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Licensed Unlicensed Requires Authentication Published by De Gruyter December 21, 2017

Amla (Emblica officinalis) improves hepatic and renal oxidative stress and the inflammatory response in hypothyroid female wistar rats fed with a high-fat diet

  • P. Rajaa Muthu , Zachariah Bobby EMAIL logo , P. Sankar , V. Vickneshwaran and Sajini Elizabeth Jacob



We investigated the protective effects of amla (Emblica officinalis) on the pathogenesis of oxidative stress (OS) and inflammatory response in hypothyroid rats fed with a high-fat diet (HFD) as an experimental model of hypothyroidism (HT) with obesity.


A total of 80 female wistar rats (5-months-old) were divided into eight different groups. Propylthiouracil (PTU) and HFD were used to induce the experimental HT and obesity, respectively. The euthyroid and hypothyroid rats were fed either normal chow or HFD with and without amla extract (AE, 100 mg/kg bw/day) for 6 weeks. The blood and tissues, liver and kidney OS and inflammatory parameters were studied using appropriate biochemical and molecular techniques.


PTU and HFD per se caused OS and inflammatory response as evidenced by increased plasma MDA, TNF-α, CRP and GPx in association with decreased levels of TAS and reduced glutathione (GSH). The proteomic analysis revealed that the expressions of pERK, pP38, TNF-α, IL6, COX2 and NOX-4 were up-regulated in the liver and kidney of these rats. In addition, all these metabolic derangements were further augmented when HT was followed by the addition of HFD. This suggested that there was a synergism between HT and the intake of HFD on the development of OS and inflammatory response.


The treatment with amla fruit extract significantly restored the redox imbalance and inflammatory signaling and ameliorated OS and inflammatory response, suggesting the use of this natural compound as an alternative remedy or adjuvant for the management of metabolic complications concomitant with HT.

Corresponding author: Dr. Zachariah Bobby, PhD, Professor and Head of Biochemistry, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry 605 006, India, Phone: +91-413-2273078/+91 94436 02996, Fax: 0413-2272067/66


We acknowledge Dr. Mohan Raj P.S., JIPMER for reviewing the manuscript. We thank Council of Scientific and Industrial Research (CSIR), New Delhi, India for supporting the first author financially in the form of junior research fellowship. We are grateful to Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India for providing financial assistance in the form of an intramural research grant (Grant sanction order No. Edn. 7(1)/2013, dated 05 Feb 2013).

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved its submission.

  2. Research funding: None declared.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.


1. Walker BR, Colledge NR, Ralston SH, Penman I. Davidson’s principles and practice of medicine, 22nd ed. London,UK: Elsevier, Churchill Livingstone, 2014.Search in Google Scholar

2. Unnikrishnan AG, Kalra S, Sahay RK, Bantwal G, John M, Tewari N. Prevalence of hypothyroidism in adults: an epidemiological study in eight cities of India. Indian J Endocrinol Metab 2013;17:647.10.4103/2230-8210.113755Search in Google Scholar

3. Tunbridge WM, Evered DC, Hall R, Appleton D, Brewis M, Clark F, et al. Lipid profiles and cardiovascular disease in the Whickham area with particular reference to thyroid failure. Clin Endocrinol (Oxf) 1977;7:495–508.10.1111/j.1365-2265.1977.tb01341.xSearch in Google Scholar

4. Dimitriadis GD, Raptis SA. Thyroid hormone excess and glucose intolerance. Exp Clin Endocrinol Diabetes Off J Ger Soc Endocrinol Ger Diabetes Assoc 2001;109:S225–39.10.1055/s-2001-18584Search in Google Scholar

5. Krassas GE. Thyroid disease and female reproduction. Fertil Steril 2000;74:1063–70.10.1016/S0015-0282(00)01589-2Search in Google Scholar

6. Taddei S, Caraccio N, Virdis A, Dardano A, Versari D, Ghiadoni L, et al. Low-grade systemic inflammation causes endothelial dysfunction in patients with Hashimoto’s thyroiditis. J Clin Endocrinol Metab 2006;91:5076–82.10.1210/jc.2006-1075Search in Google Scholar PubMed

7. Safayee S, Karbalaei N, Noorafshan A, Nadimi E. Induction of oxidative stress, suppression of glucose-induced insulin release, ATP production, glucokinase activity, and histomorphometric changes in pancreatic islets of hypothyroid rat. Eur J Pharmacol 2016;791:147–56.10.1016/j.ejphar.2016.08.024Search in Google Scholar PubMed

8. Yasmeen R, Jeyakumar SM, Reichert B, Yang F, Ziouzenkova O. The contribution of vitamin A to autocrine regulation of fat depots. Biochim Biophys Acta 2012;1821:190–7.10.1016/j.bbalip.2011.06.004Search in Google Scholar PubMed PubMed Central

9. Chakrabarti SK, Ghosh S, Banerjee S, Mukherjee S, Chowdhury S. Oxidative stress in hypothyroid patients and the role of antioxidant supplementation. Indian J Endocrinol Metab 2016;20:674–8.10.4103/2230-8210.190555Search in Google Scholar PubMed PubMed Central

10. Torun AN, Kulaksizoglu S, Kulaksizoglu M, Pamuk BO, Isbilen E, Tutuncu NB. Serum total antioxidant status and lipid peroxidation marker malondialdehyde levels in overt and subclinical hypothyroidism. Clin Endocrinol (Oxf) 2009;70: 469–74.10.1111/j.1365-2265.2008.03348.xSearch in Google Scholar PubMed

11. Nanda N, Bobby Z, Hamide A. Association of thyroid stimulating hormone and coronary lipid risk factors with lipid peroxidation in hypothyroidism. Clin Chem Lab Med 2008;46:674–9.10.1515/CCLM.2008.139Search in Google Scholar PubMed

12. Baliga MS, Dsouza JJ. Amla (Emblica officinalis Gaertn), a wonder berry in the treatment and prevention of cancer. Eur J Cancer Prev Off J Eur Cancer Prev Organ ECP 2011;20:225–39.10.1097/CEJ.0b013e32834473f4Search in Google Scholar

13. Rao TP, Sakaguchi N, Juneja LR, Wada E, Yokozawa T. Amla (Emblica officinalis Gaertn.) extracts reduce oxidative stress in streptozotocin-induced diabetic rats. J Med Food 2005;8: 362–8.10.1089/jmf.2005.8.362Search in Google Scholar

14. Rajeshkumar NV, Pillai MR, Kuttan R. Induction of apoptosis in mouse and human carcinoma cell lines by Emblica officinalis polyphenols and its effect on chemical carcinogenesis. J Exp Clin Cancer Res CR 2003;22:201–12.Search in Google Scholar

15. Sultana S, Ahmed S, Jahangir T. Emblica officinalis and hepatocarcinogenesis: a chemopreventive study in wistar rats. J Ethnopharmacol 2008;118:1–6.10.1016/j.jep.2007.04.021Search in Google Scholar

16. Muthuraman A, Sood S, Singla SK. The antiinflammatory potential of phenolic compounds from Emblica officinalis L. in rat. Inflammopharmacology 2011;19:327–34.10.1007/s10787-010-0041-9Search in Google Scholar

17. Liu X, Zhao M, Wu K, Chai X, Yu H, Tao Z, et al. Immunomodulatory and anticancer activities of phenolics from emblica fruit (Phyllanthus emblica L.). Food Chem 2012;131: 685–90.10.1016/j.foodchem.2011.09.063Search in Google Scholar

18. Anila L, Vijayalakshmi NR. Antioxidant action of flavonoids from Mangifera indica and Emblica officinalis in hypercholesterolemic rats. Food Chem 2003;83:569–74.10.1016/S0308-8146(03)00155-9Search in Google Scholar

19. Achliya GS, Wadodkar SG, Dorle AK. Evaluation of hepatoprotective effect of Amalkadi Ghrita against carbon tetrachloride-induced hepatic damage in rats. J Ethnopharmacol 2004;90:229–32.10.1016/j.jep.2003.09.037Search in Google Scholar PubMed

20. Pramyothin P, Samosorn P, Poungshompoo S, Chaichantipyuth C. The protective effects of Phyllanthus emblica Linn. extract on ethanol induced rat hepatic injury. J Ethnopharmacol 2006;107:361–4.10.1016/j.jep.2006.03.035Search in Google Scholar PubMed

21. Yokozawa T, Kim HY, Kim HJ, Okubo T, Chu D-C, Juneja LR. Amla (Emblica officinalis Gaertn.) prevents dyslipidaemia and oxidative stress in the ageing process. Br J Nutr 2007;97:1187–95.10.1017/S0007114507691971Search in Google Scholar PubMed

22. Koshy SM, Bobby Z, Hariharan AP, Gopalakrishna SM. Amla (Emblica officinalis) extract is effective in preventing high fructose diet-induced insulin resistance and atherogenic dyslipidemic profile in ovariectomized female albino rats. Menopause 2012;19:1146–55.10.1097/gme.0b013e31824e5bf7Search in Google Scholar PubMed

23. Storlien LH, James DE, Burleigh KM, Chisholm DJ, Kraegen EW. Fat feeding causes widespread in vivo insulin resistance, decreased energy expenditure, and obesity in rats. Am J Physiol Endocrinol Metab 1986;251:E576–83.10.1152/ajpendo.1986.251.5.E576Search in Google Scholar

24. Pan T, Zhong M, Zhong X, Zhang Y, Zhu D. Levothyroxine replacement therapy with vitamin E supplementation prevents oxidative stress and cognitive deficit in experimental hypothyroidism. Endocrine 2013;43:434–9.10.1007/s12020-012-9801-1Search in Google Scholar

25. Beutler E, Duron O, Kelly BM. Improved method for the determination of blood glutathione. J Lab Clin Med 1963;61:882–8.Search in Google Scholar

26. Wendel A. Glutathione peroxidase. Methods Enzymol 1981;77:325–33.10.1016/B978-0-12-380001-5.50022-0Search in Google Scholar

27. Yagi K. Assay for blood plasma or serum. Methods Enzymol 1984;105:328–31.10.1016/S0076-6879(84)05042-4Search in Google Scholar

28. Benzie IF, Strain JJ. The ferric reducing ability of plasma (FRAP) as a measure of ‘antioxidant power’: the FRAP assay. Anal Biochem 1996;239:70–6.10.1006/abio.1996.0292Search in Google Scholar PubMed

29. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods San Diego Calif 2001;25:402–8.10.1006/meth.2001.1262Search in Google Scholar PubMed

30. Damodara Reddy V, Padmavathi P, Gopi S, Paramahamsa M, Varadacharyulu NC. Protective effect of Emblica officinalis against alcohol-induced hepatic injury by ameliorating oxidative stress in rats. Indian J Clin Biochem 2010;25:419–24.10.1007/s12291-010-0058-2Search in Google Scholar PubMed PubMed Central

31. Andican G, Gelisgen R, Unal E, Tortum OB, Dervisoglu S, Karahasanoglu T, et al. Oxidative stress and nitric oxide in rats with alcohol-induced acute pancreatitis. World J Gastroenterol 2005;11:2340–5.10.3748/wjg.v11.i15.2340Search in Google Scholar PubMed PubMed Central

32. Shivananjappa MM, Joshi MK. Influence of Emblica officinalis aqueous extract on growth and antioxidant defense system of human hepatoma cell line (HepG2). Pharm Biol 2012;50:497–505.10.3109/13880209.2011.618501Search in Google Scholar PubMed

33. Siti HN, Kamisah Y, Kamsiah J. The role of oxidative stress, antioxidants and vascular inflammation in cardiovascular disease (a review). Vascul Pharmacol 2015;71:40–56.10.1016/j.vph.2015.03.005Search in Google Scholar PubMed

34. Old LJ. Tumor necrosis factor (TNF). Science 1985;230:630–2.10.1126/science.2413547Search in Google Scholar

35. Christ-Crain M, Meier C, Guglielmetti M, Huber PR, Riesen W, Staub JJ, et al. Elevated C-reactive protein and homocysteine values: cardiovascular risk factors in hypothyroidism? A cross-sectional and a double-blind, placebo-controlled trial. Atherosclerosis 2003;166:379–86.10.1016/S0021-9150(02)00372-6Search in Google Scholar

36. Tuzcu A, Bahceci M, Gokalp D, Tuzun Y, Gunes K. Subclinical hypothyroidism may be associated with elevated high-sensitive c-reactive protein (low grade inflammation) and fasting hyperinsulinemia. Endocr J 2005;52:89–94.10.1507/endocrj.52.89Search in Google Scholar

37. Abbas AM, Sakr HF. Effect of magnesium sulfate and thyroxine on inflammatory markers in a rat model of hypothyroidism. Can J Physiol Pharmacol 2015;94:426–32.10.1139/cjpp-2015-0247Search in Google Scholar

38. Basu G, Mohapatra A. Interactions between thyroid disorders and kidney disease. Indian J Endocrinol Metab 2012;16:204–13.10.4103/2230-8210.93737Search in Google Scholar

39. Malik R, Hodgson H. The relationship between the thyroid gland and the liver. QJM Mon J Assoc Physicians 2002;95:559–69.10.1093/qjmed/95.9.559Search in Google Scholar

40. Chen K-H, Lin B-R, Chien C-T, Ho C-H. Emblica officinalis Gaertn. attentuates N-nitrosodiethylamine-induced apoptosis, autophagy, and inflammation in rat livers. J Med Food 2011;14:746–55.10.1089/jmf.2010.1459Search in Google Scholar

41. Yokozawa T, Kim HY, Kim HJ, Tanaka T, Sugino H, Okubo T, et al. Amla (Emblica officinalis Gaertn.) attenuates age-related renal dysfunction by oxidative stress. J Agric Food Chem 2007;55:7744–52.10.1021/jf072105sSearch in Google Scholar

42. Marshall PJ, Kulmacz RJ, Lands WE. Constraints on prostaglandin biosynthesis in tissues. J Biol Chem 1987;262:3510–7.10.1016/S0021-9258(18)61380-8Search in Google Scholar

43. Calixto JB, Otuki MF, Santos ARS. Anti-inflammatory compounds of plant origin. Part I. Action on arachidonic acid pathway, nitric oxide and nuclear factor κ B (NF-κB). Planta Med 2003;69: 973–83.10.1055/s-2003-45141Search in Google Scholar PubMed

44. Schulze-Osthoff K, Bakker AC, Vanhaesebroeck B, Beyaert R, Jacob WA, Fiers W. Cytotoxic activity of tumor necrosis factor is mediated by early damage of mitochondrial functions. Evidence for the involvement of mitochondrial radical generation. J Biol Chem 1992;267:5317–23.10.1016/S0021-9258(18)42768-8Search in Google Scholar

45. Schulze-Osthoff K, Beyaert R, Vandevoorde V, Haegeman G, Fiers W. Depletion of the mitochondrial electron transport abrogates the cytotoxic and gene-inductive effects of TNF. EMBO J 1993;12:3095–104.10.1002/j.1460-2075.1993.tb05978.xSearch in Google Scholar PubMed PubMed Central

46. Jiang F, Zhang Y, Dusting GJ. NADPH oxidase-mediated redox signaling: roles in cellular stress response, stress tolerance, and tissue repair. Pharmacol Rev 2011;63:218–42.10.1124/pr.110.002980Search in Google Scholar PubMed

47. Turrens JF, Boveris A. Generation of superoxide anion by the NADH dehydrogenase of bovine heart mitochondria. Biochem J 1980;191:421–7.10.1042/bj1910421Search in Google Scholar PubMed PubMed Central

48. Koga K, Taguchi A, Koshimizu S, Suwa Y, Yamada Y, Shirasaka N, et al. Reactive oxygen scavenging activity of matured whiskey and its active polyphenols. J Food Sci 2007;72:S212–7.10.1111/j.1750-3841.2007.00311.xSearch in Google Scholar PubMed

Received: 2017-7-27
Accepted: 2017-11-5
Published Online: 2017-12-21
Published in Print: 2018-3-28

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