Anti-Diabetic Effect of a Flavonoid and Sitosterol - Rich Aqueous Extract of Pleurotus tuberregium Sclerotia in Alloxan-Induced Diabetic Rabbits

Author(s): Ifeanacho Mercy Onuekwuzu, Ikewuchi Catherine Chidinma, Ikewuchi Jude Chigozie*

Journal Name: Endocrine, Metabolic & Immune Disorders - Drug Targets
Formerly Current Drug Targets - Immune, Endocrine & Metabolic Disorders

Volume 19 , Issue 8 , 2019

Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Objective: Traditionally prepared infusions and decoctions are commonly used in the management of diabetes mellitus, in southern Nigeria; one of such is the aqueous extract of the sclerotia of Pleurotus tuberregium (“usu” milk). In this study, the effects of the extract on the body weights, tissue/ organ weights, fasting blood glucose, blood/plasma lipid profiles and atherogenic indices were investigated in normal and alloxan-induced diabetic rabbits.

Methods: Diabetes mellitus was induced by the injection of alloxan (120 mg/kg body weight) via the marginal ear vein. The extract was administered orally at 100, 200 and 300 mg/kg to normal and diabetic rabbits; while metformin was administered at 50 mg/kg. The crude extract was analyzed by gas chromatography, coupled to flame ionization detector.

Results: Thirty-one known flavonoids were detected, consisting mainly of isoquercetin (28.5%), luteolin (24.3%), quercetin (18.8%) and kaempferol (11.3%). Sitosterol (82.0%) and stigmasterol (12.5%) were the most abundant of the seven phytosterols detected. Compared to the diabetic control, the treatment significantly (p<0.05) lowered the weights of the kidney and liver, as well as the levels of blood glucose and triglyceride, plasma VLDL, LDL and non-HDL cholesterol, atherogenic index of plasma, cardiac risk ratio, atherogenic coefficient and Castelli’s risk index II. It, however, significantly (p<0.05) increased plasma HDL cholesterol, without significantly affecting blood total cholesterol levels.

Conclusion: This study showed that the extract was hypoglycemic, and improved lipid profile and atherogenic indices, thus highlighting its cardioprotective potential, thereby supporting its use in the management of diabetes mellitus.

Keywords: Atherogenic indices, diabetes mellitus, isoquercetin, lipid profile, luteolin, phytosterols, Pleurotus tuberregium.

International Diabetes Federation. IDF Diabetes Atlas, 7th ed; International Diabetes Federation, 2015.
Daya, R.; Bayat, Z.; Raal, F.J. Prevalence and pattern of dyslipidaemia in type 2 diabetes mellitus patients at a tertiary care hospital. J. Endocrinol. Metab. Diabet. South Africa, 2017, 1, 1-5.
Goldberg, I.J. Clinical review 124: Diabetic dyslipidemia: causes and consequences. J. Clin. Endocrinol. Metab., 2001, 86(3), 965-971.
[] [PMID: 11238470]
Sugden, M.; Holness, M. Pathophysiology of diabetic dyslipidemia: Implications for atherogenesis and treatment. Clin. Lipidol., 2011, 6, 401-411.
Debas, H.T.; Laxminarayan, R.; Straus, S.E. Complementary and alternative medicine. Disease control priorities in developing countries; 2nd ed; Jamison, D.T.; Breman, J.G.; Measham, A.R.; Alleyne, G.; Claeson, M.; Evans, D.B.; Jha, P.; Mills, A.; Musgrove,P., Eds.; . Oxford University Press: New York , 2006, pp. 1281-1292.
Day, C. Traditional plant treatments for diabetes mellitus: pharmaceutical foods. Br. J. Nutr., 1998, 80(1), 5-6.
[] [PMID: 9797638]
Ikewuchi, C.C.; Ikewuchi, J.C. Chemical profile of Pleurotus tuberregium (Fr) Sing’s sclerotia. Pac. J. Sci. Technol., 2009, 10, 357-362.
Ikewuchi, J.C.; Ikewuchi, C.C. Nutrient composition of Pleurotus tuberregium (Fr) Sing’s sclerotia. Glob. J. Pure Appl. Sci., 2011, 17, 51-54.
Ikewuchi, J.C.; Ikewuchi, C.C.; Ifeanacho, M.O.; Igboh, N.M.; Ijeh, I.I. Moderation of hematological and plasma biochemical indices of sub-chronic salt-loaded rats by aqueous extract of the sclerotia of Pleurotus tuberregium (Fr) Sing’s: implications for the reduction of cardiovascular risk. J. Ethnopharmacol., 2013, 150(2), 466-476.
[] [PMID: 24055467]
Ikewuchi, J.C.; Ikewuchi, C.C.; Ifeanacho, M.O.; Igboh, N.M.; Ijeh, I.I. Gas chromatography-flame ionization detector analysis of the phytochemical composition of Pleurotus tuberregium (Fr) Sing’s sclerotia: Potential benefits. Pac. J. Sci. Technol., 2013, 14, 342-359.
Ikewuchi, C.C.; Ikewuchi, J.C.; Ifeanacho, M.O. Restoration of plasma markers of liver and kidney functions/integrity in alloxan-induced diabetic rabbits by aqueous extract of Pleurotus tuberregium sclerotia. Biomed. Pharmacother., 2017, 95, 1809-1814.
[] [PMID: 28968925]
Ikewuchi, J.C.; Ikewuchi, C.C.; Ifeanacho, M.O.; Igboh, N.M. Blood pressure lowering activity of a flavonoid and phytosterol rich extract of the sclerotia of Pleurotus tuberregium (Fr) Sing’s in salt-loaded rats. Biomed. Prev. Nutr, 2014, 4, 257-263.
Ikewuchi, J.C.; Onyeike, E.N.; Uwakwe, A.A.; Ikewuchi, C.C. Effect of aqueous extract of the leaves of Acalypha wilkesiana ‘Godseffiana’ Muell Arg (Euphorbiaceae) on the hematology, plasma biochemistry and ocular indices of oxidative stress in alloxan induced diabetic rats. J. Ethnopharmacol., 2011, 137(3), 1415-1424.
[] [PMID: 21864665]
AOAC International. AOAC Official Method 999.02: Oil in seeds. Supercritical Fluid Extraction (SFE) Method. AOAC Official Methods of Analysis, 18th ed; AOAC International: Gaithersburg, MD, USA, 2006.
AOAC International. AOAC Official Method 994.10: Cholesterol in foods. Direct Saponification-Gas Chromatographic Method. AOAC Official Methods of Analysis, 18th ed; AOAC International: Gaithersburg, MD, USA, 2006.
AOAC International. AOAC Official Method 970.51: Fats (animal) in vegetable fats and oils (determination of cholesterol). Gas Chromatographic Method. AOAC Official Methods of Analysis, 18th ed; AOAC International: Gaithersburg, MD, USA, 2006.
Millogo-Kone, H.; Lompo, M.; Kini, F.; Asimi, S.; Guissou, I.F.; Nacoulma, O. Evaluation of flavonoids and total phenolic contents of stem bark and leaves of Parkia biglobosa (Jacq.) Benth. (Mimosaceae)-free radical scavenging and antimicrobial activities. Res. J. Med. Sci., 2009, 3, 70-74.
FAO. Protein quality evaluation: Report of Joint FAO/WHO Expert Consultation. FAO Food and Nutrition Paper 51; Food and Agriculture Organization of the United Nations: Rome, 1991.
Ramin, N.; Thieme, R.; Fischer, S.; Schindler, M.; Schmidt, T.; Fischer, B.; Navarrete Santos, A. Maternal diabetes impairs gastrulation and insulin and IGF-I receptor expression in rabbit blastocysts. Endocrinology, 2010, 151(9), 4158-4167.
[] [PMID: 20631000]
Ikewuchi, J.C.; Ikewuchi, C.C.; Ifeanacho, M.O. Attenuation of salt-loading induced cardiomegaly and dyslipidemia in Wistar rats by aqueous leaf extract of Chromolaena odorata. Pharmacol. Pharm., 2014, 5, 160-170.
Ikewuchi, C.C.; Ikewuchi, J.C.; Ezeka, U.K.; Ifeanacho, M.O. Effect of “edible clay” (takere) suspension on serum lipid profiles and atherogenic indices of normal Wistar rats. Food Sci. Nutr., 2019, 1-10.
Friedewald, W.T.; Levy, R.I.; Fredrickson, D.S. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin. Chem., 1972, 18(6), 499-502.
[PMID: 4337382]
Chigozie, I.J.; Chidinma, I.C. Positive moderation of the hematology, plasma biochemistry and ocular indices of oxidative stress in alloxan-induced diabetic rats, by an aqueous extract of the leaves of Sansevieria liberica Gerome and Labroy. Asian Pac. J. Trop. Med., 2013, 6(1), 27-36.
[] [PMID: 23317882]
Ikewuchi, J.C.; Ikewuchi, C.C. Alteration of plasma lipid profile and atherogenic indices by Stachytarpheta jamaicensis L. (Vahl.). Biokemistri, 2009, 21, 71-77.
Bhardwaj, S.; Bhattacharjee, J.; Bhatnagar, M.K.; Tyagi, S. Atherogenic index of plasma, Castelli risk index and atherogenic coefficient - new parameters in assessing cardiovascular risk. Int. J. Pharma Bio Sci., 2013, 3, 359-364.
Zhang, R.; Yao, Y.; Wang, Y.; Ren, G. Antidiabetic activity of isoquercetin in diabetic KK -Ay mice. Nutr. Metab. (Lond.), 2011, 8, 85.
[] [PMID: 22133267]
Nualkaew, S.; Padee, P.; Talubmook, C. Hypoglycemic activity in diabetic rats of stigmasterol and sitosterol-3-O-β-D-glucopyranoside isolated from Pseuderanthemum palatiferum (Nees) Radlk. leaf extract. J. Med. Plants Res., 2015, 9, 629-635.
Vinayagam, R.; Xu, B. Antidiabetic properties of dietary flavonoids: a cellular mechanism review. Nutr. Metab. (Lond.), 2015, 12, 60.
[] [PMID: 26705405]
López-Lázaro, M. Distribution and biological activities of the flavonoid luteolin. Mini Rev. Med. Chem., 2009, 9(1), 31-59.
[] [PMID: 19149659]
Assmann, G.; Gotto, A.M. Jr HDL cholesterol and protective factors in atherosclerosis. Circulation, 2004, 109(23)(Suppl. 1), III8-III14.
[] [PMID: 15198960]
McBride, P.E. Triglycerides and risk for coronary heart disease. JAMA, 2007, 298(3), 336-338.
[] [PMID: 17635897]
McBride, P. Triglycerides and risk for coronary artery disease. Curr. Atheroscler. Rep., 2008, 10(5), 386-390.
[] [PMID: 18706279]
Shen, G.X. Lipid disorders in diabetes mellitus and current management. Curr. Pharm. Anal., 2007, 3, 17-24.
Jeong, S.M.; Kang, M.J.; Choi, H.N.; Kim, J.H.; Kim, J.I. Quercetin ameliorates hyperglycemia and dyslipidemia and improves antioxidant status in type 2 diabetic db/db mice. Nutr. Res. Pract., 2012, 6(3), 201-207.
[] [PMID: 22808343]
Hermans, M.P.; Sacks, F.M.; Ahn, S.A.; Rousseau, M.F. Non-HDL-cholesterol as valid surrogate to apolipoprotein B100 measurement in diabetes: Discriminant Ratio and unbiased equivalence. Cardiovasc. Diabetol., 2011, 10, 20.
[] [PMID: 21356116]
Brunzell, J.D.; Davidson, M.; Furberg, C.D.; Goldberg, R.B.; Howard, B.V.; Stein, J.H.; Witztum, J.L. Lipoprotein management in patients with cardiometabolic risk: consensus conference report from the American Diabetes Association and the American College of Cardiology Foundation. J. Am. Coll. Cardiol., 2008, 51(15), 1512-1524.
[] [PMID: 18402913]
Peters, A.L. Clinical relevance of non-HDL cholesterol in patients with diabetes. Clin. Diabetes, 2008, 6, 3-7.
Nimmanapalli, H.D.; Kasi, A.D.; Devapatla, P.K.; Nuttakki, V. Lipid ratios, atherogenic coefficient and atherogenic index of plasma as parameters in assessing cardiovascular risk in type 2 diabetes mellitus. Int. J. Res. Med. Sci, 2016, 4, 2863-2869.
Dobiásová, M.; Frohlich, J. The plasma parameter log (TG/HDL-C) as an atherogenic index: correlation with lipoprotein particle size and esterification rate in apoB-lipoprotein-depleted plasma (FER(HDL)). Clin. Biochem., 2001, 34(7), 583-588.
[] [PMID: 11738396]
Dobiásová, M.; Frohlich, J.; Sedová, M.; Cheung, M.C.; Brown, B.G. Cholesterol esterification and atherogenic index of plasma correlate with lipoprotein size and findings on coronary angiography. J. Lipid Res., 2011, 52(3), 566-571.
[] [PMID: 21224290]
Niroumand, S.; Khajedaluee, M.; Khadem-Rezaiyan, M.; Abrishami, M.; Juya, M.; Khodaee, G.; Dadgarmoghaddam, M. Atherogenic Index of Plasma (AIP): A marker of cardiovascular disease. Med. J. Islam. Repub. Iran, 2015, 29, 240.
[PMID: 26793631]
Wan, K.; Zhao, J.; Huang, H.; Zhang, Q.; Chen, X.; Zeng, Z.; Zhang, L.; Chen, Y. The association between triglyceride/high-density lipoprotein cholesterol ratio and all-cause mortality in acute coronary syndrome after coronary revascularization. PLoS One, 2015, 10(4)e0123521
[] [PMID: 25880982]
Ikewuchi, J.C.; Ikewuchi, C.C. Alteration of plasma lipid profile and atherogenic indices of cholesterol loaded rats by Tridax procumbens Linn: implications for the management of obesity and cardiovascular diseases. Biokemistri, 2009, 21, 95-99.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2019
Published on: 11 November, 2019
Page: [1148 - 1156]
Pages: 9
DOI: 10.2174/1871530319666190206213843
Price: $65

Article Metrics

PDF: 35
PRC: 1