Exploring the multifaceted neuroprotective actions of Emblica officinalis (Amla): a review

Abstract

Today, neurological disorders such as epilepsy, depression, tardive dyskinesia, and stress, and neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease, dementia, and Huntington’s disease affect millions of people all over the world. Existing pharmacological interventions do not meet the desired therapeutic benefits for a significant number of patients, and hence, numerous research studies are in progress to find novel therapies for these disorders. Herbal drugs, which have been used in traditional medicine for centuries, are also being explored and scientifically evaluated for the treatment of these neurological disorders. While substantial evidence exists for the antioxidant, anti-inflammatory, anti-hyperlipidemic, and anti-hyperglycemic effects of Emblica officinalis, in vivo and in vitro studies, have also revealed its beneficial therapeutic activities in numerous neurological disorders. These diverse neuroprotective pharmacodynamic actions of E. officinalis corroborated by accumulating evidence in pre-clinical research studies deserve the attention of the scientific community to develop viable pharmacotherapeutic strategies. The present review elaborates upon the latest scientific evidence pertaining to the pharmacological effects of E. officinalis in numerous neurological and neurodegenerative disorders and also gives way for future research in this area.

This is a preview of subscription content, access via your institution.

Fig. 1

References

  1. Akhtar MS, Ramzan A, Ali A, Ahmad M (2011) Effect of Amla fruit (Emblica officinalis Gaertn.) on blood glucose and lipid profile of normal subjects and type 2 diabetic patients. Int J Food Sci Nutr 62(6):609–616

    CAS  Article  PubMed  Google Scholar 

  2. Akram M, Nawaz A (2017) Effects of medicinal plants on Alzheimer’s disease and memory deficits. Neural Regen Res 12(4):660–670

    Article  PubMed  PubMed Central  Google Scholar 

  3. Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, Gamst A, Holtzman DM, Jagust WJ, Petersen RC (2011) The diagnosis of mild cognitive impairment due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 7(3):270–279

    Article  PubMed  PubMed Central  Google Scholar 

  4. Aquino CCH, Lang AE (2014) Tardive dyskinesia syndromes: current concepts. Parkinsonism Relat Disord 20:S113–S117

    Article  PubMed  Google Scholar 

  5. Arafa NM, Abdel-Rahman M, El-khadragy MF, Kassab RB (2013) Evaluation of the possible epileptogenic activity of ciprofloxacin: the role of Nigella sativa on amino acids neurotransmitters. Neurochem Res 38(1):174–185

    CAS  Article  PubMed  Google Scholar 

  6. Ashwlayan VD, Singh R (2011) Reversal effect of Phyllanthus Emblica (Euphorbiaceae) Rasayana on memory deficits in mice. Int J Appl Pharm 3:10–15

    Google Scholar 

  7. Bharathi MD, Thenmozhi AJ (2018) Attenuation of aluminum-induced neurotoxicity by tannoid principles of Emblica officinalis in Wistar rats. Int J Nutr Pharmacol Neurol Dis 8(2):35

    CAS  Google Scholar 

  8. Bhattacharya SK, Bhattacharya D, Muruganandam AV (2000a) Effect of Emblica officinalis tannoids on a rat model of tardive dyskinesia. Indian J Exp Biol 38(9):945–947

    CAS  PubMed  Google Scholar 

  9. Bhattacharya A, Ghosal S, Bhattacharya SK (2000b) Antioxidant activity of tannoid principles of Emblica officinalis (Amla) in chronic stress-induced changes in rat brain. Indian J Exp Biol 38(9):877–880

    CAS  PubMed  Google Scholar 

  10. Biswas K, AK Azad, Sultana T, Khan F, Hossain S, Alam S, Chowdhary R, Khatun Y (2017) Assessment of in-vitro Cholinesterase Inhibitory and Thrombolytic Potential of bark and seed extracts of Tamarindus indica (L.) relevant to the treatment of Alzheimer's disease and clotting disorders. Journal of Intercultural Ethnopharmacology 6(1):115

  11. Brigitta B (2002) Pathophysiology of depression and mechanisms of treatment. Dialogues Clin Neurosci 4(1):7–20

    PubMed  PubMed Central  Google Scholar 

  12. Davis KL, Berger PA, Hollister LE (1976) Tardive dyskinesia and depressive illness. Psychopharmacol Commun 2(2):125–130

    CAS  PubMed  Google Scholar 

  13. Dehaene S, Naccache L (2001) Towards a cognitive neuroscience of consciousness: basic evidence and a workspace framework. Cognition 79(1):1–37

    CAS  Article  PubMed  Google Scholar 

  14. Dhingra D, Joshi P, Gupta A, Chhillar R (2012) Possible involvement of monoaminergic neurotransmission in antidepressant-like activity of Emblica officinalis fruits in mice. CNS Neurosci Ther 18(5):419–425

    CAS  Article  PubMed  Google Scholar 

  15. Dias D, Atukorala C, Amaratunga NS, Perera B, Karunathilake L (2018) The effects of Emblica officinalis and Tinospora cordifolia herbal treatment on the prognosis of squamous cell carcinoma of the buccal mucosa and tongue. J Oral Maxillofac Surg Med Pathol 30(1):21–29

    Article  Google Scholar 

  16. Edwards S, Lawrence MJ, Cable C, Heinrich M (2018) Where do herbal medicines belong? Part 1—an overview of CAM. Lung Cancer 15:05

    Google Scholar 

  17. Fabene PF, Bramanti P, Constantin G (2010) The emerging role for chemokines in epilepsy. J Neuroimmunol 224(1–2):22–27

    CAS  Article  PubMed  Google Scholar 

  18. Golechha M, Bhatia J, Arya DS (2010) Hydroalcoholic extract of Emblica officinalis Gaertn. Affords protection against PTZ-induced seizures, oxidative stress and cognitive impairment in rats. Indian J Exp Biol 48(5):474-8

  19. Golechha M, Bhatia J, Ojha S, Arya DS (2011) Hydroalcoholic extract of Emblica officinalis protects against kainic acid-induced status epilepticus in rats: evidence for an antioxidant, anti-inflammatory, and neuroprotective intervention. Pharm Biol 49(11):1128–1136

    Article  PubMed  Google Scholar 

  20. Golechha M, Bhatia J, Arya DS (2012) Studies on effects of Emblica officinalis (Amla) on oxidative stress and cholinergic function in scopolamine induced amnesia in mice. J Environ Biol 33(1):95–100

    PubMed  Google Scholar 

  21. Hampel H, Mesulam MM, Cuello AC, Khachaturian AS, Farlow MR, Snyder PJ, Giacobini E, Khachaturian ZS, Group CSW (2017) Revisiting the cholinergic hypothesis in Alzheimer's disease: emerging evidence from translational and clinical research. Alzheimers Dement S1552-5260(17):33719-6

  22. Husain I, Akhtar M, Vohora D, Abdin MZ, Islamuddin M, Akhtar MJ, Najmi AK (2017) Rosuvastatin attenuates high-salt and cholesterol diet induced neuroinflammation and cognitive impairment via preventing nuclear factor KappaB pathway. Neurochem Res 42(8):2404-2416

  23. Husain I, Akhtar M, Shaharyar M, Islamuddin M, Abdin MZ, Akhtar MJ, Najmi AK (2018a) High-salt-and cholesterol diet-associated cognitive impairment attenuated by tannins-enriched fraction of Emblica officinalis via inhibiting NF-kB pathway. Inflammopharmacology 26(1):147–156

    CAS  Article  PubMed  Google Scholar 

  24. Husain I, Akhtar M, Madaan T, Vohora D, Abdin MZ, Islamuddin M, Najmi AK (2018b) Tannins enriched fraction of Emblica officinalis fruits alleviates high-salt and cholesterol diet-induced cognitive impairment in rats via Nrf2–ARE pathway. Front Pharmacol 9:23

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Hussain S, Singh A, Rahman SO, Habib A, Najmi AK (2018) Calcium channel blocker use reduces incident dementia risk in elderly hypertensive patients: a meta-analysis of prospective studies. Neurosci Lett 671:120–127

    CAS  Article  PubMed  Google Scholar 

  26. Jimenez S, Torres M, Vizuete M, Sanchez-Varo R, Sanchez-Mejias E, Trujillo-Estrada L, Carmona-Cuenca I, Caballero C, Ruano D, Gutierrez A (2011) Age-dependent accumulation of soluble amyloid β (Aβ) oligomers reverses the neuroprotective effect of soluble amyloid precursor protein-α (sAPPα) by modulating phosphatidylinositol 3-kinase (PI3K)/Akt-GSK-3β pathway in Alzheimer mouse model. J Biol Chem 286(21):18414–18425

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  27. Justin Thenmozhi A, Dhivyabharathi M, William Raja TR, Manivasagam T, Essa MM (2016a) Tannoid principles of Emblica officinalis renovate cognitive deficits and attenuate amyloid pathologies against aluminum chloride induced rat model of Alzheimer's disease. Nutr Neurosci 19(6):269–278

    Article  CAS  PubMed  Google Scholar 

  28. Justin Thenmozhi A, Dhivyabharathi M, Manivasagam T, Essa MM (2016b) Tannoid principles of Emblica officinalis attenuated aluminum chloride induced apoptosis by suppressing oxidative stress and tau pathology via Akt/GSK-3betasignaling pathway. J Ethnopharmacol 194:20–29

    CAS  Article  PubMed  Google Scholar 

  29. Khan KH (2009) Roles of Emblica officinalis in medicine-a review. Bot Res Int 2(4):218–228

    CAS  Google Scholar 

  30. Kosel M, Sturm V, Frick C, Lenartz D, Zeidler G, Brodesser D, Schlaepfer TE (2007) Mood improvement after deep brain stimulation of the internal globus pallidus for tardive dyskinesia in a patient suffering from major depression. J Psychiatr Res 41(9):801–803

    Article  PubMed  Google Scholar 

  31. Krishnan V, Nestler EJ (2008) The molecular neurobiology of depression. Nature. 455(7215):894–902

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  32. Kumar CP (2013) Effect of Emblica officinalis on stress induced biochemical and psychological changes in mice. Global Journal of Medical research, Veterinary Science and Veterinary Medicine 13(2):25–28

  33. LaFerla FM, Green KN, Oddo S (2007) Intracellular amyloid-[beta] in Alzheimer’s disease. Nat Rev Neurosci 8(7):499–509

    CAS  Article  PubMed  Google Scholar 

  34. LaPenna P, Tormoehlen LM (2017) The pharmacology and toxicology of third-generation anticonvulsant drugs. J Med Toxicol 13:329–342

  35. Mathew M, Subramanian S (2014) In vitro screening for anti-cholinesterase and antioxidant activity of methanolic extracts of ayurvedic medicinal plants used for cognitive disorders. PLoS One 9(1):e86804

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. McGrath CL, Kelley ME, Dunlop BW, Holtzheimer PE III, Craighead WE, Mayberg HS (2014) Pretreatment brain states identify likely nonresponse to standard treatments for depression. Biol Psychiatry 76(7):527–535

    CAS  Article  PubMed  Google Scholar 

  37. Muller T (2015) Valbenazine granted breakthrough drug status for treating tardive dyskinesia. Expert Opin Investig Drugs 24(6):737–742

    Article  CAS  PubMed  Google Scholar 

  38. Muthuraman A, Sood S, Singla SK (2011) The antiinflammatory potential of phenolic compounds from Emblica officinalis L. in rat. Inflammopharmacology 19(6):327–334

    CAS  Article  PubMed  Google Scholar 

  39. 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(1):65–71

    CAS  Article  PubMed  Google Scholar 

  40. Noor NA, Aboul Ezz HS, Faraag AR, Khadrawy YA (2012) Evaluation of the antiepileptic effect of curcumin and Nigella sativa oil in the pilocarpine model of epilepsy in comparison with valproate. Epilepsy Behav 24(2):199–206

  41. Obulesu M, Rao DM (2011) Effect of plant extracts on Alzheimer’s disease: an insight into therapeutic avenues. J Neurosci Rural Pract 2(1):56–61

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  42. Parvez MK (2018) Natural or plant products for the treatment of neurological disorders: current knowledge. Curr Drug Metab 19(5):424–428

  43. Patel S, Goyal R (2012) Emblica officinalis Geart.: a comprehensive review on phytochemistry, pharmacology and ethnomedicinal uses. Res J Med Plant 6:6–16

    CAS  Article  Google Scholar 

  44. Prokai D, Berga SL (2016) Neuroprotection via reduction in stress: altered menstrual patterns as a marker for stress and implications for long-term neurologic health in women. Int J Mol Sci 17(12):2147

    Article  CAS  PubMed Central  Google Scholar 

  45. Ramakrishna V, Gupta KP, Setty HO, Kondapi KA (2014) Neuroprotective effect of Emblica officinalis extract against H2O2 induced DNA damage and repair in neuroblastoma cells. J Homeop Ayurv Med S1002:1

  46. Reddy VD, Padmavathi P, Kavitha G, Gopi S, Varadacharyulu N (2011) Emblica officinalis ameliorates alcohol-induced brain mitochondrial dysfunction in rats. J Med Food 14(1–2):62–68

    Article  PubMed  Google Scholar 

  47. Sannino G, Pasqualini L, Ricciardelli E, Montilla P, Soverchia L, Ruggeri B, Falcinelli S, Renzi A, Ludka C, Kirchner T et al (2016) Acute stress enhances the expression of neuroprotection- and neurogenesis-associated genes in the hippocampus of a mouse restraint model. Oncotarget 7(8):8455–8465

    Article  PubMed  PubMed Central  Google Scholar 

  48. Shalini B, Sharma J (2015) Beneficial effects of emblica officinalis on fluoride-induced toxicity on brain biochemical indexes and learning-memory in rats. Toxicol Int 22(1):35–39

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  49. Singh MK, Yadav SS, Gupta V, Khattri S (2013) Immunomodulatory role of Emblica officinalis in arsenic induced oxidative damage and apoptosis in thymocytes of mice. BMC Complement Altern Med 13(1):193

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Singh MK, Dwivedi S, Yadav SS, Sharma P, Khattri S (2014a) Arsenic-induced hepatic toxicity and its attenuation by fruit extract of Emblica officinalis (Amla) in mice. Indian J Clin Biochem 29(1):29–37

    CAS  Article  PubMed  Google Scholar 

  51. Singh MK, Yadav SS, Yadav RS, Singh US, Shukla Y, Pant KK, Khatri S (2014b) Efficacy of crude extract of Emblica officinalis (amla) in arsenic-induced oxidative damage and apoptosis in splenocytes of mice. Toxicol Int 21(1):8–17

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Singh MK, Yadav SS, Yadav RS, Chauhan A, Katiyar D, Khattri S (2015) Protective effect of Emblica-officinalis in arsenic induced biochemical alteration and inflammation in mice. Springerplus. 4:438

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Suomalainen A, Battersby BJ (2017) Mitochondrial diseases: the contribution of organelle stress responses to pathology. Nat Rev Mol Cell Biol 19:77–92

    Article  CAS  PubMed  Google Scholar 

  54. Uddin MS, Al Mamun A, Hossain MS, Akter F, Iqbal MA, Asaduzzaman M (2016) Exploring the effect of Phyllanthus emblica L. on cognitive performance, brain antioxidant markers and acetylcholinesterase activity in rats: promising natural gift for the mitigation of Alzheimer’s disease. Ann Neurosci 23(4):218–229

    Article  PubMed  PubMed Central  Google Scholar 

  55. Vajda FJ (2002) Neuroprotection and neurodegenerative disease. J Clin Neurosci 9(1):4–8

    Article  PubMed  Google Scholar 

  56. Variya BC, Bakrania AK, Patel SS (2016) Emblica officinalis (Amla): a review for its phytochemistry, ethnomedicinal uses and medicinal potentials with respect to molecular mechanisms. Pharmacol Res 111:180–200

    CAS  Article  PubMed  Google Scholar 

  57. Vasudevan M, Parle M (2007a) Effect of Anwala churna (Emblica officinalis GAERTN.): an ayurvedic preparation on memory deficit rats. Yakugaku zasshi: Journal of the Pharmaceutical Society of Japan 127(10):1701–1707

    CAS  Article  PubMed  Google Scholar 

  58. Vasudevan M, Parle M (2007b) Memory enhancing activity of Anwala churna (Emblica officinalis Gaertn.): an Ayurvedic preparation. Physiol Behav 91(1):46–54

    CAS  Article  PubMed  Google Scholar 

  59. Wankhar D, Devi RS, Ashok I (2014) Emblica officinalis outcome on noise stress induced behavioral changes in Wistar albino rats. Biomed Prev Nutr 4(2):219–224

    Article  Google Scholar 

  60. Xie T, Wang W-p, Mao Z-f, Qu Z-z, Luan S-q, Jia L-j, Kan M-c (2012) Effects of epigallocatechin-3-gallate on pentylenetetrazole-induced kindling, cognitive impairment and oxidative stress in rats. Neurosci Lett 516(2):237–241

    CAS  Article  PubMed  Google Scholar 

  61. Yokozawa T, Kim HY, Kim HJ, Okubo T, Chu D-C, Juneja LR (2007) Amla (Emblica officinalis Gaertn.) prevents dyslipidemia and oxidative stress in the aging process. Br J Nutr 97(6):1187–1195

    CAS  Article  PubMed  Google Scholar 

  62. Zameer S, Najmi AK, Vohora D, Akhtar M (2017) A review on therapeutic potentials of Trigonella foenum graecum (fenugreek) and its chemical constituents in neurological disorders: complementary roles to its hypolipidemic, hypoglycemic, and antioxidant potential. Nutr Neurosci 21(8):539-545

Download references

Acknowledgments

This research work was supported by the grant funded by the Department of Science and Technology, Ministry of Science and Technology (INSPIRE FELLOWSHIP; IF130014), Government of India, New Delhi.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Abul Kalam Najmi.

Ethics declarations

Conflict of interest

The authors declare no competing financial interests or any other conflicts of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Husain, I., Zameer, S., Madaan, T. et al. Exploring the multifaceted neuroprotective actions of Emblica officinalis (Amla): a review. Metab Brain Dis 34, 957–965 (2019). https://doi.org/10.1007/s11011-019-00400-9

Download citation

Keywords

  • Emblica officinalis
  • Epilepsy
  • Depression
  • Alzheimer’s disease
  • Stress
  • Memory