Generic placeholder image

Endocrine, Metabolic & Immune Disorders - Drug Targets

Author(s): Daniel E. Uti, Item J. Atangwho*, Eyong U. Eyong, Grace U. Umoru, Godwin E. Egbung, Solomon O. Rotimi and Victor U. Nna

DOI: 10.2174/1871530319666190724114729

DownloadDownload PDF Flyer Cite As
African Walnuts (Tetracarpidium conophorum) Modulate Hepatic Lipid Accumulation in Obesity via Reciprocal Actions on HMG-CoA Reductase and Paraoxonase

Page: [365 - 379] Pages: 15

  • * (Excluding Mailing and Handling)

Explore Articles
About Journal
For Authors
For Editors
For Reviewers

Abstract

Background: Obesity is characterized by increased body fat and involves an imbalance between the synthesis and degradation of lipids.

Objective: The study aimed to investigate the effect of African walnuts (Tetracarpidium conophorum) on lipids storage and the regulatory enzymes of hepatic lipid metabolism in obese rats.

Methods: Nuts were extracted in ethanol (WE) and further separated to obtain the ethyl-acetate fraction (ET) and the residue (RES). These were administered orally to 3 groups of monosodium glutamate- obese rats (n = 6), respectively, for 6 weeks. Other groups in the study were: normal (NC), obese control (OC) and standard control (SC) which received orlistat. Hepatic total lipids, total phospholipids, triacylglycerol (TG), total cholesterol (TCHOL), 3-hydroxyl-3-methylglutaryl-CoA (HMG-CoA) reductase and paraoxonase were studied.

Results: Total lipids, TG and TCHOL which increased in OC compared to NC group, decreased. HMG-CoA reductase activity decreased in the 3 study groups relative to OC. Paraoxonase activity which decreased in OC was up-regulated, while the magnitude of hepatic cholesterol decreased from 94.32 % in OC to 52.19, 65.43 and 47.04 % with WE, ET and RES, respectively. Flavonoids, alkaloids, glycosides, tannins and saponins were detected in the nut. GC-MS analysis revealed 16, 18 and 10 volatile components in WE, ET and RES, respectively. Unsaturated fatty acids (linolenic acids: 33.33, 47.95 and 50.93 %, and α-linolenic acids: 25, 19.66 and 26.63 %) in WE, ET and RES, respectively, are the most abundant, and likely to be responsible for the observed activity.

Conclusion: African walnuts can prevent hepatic lipid accumulation through reciprocal actions on HMG-CoA reductase and paraoxonase in obesity.

Keywords: Tetracarpidium conophorum nuts, Obesity, Hepatic lipids, HMG-CoA reductase, Paraoxonase, reciprocal actions.

Graphical Abstract

[1]
Hernández Bautista, R.J.; Mahmoud, A.M.; Königsberg, M.; López Díaz Guerrero, N.E. Obesity: Pathophysiology, monosodium glutamate-induced model and anti-obesity medicinal plants. Biomed. Pharmacother., 2019, 111, 503-516.
[http://dx.doi.org/10.1016/j.biopha.2018.12.108] [PMID: 30597304]
[2]
Sikaris, K.A. The clinical biochemistry of obesity. Clin. Biochem. Rev., 2004, 25(3), 165-181.
[PMID: 18458706]
[3]
Fink, A.; Rüfer, C.E.; Le Grandois, J.; Roth, A.; Aoude-Werner, D.; Marchioni, E.; Bub, A.; Barth, S.W. Dietary walnut oil modulates liver steatosis in the obese Zucker rat. Eur. J. Nutr., 2014, 53(2), 645-660.
[http://dx.doi.org/10.1007/s00394-013-0573-z] [PMID: 23942585]
[4]
Marseglia, L.; Manti, S.; D’Angelo, G.; Nicotera, A.; Parisi, E.; Di Rosa, G.; Gitto, E.; Arrigo, T. Oxidative stress in obesity: a critical component in human diseases. Int. J. Mol. Sci., 2014, 16(1), 378-400.
[http://dx.doi.org/10.3390/ijms16010378] [PMID: 25548896]
[5]
Nguyen, P.; Leray, V.; Diez, M.; Serisier, S.; Le Bloc’h, J.; Siliart, B.; Dumon, H. Liver lipid metabolism. J. Anim. Physiol. Anim. Nutr. (Berl.), 2008, 92(3), 272-283.
[http://dx.doi.org/10.1111/j.1439-0396.2007.00752.x] [PMID: 18477307]
[6]
Dellas, N.; Thomas, S.T.; Manning, G.; Noel, J.P. Discovery of a metabolic alternative to the classical mevalonate pathway. eLife, 2013, 2e00672 .
[http://dx.doi.org/10.7554/eLife.00672] [PMID: 24327557]
[7]
Litvinov, D.; Mahini, H.; Garelnabi, M. Antioxidant and anti-inflammatory role of paraoxonase 1: implication in arteriosclerosis diseases. N. Am. J. Med. Sci., 2012, 4(11), 523-532.
[http://dx.doi.org/10.4103/1947-2714.103310] [PMID: 23181222]
[8]
Kota, S.K.; Meher, L.K.; Kota, S.K.; Jammula, S.; Krishna, S.V.S.; Modi, K.D. Implications of serum paraoxonase activity in obesity, diabetes mellitus, and dyslipidemia. Indian J. Endocrinol. Metab., 2013, 17(3), 402-412.
[http://dx.doi.org/10.4103/2230-8210.111618] [PMID: 23869295]
[9]
Mackness, M.I.; Arrol, S.; Durrington, P.N. Paraoxonase prevents accumulation of lipoperoxides in low-density lipoprotein. FEBS Lett., 1991, 286(1-2), 152-154.
[http://dx.doi.org/10.1016/0014-5793(91)80962-3] [PMID: 1650712]
[10]
Aviram, M.; Rosenblat, M.; Bisgaier, C.L.; Newton, R.S.; Primo-Parmo, S.L.; La Du, B.N. Paraoxonase inhibits high-density lipoprotein oxidation and preserves its functions. A possible peroxidative role for paraoxonase. J. Clin. Invest., 1998, 101(8), 1581-1590.
[http://dx.doi.org/10.1172/JCI1649] [PMID: 9541487]
[11]
Ogunwusi, A.A.; Ibrahim, H.D. Properties and industrial potential of walnut growing in Nigeria. Journal of Resources Development and Management, 2016, 18, 62-69.
[12]
Berryman, C.E.; Grieger, J.A.; West, S.G.; Chen, C.Y.; Blumberg, J.B.; Rothblat, G.H.; Sankaranarayanan, S.; Kris-Etherton, P.M. Acute consumption of walnuts and walnut components differentially affect postprandial lipemia, endothelial function, oxidative stress, and cholesterol efflux in humans with mild hypercholesterolemia. J. Nutr., 2013, 143(6), 788-794.
[http://dx.doi.org/10.3945/jn.112.170993] [PMID: 23616506]
[13]
Olaniyi, F.E.; Bambidele, I.O.; Omokehinde, A.O.; Ayodeji, A.A. Anti-inflammatory activities of the chloroform extract of the fruit of Tetracarpidium conophorum (Mull. Arg.) (Nigeria Walnuts). Journal of Advances in Medical and Pharmaceutical Sciences, 2016, 6, 1-7.
[http://dx.doi.org/10.9734/JAMPS/2016/22898]
[14]
Ezealisiji, K.M.; Stanley, C.N.; Ekanem, E.S. Evaluation of anti-cholesterol activity of ethyl acetate and n-hexane extracts of Tetracarpidium conophorum (Mull. Arg.) Hutch and Dalziel (African walnut) towards hypercholesterolemic rats. International Journal of Pharmacognosy and Phytochemical Research, 2016, 8, 1372-1376.
[15]
Nwaichi, E.O.; Osuoha, J.O.; Monanu, M.O. Nutraceutical potential of Tetracarpidium conophorum and Buccholzia coriacea in diet-induced hyperlipidemia. J. Chem. Health Risks, 2017, 7, 157-170.
[16]
Analike, R.; Ahaneku, J.E.; Njoku, M.C.; Ahaneku, G.I.; Ezeugwunne, I.P.; Ogbodo, E.C. Effects of Tetracarpidium conophorum-Nigerian walnuts on blood lipids, lipoproteins and glucose values in adult Nigerians. International Journal of Innovation Research and Advanced Studies, 2017, 4, 67-71.
[17]
Ebong, P.E.; Atangwho, I.J.; Eyong, E.U.; Egbung, G.E. The antidiabetic efficacy of combined extracts from two continental plants: Azadirachta indica (A. Juss) (Neem) and Vernonia amygdalina (Del.) (African bitter leaf). Am. J. Biochem. Biotechnol., 2008, 4, 239-244.
[http://dx.doi.org/10.3844/ajbbsp.2008.239.244]
[18]
Logan, S.J.; Abrams, N.M. A simple, semiquantitative device for liquid–liquid separations. J. Chem. Educ., 2012, 89, 1609-1610.
[http://dx.doi.org/10.1021/ed300086k]
[19]
Ajurul, M.G.; Williams, L.F.; Ajuru, G. Qualitative and quantitative phytochemical screening of some plants used in ethnomedicine in the Niger Delta region of Nigeria. Journal of Food and Nutrition Sciences, 2017, 5, 198-205.
[http://dx.doi.org/10.11648/j.jfns.20170505.16]
[20]
Harbone, J.B. Phytochemical Methods. A guide to modern technique of plant analysis; Chapman and Hall: London, New York, 1973, pp. 182-191.
[21]
Bohm, B.A.; Kocipai-Abyazan, R. Flavonoid and condensed tannins from leaves of Vaccinium raticulation and Vaccinum calcyimium. Pac. Sci., 1994, 48, 458-463.
[22]
Association of Official Analytical Chemist. Official methods of analysis (16thed); Washington, U.S.A 2000.
[23]
Nakagawa, T.; Ukai, K.; Ohyama, T.; Gomita, Y.; Okamura, H. Effects of chronic administration of sibutramine on body weight, food intake and motor activity in neonatally monosodium glutamate-treated obese female rats: relationship of antiobesity effect with monoamines. Exp. Anim., 2000, 49(4), 239-249.
[http://dx.doi.org/10.1538/expanim.49.239] [PMID: 11109549]
[24]
Rotimi, O.A.; Olayiwola, I.O.; Ademuyiwa, O.; Balogun, E.A. Effects of fibre-enriched diets on tissue lipid profiles of MSG obese rats. Food Chem. Toxicol., 2012, 50(11), 4062-4067.
[http://dx.doi.org/10.1016/j.fct.2012.08.001] [PMID: 22898616]
[25]
Novelli, E.L.B.; Diniz, Y.S.; Galhardi, C.M.; Ebaid, G.M.; Rodrigues, H.G.; Mani, F.; Fernandes, A.A.; Cicogna, A.C.; Novelli Filho, J.L. Anthropometrical parameters and markers of obesity in rats. Lab. Anim., 2007, 41(1), 111-119.
[http://dx.doi.org/10.1258/002367707779399518] [PMID: 17234057]
[26]
Atangwho, I.J.; Edet, E.E.; Uti, D.E.; Obi, A.U.; Asmawi, M.Z.; Ahmad, M. Biochemical and histological impact of Vernonia amygdalina supplemented diet in obese rats. Saudi J. Biol. Sci., 2012, 19(3), 385-392.
[http://dx.doi.org/10.1016/j.sjbs.2012.05.003] [PMID: 23961200]
[27]
Abam, O.E.; Funmilola, O.Y.; Violette, A.N.; Oziegbe, O.O. Effect of African walnut (Tetracarpidium conophorum (müll. arg.) hutch & dalziel syn. Plukenetia conophora) oil on cadmium – induced oxidative stress in male albino rats. Res. J. Pharm. Biol. Chem. Sci., 2013, 4, 35-42.
[28]
Folch, J.; Lees, M.; Sloane Stanley, G.H. A simple method for the isolation and purification of total lipides from animal tissues. J. Biol. Chem., 1957, 226(1), 497-509.
[PMID: 13428781]
[29]
Connerty, H.V.; Briggs, A.R.; Eaton, E.H. Determination of serum phospholipids, lipid phosphorus. Practical Clinical Biochemistry, 1961, 7, 319-320.
[30]
Rao, A.V.; Ramakrishnan, S. Indirect assessment of hydroxymethylglutaryl-CoA reductase (NADPH) activity in liver tissue. Clin. Chem., 1975, 21(10), 1523-1525.
[PMID: 1157326]
[31]
Junge, W.; Klees, H. 1,2-Arylesterase. Methods of Enzymatic Analysis, 1984, 4, 8-14.
[32]
Triwitono, P.; Yustinus, M.; Agnes, M.; Djagal, W.M. Physiological effects of mung bean starch RS-3 on the obesity index and adipose cell profile of Sprague-Dawley rats. Pak. J. Nutr., 2016, 15, 913-920.
[http://dx.doi.org/10.3923/pjn.2016.913.920]
[33]
Stephens, D.N. Does the Lee obesity index measure general obesity? Physiol. Behav., 1980, 25(2), 313-315.
[http://dx.doi.org/10.1016/0031-9384(80)90222-X] [PMID: 7413839]
[34]
Alarcon-Aguilar, F.J.; Almanza-Perez, J.; Blancas, G.; Angeles, S.; Garcia-Macedo, R.; Roman, R.; Cruz, M. Glycine regulates the production of pro-inflammatory cytokines in lean and monosodium glutamate-obese mice. Eur. J. Pharmacol., 2008, 599(1-3), 152-158.
[http://dx.doi.org/10.1016/j.ejphar.2008.09.047] [PMID: 18930730]
[35]
Roman-Ramos, R.; Almanza-Perez, J.C.; Garcia-Macedo, R.; Blancas-Flores, G.; Fortis-Barrera, A.; Jasso, E.I.; Garcia-Lorenzana, M.; Campos-Sepulveda, A.E.; Cruz, M.; Alarcon-Aguilar, F.J. Monosodium glutamate neonatal intoxication associated with obesity in adult stage is characterized by chronic inflammation and increased mRNA expression of peroxisome proliferator-activated receptors in mice. Basic Clin. Pharmacol. Toxicol., 2011, 108(6), 406-413.
[http://dx.doi.org/10.1111/j.1742-7843.2011.00671.x] [PMID: 21205225]
[36]
Kim, H.J.; Hwang, J.T.; Kim, M.J.; Yang, H.J.; Sung, M.J.; Kim, S.H.; Park, S.; Gu, E.J.; Park, Y.; Kwon, D.Y. The inhibitory effect of saponin derived from Cheonggukjang on adipocyte differentiation in vitro. Food Sci. Biotechnol., 2014, 23, 1273-1278.
[http://dx.doi.org/10.1007/s10068-014-0175-4]
[37]
Gauhar, R.; Hwang, S.L.; Jeong, S.S.; Kim, J.E.; Song, H.; Park, D.C.; Song, K.S.; Kim, T.Y.; Oh, W.K.; Huh, T.L. Heat-processed Gynostemma pentaphyllum extract improves obesity in ob/ob mice by activating AMP-activated protein kinase. Biotechnol. Lett., 2012, 34(9), 1607-1616.
[http://dx.doi.org/10.1007/s10529-012-0944-1] [PMID: 22576281]
[38]
Raclot, T.; Oudart, H. Selectivity of fatty acids on lipid metabolism and gene expression. Proc. Nutr. Soc., 1999, 58(3), 633-646.
[http://dx.doi.org/10.1017/S002966519900083X] [PMID: 10604197]
[39]
Gonabad, M.A.; Noghabi, M.S.; Niazmand, R. Evaluation of extraction percentages and physicochemical properties of walnut. Journal of Applied Environmental and Biological Sciences, 2015, 4, 74-82.
[40]
Wermuth, C.G.; Ganellin, C.R.; Lindberg, P.; Mitscher, L.A. Glossary of Terms Used in Medicinal Chemistry (IUPAC Recommendations 1998). Pure Appl. Chem., 1998, 70, 1129-1143.
[http://dx.doi.org/10.1351/pac199870051129]
[41]
Costa, L.G.; Giordano, G.; Furlong, C.E. Pharmacological and dietary modulators of paraoxonase 1 (PON1) activity and expression: the hunt goes on. Biochem. Pharmacol., 2011, 81(3), 337-344.
[http://dx.doi.org/10.1016/j.bcp.2010.11.008] [PMID: 21093416]
[42]
Kumar, S.; Pandey, A.K. Chemistry and biological activities of flavonoids: an overview. ScientificWorldJournal, 2013. 2013162750
[http://dx.doi.org/10.1155/2013/162750] [PMID: 24470791]
[43]
Udedi, S.C.A.; Ani, O.N.A.; Anajekwu, B.N.A.; Ononamadu, C.J.A.; Igwilo, I.O.A.; Ibeabuchi, C.G.A.; Ifemeje, J.C.; Lukong, C.B.; Ogbuozobe, G.O. Nutritional composition and antioxidant activity of African walnut, (Tetracarpidium conophorum). J. Appl. Biochem., 2014, 107, 170-180.
[44]
Edem, C.A.; Dounmu, M.I.; Bassey, F.I. Determination of proximate composition, ascorbic acid and heavy metal content of African walnut (Tetracarpidium conophorum). Pak. J. Nutr., 2009, 8, 225-226.
[http://dx.doi.org/10.3923/pjn.2009.225.226]
[45]
Wang, T.; Choi, R.C.; Li, J.; Bi, C.W.; Ran, W.; Chen, X.; Dong, T.T.; Bi, K.; Tsim, K.W. Trillin, a steroidal saponin isolated from the rhizomes of Dioscorea nipponica, exerts protective effects against hyperlipidemia and oxidative stress. J. Ethnopharmacol., 2012, 139(1), 214-220.
[http://dx.doi.org/10.1016/j.jep.2011.11.001] [PMID: 22100563]
[46]
Trigueros, L.; Peña, S.; Ugidos, A.V.; Sayas-Barberá, E.; Pérez-Álvarez, J.A.; Sendra, E. Food ingredients as anti-obesity agents: a review. Crit. Rev. Food Sci. Nutr., 2013, 53(9), 929-942.
[http://dx.doi.org/10.1080/10408398.2011.574215] [PMID: 23768185]
[47]
Singh, G.; Suresh, S.; Bayineni, V.K.; Kadeppagari, R.K. Lipase inhibitors from plants and their medical applications. Int. J. Pharm. Pharm. Sci., 2015, 7, 1-5.
[48]
Wijendran, V.; Hayes, K.C. Dietary n-6 and n-3 fatty acid balance and cardiovascular health. Annu. Rev. Nutr., 2004, 24, 597-615.
[http://dx.doi.org/10.1146/annurev.nutr.24.012003.132106] [PMID: 15189133]