Generic placeholder image

Cardiovascular & Hematological Agents in Medicinal Chemistry


ISSN (Print): 1871-5257
ISSN (Online): 1875-6182

Research Article

Antiobesity Effect of Biochanin-A: Effect on Trace Element Metabolism in High Fat Diet-Induced Obesity in Rats

Author(s): Jansy Isabella Rani Antony Rathinasamy, Veera Venkata Sathibabu Uddandrao , Nivedha Raveendran and Vadivukkarasi Sasikumar*

Volume 18, Issue 1, 2020

Page: [21 - 30] Pages: 10

DOI: 10.2174/1871524920666200207101920

Price: $65


Background: Imbalanced diets have contributed to the increased prevalence of obesity and other metabolic disorders in the modern world including trace element metabolism. However, the underlying mechanisms are not fully understood.

Aim and Objectives: The present study investigated the effects of Biochanin A (BCA) on the changes in element metabolism induced by HFD-induced obese rats.

Methods: BCA was administered orally for 30 days to experimental obese rats. Changes in body weight, glucose, insulin resistance and lipid profiles of plasma, as well as the level of trace elements (Fe, Zn, Mg and Cu) in various tissues (liver, kidney, heart and pancreas) and hepsidine and heme oxygenase, were observed in experimental rats.

Results: The administration of BCA elicited a significant (p<0.05) reduction in, glucose, insulin, ferritin, total cholesterol, phospholipids, free fatty acids, VLDL-C, LDL-C, triglycerides and hepsidin. Significant alterations were observed in trace elements level, HDL-C, transferrin, bilirubin and HO - 1 level.

Conclusion: These findings suggested that HFD results in derangement of trace elements in the tissues of rats fed with HFD. BCA may alleviate the derangement of HFD induced trace elements metabolism by modulating hyperglycemic and insulin resistance status and altering hepcidin and HO-1.

Keywords: Biochanin A, insulin resistance, natural products, obesity, trace elements, high fat diet.

Graphical Abstract
Meriga, B.; Parim, B.; Chunduri, V.R.; Naik, R.R.; Nemani, H.; Suresh, P.; Ganapathy, S.; Sathibabu Uddandrao, V.V. Antiobesity potential of Piperonal: promising modulation of body composition, lipid profiles and obesogenic marker expression in HFD-induced obese rats. Nutr. Metab. (Lond.), 2017, 14, 72.
[] [PMID: 29176994]
Brahma Naidu, P.; Uddandrao, V.V.; Ravindar Naik, R.; Suresh, P.; Meriga, B.; Begum, M.S.; Pandiyan, R.; Saravanan, G. Ameliorative potential of gingerol: Promising modulation of inflammatory factors and lipid marker enzymes expressions in HFD induced obesity in rats. Mol. Cell. Endocrinol., 2016, 419, 139-147.
[] [PMID: 26493465]
Chung, J.; Kim, M.S.; Han, S.N. Diet-induced obesity leads to decreased hepatic iron storage in mice. Nutr. Res., 2011, 31(12), 915-921.
[] [PMID: 22153517]
Yang, G.; Kong, L.; Zhao, W.; Wan, X.; Zhai, Y.; Chen, L.C.; Koplan, J.P. Emergence of chronic non-communicable diseases in China. Lancet, 2008, 372(9650), 1697-1705.
[] [PMID: 18930526]
Tussing-Humphreys, L.M.; Nemeth, E.; Fantuzzi, G.; Freels, S.; Guzman, G.; Holterman, A.X.; Braunschweig, C. Elevated systemic hepcidin and iron depletion in obese premenopausal females. Obesity (Silver Spring), 2010, 18(7), 1449-1456.
[] [PMID: 19816411]
Hessah, M.A.; Kamal, A.A. Alteration of serum and hepatic trace element level in non-alcoholic fatty liver disease-induced by high-fat sucrose diet. Asi. J. Sci. Res., 2019, 12, 323-332.
Colagiuri, S.; Lee, C.M.; Colagiuri, R.; Magliano, D.; Shaw, J.E.; Zimmet, P.Z.; Caterson, I.D. The cost of overweight and obesity in Australia. Med. J. Aust., 2010, 192(5), 260-264.
[] [PMID: 20201759]
Rameshreddy, P.; Uddandrao, V.V.S.; Brahmanaidu, P.; Vadivukkarasi, S.; Ravindarnaik, R.; Suresh, P.; Swapna, K.; Kalaivani, A.; Parvathi, P.; Tamilmani, P.; Saravanan, G. Obesity-alleviating potential of asiatic acid and its effects on ACC1, UCP2, and CPT1 mRNA expression in high fat diet-induced obese Sprague-Dawley rats. Mol. Cell. Biochem., 2018, 442(1-2), 143-154.
[] [PMID: 28993954]
Uddandrao, V.V.S.; Rameshreddy, P.; Brahmanaidu, P.; Ponnusamy, P.; Balakrishnan, S.; Ramavat, R.N.; Swapna, K.; Pothani, S.; Nemani, H.; Meriga, B.; Vadivukkarasi, S.; P R, N.; Ganapathy, S. Antiobesity efficacy of asiatic acid: down-regulation of adipogenic and inflammatory processes in high fat diet induced obese rats. Arch. Physiol. Biochem., 2019, 1-10.
[] [PMID: 30739501]
Kalaivani,, A.; Uddandrao, V.V.S.; Parim, B.; Ganapathy, S.; Sushma, N.P.R; Kancharla, C.; Rameshreddy, P.; Swapna, K.; Sasikumar, V. Reversal of high fat diet-induced obesity through modulating lipid metabolic enzymes and inflammatory markers expressions in rats. Arch. Physiol. Biochem., 2019, 125(3), 228-234.
[] [PMID: 29553847]
Kalaivani, A.; Uddandrao, V.V.S.; Brahmanaidu, P.; Ganapathy, S.; Nivedha, P.R.; Tamilmani, P.; Swapna, K.; Vadivukkarasi, S. Anti obese potential of Cucurbita maxima seeds oil: effect on lipid profile and histoarchitecture in high fat diet induced obese rats. Nat. Prod. Res., 2018, 32(24), 2950-2953.
[] [PMID: 29047298]
Saviranta, N.M.M.; Anttonen, M.J.; von Wright, A.; Karjalainen, R.O. Red clover (Trifoliumpratense L.) isoflavones: Determination of concentrations by plant stage, flower colour, plant part and cultivar. J. Sci. Food Agric., 2008, 88, 125-132.
Azizi, R.; Goodarzi, M.T.; Salemi, Z. Effect of biochanin a on serum visfatin level of streptozocin-induced diabetic rats. Iran. Red Crescent Med. J., 2014, 16(9), e15424-e15428.
[] [PMID: 25593725]
Tan, J.W.; Kim, M.K. Neuroprotective effects of Biochanin A against β-amyloid-induced neurotoxicity in PC12 cells via a mitochondrial-dependent apoptosis pathway. Molecules, 2016, 21(5), 548-561.
[] [PMID: 27120593]
Saravanan, G.; Ponmurugan, P. Ameliorative potential of S-allylcysteine: effect on lipid profile and changes in tissue fatty acid composition in experimental diabetes. Exp. Toxicol. Pathol., 2012, 64(6), 639-644.
[] [PMID: 21216577]
Rattanachongkiat, S.; Millward, G.E.; Foulkes, M.E. Determination of arsenic species in fish, crustacean and sediment samples from Thailand using high performance liquid chromatography (HPLC) coupled with inductively coupled plasma mass spectrometry (ICP-MS). J. Environ. Monit., 2004, 6(4), 254-261.
[] [PMID: 15054532]
De Blas Bravo, I.; Sanz Castro, R.; López Riquelme, N.; Tormo Díaz, C.; Apraiz Goyenaga, D. Optimization of the trace element determination by ICP-MS in human blood serum. J. Trace Elem. Med. Biol., 2007, 21(Suppl. 1), 14-17.
[] [PMID: 18039488]
Bradford, M.M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem., 1976, 72, 248-254.
[] [PMID: 942051]
Abraham, N.G.; Lavrovsky, Y.; Schwartzman, M.L.; Stoltz, R.A.; Levere, R.D.; Gerritsen, M.E.; Shibahara, S.; Kappas, A. Transfection of the human heme oxygenase gene into rabbit coronary microvessel endothelial cells: protective effect against heme and hemoglobin toxicity. Proc. Natl. Acad. Sci. USA, 1995, 92(15), 6798-6802.
[] [PMID: 7624322]
Ansari, J.A.; Uma, B.; Pillai, K.K. Effect of rosuvastin on obese induced cardiac oxidative stress in rats. Indian J. Exp. Biol., 2012, 50, 216-222.
[PMID: 22439437]
Kim, K.J.; Lee, M.S.; Jo, K.; Hwang, J.K. Piperidine alkaloids from Piper retrofractum Vahl. protect against high-fat diet-induced obesity by regulating lipid metabolism and activating AMP-activated protein kinase. Biochem. Biophys. Res. Commun., 2011, 411(1), 219-225.
[] [PMID: 21741367]
Shah, A.; Mehta, N.; Reilly, M.P. Adipose inflammation, insulin resistance, and cardiovascular disease. J. Parenter. Enteral Nutr., 2008, 32(6), 638-644.
[] [PMID: 18974244]
Sathibabu Uddandrao, V.V.; Brahmanaidu, P.; Ravindarnaik, R.; Suresh, P.; Vadivukkarasi, S.; Ganapathy, S. Restorative potentiality of S-allylcysteine against diabetic nephropathy through attenuation of oxidative stress and inflammation in streptozotocin-nicotinamide-induced diabetic rats. Eur. J. Nutr., 2019, 58(6), 2425-2437.
[] [PMID: 30062492]
Saltiel, A.R.; Kahn, C.R. Insulin signalling and the regulation of glucose and lipid metabolism. Nature, 2001, 414(6865), 799-806.
[] [PMID: 11742412]
Lichtenstein, A.H.; Schwab, U.S. Relationship of dietary fat to glucose metabolism. Atherosclerosis, 2000, 150(2), 227-243.
[] [PMID: 10856515]
Riccardi, G.; Giacco, R.; Rivellese, A.A. Dietary fat, insulin sensitivity and the metabolic syndrome. Clin. Nutr., 2004, 23(4), 447-456.
[] [PMID: 15297079]
Kumar, S.; Sharma, S.; Vasudeva, N. Screening of antidiabetic and antihyperlipidemic potential of oil from Piper longum and piperine with their possible mechanism. Expert Opin. Pharmacother., 2013, 14(13), 1723-1736.
[] [PMID: 23875561]
Park, Y.; Storkson, J.M.; Liu, W.; Albright, K.J.; Cook, M.E.; Pariza, M.W. Structure-activity relationship of conjugated linoleic acid and its cognates in inhibiting heparin-releasable lipoprotein lipase and glycerol release from fully differentiated 3T3-L1 adipocytes. J. Nutr. Biochem., 2004, 15(9), 561-568.
[] [PMID: 15350989]
Lavie, C.J.; Milani, R.V.; O’Keefe, J.H. Dyslipidemia intervention in metabolic syndrome: emphasis on improving lipids and clinical event reduction. Am. J. Med. Sci., 2011, 341(5), 388-393.
[] [PMID: 21519201]
Maneesai, P.; Scholfield, C.N.; Chootip, K. Piperine is anti-hyperlipidemic and improves endothelium-dependent vasorelaxation in rats on a high cholesterol diet. J. Physiol. Biomedsci., 2012, 25, 27-30.
Heeney, M.M.; Andrews, N.C. Iron homeostasis and inherited iron overload disorders: An overview. Hematol. Oncol. Clin. North Am., 2004, 18(6), 1379-1403. ix.
[] [PMID: 15511621]
Seltzer, C.C.; Mayer, J. Serum iron and iron-binding capacity in adolescents. II. Comparison of obese and nonobese subjects. Am. J. Clin. Nutr., 1963, 13, 354-361.
[] [PMID: 14101396]
Iwasaki, T.; Nakajima, A.; Yoneda, M.; Yamada, Y.; Mukasa, K.; Fujita, K.; Fujisawa, N.; Wada, K.; Terauchi, Y. Serum ferritin is associated with visceral fat area and subcutaneous fat area. Diabetes Care, 2005, 28(10), 2486-2491.
[] [PMID: 16186284]
Cepeda-Lopez, A.C.; Aeberli, I.; Zimmermann, M.B. Does obesity increase risk for iron deficiency? A review of the literature and the potential mechanisms. Int. J. Vitam. Nutr. Res., 2010, 80(4-5), 263-270.
[] [PMID: 21462109]
Tajima, S.; Ikeda, Y.; Sawada, K.; Yamano, N.; Horinouchi, Y.; Kihira, Y.; Ishizawa, K.; Izawa-Ishizawa, Y.; Kawazoe, K.; Tomita, S.; Minakuchi, K.; Tsuchiya, K.; Tamaki, T. Iron reduction by deferoxamine leads to amelioration of adiposity via the regulation of oxidative stress and inflammation in obese and type 2 diabetes KKAy mice. Am. J. Physiol. Endocrinol. Metab., 2012, 302(1), E77-E86.
[] [PMID: 21917632]
Fargnoli, J.L.; Fung, T.T.; Olenczuk, D.M.; Chamberland, J.P.; Hu, F.B.; Mantzoros, C.S. Adherence to healthy eating patterns is associated with higher circulating total and high-molecular-weight adiponectin and lower resistin concentrations in women from the Nurses’ Health Study. Am. J. Clin. Nutr., 2008, 88(5), 1213-1224.
[PMID: 18996855]
Mojiminiyi, O.A.; Marouf, R.; Abdella, N.A. Body iron stores in relation to the metabolic syndrome, glycemic control and complications in female patients with type 2 diabetes. Nutr. Metab. Cardiovasc. Dis., 2008, 18(8), 559-566.
[] [PMID: 18063352]
Williams, M.J.; Poulton, R.; Williams, S. Relationship of serum ferritin with cardiovascular risk factors and inflammation in young men and women. Atherosclerosis, 2002, 165(1), 179-184.
[] [PMID: 12208485]
Furukawa, S.; Fujita, T.; Shimabukuro, M.; Iwaki, M.; Yamada, Y.; Nakajima, Y.; Nakayama, O.; Makishima, M.; Matsuda, M.; Shimomura, I. Increased oxidative stress in obesity and its impact on metabolic syndrome. J. Clin. Invest., 2004, 114(12), 1752-1761.
[] [PMID: 15599400]
Ferrannini, E. Insulin resistance, iron, and the liver. Lancet, 2000, 355(9222), 2181-2182.
[] [PMID: 10881887]
Gabay, C.; Kushner, I. Acute-phase proteins and other systemic responses to inflammation. N. Engl. J. Med., 1999, 340(6), 448-454.
[] [PMID: 9971870]
Abo Zeid, A.A.; Mervat, H. Potential factors contributing to poor iron status with obesity. Alexandria J. Med., 2014, 50, 45-48.
Andrews, N.C.; Levy, J.E. Iron is hot: an update on the pathophysiology of hemochromatosis. Blood, 1998, 92(6), 1845-1851.
[] [PMID: 9731040]
Marx, J.J.; Gebbink, J.A.; Nishisato, T.; Aisen, P. Molecular aspects of the binding of absorbed iron to transferrin. Br. J. Haematol., 1982, 52(1), 105-110.
[] [PMID: 7115619]
Ritchie, R.F.; Palomaki, G.E.; Neveux, L.M.; Navolotskaia, O.; Ledue, T.B.; Craig, W.Y. Reference distributions for the negative acute-phase serum proteins, albumin, transferrin and transthyretin: a practical, simple and clinically relevant approach in a large cohort. J. Clin. Lab. Anal., 1999, 13(6), 273-279.
[<273:aid-jcla4>;2-x] [PMID: 10633294]
Hegde, M.L.; Shanmugavelu, P.; Vengamma, B.; Rao, T.S.; Menon, R.B.; Rao, R.V.; Rao, K.S. Serum trace element levels and the complexity of inter-element relations in patients with Parkinson’s disease. J. Trace Elem. Med. Biol., 2004, 18(2), 163-171.
[] [PMID: 15646263]
Sarwar, M.S.; Ahmed, S.; Ullah, M.S.; Kabir, H.; Rahman, G.K.; Hasnat, A.; Islam, M.S. Comparative study of serum zinc, copper, manganese, and iron in preeclamptic pregnant women. Biol. Trace Elem. Res., 2013, 154(1), 14-20.
[] [PMID: 23749478]
Suliburska, J.; Bogdanski, P.; Krejpcio, Z.; Pupek-Musialik, D.; Jablecka, A. The effects of L-arginine, alone and combined with vitamin C, on mineral status in relation to its antidiabetic, anti-inflammatory, and antioxidant properties in male rats on a high-fat diet. Biol. Trace Elem. Res., 2014, 157(1), 67-74.
[] [PMID: 24293384]
Omar, S.; Abdennebi, M.; Ben Mami, F.; Ghanem, A.; Azzabi, S.; Hedhili, A.; Zouari, B.; Achour, A.; Guemira, F. [Serum copper levels in obesity: a study of 32 cases]. Tunis. Med., 2001, 79(6-7), 370-373.
[PMID: 11771433]
Clouet, P.; Henninger, C.; Bézard, J. Study of some factors controlling fatty acid oxidation in liver mitochondria of obese Zucker rats. Biochem. J., 1986, 239(1), 103-108.
[] [PMID: 3800970]
Saradesai, V.M. Introduction to clinical nutrition, In: Inorganic elements (minerals), 1st Ed; Marcel Dekker, Inc.: NY, USA, 1998, pp. 98-100.
Konukoglu, D.; Turhan, M.S.; Ercan, M.; Serin, O. Relationship between plasma leptin and zinc levels and the effect of insulin and oxidative stress on leptin levels in obese diabetic patients. J. Nutr. Biochem., 2004, 15(12), 757-760.
[] [PMID: 15607649]
Di Martino, G.; Matera, M.G.; De Martino, B.; Vacca, C.; Di Martino, S.; Rossi, F. Relationship between zinc and obesity. J. Med., 1993, 24(2-3), 177-183.
[PMID: 8409780]
Muhammad, S.; Mushtaq, A.; Khawaja, M.; Sajjad, H. Beneficial effects of magnesium supplementation in diabetes mellitus. Pak. J. Med. Res., 2002, 41, 150-155.
Chetan, P.; Hans, R. Magnesium deficiency and diabetes mellitus. Curr. Sci., 2002, 83, 1456-1463.
Paolisso, G.; Sgambato, S.; Pizza, G.; Passariello, N.; Varricchio, M.; D’Onofrio, F. Improved insulin response and action by chronic magnesium administration in aged NIDDM subjects. Diabetes Care, 1989, 12(4), 265-269.
[] [PMID: 2651054]
Ganz, T. Hepcidin, a key regulator of iron metabolism and mediator of anemia of inflammation. Blood, 2003, 102(3), 783-788.
[] [PMID: 12663437]
Dao, M.C.; Meydani, S.N. Iron biology, immunology, aging, and obesity: four fields connected by the small peptide hormone hepcidin. Adv. Nutr., 2013, 4(6), 602-617.
[] [PMID: 24228190]
del Giudice, E.M.; Santoro, N.; Amato, A.; Brienza, C.; Calabrò, P.; Wiegerinck, E.T.; Cirillo, G.; Tartaglione, N.; Grandone, A.; Swinkels, D.W.; Perrone, L. Hepcidin in obese children as a potential mediator of the association between obesity and iron deficiency. J. Clin. Endocrinol. Metab., 2009, 94(12), 5102-5107.
[] [PMID: 19850683]
Yanoff, L.B.; Menzie, C.M.; Denkinger, B.; Sebring, N.G.; McHugh, T.; Remaley, A.T.; Yanovski, J.A. Inflammation and iron deficiency in the hypoferremia of obesity. Int. J. Obes., 2007, 31(9), 1412-1419.
[] [PMID: 17438557]
Nemeth, E.; Tuttle, M.S.; Powelson, J.; Vaughn, M.B.; Donovan, A.; Ward, D.M.; Ganz, T.; Kaplan, J. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science, 2004, 306(5704), 2090-2093.
[] [PMID: 15514116]
Bekri, S.; Gual, P.; Anty, R.; Luciani, N.; Dahman, M.; Ramesh, B.; Iannelli, A.; Staccini-Myx, A.; Casanova, D.; Ben Amor, I.; Saint-Paul, M.C.; Huet, P.M.; Sadoul, J.L.; Gugenheim, J.; Srai, S.K.; Tran, A.; Le Marchand-Brustel, Y. Increased adipose tissue expression of hepcidin in severe obesity is independent from diabetes and NASH. Gastroenterology, 2006, 131(3), 788-796.
[] [PMID: 16952548]
Chung, B.; Matak, P.; McKie, A.T.; Sharp, P. Leptin increases the expression of the iron regulatory hormone hepcidin in HuH7 human hepatoma cells. J. Nutr., 2007, 137(11), 2366-2370.
[] [PMID: 17951471]
Bang, J.S.; Oh, D.H.; Choi, H.M.; Sur, B.J.; Lim, S.J.; Kim, J.Y.; Yang, H.I.; Yoo, M.C.; Hahm, D.H.; Kim, K.S. Anti-inflammatory and antiarthritic effects of piperine in human interleukin 1β-stimulated fibroblast-like synoviocytes and in rat arthritis models. Arthritis Res. Ther., 2009, 11(2), R49.
[] [PMID: 19327174]
Wu, Y.; Li, M.; Xu, M.; Bi, Y.; Li, X.; Chen, Y.; Ning, G.; Wang, W. Low serum total bilirubin concentrations are associated with increased prevalence of metabolic syndrome in Chinese. J. Diabetes, 2011, 3(3), 217-224.
[] [PMID: 21631904]
Huang, J.Y.; Chiang, M.T.; Yet, S.F.; Chau, L.Y. Myeloid heme oxygenase-1 haploinsufficiency reduces high fat diet-induced insulin resistance by affecting adipose macrophage infiltration in mice. PLoS One, 2012, 7(6); e38626
[] [PMID: 22761690]
Kim, D.H.; Burgess, A.P.; Li, M.; Tsenovoy, P.L.; Addabbo, F.; McClung, J.A.; Puri, N.; Abraham, N.G. Heme oxygenase-mediated increases in adiponectin decrease fat content and inflammatory cytokines tumor necrosis factor-alpha and interleukin-6 in Zucker rats and reduce adipogenesis in human mesenchymal stem cells. J. Pharmacol. Exp. Ther., 2008, 325(3), 833-840.
[] [PMID: 18334666]
Cao, J.; Peterson, S.J.; Sodhi, K.; Vanella, L.; Barbagallo, I.; Rodella, L.F.; Schwartzman, M.L.; Abraham, N.G.; Kappas, A. Heme oxygenase gene targeting to adipocytes attenuates adiposity and vascular dysfunction in mice fed a high-fat diet. Hypertension, 2012, 60(2), 467-475.
[] [PMID: 22753217]
Kang, K.; Reilly, S.M.; Karabacak, V.; Gangl, M.R.; Fitzgerald, K.; Hatano, B.; Lee, C.H. Adipocyte-derived Th2 cytokines and myeloid PPARdelta regulate macrophage polarization and insulin sensitivity. Cell Metab., 2008, 7(6), 485-495.
[] [PMID: 18522830]

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy