Tannoid principles of Emblica officinalis attenuated aluminum chloride induced apoptosis by suppressing oxidative stress and tau pathology via Akt/GSK-3βsignaling pathway

Arokiasamy Justin Thenmozhi, Mathiyazahan Dhivyabharathi, Thamilarasan Manivasagam, Musthafa Mohamed Essa

Research output: Contribution to journalArticle

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Abstract

Ethnopharmacological relevance 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. Aim of the study 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. Materials and methods Rats were treated with AlCl3 for 60 days to induce biochemical and physiological abnormalities similar to AD patients. AD rats were treated with EoT (100 mg/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 (100 mg/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 AlCl3 is 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 AlCl3 treatment. 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.

Original languageEnglish
Pages (from-to)20-29
Number of pages10
JournalJournal of Ethnopharmacology
Volume194
DOIs
Publication statusPublished - Dec 24 2016

Fingerprint

Phyllanthus emblica
Oxidative Stress
Apoptosis
Pathology
Memory Disorders
Neuroprotective Agents
Glycogen Synthase Kinase 3
Amyloidogenic Proteins
Caspase 9
Protein Biosynthesis
Esterases
Cytochromes c
aluminum chloride
Intraperitoneal Injections
Intelligence
Caspase 3
Acetylcholine
Glutathione
Hippocampus
Fruit

Keywords

  • Akt/GSK-3β signaling pathways
  • Alzheimer's disease
  • Apoptosis
  • Memory loss
  • Oxidative stress
  • Tannoids of Emblica officinalis
  • Tau pathology

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

Cite this

Tannoid principles of Emblica officinalis attenuated aluminum chloride induced apoptosis by suppressing oxidative stress and tau pathology via Akt/GSK-3βsignaling pathway. / Justin Thenmozhi, Arokiasamy; Dhivyabharathi, Mathiyazahan; Manivasagam, Thamilarasan; Essa, Musthafa Mohamed.

In: Journal of Ethnopharmacology, Vol. 194, 24.12.2016, p. 20-29.

Research output: Contribution to journalArticle

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abstract = "Ethnopharmacological relevance 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. Aim of the study 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. Materials and methods Rats were treated with AlCl3 for 60 days to induce biochemical and physiological abnormalities similar to AD patients. AD rats were treated with EoT (100 mg/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 (100 mg/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 AlCl3 is 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 AlCl3 treatment. 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.",
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T1 - Tannoid principles of Emblica officinalis attenuated aluminum chloride induced apoptosis by suppressing oxidative stress and tau pathology via Akt/GSK-3βsignaling pathway

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AU - Dhivyabharathi, Mathiyazahan

AU - Manivasagam, Thamilarasan

AU - Essa, Musthafa Mohamed

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N2 - Ethnopharmacological relevance 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. Aim of the study 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. Materials and methods Rats were treated with AlCl3 for 60 days to induce biochemical and physiological abnormalities similar to AD patients. AD rats were treated with EoT (100 mg/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 (100 mg/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 AlCl3 is 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 AlCl3 treatment. 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.

AB - Ethnopharmacological relevance 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. Aim of the study 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. Materials and methods Rats were treated with AlCl3 for 60 days to induce biochemical and physiological abnormalities similar to AD patients. AD rats were treated with EoT (100 mg/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 (100 mg/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 AlCl3 is 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 AlCl3 treatment. 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.

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KW - Alzheimer's disease

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