Ethylacetate Flavonoid Bio-compounds of Honey with Mitigating Anti-hyperlipidemic and Antioxidant Properties in Carbohydrate and Lipid Enriched Diets – Obese Rats
Annual Research & Review in Biology,
Page 1-23
DOI:
10.9734/arrb/2023/v38i930603
Abstract
Honey is a rich material source of medicinal nutrients. This study investigated the hypolipidemic and antioxidant effects of honey, 50% fresh lime juice, and 50% honey (MIX) and ethylacetate flavonoid-rich fraction of honey (EAFH) in carbohydrate and lipid-enriched diets-obese rats.
At phase 1, 54 male neonate Wistar albino rats were, divided into 3 groups of 18 rats. Groups 2 and 3 were fed a carbohydrate-enriched diet (CHD) and lipid-enriched diet (LP) for 14 days, and rats with Lee index ≥ 0.3 were considered obese. Rats (phase-2) were regrouped into 7 groups of 6 rats, and treated with honey, MIX, and EAFH. Flavonoids bio-compounds in EAFH characterized by HPLC (High-performance liquid chromatography) include; gallic acid, epigallocatechin, napthoresorcinol, and quercetin. Lee's index after obesity induction was ≥ 0.3. Adiposity index, diet intake, and body and organ weight of obese rats were significantly (p < 0.05) reduced after honey, MIX, and EAFH treatments compared to control. Significant (p < 0.05) decreased concentrations of glucose, leptin, insulin, low-density lipoprotein (LDL), total cholesterol (TC), triacylglycerol (TAG), very low-density lipoprotein (VLDL), 3-Hydroxy-3-methylglutaryl (HMG) coenzyme A (CoA) reductase activity (HMGCOARA), atherogenic risk index (ARI) and coronary risk index (CRI) and increase in high-density lipoprotein (HDL) after treatment with honey, MIX and EAFH was observed compared control and AOI. Antioxidant parameters of obese rats were significantly (p < 0.05) improved compared to control and AOI rats. Honey could serve as a model pharmacotherapy for treating dyslipidemia and oxidative stress linked to obesity.
Keywords:
- Hypolipidemic
- hyperlipidemic
- flavonoids
- obesity
- hypoglycemic
- hyperglycemia
How to Cite
References
Okafor JNC, Meyer M, Le Roes-Hill M. Flavonoid and Phenolic Acid Profiles of Dehulled and Whole Vigna subterranea (L.) Verdc Seeds Commonly Consumed in South Africa. Mol. 2022; 27:5265. Available:https://doi.org/10.3390/ molecules27165265.
Ying-Yin C, Sheng-Yi C, Jer-An L. Preventive Effect of Indian Gooseberry (Phyllanthus emblica L.) Fruit Extract on Cognitive Decline in High-Fat Diet (HFD)-Fed Rats. Mol. Nutr. Food Res. 2023;67: 4.2200791. DOI:org/10.1002/mnfr.202200461
Agunloye OM, Oboh G, Ademiluyi AO. Cardio-protective and antioxidant properties of caffeic acid and chlorogenic acid: Mechanistic role of angiotensin converting enzyme, cholinesterase and arginase activities in cyclosporine induced hypertensive rats. Biomed. Pharmaco. 2019;109:450–458.
Ayman MM, Rene JHB, Mansur AS. Beneficial Effects of Citrus Flavonoids on Cardiovascular and Metabolic Health. Oxi. Med. Cellullar Longevity. 2019;1-19.
Erejuwa OO, Nwobodo NN, Akpan JL. Nigerian honey ameliorates hyperglycemia and dyslipidemia in alloxan-induced diabetic rats. Nutrition. 2016;8(95):1-5.
Shahidi F, Hossain A. Importance of Insoluble-Bound Phenolics to the Antioxidant Potential Is Dictated by Source Material. Antioxidant. 2023; 12:203. Available:https://doi.org/10.3390/ antiox12010203.
Lotito SB, Fraga CG. (+)-Catechin prevents human plasma oxidation. Free Radic. Biol. Med. 1997;24:435–441.
Grzesik M, Naparło K, Bartosz G. Antioxidant properties of catechins: Comparison with other antioxidants. Food Chem. 2018;241:480–492.
Alam MM, Meerza D, Naseem I. Protective effect of quercetin on hyperglycemia, oxidative stress and DNA damage in alloxan induced type 2 diabetic mice. Life Sciences. 2014;109:8–14.
Mohammed KH, Ahmed AD, Jihae H. Molecular Mechanisms of the Anti-Obesity and Anti-Diabetic Properties of Flavonoids. Inter. J. Mol. Sc. 2016;17(569):1-32.
DOI:10.3390/ijms17040569.
Klaus S, Pultz S, Thone-Reineke C. Epigallocatechin gallate attenuates diet-induced obesity in mice by decreasing energy absorption and increasing fat oxidation. Int. J. Obes. 2005;29:615–623.
Darwish AG, Moniruzzaman M, Tsolova V. Integrating Metabolomics and Gene Expression Underlying Potential Biomarkers Compounds Associated with Antioxidant Activity in Southern Grape Seeds. Metabol. 2023;13:210. Available:https://doi.org/10.3390/ metabo13020210
Zaidun NH, Thent ZC, Latiff AA. Combating oxidative stress disorders with citrus flavonoid: Naringenin. Life Sc. 2018; 208:111–122.
Hernandez-Aquino E, Muriel P. Beneficial effects of naringenin in liver diseases: molecular mechanisms.” World J. Gastro. 2018;24(16):1679–1707.
Nur ZR, Kok-Yong C, Khairul AZ. A Review on the Protective Effects of Honey against Metabolic Syndrome. Nutrition. 2018;10(1009):1-21.
Mariarosaria B, Stefania D. Anti-Obesity Effects of Polyphenol Intake: Current Status and Future Possibilities. Inter. J. Mol. Sc. 2020; 20(5642):1-24.
Krishnasree V, Mary UP. In vitro antidiabetic activity and glycemic index of bee honeys. Ind. J. Trad. Knowledge. 2017;16(1):134–140.
Rochlani Y, Pothineni NV, Kovelamudi S. Metabolic syndrome: Pathophysiology, management, and modulation by natural compounds. Ther. Adv. Cardiov. Dis. 2017;11:215–225.
Nordestgaard BG. Triglyceride-rich lipoproteins and atherosclerotic cardiovascular disease. Circ. Res. 2016;118(4):547–563.
Idoko A, Ikpe VPO, Nelson NO. Effects of Lime Juice and Honey on Lipid Profile of Cholesterol Enriched Diet Fed Rat Model. Annual Research and Review in Biology. 2017;20(3):1-10.
Suhana S, Francis KE, Fuzina NH. Four-Week Consumption of Malaysian Honey Reduces Excess Weight Gain and Improves Obesity-Related Parameters in High Fat Diet Induced Obese Rats. Evi. Comp. Altern. Med. 2017:1-9.
Facey A, Dilworth L, Irving R. A Review of the Leptin Hormone and the Association with Obesity and Diabetes Mellitus. J. Diabet. Metab. 2017;8(727):1-3.
Gilberto JP, Alexei V, Henrique LS, et al. Decrease in leptin production by the adipose tissue in obesity associated with severe metabolic syndrome. Arq Bras Endocrinol Metab. 2009;53(9):1088-1095.
Item JA, Chidimma EI, Godwin EE. Effect of long-term feeding of the Obudu natural honey and table sugar-sweetened diets on obesity and pro-inflammatory biomarkers in rats. BMC Nutrition. 2020;6(3):1-11.
Soria AC, Martínez-Castro I, Sanz J. Analysis of volatile composition of honey by solid phase micro extraction and gas chromatography-mass spectrometry. Journal of Seperation Science. 2003;26: 793-801.
Fuad A, Fadi A, Wael AA, Hammad KA, Saleh A, Ghassab MA, Haya JAS. HPLC Analysis of Chemical Composition of Selected Jordanian Medicinal Plants and their Bioactive Properties. Orien J Chem. 2018;34(5):2397-2403.
National Institute of Health (NIH). Guidelines for the Care and Use of Laboratory Animals. Nat. Acad. Press. 1937;85:23.
Zimmerman M. Ethical Guidelines for Investigations of Experimental Pain in Conscious Animals. Pain. 1995;16(2):109-111.
Nakagawa T, Ukai K, Ohyama T. 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. Expe. Animals. 2000;49:239–249.
Rotimi OA, Olayiwola IO, Ademuyiwa O. Effects of fibre-enriched diets on tissue lipid profiles of MSG obese rats. Food Chem. Toxicology. 2012;50:4062–4067.
Kamal MSA, Ghazali AR, Yahya NA. Acute toxicity study of standardized Mitragyna speciosa korth aqueous extract in Sprague dawley rats. J. Plant Study. 2012;1(2): 404–409.
Daniel EU, Item JA, Eyong UE. African walnuts attenuate ectopic fat accumulation and associated peroxidation and oxidative stress in monosodium glutamate-obese Wistar rats. Biomed. Pharmaco. 2020; 124(109879):1-10.
Idoko A. Exploitative Beneficial Effects of Citrus Fruits. In: Citrus - Health Benefits and Production Technology. Muhammad Sajid, Amanullah (Eds). IntechOpen. 2019; 32-55.
Shen W, Xu Y, Lu YH. Inhibitory effects of Citrus flavonoids on starch digestion and antihyperglycemic effects in HepG2 cells. J. Agric. Food Chem. 2012;60(38):9609-9619.
Burke AC, Sutherland BG, Telford DE. “Intervention with citrus flavonoids reverses obesity and improves metabolic syndrome and atherosclerosis in obese Ldlr-/- mice, J. Lip. Res. 2018; 59(9):1714–1728.
Waleed FA. Nutritional benefits of citrus fruits. Am. J. Biomed. Sc. Res. 2019;3(4): 1-4.
Pan MH, Wu JC, Ho CT. Antiobesity molecular mechanisms of action: Resveratrol and pterostilbene. BioFact. 2018;44:50–60.
Tan Y, Chang SKC. Digestive enzyme inhibition activity of the phenolic substances in selected fruits, vegetables and tea as compared to black legumes. J. Funct. Foods. 2017;38:644–655.
Mohammed KA, Khaled AA, Abdullah HA. Effect of natural honey on lowering lipid profile. Saudi Med. J. 2021;42(5):473-480.
Panche AN, Diwan AD, Chandra SR. Flavonoids: An overview. J. Nutr. Sc. 2016;5(e47).
Assini JM, Mulvihill EE, Huff MW. Citrus flavonoids and lipid metabolism. Curr. Opin. Lipido. 2013;24(1):34–40.
Mahmoud AM, Abd El-Twab SM, Abdel-Reheim ES. Consumption of polyphenol-rich Morus alba leaves extract attenuates early diabetic retinopathy: the underlying mechanism. Eur. J. Nutr. 2017;56(4): 1671–1684.
Kamel EM, Mahmoud AM, Ahmed SA. A phytochemical and computational study on flavonoids isolated from Trifolium resupinatum L. and their novel hepatoprotective activity. Food and Funct. 2016;7(4):2094–2106.
Patti AM, Al-Rasadi K, Giglio RV. Natural approaches in metabolic syndrome management. Arch. Med. Sc. 2018;14: 422-441.
Kumaraswamy A, Rangaraju S, Gnanasekaran J. Evaluation of anti-obesity potential of aqueous extract of Achyranthes aspera Linn. in high fat diet induced obese rats. Clin. Phytosc. 2020; 6(69):1-13.
Terzo S, Calvi P, Nuzzo D. Preventive Impact of Long-Term Ingestion of Chestnut Honey on Glucose Disorders and Neurodegeneration in Obese Mice. Nutr. 2022;14(4):756.
Lee TH, Cheng KK, Hoo RL. The Novel Perspectives of Adipokines on Brain Health. Inter. J. Mol. Sc. 2019;20(5638):1-7.
Manuha MI, Paranagama PA, Nageeb BM. Quantitative Analysis of Vitamin C in Lime and Lemon in Vitro: Verification of Vitamin C on the Impairment of Obesity. International J. Adv. Sc Res Eng. 2019; 5(10):157-161.
Radic R, Nikolic V, Karner I. Circadian rhythm of blood leptin level in obese and non-obese people. Coll Antrop. 2003; 27(2):555-61.
Neveen HA, Nabila AE, Eman RY. Natural honey lowers plasma glucose, insulin and C-peptide in streptozotocin induced diabetic rats: Comparison with metformin. Sch. Res. Lib. Der Pharm. Lett. 2016;8(9): 141-145.
Ajibola A, Chamunorwa JP, Erlwanger KH. Nutraceutical values of natural honey and its contribution to human health and wealth. Nutr. Metab. 2012;9(61):1–12.
Herin M, Khotimah MZ, Mukhammad R. Ameliorative effect of Citrus aurantifolia and Cinnamomum burmannii extracts on diabetic complications in a hyperglycemic rat model. Trop. J. Pharma. Res. 2018; 17(5):823-829.
Nemseck TM, Carmody E, Furchner-Evansona G. Honey promotes lower weight gain, adiposity and triglyceride than sucrose in rats. Nutr. Res. 2011;31: 55–60.
Eidenberger T, Selg M, Krennhuber K. Inhibition of dipeptidyl peptidase activity by flavonol glycosides of guava (Psidium guajava L.): a key to the beneficial effects of guava in type IIdiabetes mellitus. Food Sc. Tech. Camp. 2013;40(1):33-41.
Dongiovanni P, Lanti C, Riso P. Nutritional therapy for nonalcoholic fatty liver disease. The J. Nutr. Biochem. 2016;29:1-11.
Idoko A, Emmanuel U, Yakubu O. Hepatocurative and Gluco-stabilizing Potentials of Ethanol Extract of Stem bark of Flacourtia indica in Aluminium Chloride induced Toxicity in Albino Wistar rats. Curr. Trends Biomed. Eng. Biosc. 2019; 17(5):1-7.
Olukanni OD, Alagbe YO, Akande OT. Natural honey reduced atherogenic and coronary risk indices in Wistar rats. Uni. Medi. 2020;39(1):3-11.
Zaidatul AO, Wan SWG, Liza N. Phenolic Compounds and the Anti-Atherogenic E ect of Bee Bread in High-Fat Diet Induced Obese Rats. Antioxidant. 2020;9(33):1-12.
Zeka K, Ruparelia K, Arroo RRJ. Flavonoids and their metabolites: prevention in cardiovascular diseases and diabetes. Dis. 2017;5:16-19.
Istvan ES, Deisenhofer J. The structure of the catalytic portion of human HMG-CoA reductase. Biochim. Biophys. Acta. 2000; 1529:9-18.
Kleemann R, Kooistra T. HMG-CoA reductase inhibitors: effects on chronic subacute inflammation and onset of atherosclerosis induced by dietary cholesterol. Curr. Drug Targ. Cardiov. Haemat. Disor. 2005;5:441-453.
Yuko M, Shoko Y, Shoichiro H. Early life high-fat diet exposure evokes normal weight obesity. Nutr. Metab. 2020;17(48): 1-8.
Kexin H, Wenzhong H, Mengyang H. Optimization of Ultrasonic-Assisted Extraction of Total Phenolics from Citrus aurantium L. Blossoms and Evaluation of Free Radical Scavenging, Anti-HMG-CoA Reductase Activities. Mol. 2019;24(2368): 1-16.
Marco G, Fulvio P, Manfredi MG. Bioactive effects of citrus flavonoids and role in the prevention of atherosclerosis and cancer. J. Bio. Res. 2022;95(10313):1-11.
Kiortsis DN, Filippatos TD, Mikhailidis DP. Statin associated adverse effects beyond muscle and liver toxicity. Atheroscl. 195:7–16.
Suleiman JB, Mohamed M, Abubakar AB. Therapeutic effects of bee bread on obesity- induced testicular- derived oxidative stress, inflammation, and apoptosis in high-fat diet obese rat model. Antioxidant. 2022;11(255):1-18.
Sani NFA, Levin KB, Chong PS. Effect of the combination of gelam honey and ginger on oxidative stress and metabolic profile in streptozotocin-induced diabetic sprague-dawley rats. BioMed. Res. Inter. 2014;2014(160695):1-9.
Machado DAA, Almeida-Muradian LBD, Sancho MT. Composition and properties of Apis mellifera honey: A review. J. Apicul. Res. 2018;57:35–37.
Sunitha D. A review on antioxidant methods. Asian J. Pharma. Clin. Res. 2016;9(2):14-32.
Seo H, Lee NH, Ryu S. Antioxidant and antiapoptotic effects of pine needle powder ingestion and endurance training in high cholesterol-fed rats. J. exer. nutr. biochem. 2014;18(3):301–309.
Emami SR, Mahvash J, Rouhollah H. Impact of eight weeks endurance training on biochemical parameters and obesity-induced oxidative stress in high fat diet-fed rats. J. exer. nutr. biochem. 2016;20(1): 029–035.
Kamaruzzaman MA, Thanu A, Yusof MR. Kelulut honey ameliorates glucocorticoid induced osteoporosis via its antioxidant activity in rats. Asian Pac. J. Trop. Biomed. 2019;9(12):493-500.
Chinedum E, Joseph BS, Zaidatul AO. Bee bread attenuates high fat diet induced renal pathology in obese rats via modulation of oxidative stress, downregulation of NF-kB mediated inflammation and Bax signalling, Arch. Physio. Biochem. 2020;1-18.
Cui R, Gao M, Qu S. Overexpression of Superoxide Dismutase 3 Gene Blocks High Fat Diet-Induced Obesity, Fatt Liver and Insulin Resistance. Gene Ther. 2014; 2014(21):840–848.
Oihane G, Fabiola B, Marilidia P. Enterocyte superoxide dismutase 2 deletion drives obesity. Sciences. 2022; 25(103707):1-19.
Domazetovic V. Oxidative stress in bone remodeling: Role of antioxidants. Clin. Cases Min. Bone Metabo. 2017;14(2):209-216.
Christophe G, Pedro BC. Catalase, a remarkable enzyme: targeting the oldest antioxidant enzyme to find a new cancer treatment approach. Biol. Chem. 2017; 398(10):1095–1108.
Abdulsamie HA, Mahmoud HH, Lamia, AA. The balance between superoxide dismutase and catalase activi-ties in sera of obese iraqi men. Euromedi. Biomed. J. young doctors. 2015; 10(17):198-202.
Oluwatobi TS, Oluseyi AA, Michael OA. Quercetin, a natural phytochemical and antioxidant protects against sodium azide-induced hepatic and splenic oxidative stress in rats. J. Invest. Biochem. 2015; 4(3):69-74.
Gusti AMT, Qusti SY, Alshammari EM. Antioxidants-Related Superoxide Dismutase (SOD), Catalase (CAT), Glutathione Peroxidase (GPX), Glutathione-S-Transferase (GST), and Nitric Oxide Synthase (NOS) Gene Variants Analysis in an Obese Population: A Preliminary Case-Control Study. Antioxidant. 2021;10(595):1-16.
Lewandowski Ł, Kepinska M, Milnerowicz H. The Copper-Zinc Superoxide Dismutase Activity in Selected Diseases. Eur. J. Clin. Invest. 2019;49(e13036):1-5.
Choe SS, Huh JY, Hwang IJ. Adipose Tissue Remodeling: Its Role in Energy Metabolism and Metabolic Disorders. Front. Endocr. 2016;7(30):1-16.
Michele L, Federica Z, Jamal N. Adipose Tissue Dysfunction as Determinant of Obesity-Associated Metabolic Complications. Inter. J. Mol. Sc. 2019; 20(2358):1-23.
Yang SA. Lack of Association Between Glutathione s-Transferase Mu 1 (GSTM1) Gene Polymorphisms and Obesity. J. Exer. Rehab. 2017; 3:608–612.
Caira S, Iannelli A, Sciarrillo R. Differential representation of liver proteins in obese human subjects suggests novel biomarkers and promising targets for drug development in obesity. J. Enz. Inhib. Med. Chem. 2017;32:672–682.
Can Y, Hakan B, Serpil O. The activities of GST isozymes in stomach tissues of female obese patients. Turk. J. Biochem. 2020;45(6):1-8.
Simona T, Flavia M, Antonella A. Honey and obesity-related dysfunctions: a summary on health benefits. J. Nutr. Biochem. 2020;82( 2020):108401.
Dżugan M, Tomczyk M, Sowa P. Antioxidant activity as biomarker of honey variety. Mol. 2018;23 pii: E2069.
Block G, Jensen CD, Dalvi TB. Vitamin C treatment reduces elevated C-reactive protein. Free Rad. Bio. Med. 2009;46(1): 70-77.
Cepeda-Lopez AC, Melse-Boonstra A, Zimmermann MB. In overweight and obese women, dietary iron absorption is reduced and the enhancement of iron absorption by ascorbic acid is one-half that in normal-weight women. Am. J. Clin. Nutr. 2015;102(6):1389-97.
Büşra T, Hatice B, Makbule GK. “Vitamin C Physiology: The Known and the Unknown in Obesity.” J. Food Nutr. Res. 2019;7(8):613-618.
Gariballa S, Afandi B, Abuhaltem M. Oxidative damage and inflammation in obese diabetic emirati subjects supplemented with antioxidants and B-vitamins: a randomized placebo-controlled trail. Nutr. Metab. 2013;(Lond),10:21.
Zeng G, Zhong F, Li J. Resveratrol-mediated reduction of collagen by inhibiting proliferation and producing apoptosis in human hypertrophic scar fibroblasts. Biosc. Biotech. Biochem. 2013; 77:2389–2296.
Martín A, Isabel S, Julio S. Vitamin E reduces adipose tissue fibrosis, inflammation, and oxidative stress and improves metabolic profile in obesity. Obesity. 2015;23(8):1598-1606.
Nemani H, Uday K, Boindala S. Obesity associated pathophysiological & histological changes in WNIN obese mutant rats. Ind. J. Med. Res. 2011;134(3): 330–340.
Magdalena J, Leslie PK. Obesity and related consequences to ageing. AGE. 2016;38(23):1-18.
Choi C, Hyun-Doo S, Yeonho S. Epigallocatechin-3-Gallate Reduces Visceral Adiposity Partly through the Regulation of Beclin1-Dependent Autophagy in White Adipose Tissues. Nutr. 2020; 12(10):3072.
-
Abstract View: 82 times
PDF Download: 22 times