNF-α, IL-2, IFN- γ and IL-4 (p<0.05) significantly and decreased the production of IL-1β and NF-kB. The methanolic extracts of O. sanctum showed free radical scavenging activity at 140 μg mL-1 concentration as IC50. This study documented improved haemoglobin concentration with O. sanctum treatment. These results support the use of this herb for wound healing and infection. The results also suggest potential use of O. sanctum as adjuvant in cancer therapy, myelotoxicity and in nutritional anemia.
Article
Background: Chronic fatigue syndrome (CFS) is characterised by persistent, medically unexplained fatigue, as well as symptoms such as musculoskeletal pain, sleep disturbance, headaches and impaired concentration and short-term memory. CFS presents as a common, debilitating and serious health problem. Treatment may include physical interventions, such as exercise therapy, which was last reviewed in 2004. Objectives: The objective of this review was to determine the effects of exercise therapy (ET) for patients with CFS as compared with any other intervention or control.• Exercise therapy versus 'passive control' (e.g. treatment as usual, waiting-list control, relaxation, flexibility).• Exercise therapy versus other active treatment (e.g. cognitive-behavioural therapy (CBT), cognitive treatment, supportive therapy, pacing, pharmacological therapy such as antidepressants).• Exercise therapy in combination with other specified treatment strategies versus other specified treatment strategies (e.g. exercise combined with pharmacological treatment vs pharmacological treatment alone). Search methods: We searched The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR), the Cochrane Central Register of Controlled Trials (CENTRAL) and SPORTDiscus up to May 2014 using a comprehensive list of free-text terms for CFS and exercise. We located unpublished or ongoing trials through the World Health Organization (WHO) International Clinical Trials Registry Platform (to May 2014). We screened reference lists of retrieved articles and contacted experts in the field for additional studies Selection criteria: Randomised controlled trials involving adults with a primary diagnosis of CFS who were able to participate in exercise therapy. Studies had to compare exercise therapy with passive control, psychological therapies, adaptive pacing therapy or pharmacological therapy. Data collection and analysis: Two review authors independently performed study selection, risk of bias assessments and data extraction. We combined continuous measures of outcomes using mean differences (MDs) and standardised mean differences (SMDs). We combined serious adverse reactions and drop-outs using risk ratios (RRs). We calculated an overall effect size with 95% confidence intervals (CIs) for each outcome. Main results: We have included eight randomised controlled studies and have reported data from 1518 participants in this review. Three studies diagnosed individuals with CFS using the 1994 criteria of the Centers for Disease Control and Prevention (CDC); five used the Oxford criteria. Exercise therapy lasted from 12 to 26 weeks. Seven studies used variations of aerobic exercise therapy such as walking, swimming, cycling or dancing provided at mixed levels in terms of intensity of the aerobic exercise from very low to quite rigorous, whilst one study used anaerobic exercise. Control groups consisted of passive control (eight studies; e.g. treatment as usual, relaxation, flexibility) or CBT (two studies), cognitive therapy (one study), supportive listening (one study), pacing (one study), pharmacological treatment (one study) and combination treatment (one study). Risk of bias varied across studies, but within each study, little variation was found in the risk of bias across our primary and secondary outcome measures.Investigators compared exercise therapy with 'passive' control in eight trials, which enrolled 971 participants. Seven studies consistently showed a reduction in fatigue following exercise therapy at end of treatment, even though the fatigue scales used different scoring systems: an 11-item scale with a scoring system of 0 to 11 points (MD -6.06, 95% CI -6.95 to -5.17; one study, 148 participants; low-quality evidence); the same 11-item scale with a scoring system of 0 to 33 points (MD -2.82, 95% CI -4.07 to -1.57; three studies, 540 participants; moderate-quality evidence); and a 14-item scale with a scoring system of 0 to 42 points (MD -6.80, 95% CI -10.31 to -3.28; three studies, 152 participants; moderate-quality evidence). Serious adverse reactions were rare in both groups (RR 0.99, 95% CI 0.14 to 6.97; one study, 319 participants; moderate-quality evidence), but sparse data made it impossible for review authors to draw conclusions. Study authors reported a positive effect of exercise therapy at end of treatment with respect to sleep (MD -1.49, 95% CI -2.95 to -0.02; two studies, 323 participants), physical functioning (MD 13.10, 95% CI 1.98 to 24.22; five studies, 725 participants) and self-perceived changes in overall health (RR 1.83, 95% CI 1.39 to 2.40; four studies, 489 participants). It was not possible for review authors to draw conclusions regarding the remaining outcomes.Investigators compared exercise therapy with CBT in two trials (351 participants). One trial (298 participants) reported little or no difference in fatigue at end of treatment between the two groups using an 11-item scale with a scoring system of 0 to 33 points (MD 0.20, 95% CI -1.49 to 1.89). Both studies measured differences in fatigue at follow-up, but neither found differences between the two groups using an 11-item fatigue scale with a scoring system of 0 to 33 points (MD 0.30, 95% CI -1.45 to 2.05) and a nine-item Fatigue Severity Scale with a scoring system of 1 to 7 points (MD 0.40, 95% CI -0.34 to 1.14). Serious adverse reactions were rare in both groups (RR 0.67, 95% CI 0.11 to 3.96). We observed little or no difference in physical functioning, depression, anxiety and sleep, and we were not able to draw any conclusions with regard to pain, self-perceived changes in overall health, use of health service resources and drop-out rate.With regard to other comparisons, one study (320 participants) suggested a general benefit of exercise over adaptive pacing, and another study (183 participants) a benefit of exercise over supportive listening. The available evidence was too sparse to draw conclusions about the effect of pharmaceutical interventions. Authors' conclusions: Patients with CFS may generally benefit and feel less fatigued following exercise therapy, and no evidence suggests that exercise therapy may worsen outcomes. A positive effect with respect to sleep, physical function and self-perceived general health has been observed, but no conclusions for the outcomes of pain, quality of life, anxiety, depression, drop-out rate and health service resources were possible. The effectiveness of exercise therapy seems greater than that of pacing but similar to that of CBT. Randomised trials with low risk of bias are needed to investigate the type, duration and intensity of the most beneficial exercise intervention.
Article
Ocimum sanctum L. is known for its medicinal properties and also has been considered sacred in India since Vedic times. The aqueous suspension of 70% alcoholic extract of Ocimum sanctum L. was investigated for antifatigue activity. Rats were subjected to Weight-loaded Forced Swim Test (WFST) every alternate day for 2 weeks. O. sanctum at a dosage of 150, 300 and 450 mg kg -1 b.wt. was administrated to rats every day. Swimming time, change in body weight, lipid peroxidation, Lactic Acid (LA), glycogen and blood biochemical parameters namely heamoglobin (Hb%), Blood Urea Nitrogen (BUN) and Creatine Kinase (CK) were evaluated as biomarkers of physical fatigue. The O. sanctum treatment was found to lower malondialdehyde (MDA) and lactic acid levels in liver and muscle tissues compared with control exercise group (p<0.05). Serum biochemical parameters viz., BUN and CK activity were also reduced as compared with control exercise group (p<0.05). The present study thus indicates that out of three studied treatments of O. sanctum (O. sanctum -150, 300 and 450); the O. sanctum at the dose of 300 mg kg -1 b.wt. showed better performance against fatigue when compared with other two treatments. As treatment at 300 mg kg -1 b.wt. facilitated the aerobic glucose metabolism and promote swimming time, suggesting that O. sanctum ameliorates the various impairments associated with physical fatigue.
Article
Flavonoids are major active ingredient in corn silk (CS) and possess various pharmacological activities. In this study, microporous resin adsorption technology was used for obtaining purified flavonoids from corn silk (FCS) and its anti-fatigue activity was evaluated. Eight kinds of macroporous resins with different properties were tested through static adsorption and one macroporous resin labeled as AB-8 was selected. Some important parameters were optimized for most effective enrichment and preparative separation. As follows: 1. for adsorption: sample solution FCS concentration was 2.636 mg/ml; processing volume was 4 BV; flow rate was 2 BV/h; temperature was 25°C; 2. for desorption: elution solvent ethanol-water (90%, v/v) solution was 4BV; flow rate was 1.0 BV/h. Flavonoids with content of 63.15% was obtained with a flavonoid recovery of 94.27% in the purification process. The results showed that AB-8 resin revealed a good ability to purify FCS. Swimming exercise results indicated that FCS had anti-fatigue activity of mice by inhibiting the production of blood lactic acid, retarding the formation of BUN and increasing hepatic glycogen concentration.
Article
Curcumin and its two related compounds, that is, demethoxycurcumin and bis-demethoxycurcumin (curcuminoids) are the main secondary metabolites of Curcuma longa and other Curcuma spp. Curcumin is commonly used as coloring agent as well as food additive; curcumin has also shown some therapeutic activities. This review summarizes stability of curcumin in solutions, spectroscopy characteristics of curcumin (UV, IR, Raman, MS, and NMR), polymorphism forms, method of analysis in both of biological and nonbiological samples, and metabolite studies of curcumin. For analysis of curcumin and its related compounds in complex matrices, application of LC-MS/MS is recommended.
Article
This study investigated the antifatigue effects of rutin, a flavonoid extracted from the ethyl acetate extract of S. involucrata. Mice were subjected to a weight-loaded forced swim test (WFST) on alternate days for 3 wk. Rutin was administered orally to the mice for 7 days in dosages of 15, 30, and 60 mg/kg body weight, and several biomarkers of physical fatigue were evaluated: swimming time, change in body weight, lipid peroxidation, lactic acid (LA), glycogen, and the activities of the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx). On Day 7, the rutin-treated mice had a 3-fold longer exhaustive swimming time than the control mice, as well as significantly reduced blood LA concentrations. The 15, 30, and 60 mg/kg body weight rutin-supplemented groups displayed 11.2%, 22.5%, and 37.7% reduced malondialdehyde (MDA) concentrations, respectively, in brain and muscle tissues compared with the control exercised group. Our results indicated that the administration of rutin protected the mice against the depletion of SOD and GPx activities significantly. Following 7 days of rutin treatment, we sacrificed the mice and analyzed their soleus muscle and brain for peroxisome proliferator-activated receptor-α coactivator (PGC-1α) and sirtuin 1 (SIRT1) mRNA expression. We observed that rutin treatment increased PGC-1α and SIRT1 mRNA and protein expression. The changes in these markers of mitochondrial biogenesis were associated with increased maximal endurance capacity. The application of 2D gel electrophoresis to analyze the rutin-responsive protein profiles in the WFST mouse brain further revealed the upregulation of the CB1 cannabinoid receptor-interacting protein 1, myelin basic protein, Rho GDP dissociation inhibitor (GDI) alpha, and TPI, indicating that rutin might inhibit anxiety through the upregulation of the expression of anxiety-associated proteins. Western blot analysis of MAPK expression further confirmed the antianxiety effects of rutin. Our study results thus indicate that rutin treatment ameliorates the various impairments associated with physical fatigue.
Article
There is no known treatment for chronic fatigue syndrome (CFS). Little is known about its pathogenesis. Human herpesvirus 6 (HHV-6) and Epstein-Barr virus (EBV) have been proposed as infectious triggers. Thirty CFS patients with elevated IgG antibody titers against HHV-6 and EBV were randomized 2:1 to receive valganciclovir (VGCV) or placebo for 6 months in a double-blind, placebo-controlled trial. Clinical endpoints aimed at measuring physical and mental fatigue included the Multidimensional Fatigue Inventory (MFI-20) and Fatigue Severity Scale (FSS) scores, self-reported cognitive function, and physician-determined responder status. Biological endpoints included monocyte and neutrophil counts and cytokine levels. VGCV patients experienced a greater improvement by MFI-20 at 9 months from baseline compared to placebo patients but this difference was not statistically significant. However, statistically significant differences in trajectories between groups were observed in MFI-20 mental fatigue subscore (P = 0.039), FSS score (P = 0.006), and cognitive function (P = 0.025). VGCV patients experienced these improvements within the first 3 months and maintained that benefit over the remaining 9 months. Patients in the VGCV arm were 7.4 times more likely to be classified as responders (P = 0.029). In the VGCV arm, monocyte counts decreased (P < 0.001), neutrophil counts increased (P = 0.037) and cytokines were more likely to evolve towards a Th1-profile (P < 0.001). Viral IgG antibody titers did not differ between arms. VGCV may have clinical benefit in a subset of CFS patients independent of placebo effect, possibly mediated by immunomodulation and/or antiviral effect. Further investigation with longer treatment duration and a larger sample size is warranted. J. Med. Virol. 9999:1-9, 2013. © 2013 Wiley Periodicals, Inc.
Article
Hypericum perforatum (HP) belongs to the Hypericaceae family and is one of the oldest used and most extensively investigated medicinal herbs. The medicinal form comprises the leaves and flowering tops of which the primary ingredients of interest are naphthodianthrones, xanthones, flavonoids, phloroglucinols (e.g. hyperforin), and hypericin. Although several constituents elicit pharmacological effects that are consistent with HP's antidepressant activity, no single mechanism of action underlying these effects has thus far been found. Various clinical trials have shown that HP has a comparable antidepressant efficacy as some currently used antidepressant drugs in the treatment of mild/moderate depression. Interestingly, low-hyperforin-content preparations are effective in the treatment of depression. Moreover, HP is also used to treat certain forms of anxiety. However, HP can induce various cytochrome P450s isozymes and/or P-glycoprotein, of which many drugs are substrates and which are the main origin of HP-drug interactions. Here, we analyse the existing evidence describing the clinical consequence of HP-drug interactions. Although some of the reported interactions are based on findings from in vitro studies, the clinical importance of which remain to be demonstrated, others are based on case reports where causality can, in some cases, be determined to reveal clinically significant interactions that suggest caution, consideration, and disclosure of potential interactions prior to informed use of HP. Copyright © 2013 John Wiley & Sons, Ltd.
Article
This study examined the effects and comparative efficacy of various antidepressants and herbal psychotropic drugs in a mouse model of chronic fatigue. Animals were subjected daily to forced swimming (Porsolt's forced swimming test) and the duration of the immobility period was recorded in 6-minute sessions on each day for 7 days. Chronic forced swimming resulted in significant increases in immobility time on day 7 as compared to day 1 in control mice. Pretreatment with imipramine (10 mg/kg, i.p.), desipramine (10 mg/kg, i.p.), tranyl-cypromine (10 mg/kg, i.p.), alprazolam (0.5 mg/kg, i.p.), fhioxetine (10 mg/kg, i.p.) and melatonin (10 mg/kg, i.p.) produced significant decreases in immobility time as compared to control on each day. Similar decreases in immobility periods were observed with herbal psychotropic preparations-Withania somniferaroot extract (100 mg/kg, p.o.), BR-16A(r) (200 mg/kg, p.o.), siotone(r) granules (200 mg/kg, p.o.) and evening primrose oil (0.2 ml/20 g, p.o.). However, trazodone and ida-zoxan failed to modify the immobility times on all the days. The present observations underscore the established use of antidepressants in providing symptomatic relief of fatigue in Chronic Fatigue Syndrome (CFS) patients and further reinforce the potential therapeutic usefulness of herbal psychotropic preparations in CFS patients.
Article
Anutrition survey carried out in India revealed that the diets of the rural population are inadequate and deficient in most of the nutrients especially protein. India being the 5th-largest producer of soybean, a protein-rich cereal, can redress protein-energy malnutrition through diversification of soybean uses by developing high-value and health-based food products. Tofu, a nonfermented soybean product rich in high-quality protein, B-vitamins, and isoflavones, could be an excellent substitute for meat in Indian recipes. Tofu being rich in protein has a very short shelf life. Hence an attempt was made to improve the shelf life using extracts of tulsi (Ocimum sanctum) commonly available in rural areas. Tofu was prepared traditionally using MgCl2:CaSO4 as coagulating agents. Aqueous extract of Ocimum sanctum (tulsi) was added during the preparation and storage of tofu to prolong its shelf life.Water used in this study was free from microflora, plant extract used contained mesophilic count of 2.527×104 CFU/g, and no yeasts and molds were detected. Tofu with tulsi extract had 76.4% moisture and was softer than control. Not much difference in mesophilic count was observed between control and treated samples during storage; however, treated tofu was organoleptically good until the end of the study with less lipid-peroxidation and exhibited 50% (4.7 units) less protease activity than control (9.6 units) after 7 d. By using extracts of naturally available, easily cultivable tulsi, the shelf life was successfully extended to 7 to 8 d from 3 to 4 d of normal storage without refrigeration.
Article
Callosin and callosinin, two new stilbenoids, were isolated from the orchid Agrostophyllum callosum, which also afforded, 4-hydroxy-3,5-dimethoxybenzoic acid, orchinol, 6-methoxycoelonin, imbricatin, flaccidin, oxoflaccidin, iso-oxoflaccidin, flaccidinin and agrostophyllin of previously known structures. Callosin was also isolated from another orchid, Coelogyne flaccida. The structures of callosin and callosinin were established as 2,6-dihyroxy-4,7-dimethoxy-9,10- dihydrophenanthrene and 2,6,7-trimethoxy-9,10-dihydro-5H-phenanthro [4,5-bcd]pyran-5-one, respectively, from spectral and chemical evidence. For ease of comparison of the spectral data the phenanthrene numbering system is used in this paper.
Article
The chemical polemics in the reported literature on shilajit are resolved. This study shows that humification of latex and resin-bearing plants is responsible for the major organic mass (80-85%) of shilajit. The low mol. wt. chemical markers (&lo%), viz. aucuparins, oxygenated dibenzo-K -pyrones and triterpenic acids of the tirucallane type (free and conjugated), occurring in the core structure of shilajit humus, are the major active constituents of Himalayan shilajit. The therapeutic effects of shilajit are the consequences of hormonal control and regulation of immunity.