Advertisement

Neurotoxicity Research

, Volume 35, Issue 2, pp 318–330 | Cite as

Amelioration of Aluminum Maltolate-Induced Inflammation and Endoplasmic Reticulum Stress-Mediated Apoptosis by Tannoid Principles of Emblica officinalis in Neuronal Cellular Model

  • Mathiyazahan Dhivya Bharathi
  • Arokiasamy Justin-ThenmozhiEmail author
  • Thamilarasan Manivasagam
  • Mashoque Ahmad Rather
  • Chidambaram Saravana Babu
  • Musthafa Mohamed Essa
  • Gilles J. Guillemin
ORIGINAL ARTICLE
First Online:

Abstract

The neuroprotective role of tannoid principles of Emblica officinalis (EoT), an Indian and Chinese traditional medicinal plant against memory loss in aluminum chloride-induced in vivo model of Alzheimer’s disease through attenuating AChE activity, oxidative stress, amyloid and tau toxicity, and apoptosis, was recently reported in our lab. However, to further elucidate the mechanism of neuroprotective effect of EoT, the current study was designed to evaluate endoplasmic reticulum stress-suppressing and anti-inflammatory role of EoT in PC 12 and SH-SY 5Y cells. These cells were divided into four groups: control (aluminum maltolate (Al(mal)3), EoT + Al(mal)3, and EoT alone based on 3-(4, 5-dimethyl 2-yl)-2, and 5-diphenyltetrazolium bromide (MTT) assay. EoT significantly reduced Al(mal)3-induced cell death and attenuated ROS, mitochondrial membrane dysfunction, and apoptosis (protein expressions of Bax; Bcl-2; cleaved caspases 3, 6, 9, 12; and cytochrome c) by regulating endoplasmic reticulum stress (PKR-like ER kinase (PERK), α subunit of eukaryotic initiation factor 2 (EIF2-α), C/EBP-homologous protein (CHOP), and high-mobility group box 1 protein (HMGB1)). Moreover, inflammatory response (NF-κB, IL-1β, IL-6, and TNF-α) and Aβ toxicity (Aβ1–42) triggered by Al(mal)3 was significantly normalized by EoT. Our results suggested that EoT could be a possible/promising and novel therapeutic lead against Al-induced neurotoxicity. However, further extensive research is needed to prove its efficacy in clinical studies.

Keywords

Aluminum maltolate Tannoids principles of Emblica officinalis Endoplasmic reticulum stress Inflammation Neurotoxicity 
This is a preview of subscription content, log in to check access.

Notes

Acknowledgments

We gratefully acknowledge the Indian Herbs Research & Supply Company, Saharanpur, India, for the generous supply of standardized extract of E. officinalis tannoids.

Funding Information

Financial assistance in the form of a major research project from the University Grants Commission, India (42–664/2013(SR)/22.03.2013) to Dr. A. Justin Thenmozhi is gratefully acknowledged.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

References

  1. Abreo K, Abreo F, Sella ML, Jain S (1999) Aluminum enhances Iron uptake and expression of neurofibrillary tangle protein in neuroblastoma cells. J Neurochem 72:2059–2064CrossRefGoogle Scholar
  2. Adil MD, Kaiser P, Satti NK, Zargar AM, Vishwakarma RA, Tasduq SA (2010) Effect of Emblica officinalis (fruit) against UVB-induced photo-aging in human skin fibroblasts. J Ethnopharmacol 132:109–114CrossRefGoogle Scholar
  3. Banasik A, Lankoff A, Piskulak A, Adamowska K, Lisowska H, Wojcik A (2005) Aluminum-induced micronuclei and apoptosis in human peripheral-blood lymphocytes treated during different phases of the cell cycle. Environ Toxicol 20:402–406CrossRefGoogle Scholar
  4. Berthold RL, Herman MM, Savory J, Carpenter RM, Sturgill BC et al (1989) A long-term intravenous model of aluminum maltol toxicity in rabbits: tissue distribution, hepatic, renal, and neuronal cytoskeletal changes associated with systemic exposure. Toxicol Appl Pharmacol 15:58–74CrossRefGoogle Scholar
  5. Bomfim TR, Forny-Germano L, Sathler LB, Brito-Moreira J, Houzel JC, Decker H, Silverman MA, Kazi H, Melo HM, McClean PL, Holscher C, Arnold SE, Talbot K, Klein WL, Munoz DP, Ferreira ST, de Felice FG (2012) An anti-diabetes agent protects the mouse brain from defective insulin signaling caused by Alzheimer’s disease-associated Aβ oligomers. J Clin Invest 122:1339–1353CrossRefGoogle Scholar
  6. Cullinan SB, Diehl JA (2004) PERK-dependent activation of Nrf2 contributes to redox homeostasis and cell survival following endoplasmic reticulum stress. J Biol Chem 279:20108–20117CrossRefGoogle Scholar
  7. Dang GK, Parekar RR, Kamat SK, Scindia AM, Rege NN (2011) Antiinflammatory activity of Phyllanthus emblica, Plumbago zeylanica and Cyperus rotundus in acute models of inflammation. Phytother Res 25:904–908CrossRefGoogle Scholar
  8. Dewitt DA, Hurd JA, Fox N, Townsend BE, Griffioen KJ et al (2006) Peri-nuclear clustering of mitochondria is triggered during aluminum maltolate induced apoptosis. J Alzheimers Dis 9:195–205CrossRefGoogle Scholar
  9. Dhivya Bharathi M, Justin Thenmozhi A, Manivasagam T (2015) Protective effect of black tea extract against aluminium chloride-induced Alzheimer’s disease in rats: a behavioural, biochemical and molecular approach. J Funct Foods 16:423–435CrossRefGoogle Scholar
  10. Ghosal S, Tripathi VK, Chauhan S (1996) Active constituents of Emblica officinalis part I, the chemistry and antioxidative effects of two hydrolysable tannins, emblicanin a and B. Indian J Chem 35:941–948Google Scholar
  11. Görlach A, Klappa P, Kietzmann T (2006) The endoplasmic reticulum: folding, calcium homeostasis, signaling, and redox control. Antioxi Redox Signal 8:1391–1418CrossRefGoogle Scholar
  12. Griffioen KJ, Ghribi O, Fox N, Savory J, DeWitt DA (2004) Aluminum maltolate-induced toxicity in NT2 cells occurs through apoptosis and includes cytochrome c release. Neurotoxicology 25:859–867CrossRefGoogle Scholar
  13. Halliwell B, Whiteman M (2004) Measuring reactive species and oxidative damage in vivo and in cell culture: how should you do it and what do the results mean? Br J Pharmacol 142:231–255CrossRefGoogle Scholar
  14. Justin Thenmozhi A, William Raja T, Janakiraman U, Manivasagam T (2015) Neuroprotective effect of hesperidin on aluminium chloride induced Alzheimer’s disease in Wistar rats. Neurochem Res 40:767–776CrossRefGoogle Scholar
  15. Justin Thenmozhi A, Dhivya Bharathi M, Manivasagam T, Essa MM (2016a) Tannoid principles of Emblica officinalis attenuated aluminum chloride induced apoptosis by suppressing oxidative stress and tau pathology via Akt/GSK-3βsignaling pathway. J Ethnopharmacol 194:20–29CrossRefGoogle Scholar
  16. Justin Thenmozhi A, Dhivya Bharathi M, William Raja TR, Manivasagam T, Essa MM (2016b) Tannoid principles of Emblica officinalis renovate cognitive deficits and attenuate amyloid pathologies against aluminum chloride induced rat model of Alzheimer’s disease. Nutr Neurosci 6:269–278CrossRefGoogle Scholar
  17. Kim JB, Sig Choi J, Yu YM, Nam K, Piao CS, Kim SW (2006) HMGB1 a novel cytokine like mediator linking acute neuronal death and delayed neuroinflammation in the postischemic brain. J Neurosci 26:6413–6421CrossRefGoogle Scholar
  18. Kim JB, Lim CM, Yu YM, Lee JK (2008) Induction and subcellular localization of high-mobility group box-1 (HMGB1) in the postischemic rat brain. J Neurosci Res 86:1125–1131CrossRefGoogle Scholar
  19. Lourenco MV, Clarke JR, Frozza RL, Bomfim TR, Forny-Germano L, Batista AF, Sathler LB, Brito-Moreira J, Amaral OB, Silva CA, Freitas-Correa L, Espírito-Santo S, Campello-Costa P, Houzel JC, Klein WL, Holscher C, Carvalheira JB, Silva AM, Velloso LA, Munoz DP, Ferreira ST, de Felice FG (2013) TNF-alpha mediates PKR-dependent memory impairment and brain IRS-1 inhibition induced by Alzheimer’s beta-amyloid oligomers in mice and monkeys. Cell Metab 18:831–843CrossRefGoogle Scholar
  20. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275PubMedGoogle Scholar
  21. Mashoque AR, Justin Thenmozhi A, Manivasagam T, Nataraj J, Essa MM, Chidambaram SB (2018) Asiatic acid nullified aluminium toxicity in in vitro model of Alzheimer’s disease. Front Biosci (Elite Ed) 10:287–299Google Scholar
  22. Muthuraman A, Sood S, Singla SK (2011) The anti-inflammatory potential of phenolic compounds from Emblica officinalis L. in rat. Inflammopharmacology 19:327–334CrossRefGoogle Scholar
  23. Nain P, Saini V, Sharma S, Nain J (2012) Antidiabetic and antioxidant potential of Emblica officinalis Gaertn. leaves extract in streptozotocin-induced type-2 diabetes mellitus (T2DM) rats. J Ethnopharmacol 142:65–71CrossRefGoogle Scholar
  24. Nakagawa T, Zhu H, Morishima N, Li E, Xu J, Yankner BA, Yuan J (2000) Caspase­12 mediates endoplasmic reticulum­specific apoptosis and cytotoxicity by amyloid­β. Nature 403:98–103CrossRefGoogle Scholar
  25. Nishida Y (2003) Elucidation of endemic neurodegenerative diseases-a commentary. Z Naturforsch C 58:752–758CrossRefGoogle Scholar
  26. Ohyashiki T, Satoh E, Okada M, Takadera T, Sahara M (2002) Nerve growth factor protects against aluminum-mediated cell death. Toxicology 176:195–207CrossRefGoogle Scholar
  27. Penke B, Bogar F, Fulop L (2016) Protein folding and misfolding, endoplasmic reticulum stress in neurodegenerative diseases: in trace of novel drug targets. Curr Protein Pept Sci 17:169–182CrossRefGoogle Scholar
  28. Platt B (2006) Experimental approaches to assess metallotoxicity and ageing in models of Alzheimer’s disease. J Alzheimers Dis 10:203–213CrossRefGoogle Scholar
  29. Pramyothin P, Samosorn P, Poungshompoo S, Chaichantipyuth C (2006) The protective effects of Phyllanthus emblica Linn. extract on ethanol induced rat hepatic injury. J Ethnopharmacol 107:361–364CrossRefGoogle Scholar
  30. Reddy VD, Padmavathi P, Kavitha G, Gopi S, Varadacharyulu N (2011) Emblica officinalis ameliorates alcohol-induced brain mitochondrial dysfunction in rats. J Med Food 4:62–68CrossRefGoogle Scholar
  31. Ribble D, Goldstein NB, Norris DA, Shellman YG (2005) A simple technique for quantifying apoptosis in 96-well plates. BMC Biotechnol 5:1–7CrossRefGoogle Scholar
  32. Rizvi SH, Parveen A, Verma AK, Ahmad I, Arshad M, Mahdi AA (2014) Aluminium induced endoplasmic reticulum stress mediated cell death in SH-SY5Y neuroblastoma cell line is independent of p53. PLoS One 9:e98409CrossRefGoogle Scholar
  33. Rizvi SH, Parveen A, Ahmad I, Ahmad I, Verma AK, Arshad M, Mahdi AA (2016) Aluminum activates PERK-EIF2α signaling and inflammatory proteins in human neuroblastoma SH-SY5Y cells. Biol Trace Elem Res 72:108–119CrossRefGoogle Scholar
  34. Satoh E, Okada M, Takadera T, Ohyashiki T (2005) Glutathione depletion promotes aluminum-mediated cell death of PC12 cells. Biol Pharm Bull 28:941–946CrossRefGoogle Scholar
  35. Scaduto RC, Grotyohann LW (1999) Measurement of mitochondrial membrane potential using fluorescent rhodamine derivatives. J Biophysical 76:469–477CrossRefGoogle Scholar
  36. Scheper W, Hoozemans JJ (2015) The unfolded protein response in neurodegenerative diseases: a neuropathological perspective. Acta Neuropathol 130:315–331CrossRefGoogle Scholar
  37. Sharma A, Sharma KK (2011) Chemoprotective role of triphala against 1,2-dimethylhydrazine dihydrochloride induced carcinogenic damage to mouse liver. Indian J Clin Biochem 26:290–295CrossRefGoogle Scholar
  38. Shore GC, Papa FR, Oakes SA (2011) Signaling cell death from the endoplasmic reticulum stress response. Curr Opin Cell Biol 23:143–149CrossRefGoogle Scholar
  39. Sprenkle NT, Sims SG, Sánchez CL, Meares GP (2017) Endoplasmic reticulum stress and inflammation in the central nervous system. Mol Neurodegener 12:42CrossRefGoogle Scholar
  40. Todd DJ, Lee AH, Glimcher LH (2008) The endoplasmic reticulum stress response in immunity and autoimmunity. Nat Rev Immunol 8:663–674CrossRefGoogle Scholar
  41. Tsubouchi R, Htay HH, Murakami K, Haneda M, Yoshino M (2001) Aluminum-induced apoptosis in PC12D cells. Biometals 4:181–185CrossRefGoogle Scholar
  42. Urra H, Dufey E, Lisbona F, Rojas-Rivera D, Hetz C (2013) When ER stress reaches a dead end. Biochim Biophys Acta 1833:3507–3517CrossRefGoogle Scholar
  43. Vasudevan M, Parle M (2007) Memory enhancing activity of Anwala churna (Emblica officinalis Gaertn.): an Ayurvedic preparation. Physiol Behav 91:46–54CrossRefGoogle Scholar
  44. Wang WL, Dai R, Yan H, Han C, Liu LS, Duan XH (2015) Current situation of PC 12 cell use in neuronal injury study. Int J Biotechnol Wellness Ind 4:61–66CrossRefGoogle Scholar
  45. Wang C, Lou Y, Xu J, Feng Z, Chen Y, Tang Q, Wang Q, Jin H, Wu Y, Tian N, Zhou Y, Xu H, Zhang X (2017) Endoplasmic reticulum stress and NF-κb pathway in salidroside mediated neuroprotection: potential of salidroside in neurodegenerative diseases. Am J Chin Med 45:1459–1475CrossRefGoogle Scholar
  46. Xie HR, Hu LS, Li GY (2010) SH-SY5Y human neuroblastoma cell line: in vitro cell model of dopaminergic neurons in Parkinson’s disease. Chin Med J 123:1086–1092PubMedGoogle Scholar
  47. Yamamoto H, Morino K, Mengistu L, Ishibashi T, Kiriyama K, Ikami T, Maegawa H (2016) Amla enhances mitochondrial spare respiratory capacity by increasing mitochondrial biogenesis and antioxidant systems in a murine skeletal muscle cell line. Oxid Med Cell Long 1735841:1735841Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Mathiyazahan Dhivya Bharathi
    • 1
  • Arokiasamy Justin-Thenmozhi
    • 1
    Email author
  • Thamilarasan Manivasagam
    • 1
  • Mashoque Ahmad Rather
    • 1
  • Chidambaram Saravana Babu
    • 2
  • Musthafa Mohamed Essa
    • 3
    • 4
    • 5
  • Gilles J. Guillemin
    • 6
  1. 1.Department of Biochemistry and Biotechnology, Faculty of ScienceAnnamalai UniversityAnnamalai NagarIndia
  2. 2.Department of Pharmacology, JSS College of PharmacyJSS UniversityMysoreIndia
  3. 3.Department of Food Science and Nutrition, CAMSSultan Qaboos UniversityMuscatOman
  4. 4.Ageing and Dementia Research GroupSultan Qaboos UniversityMuscatOman
  5. 5.Food and Brain Research FoundationChennaiIndia
  6. 6.Neuroinflammation group, Faculty of Medicine and Health SciencesMacquarie UniversitySydneyAustralia

Personalised recommendations

Cite article

Buy options