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Effect of oral administration of methanolic root extract of Saussurea costus to rats after propylthiouracil-induced hypothyroid obesity

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Abstract

Hypothyroid obesity is associated with various metabolic abnormalities. This study aimed to assess the ameliorating property of Saussurea costus methanolic extract (SME) in hypothyroid obese rats via its oral administration for 30 consecutive days. Blood samples were collected for biochemical determinations; the liver and heart were removed for the determination of oxidative stress markers; and the thyroid gland was dissected out for histopathological examination. The total phenolic compounds, radical scavenging activity, and reducing power of the extract were also determined. The results showed that the extract possessed considerable values of phenolic compounds, radical scavenging activity, and reducing power. Also, hypothyroid obesity induced significant increases in serum insulin, glucose, and TSH levels concomitant with significant decreases in the levels of total T3, free T3, free T4, and total T4 hormones. The levels of hepatic and cardiac MDA and NO increased significantly while the values of GSH, GPx, and catalase decreased significantly in hypothyroid obese modeled rats. Moreover, hypothyroid obesity significantly increased serum ASAT, ALAT, CK-MB, and LDH activities but did not affect levels of urea and creatinine. In addition, serum cytokines TNFα, IL-1β, IL- 6, IL-4, and IL-10 levels increased significantly in hypothyroid obese rats compared to control group. Lipid profile markers also disturbed significantly in hypothyroid obese rats. Interestingly, both SME and the reference drugs (L-Thyroxine) succeeded to counteract the alterations in the values of the above parameters and improve the histological picture of thyroid gland but with different levels, where SME was more safe than L-Thyroxine. It could be concluded that the Saussurea costus extract is a promising natural source that could be used more safely than L-Thyroxine to prevent and reduce thyroid dysfunction associated with obesity and its complications, benefiting patients and health institutions.

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References

  • Abdel-Wahhab KG, Mourad HH, Mannaa FA, Morsy FA, Hassan LK, Taher RF (2019) Role of ashwagandha methanolic extract in the regulation of thyroid profile in hypothyroidism modeled rats. Mol Biol Rep 46:3637–3649

    Article  CAS  PubMed  Google Scholar 

  • Alkalby MAJ, Alzerjawi JSS (2013) Effect of propylthiouracil-induced hypothyroidism on reproductive efficiency of adult male rats. Bas j vet Res 12(2):113–121

  • Alnahdi HS (2017) Injury in metabolic gland induced by pyrethroid insecticide could be reduced by aqueous extract of Sassura lappa. International Journal of Pharmaceutical Research & Allied Sciences 6:86–97

    CAS  Google Scholar 

  • Baskol G, Atmaca H, Tanriverdi F, Baskol M, Kocer D, Bayram F (2007) Oxidative stress and enzymatic antioxidant status in patients with hypothyroidism before and after treatment. Exp Clin Endocrinol Diabetes 115:522–526

    Article  CAS  PubMed  Google Scholar 

  • Bétry C, Challan-Belval MA, Bernard A, Charrié A, Drai J, Laville M, Thivolet C, Disse E (2015) Increased TSH in obesity: evidence for a BMI-independent association with leptin. Diabetes Metab 41:248–251

    Article  CAS  PubMed  Google Scholar 

  • Bhanja S, Chainy GBN (2010) PTU-induced hypothyroidism modulates antioxidant defence status in the developing cerebellum. Neuroscience 28:251–262

    CAS  Google Scholar 

  • Bonetti PO, Lerman LO, Lerman A (2003) Endothelial dysfunction: a marker of atherosclerotic risk. Arterioscler Thromb Vasc Biol 23:168–175

    Article  CAS  PubMed  Google Scholar 

  • Carrion AF, Czul F, Arosemena LR, Selvaggi G, Garcia MT, Tekin A, Tzakis AG, Martin P, Ghanta RK (2010) Propylthiouracil-induced acute liver failure: role of liver transplantation. Int J Endocrinol 2010:1–5

    Article  Google Scholar 

  • Chakrabarti SK, Ghosh S, Banerjee S, Mukherjee S, Chowdhury S (2016) Oxidative stress in hypothyroid patients and the role of antioxidant supplementation. Indian J Endocrinol Metab 20:674–678

    Article  PubMed  PubMed Central  Google Scholar 

  • Chang KM, Choi SI, Kim GH (2012) Antioxidant activity of Saussurea lappa C.B. Clarke Roots Prev Nutr Food Sci 17:306–309

    Article  CAS  PubMed  Google Scholar 

  • Cho JY, Park JS, Yoo ES, Baik KU, Jung JH, Lee JS, Park MH (1998) Inhibitory effect of sesquiterpene lactones from Saussurea lappa on tumor necro-sis factor-alpha production in murine macrophage-like cells. Planta Med 64:594–597

    Article  CAS  PubMed  Google Scholar 

  • de Souza LL, Guedes EP, Teixeira PF, Moreira RO, Godoy-Matos AF, Vaisman M (2016) Serum TSH levels are associated with cardiovascular risk factors in overweight and obese adolescents. J Pediatr (rio j) 92:532–538

    Article  Google Scholar 

  • Didushko OM (2014) Risk factors for renal dysfunction in patients with hypothyroidism. Wiad Lek 67:184–186

    CAS  PubMed  Google Scholar 

  • Drury RA, Wallington EA (1980) Carleton’s histological technique. Oxford University Press, USA

    Google Scholar 

  • Eke KC, Turkmen YS, Temizel M, Ozpacaci T, Gunel P, Cakmak M, Ozbanazi YG (2013) Serum resistin and insulinlike growth factor-1 levels in patients with hypothyroidism and hyperthyroidism. J Thyroid Res 2013:1–7

    Google Scholar 

  • Eliza J, Daisy P, Ignacimuthu S, Duraipandiyan V (2009) Normo-glycemic and hypolipidemic effect of costunolide isolated from Costus speciosus (Koen ex. Retz.) Sm. in streptozotocin-induced diabetic rats. Chem Biol Interact 179:329–234

    Article  CAS  PubMed  Google Scholar 

  • Eshita P, Priya BD, Sudhakar G (2014) A novel link between leptin, TSH and obesity among hypothyroid patients. Int J Curr Sci 13:E98–E103

    Google Scholar 

  • Fox SI (2010) Human physiology. Mc Graw Hill, USA

    Google Scholar 

  • Franco R, Schoneveld OJ, Pappa A, Panayiotidis MI (2007) The central role of glutathione in the pathophysiology of human diseases. Arch Physiol Biochem 113:234–258

    Article  CAS  PubMed  Google Scholar 

  • Gajda SN, Kuryłowicz A, Żach M, Bednarczuk T, Wyleżoł M (2019) Diagnosis and treatment of thyroid disorders in obese patients - what do we know? Endokrynol Pol 70:271–276

    Article  PubMed  Google Scholar 

  • Garber JR, Cobin RH, Gharib H, Hennessey JV, Klein I, Mechanick JI, Pessah-Pollack R, Singer PA, Woeber KA (2012) Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Endocr Pract 18:988–1028

    Article  PubMed  Google Scholar 

  • García-Solís P, García OP, Hernández-Puga G, Sánchez-Tusie AA, Sáenz-Luna CE, Hernández-Montiel HL, Solis-S JC (2018) Thyroid hormones and obesity: a known but poorly understood relationship. Endokrynol Pol 69:292–303

    Article  PubMed  Google Scholar 

  • Gómez-Zamudio JH, Mendoza-Zubieta V, Ferreira-Hermosillo A, Molina-Ayala MA, Valladares-Sálgado A, Suárez-Sánchez F, Peralta-Romero JJ, Cruz M (2016) High Thyroid-stimulating hormone levels increase proinflammatory and cardiovascular markers in patiens with extreme obesity. Arch Med Res 47:476–482

    Article  CAS  PubMed  Google Scholar 

  • Gutteridge JM (1995) Lipid peroxidation and antioxidants as biomarkers of tissue damage. Clin Chem 41:1819–1828

    Article  CAS  PubMed  Google Scholar 

  • Hall JE, Kuo JJ, da Silva AA, de Paula RB, Liu J, Tallam L (2003) Obesity-associated hypertension and kidney disease. Curr Opin Nephrol Hypertens 12:195–200

    Article  CAS  PubMed  Google Scholar 

  • Hanh TTH, Cham PT, My NTT, Cuong NT, Dang NH, Quang TH, Huong TT, Cuong NX, Nam NH, Minh CV (2021) Sesquiterpenoids from Saussurea costus. Nat Prod Res 35(9):1399–1405

    Article  CAS  PubMed  Google Scholar 

  • Jain KS, Kathiravan MK, Somani RS, Shishoo CJ (2007) The biology and chemistry of hyperlipidemia. Bioorg Med Chem 15:4674–4699

    Article  CAS  PubMed  Google Scholar 

  • Jayaprakasha GKM, Tamil S, Sakariah KK (2003) Antibacterial and antioxidant activities of grape (Vitis vinifera) seed extracts. Food Res Int 36:117–122

    Article  CAS  Google Scholar 

  • Jialal I, Devaraj S (2003) Antioxidants and atherosclerosis: don’t throw out the baby with the bath water. Circulation 107:926–928

    Article  CAS  PubMed  Google Scholar 

  • Kaltenbach TEM, Graeter T, Oeztuerk S, Holzner D, Kratzer W, Wabitsch M, Denzer Denzer (2017) Thyroid dysfunction and hepatic steatosis in overweight children and adolescents. Pediatr Obes 12:67–74

    Article  PubMed  Google Scholar 

  • Kang H, Choi JD, Jung IG, Kim DW, Kim TB, Shin HK, Kim BT, Park CK, Yoo JY (1990) A case of methimazole-induced acute hepatic failure in a patient with chronic hepatitis B carrier. Korean J Intern Med 5:69–73

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Khalawi AA, Al-Robai AA, Khoja SM, Ali SS (2013) Can Nigella Sativa oil (NSO) reverse hypothyroid status induced by PTU in rat?. Biochemical and histological studies. Life Science Journal 10:802–811

    Google Scholar 

  • Kılıçaslan B, Tigen MK, Tekin AS, Ciftçi H (2013) Cardiac changes with subclinical hypothyroidism in obese women. Arch Turk Soc Cardiol 41:471–477

    Article  Google Scholar 

  • Kim B (2008) Thyroid hormone as a determinant of energy expenditure and the basal metabolic rate. Thyroid 18:141–144

    Article  CAS  PubMed  Google Scholar 

  • Kuznetsova LA, Derkach KV, Sharova TS, Bondareva VM, Shpakov AO (2015) Effect of long-term L-thyroxine treatment on the activity of NO-synthases in tissues of rats with obesity induced by high-fat diet. J Evol Biochem Physiol 51:485–494

    Article  CAS  Google Scholar 

  • Lee BK, Park SJ, Nam SY, Kang S, Hwang J, Lee SJ, Im DS (2018) Anti-allergic effects of sesquiterpene lactones from Saussurea costus (Falc.) Lipsch. determined using in vivo and in vitro experiments. J Ethnopharmacol 213:256–261

    Article  CAS  PubMed  Google Scholar 

  • Lorenzi M (2007) The polyol pathway as a mechanism for diabetic retinopathy: attractive, elusive, and resilient. Exp Diabetes Res 2007:1–10

    Article  CAS  Google Scholar 

  • Mannisto T, Mendola P, Grewal J, Xie Y, Chen Z, Laughon SK (2013) Thyroid diseases and adverse pregnancy outcomes in a contemporary US cohort. J Clin Endocrinol Metab 98:2725–2733

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mujammami M (2020) Clinical significance of Saussurea Costus in thyroid treatment. Saudi Med J 41(10):1047–1053

    Article  PubMed  PubMed Central  Google Scholar 

  • Murray CJ, Lopez AD (1997) Mortality by cause for eight regions of the world: global burden of disease study. Lancet 349:1269–1276

    Article  CAS  PubMed  Google Scholar 

  • Nogala-Kalucka M, Korczak J, Dratwia M, Lampart-Szczapa E, Siger A, Buchowski M (2005) Changes in antioxidant activity and free radical scavenging potential of rosemary extract and tocopherols in isolated rapeseed oil triacylglycerols during accelerated tests. Food Chem 93:227–235

    Article  CAS  Google Scholar 

  • Novelli ELB, Diniz YS, Galhardi CM, Ebaid GMX, Rodrigues HG, Mani F et al (2007) Anthropometrical parameters and markers of obesity in rats. Lab Anim 41:111–119

    Article  CAS  PubMed  Google Scholar 

  • Pandey MM, Rastogi S, Rawat AK (2007) Saussurea costus: botanical, chemical and pharmacological review of an ayurvedic medicinal plant. J Ethnopharmacol 110:379–390

    Article  CAS  PubMed  Google Scholar 

  • Pandey MM, Govindarajan R, Rawat AKS, Pushpangadan P (2005) Free radical scavenging potential of Saussarea Costus. Acta Pharm 55:297–304

    CAS  PubMed  Google Scholar 

  • Pant S, Deshmukh A, Gurumurthy GS, Pothineni NV, Watts TE, Romeo F, Mehta JL (2014) Inflammation and atherosclerosis—revisited. J Cardiovasc Pharmacol Ther 19:170–178

    Article  CAS  PubMed  Google Scholar 

  • Piché ME, Tchernof A, Després JP (2020) Obesity phenotypes, diabetes, and cardiovascular diseases. Circ Res 126:1477–1500

    Article  CAS  PubMed  Google Scholar 

  • Poncin S, Van Eeckoudt S, Humblet K, Colin IM, Gérard AC (2010) Oxidative stress: a required condition for thyroid cell proliferation. Am J Pathol 176:1355–1363

    Article  PubMed  PubMed Central  Google Scholar 

  • Preus M, Bhargava AS, Khater AE, Gunzel P (1988) Diagnostic value of serum creatine kinase and lactate dehydrogenase isoenzyme determinations for monitoring early cardiac damage in rats. Toxicol Lett 42:225–233

    Article  CAS  PubMed  Google Scholar 

  • Pucci E, Chiovato L, Pinchera A (2000) Thyroid and lipid metabolism. Int J Obes Relat Metab Disord 24:S109-112

    Article  CAS  PubMed  Google Scholar 

  • Revathy J, Abdullah SS, Kumar PS (2014) Antidiabetic effect of Costus speciosus rhizome extract in alloxan induced albino rats. J Chem Biochem 2:13–22

    Google Scholar 

  • Rivkees SA, Mattison DR (2009) Ending propylthiouracil-induced liver failure in children. N Engl J Med 360:1574–1575

    Article  CAS  PubMed  Google Scholar 

  • Roberts CG, Ladenson PW (2004) Hypothyroidism Lancet 363:793–803

    Article  CAS  PubMed  Google Scholar 

  • Rosamond WD, Chambless LE, Folsom AR, Cooper LS, Conwill DE, Clegg L, Wang CH, Heiss G (1998) Trends in the incidence of myocardial infarction and in mortality due to coronary heart disease, 1987 to 1994. N Engl J Med 339:861–867

    Article  CAS  PubMed  Google Scholar 

  • Ruiz-Larnea MB, Leal AM, Liza M, Lacort M, de Groot H (1994) Antioxidant effects of estradiol and 2 hydroxyestradiol on iron induced lipid peroxidation of rat liver microsome. Steriod 59:383–388

    Article  Google Scholar 

  • Sahoo D, Roy A, Bhanja S, Chainy G (2008) Hypothyroidism impairs antioxidant defense system and testicular physiology during development and maturation. Gen Comp Endocrinol 156:63–70

    Article  CAS  PubMed  Google Scholar 

  • Santini F, Marzullo P, Rotondi M, Ceccarini G, Pagano L, Ippolito S, Chiovato L, Biondi B (2014) Mechanisms in endocrinology. The crosstalk between thyroid gland and adipose tissue: signal integration in health and disease. Eur J Endocrinol 171:137–152

    Article  CAS  Google Scholar 

  • Sanyal D, Raychaudhuri M (2016) Hypothyroidism and obesity: an intriguing link. Indian J Endocrinol Metab 20:554–557

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sarandol E, Tas S, Dirican M, Serdar Z (2005) Oxidative stress and serum paraoxonase activity in experimental hypothyroidism: effect of vitamin E supplementation. Cell Biochem Funct 23:1–8

    Article  PubMed  Google Scholar 

  • Sert A, Pirgon O, Aypar E, Yilmaz H, Odabas D (2013) Subclinical hypothyroidism as a risk factor for the development of cardiovascular disease in obese adolescents with nonalcoholic fatty liver disease. Pediatr Cardiol 34:1166–1174

    Article  PubMed  Google Scholar 

  • Sethiya NK, Trivedi A, Mishra S (2014) The total antioxidant content and radical scavenging investigation on 17 phytochemical from dietary plant sources used globally as functional food. Biomed Prev Nut 4:439–444

    Article  Google Scholar 

  • Singh R, Chahal KK (2018) Phytochemical analysis and in vitro antioxidant capacity of different solvent extracts of Saussurea lappa L. roots. J Pharmacogn Phytother 7:427–432

    Google Scholar 

  • Torun N, Kulaksizoglu S, Kulaksizoglu M, Pamuk BO, Isbilen E, Tutuncu NB (2009) Serum total antioxidant status and lipid peroxidation marker malondialdehyde levels in overt and subclinical hypothyroidism. Clin Endocrinol 70:469–474

    Article  CAS  Google Scholar 

  • Townsend D, Tew K (2003) The role of glutathione-S-transferase in anti-cancer drug resistance. Oncogene 22:7369–7375

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Umezu M, Kagabu S, Jiang J, Sato E (1998) Evaluation and characterization of congenital hypothyroidism in rdw dwarf rats. Lab Anim Sci 48:496–501

    CAS  PubMed  Google Scholar 

  • Wang Y, Beydoun MA, Liang L, Caballero B, Kumanyika SK (2008) Will all Americans become overweight or obese?. Estimating the progression and cost of the US obesity epidemic. Obesity 16:2323–2330

    Article  PubMed  Google Scholar 

  • Wilding JPH (2020) Endocrine testing in obesity. Eur J Endocrinol 182(4):13–15

    Article  Google Scholar 

  • Williams KV, Nayak S, Becker D, Reyes J, Burmeister LA (1997) Fifty years of experience with propylthiouracil-associated hepatotoxicity: what have we learned?. J Clin Endocrinol Metab 82:1727–1733

    CAS  PubMed  Google Scholar 

  • Yaturu S, Prado S, Grimes SR (2004) Changes in adipocyte hormones leptin, resistin, and adiponectin in thyroid dysfunction. J Cell Biochem 93:491–496

    Article  CAS  PubMed  Google Scholar 

  • Zhang Y, Zitsman JL, Hou J, Fennoy I, Guo K, Feinberg J, Leibel RL (2014) Fat cell size and adipokine expression in relation to gender, depot, and metabolic risk factors in morbidly obese adolescents. Obesity (silver Spring) 22:691–697

    Article  CAS  Google Scholar 

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Correspondence to Khaled G. Abdel-Wahhab.

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All animals received human care in accordance with the standard institutional criteria for the care and use of experimental animals according to the Ethical Committee of the National Research Center (FWA 00014747).

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Abdel-Wahhab, K.G., Mannaa, F.A., El-Sahra, D.G. et al. Effect of oral administration of methanolic root extract of Saussurea costus to rats after propylthiouracil-induced hypothyroid obesity. Comp Clin Pathol 31, 377–390 (2022). https://doi.org/10.1007/s00580-022-03337-1

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