Research Article | Volume: 12, Issue: 8, August, 2022

In vitro and in vivo studies of the antidiabetic potential of Red Sea sponge-associated fungus “Aspergillus unguis” isolate SP51-EGY with correlations to its chemical composition

Mona E. Aboutabl Yousreya. A. Maklad Mohamed S. Abdel-Aziz Faten K. Abd El-Hady   

Open Access   

Published:  Aug 04, 2022

DOI: 10.7324/JAPS.2022.120817
Abstract

Diabetes mellitus is one of the most prevalent chronic diseases. The main objective is to determine ‎antidiabetic and antioxidant activities of Red Sea sponge-associated fungus “Aspergillus ‎unguis” isolate SP51-EGY secondary metabolites with concomitant gas chromatography/mass spectrometry (GC/MS) analysis of active extracts.‎ In vitro α-glucosidase inhibition and antioxidant capacity were determined. In vivo, LD50 was determined in mice. Streptozotocin-induced diabetic mice were treated with mycelial-free culture filtrate and mycelial extracts. Serum blood glucose, serum C-peptide, glucagon-like peptide-1 (GLP-1), α-glucosidase, and adiponectin levels were estimated. Shake (Sh) filtrate and mycelial extracts demonstrated the highest significant in vitro α-glucosidase inhibitory activity. Sh mycelia demonstrated higher antioxidant capacity compared to Sh filtrate. In vivo, treatment with Sh mycelia (50 and 100 mg/kg) significantly lowered the blood glucose level by 27% and 54%, respectively, while Sh filtrate (125 and 250 mg/kg) significantly decreased the blood glucose level by 49% and 70%, respectively, compared to the diabetic group, respectively. Filtrate and mycelial extracts significantly increased C-peptide, GLP-1, and adiponectin, while significantly inhibiting α-glucosidase serum level compared to the diabetic group. GC/MS analysis revealed a high percentage of isovanillic acid; d-friedoolean-14-en-3-one; isochromanone derivative in filtrate extract; and palmitic, linolenic acids, and their esters in the mycelial extract. Therefore, secondary metabolites could be considered an effective strategy in the regulation of blood glucose level.


Keyword:     Red Sea sponge-associated fungus Aspergillus unguis SP51-EGY antidiabetic α-glucosidase inhibition antioxidant GC/MS analysis


Citation:

Aboutabl ME, Maklad YA, Abdel-Aziz MS, Abd El-Hady FK. In vitro and in vivo studies of the antidiabetic potential of Red Sea sponge-associated fungus “Aspergillus unguis” isolate SP51-EGY with correlations to its chemical composition. J Appl Pharm Sci, 2022;12(08):165–178.

Copyright: © The Author(s). This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Reference

Abd El-Hady FK, Abdel-Aziz MS, Shaker KH, El-Shahid ZA, Ghani MA. Coral-derived fungi inhibit acetylcholinesterase, superoxide anion radical, and microbial activities. Int J Pharm Sci Rev Res, 2014; 26(1):301-8.

Abd El-Hady FK, Abdel-Aziz MS, Shaker KH, El-Shahid ZA, Ibrahim LS. Antioxidant, acetylcholinesterase and α-Glucosidase potentials of metabolites from the marine fungus Aspergillus unguis RSPG_204 associated with the sponge (Agelas sp.). J Pharm Sci Rev Res, 2015; 30(1):272-8.

Abd El-Hady FK, Abdel-Aziz MS, Souleman AMA, El-Shahid ZA, Shaker KH. Enhancement of acetylcholinesterase inhibitory activity for the soft coral associated fungus Aspergillus unguis SPMD-EGY by media composition. Int J Pharm Sci Rev Res, 2016; 41:349-57.

Aboul-Enein MN, El-Azzouny A, Saleh O, Maklad Y, Aboutabl M, Gamal El-Din M. Synthesis, bio-evaluation and molecular modeling studies of (2S)-1-[({[1-substituted cyclohexyl] methyl} amino) acetyl] pyrrolidine-2-carbonitriles for their DPP-4 Inhibiting Activity. Int J Pharm Sci Rev Res, 2016; 39(2):230-40.

Alsterberg C, Roger F, Sundbäck K, Juhanson J, Hulth S, Hallin S, Gamfeldt L. Habitat diversity and ecosystem multifunctionality-The importance of direct and indirect effects. Sci Adv, 2017; 3(2):e1601475. https://doi.org/10.1126/sciadv.1601475

Amalan V, Vijayakumar N, Indumathi D, Ramakrishnan A. Antidiabetic and antihyperlipidemic activity of p-coumaric acid in diabetic rats, role of pancreatic GLUT 2: in vivo approach. Biomed Pharmacother, 2016; 84:230-6. https://doi.org/10.1016/j.biopha.2016.09.039

Antony P, Vijayan R. Bioactive peptides as potential nutraceuticals for diabetes therapy: a comprehensive review. Int J Mol Sci, 2021; 22(16):9059. https://doi.org/10.1016/j.biopha.2016.09.039

Barham D, Trinder P. An improved colour reagent for the determination of blood glucose by the oxidase system. Analyst, 1972; 97(151):142-5. https://doi.org/10.1039/an9729700142

Bommer C, Sagalova V, Heesemann E, Manne-Goehler J, Atun R, Bärnighausen T, Davies J, Vollmer S. Global economic burden of diabetes in adults: projections from 2015 to 2030.

Diabetes Care, 2018; 41(5):963. Chae SY, Choi YG, Son S, Jung SY, Lee DS, Lee KC. The fatty acid conjugated exendin-4 analogs for type 2 antidiabetic therapeutics. J Control Release, 2010; 144(1):10-6. https://doi.org/10.1016/j.jconrel.2010.01.024

Eid HM, Thong F, Nachar A, Haddad PS. Caffeic acid methyl and ethyl esters exert potential antidiabetic effects on glucose and lipid metabolism in cultured murine insulin-sensitive cells through mechanisms implicating activation of AMPK. Pharm Biol, 2017; 55(1):2026-34. https://doi.org/10.1080/13880209.2017.1345952

Fu Z, Gilbert ER, Liu D. Regulation of insulin synthesis and secretion and pancreatic Beta-cell dysfunction in diabetes. Curr Diabetes Rev, 2013; 9(1):25-53. https://doi.org/10.2174/157339913804143225

Gayathri M, Kannabiran K. Antidiabetic activity of 2-hydroxy 4-methoxy benzoic acid isolated from the roots of Hemidesmus indicus on streptozotocin-induced diabetic rats. Int J Diabetes Metab, 2009a; 17:53-7. https://doi.org/10.1159/000497673

Gayathri M, Kannabiran K. Effect of 2-hydroxy-4-methoxy benzoic acid from the roots of Hemidesmus indicus on streptozotocininduced diabetic rats. Indian J Pharm Sci, 2009b; 71(5):581-5. https://doi.org/10.4103/0250-474X.58180

Gayathri M, Kannabiran K. 2-hydroxy 4-methoxy benzoic acid isolated from roots of Hemidesmus indicus ameliorates liver, kidney and pancreas injury due to streptozotocin-induced diabetes in rats. Indian J Exp Biol, 2010; 48(2):159-64.

Greenaway W, May J, Scaysbrook T, Whatley FR. Identification by gas chromatography-mass spectrometry of 150 compounds in propolis. Zeitschrift für Naturforschung C, 1991; 46(1-2):111-21. https://doi.org/10.1515/znc-1991-1-218

Hegazi R, El-Gamal M, Abdel-Hady N, Hamdy O. Epidemiology of and risk factors for type 2 diabetes in Egypt. Ann Glob Health, 2015; 81(6):814-20. https://doi.org/10.1016/j.aogh.2015.12.011

Huang J, Guo Z-h, Cheng P, Sun B-h, Gao H-Y. Three new triterpenoids from Salacia hainanensis Chun et How showed effective antiα-glucosidase activity. Phytochem Lett, 2012; 5(3):432-37. https://doi.org/10.1016/j.phytol.2012.03.016

IDF (2019) International Diabetes Federation. Diabetes atlas, 9th edition. Available via https://www.diabetesatlas.org/upload/resources/ material/20200302_133351_IDFATLAS9e-final-web.pdf Kalra S. Incretin enhancement without hyperinsulinemia: α-glucosidase inhibitors. Expert Rev Endocrinol Metab, 2014; 9(5):423-5. https://doi.org/10.1586/17446651.2014.931807

Kato M, Miura T, Nakao M, Iwamoto N, Ishida T, Tanigawa K. Effect of alpha-linolenic acid on blood glucose, insulin and GLUT4 protein content of type 2 diabetic mice. J Health Sci, 2000; 46(6):489-92. https://doi.org/10.1248/jhs.46.489

Kentrup H, Bongers H, Spengler M, Kusenbach G, Skopnik H. Efficacy and safety of acarbose in patients with cystic fibrosis and impaired glucose tolerance. Eur J Pediatr, 1999; 158(6):455-9. https://doi.org/10.1007/s004310051119

Litchfield J, Wilcoxon F. A simplified method of evaluating dose-effect experiments. J Pharmacol Exp Ther, 1949; 96(2):99-113.

Liu M, Qi C, Sun W, Shen L, Wang J, Liu J, Lai Y, Xue Y, Hu Z, Zhang Y. α-Glucosidase inhibitors from the coral-associated fungus Aspergillus terreus. Front Chem, 2018; 6:422. https://doi.org/10.3389/fchem.2018.00422

Luppi P, Drain P. C-peptide antioxidant adaptive pathways in β cells and diabetes. J Intern Med, 2017; 281(1):7-24. https://doi.org/10.1111/joim.12522

Manilal A, Sabarathnam B, Kiran GS, Sujith S, Shakir C, Selvin J. Antagonistic potentials of marine sponge associated fungi Aspergillus clavatus MFD15. Asian J Med Sci, 2010; 2(4):195-200.

Marín-Peñalver JJ, Martín-Timón I, Sevillano-Collantes C, Del Cañizo-Gómez FJ. Update on the treatment of type 2 diabetes mellitus. World J Diabetes, 2016; 7(17):354-95. https://doi.org/10.4239/wjd.v7.i17.354

Matboli M, Eissa S, Ibrahim D, Hegazy MGA, Imam SS, Habib EK. Caffeic acid attenuates diabetic kidney disease via modulation of autophagy in a high-fat diet/streptozotocin-induced diabetic rat. Sci Rep, 2017; 7(1):2263. https://doi.org/10.1038/s41598-017-02320-z

Mehaya FM, Mohammad AA. Thermostability of bioactive compounds during roasting process of coffee beans. Heliyon, 2020; 6(11):e05508. https://doi.org/10.1016/j.heliyon.2020.e05508

Mohammed FZ, El-Shehabi M. Antidiabetic activity of caffeic acid and 18β-glycyrrhetinic acid and its relationship with the antioxidant property. Asian J Pharm Clin Res, 2015; 8:229-35.‏

Moloney F, Toomey S, Noone E, Nugent A, Allan B, Loscher CE, Roche HM. Antidiabetic effects of cis-9, trans-11-conjugated linoleic acid may be mediated via anti-inflammatory effects in white adipose tissue. Diabetes, 2007; 56(3):574-82. https://doi.org/10.2337/db06-0384

Moritoh Y, Takeuchi K, Hazama M. Chronic administration of voglibose, an alpha-glucosidase inhibitor, increases active glucagonlike peptide-1 levels by increasing its secretion and decreasing dipeptidyl peptidase-4 activity in ob/ob mice. J Pharmacol Exp Ther, 2009; 329(2):669-76. https://doi.org/10.1124/jpet.108.148056

Moselhy SS, Razvi SS, Alshibili FA, Kuerban A, Hasan MN, Balamash KS, Huwait EA, Abdulaal WH, Al-Ghamdi MA, Kumosani TA. m-Coumaric acid attenuates non-catalytic protein glycosylation in the retinas of diabetic rats. J Pesticide Sci, 2018; 43(3):180-5. https://doi.org/10.1584/jpestics.D17-091

Nadeem F, Oves M, Qari H, Ismail I. Red sea microbial diversity for antimicrobial and anticancer agents. J Mol Biomark Diagn, 2015; 7(267):2.

Nagao K, Inoue N, Wang YM, Yanagita T. Conjugated linoleic acid enhances plasma adiponectin level and alleviates hyperinsulinemia and hypertension in Zucker diabetic fatty (fa/fa) rats. Biochem Biophys Res Commun, 2003; 310(2):562-6. https://doi.org/10.1016/j.bbrc.2003.09.044

Nakamura K, Oe H, Kihara H, Shimada K, Fukuda S, Watanabe K, Takagi T, Yunoki K, Miyoshi T, Hirata K, Yoshikawa J, Ito H. DPP4 inhibitor and alpha-glucosidase inhibitor equally improve endothelial function in patients with type 2 diabetes: EDGE study. Cardiovasc Diabetol, 2014; 13:110. https://doi.org/10.1186/s12933-014-0110-2

Obici S, Feng Z, Morgan K, Stein D, Karkanias G, Rossetti L. Central administration of oleic acid inhibits glucose production and food intake. Diabetes, 2002; 51(2):271. https://doi.org/10.2337/diabetes.51.2.271

Ochiai H, Ooka H, Shida C, Ishikawa T, Inoue D, Okazaki R. Acarbose treatment increases serum total adiponectin levels in patients with type 2 diabetes. Endocr J, 2008; 55(3):549-56. https://doi.org/10.1507/endocrj.K07E-107

Papagianni M and Mattey M. Physiological aspects of free and immobilized Aspergillus niger cultures producing citric acid under various glucose concentrations. Process Biochem, 2004; 39(12):1963-70. https://doi.org/10.1016/j.procbio.2003.09.027

Peungvicha P, Thirawarapan SS, Watanabe H. Possible mechanism of hypoglycemic effect of 4-hydroxybenzoic acid, a constituent of Pandanus odorus root. Jpn J Pharmacol, 1998; 78(3):395-8. https://doi.org/10.1254/jjp.78.395

Phelan SA, Ito M, Loeken MR. Neural tube defects in embryos of diabetic mice: role of the Pax-3 gene and apoptosis. Diabetes, 1997; 46(7):1189-97. https://doi.org/10.2337/diab.46.7.1189

Proença C, Ribeiro D, Freitas M, Fernandes E. Flavonoids as potential agents in the management of type 2 diabetes through the modulation of α-amylase and α-glucosidase activity. Crit Rev Food Sci Nutr, 2021; 1-71. https://doi.org/10.1080/10408398.2020.1862755

Pu J, Peng G, Li L, Na H, Liu Y, Liu P. Palmitic acid acutely stimulates glucose uptake via activation of Akt and ERK1/2 in skeletal muscle cells. J Lipid Res, 2011; 52(7):1319-27. https://doi.org/10.1194/jlr.M011254

Rateb ME, Ebel R. Secondary metabolites of fungi from marine habitats. Nat Prod Rep, 2011; 28(2):290-344. https://doi.org/10.1039/c0np00061b

Roglic G. WHO global report on diabetes: a summary. Int J Noncommun Dis, 2016; 1(1):3. https://doi.org/10.4103/2468-8827.184853

Rossi M, Caruso F, Crespi EJ, Pedersen JZ, Nakano G, Duong M, McKee C, Lee S, Jiwrajka M, Caldwell C, Baffour F, Karlin DA, Lidoff G, Leone S, Balducci V, Miler J, Incerpi S. Probing antioxidant activity of 2′-hydroxychalcones: crystal and molecular structures, in vitro antiproliferative studies and in vivo effects on glucose regulation. Biochimie, 2013; 95(10):1954-963. https://doi.org/10.1016/j.biochi.2013.07.002

Sadiq A, Rashid U, Ahmad S, Zahoor M, AlAjmi MF, Ullah R, Noman OM, Ullah F, Ayaz M, Khan I, Islam Z-U, Ali W. Treating hyperglycemia from Eryngium caeruleum M. Bieb: in-vitro α-glucosidase, antioxidant, in-vivo antidiabetic and molecular docking-based approaches. Front Chem, 2020; 8:1064. https://doi.org/10.3389/fchem.2020.558641

Saeedi P, Petersohn I, Salpea P, Malanda B, Karuranga S, Unwin N, Colagiuri S, Guariguata L, Motala AA, Ogurtsova K, Shaw JE, Bright D, Williams R. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: results from the International Diabetes Federation Diabetes Atlas, 9 (th) edition. Diabetes Res Clin Pract, 2019; 157:107843. https://doi.org/10.1016/j.diabres.2019.107843

Sancheti S, Sancheti S, Lee SH, Lee JE, Seo SY. Screening of Korean medicinal plant extracts for α-glucosidase inhibitory activities. Iran J Pharm Res, 2011; 10(2):261-4.

Shin J, Jang MG, Park JC, Koo YD, Lee JY, Park KS, Chung SS, Park K. Antidiabetic effects of trihydroxychalcone derivatives via activation of AMP-activated protein kinase. J Indus Eng Chem, 2018; 60:177-84. https://doi.org/10.1016/j.jiec.2017.11.003

Shu X-S, Lv J-H, Tao J, Li G-M, Li H-D, Ma N. Antihyperglycemic effects of total flavonoids from Polygonatum odoratum in STZ and alloxaninduced diabetic rats. J Ethnopharmacol, 2009; 124(3):539-43. https://doi.org/10.1016/j.jep.2009.05.006

Srinivasan S, Rayar A. Isolation and identification of linoleic acid as an antidiabetic agent from the dry walnuts. Int J Recent Sci Res, 2020; 11(12):40213-6.

Subramani R, Kumar R, Prasad P, Aalbersberg W. Cytotoxic and antibacterial substances against multi-drug resistant pathogens from marine sponge symbiont: citrinin, a secondary metabolite of Penicillium sp. Asian Pac J Trop Biomed, 2013; 3(4):291-6. https://doi.org/10.1016/S2221-1691(13)60065-9

Sultanova NA, Abilov ZA, Umbetova AK, Choudhary MI. Biologically Active terpenoids from Tamarix species. Eurasian ChemTechnol J, 2013; 15(3):219-26. https://doi.org/10.18321/ectj225

Vassiliou EK, Gonzalez A, Garcia C, Tadros JH, Chakraborty G, Toney JH. Oleic acid and peanut oil high in oleic acid reverse the inhibitory effect of insulin production of the inflammatory cytokine TNF-α both in vitro and in vivo systems. Lipids Health Dis, 2009; 8(1):25. https://doi.org/10.1186/1476-511X-8-25

Verhaegen AA, Van Gaal LF. Drugs that affect body weight, body fat distribution, and metabolism. In: Feingold KR, Editor-in-chief, Anawalt B, Boyce A, Chrousos G, de Herder WW, Dhatariya K, Dungan K, Hershman JM, Hofland J, Kalra S, Kaltsas G, Koch C, Kopp P, Korbonits M, Kovacs CS, Kuohung W, Laferrère B, Levy M, McGee EA, McLachlan R, Morley JE, New M, Purnell J, Sahay R, Singer F, Sperling MA, Stratakis CA, Trence DL Wilson DP. (eds.). Endotext [Internet], 2019; South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK537590/

Yamada Y, Muraki A, Oie M, Kanegawa N, Oda A, Sawashi Y, Kaneko K, Yoshikawa M, Goto T, Takahashi N, Kawada T, Ohinata K. Soymorphin-5, a soy-derived μ-opioid peptide, decreases glucose and triglyceride levels through activating adiponectin and PPARα systems in diabetic KKAy mice. Am J Physiol Endocrinol Metab, 2012; 302(4):E433- 40. https://doi.org/10.1152/ajpendo.00161.2011

Yamauchi T, Kamon J, Minokoshi Y, Ito Y, Waki H, Uchida S, Yamashita S, Noda M, Kita S, Ueki K, Eto K, Akanuma Y, Froguel P, Foufelle F, Ferre P, Carling D, Kimura S, Nagai R, Kahn BB, Kadowaki T. Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med, 2002; 8(11):1288-95. https://doi.org/10.1038/nm788

Yanai H, Yoshida H. Beneficial Effects of Adiponectin on glucose and lipid metabolism and atherosclerotic progression: mechanisms and perspectives. Int J Mol Sci, 2019; 20(5):1190. https://doi.org/10.3390/ijms20051190

Zheng MY, Yang JH, Shan CY, Zhou HT, Xu YG, Wang Y, Ren HZ, Chang BC, Chen LM. Effects of 24-week treatment with acarbose on glucagon-like peptide 1 in newly diagnosed type 2 diabetic patients: a preliminary report. Cardiovasc Diabetol, 2013; 12:73. https://doi.org/10.1186/1475-2840-12-73

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