Arokiasamy Justin Thenmozhi1, Mathiyazahan Dhivyabharathi2, Thamilarasan Manivasagam2, Musthafa Mohamed Essa3. 1. Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalai Nagar, Tamilnadu 608 002, India. Electronic address: justinthenmozhi@rediffmail.com. 2. Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalai Nagar, Tamilnadu 608 002, India. 3. 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.
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 (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 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.
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 ADpatients. ADrats 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 ADrats. 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 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.
Authors: Maryam Gul; Zhi-Wei Liu; Roshina Rabail; Fatima Faheem; Noman Walayat; Asad Nawaz; Muhammad Asim Shabbir; Paulo E S Munekata; José M Lorenzo; Rana Muhammad Aadil Journal: Antioxidants (Basel) Date: 2022-04-22
Authors: Ibraheem Husain; Mohd Akhtar; Tushar Madaan; Divya Vohora; Malik Z Abdin; Mohammad Islamuddin; Abul K Najmi Journal: Front Pharmacol Date: 2018-01-30 Impact factor: 5.810