title: Tannoid principles of Emblica officinalis attenuated aluminum chloride induced apoptosis by suppressing oxidative stress and tau pathology via Akt/GSK-3βsignaling pathway.
abstract: BACKGROUND
  Fruits of Phyllanthus emblica Linn. or Emblica officinalis Gaertn. (Phyllanthaceae) are used in Ayurveda, Siddha, Unani, Arabic, Tibetan and various other folk medicinal systems to promote intelligence and memory. Recent study from our lab indicated the neuroprotective effect of tannoids principles of Emblica officinalis (EoT) against memory loss caused by aluminum chloride (AlCl3) intoxication through attenuating acetylcholine esterase activity and the expression of amyloid β protein biosynthesis related markers. However the molecular mechanism of EoT has not yet been fully elucidated.
  
  
  OBJECTIVE
  The aim of the present study was to further investigate the neuroprotective mechanisms of EoT against AlCl3-induced cognitive deficits, tau hyperphosphorylation, oxidative stress and apoptosis.
  
  
  METHODS
  Rats were treated with AlCl3for 60 days to induce biochemical and physiological abnormalities similar to AD patients. AD rats were treated with EoT (100mg/kg., bw. oral) for 60 days. For the examination of neuroprotective effect of EoT, behavior analysis, biochemical estimations and western blot were performed in the hippocampus and cortex of control, EoT treated and untreated AD rats.
  
  
  RESULTS
  Intraperitoneal injections of AlCl3(100mg/kg., b.w.) for 60 days enhanced the learning and memory deficits, levels of TBARS and diminished the levels of reduced glutathione and activities of enzymatic antioxidants as compared to control group. Moreover toxicity of AlCl3is accompanied by the enhanced expressions of Bax, caspases-3,-9, cytosolic cytochrome c (cyto c), and pTau along with diminished expressions of Bcl-2, mitochondrial cyto c, pGSK-3β and pAkt. Coadministration of EoT nullified the cognitive deficits, biochemical abnormalities and apoptosis induced by AlCl3treatment. Moreover EoT prevents tau hyperphosphorylation by targeting the GSK-3β/Akt signaling pathway.
  
  
  CONCLUSIONS
  This study confirms that EoT would be used as a potential drug candidate for AD and other tau pathology-related neuronal degenerative diseases.
authors: Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalai Nagar, Tamilnadu 608 002, India. Electronic address: justinthenmozhi@rediffmail.com.
authors: Arokiasamy
authors: A
authors: Justin Thenmozhi
authors: Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalai Nagar, Tamilnadu 608 002, India.
authors: Mathiyazahan
authors: M
authors: Dhivyabharathi
authors: Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalai Nagar, Tamilnadu 608 002, India.
authors: Thamilarasan
authors: T
authors: Manivasagam
authors: Department of Food Science and Nutrition, CAMS, Sultan Qaboos University, Muscat, Oman; Ageing and Dementia Research Group, Sultan Qaboos University, Muscat, Oman; Food and Brain Research Foundation, Chennai, Tamil Nadu 600094, India.
authors: Musthafa Mohamed
authors: MM
authors: Essa
mesh_terms: D000077410:Aluminum Chloride; D017607:Aluminum Compounds / Q000633:toxicity*; D000544:Alzheimer Disease / Q000628:therapy*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002712:Chlorides / Q000633:toxicity*; D004195:Disease Models, Animal; D020834:Ethnopharmacology; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism*; D008297:Male; D018384:Oxidative Stress; D029842:Phyllanthus emblica / Q000737:chemistry*; D010946:Plants, Medicinal; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D017607:Aluminum Compounds; D002712:Chlorides; D016875:tau Proteins; D000077410:Aluminum Chloride; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt
keywords: Akt/GSK-3β signaling pathways; Aluminium chloride (PubChem CID: 24012); Alzheimer's disease; Apoptosis; Emblicanin A (PubChem CID: 119058016); Emblicanin B (PubChem CID: 119058017); Memory loss; Oxidative stress; Pedunculagin (PubChem CID: 442688); Punigluconin (PubChem CID: 44631480); Tannoids of Emblica officinalis; Tau pathology