title: Shilajit attenuates behavioral symptoms of chronic fatigue syndrome by modulating the hypothalamic-pituitary-adrenal axis and mitochondrial bioenergetics in rats.
abstract: BACKGROUND
  Shilajit has been used as a rejuvenator for ages in Indian ancient traditional medicine and has been validated for a number of pharmacological activities.
  
  
  OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: Neurotherapeutics Lab, Department of Pharmaceutics, Indian Institute of Technology (Banaras Hindu University), Varanasi 221005 U.P., India.
authors: Dinesh Kumar
authors: DK
authors: Surapaneni
authors: Sree Rama Shiva Shanker
authors: SR
authors: Adapa
authors: Kumari
authors: K
authors: Preeti
authors: Gangineni Ravi
authors: GR
authors: Teja
authors: Muruganandam
authors: M
authors: Veeraragavan
authors: Sairam
authors: S
authors: Krishnamurthy
mesh_terms: D000311:Adrenal Glands / Q000187:drug effects; D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D001007:Anxiety / Q000188:drug therapy; D001522:Behavior, Animal / Q000187:drug effects; D001526:Behavioral Symptoms / Q000188:drug therapy; D001578:Benzopyrans / Q000494:pharmacology / Q000627:therapeutic use*; D001580:Benzopyrenes / Q000494:pharmacology / Q000627:therapeutic use*; D003345:Corticosterone / Q000097:blood; D015673:Fatigue Syndrome, Chronic / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D006812:Humic Substances; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D018782:Maze Learning; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D008517:Phytotherapy; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D011919:Rats, Inbred Strains; D013550:Swimming
chemical_list: D000975:Antioxidants; D001578:Benzopyrans; D001580:Benzopyrenes; D006812:Humic Substances; D010936:Plant Extracts; D009569:Nitric Oxide; D003345:Corticosterone; C005023:fulvic acid