Login Register Cart 0
Generic placeholder image

Pharmaceutical Nanotechnology

Editor-in-Chief

ISSN (Print): 2211-7385
ISSN (Online): 2211-7393

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Tyrosol-loaded Nano-niosomes Attenuate Diabetic Injury by Targeting Glucose Metabolism, Inflammation, and Glucose Transfer

Author(s): Nima Jafari-Rastegar, Haniyeh Sadat Hosseininia, Neda Mousavi-Niri, Fatemeh Khakpai and Maryam Naseroleslami*

Volume 12, Issue 4, 2024

Published on: 03 November, 2023

Page: [351 - 364] Pages: 14

DOI: 10.2174/0122117385251271231018104311

Price: $65

Abstract

Introduction: The increasing prevalence of type 2 diabetes, has become a global concern, making it imperative to control. Chemical drugs commonly recommended for diabetes treatment cause many complications and drug resistance over time.

Methods: The polyphenol tyrosol has many health benefits, including anti-diabetes properties. Tyrosol's efficacy can be significantly increased when it is used as a niosome in the treatment of diabetes. In this study, Tyrosol and nano-Tyrosol are examined for their effects on genes implicated in type 2 diabetes in streptozotocin-treated rats. Niosome nanoparticles containing 300 mg surfactant (span60: tween60) and 10 mg cholesterol were hydrated in thin films with equal molar ratios. After 72 hours, nano-niosomal formulas were assessed for their physicochemical properties. MTT assays were conducted on HFF cells to assess the cellular toxicity of the nano niosome contacting optimal Tyrosol. Finally, the expression of PEPCK, GCK, TNF-ɑ, IL6, GLUT2 and GLUT9 was measured by real-time PCR. Physiochemical properties of the SEM images of niosomes loaded with Tyrosol revealed the nanoparticles had a vehicular structure.

Results: In this study, there were two stages of release: initial release (8 hours) and sustainable release (72 hours). Meanwhile, free-form drugs were considerably more toxic than niosomal drugs in terms of their cellular toxicity. An in vivo comparison of oral Tyrosol gavage with nano-Tyrosol showed a significant increase in GCK (P < 0.001), GLUT2 (P < 0.001), and GLUT9 (P < 0.001). Furthermore, nano-Tyrosol decreased the expression of TNF-ɑ (P < 0.05), PEPCK (P < 0.001), and IL-6 (P < 0.05) which had been increased by diabetes mellitus. The results confirmed nano-Tyrosol's anti-diabetes and anti-inflammatory effects.

Conclusion: These findings suggest that nano-Tyrosol has potential applications in diabetes treatment and associated inflammation. Further research is needed to better understand the mechanism of action.

« Previous Next »
Graphical Abstract

[1]
Dkhar B, Khongsti K, Thabah D, Syiem D, Satyamoorthy K, Das B. Genistein represses PEPCK‐C expression in an insulin‐independent manner in HepG2 cells and in alloxan‐induced diabetic mice. J Cell Biochem 2018; 119(2): 1953-70.
[http://dx.doi.org/10.1002/jcb.26356] [PMID: 28816409]
[2]
Imelda SI. Faktor-faktor yang mempengaruhi terjadinya diabetes melitus di Puskesmas Harapan Raya tahun 2018. Sci J 2019; 8(1): 28-39.
[http://dx.doi.org/10.35141/scj.v8i1.406]
[3]
Mir M, Mir R, Alghamdi M, et al. Potential impact of GCK, MIR-196A-2 and MIR-423 gene abnormalities on the development and progression of type 2 diabetes mellitus in Asir and Tabuk regions of Saudi Arabia. Mol Med Rep 2022; 25(5): 162.
[http://dx.doi.org/10.3892/mmr.2022.12675] [PMID: 35293603]
[4]
Prawitasari DS. Diabetes melitus dan antioksidan. KELUWIH: J Kesehatan Kedokteran 2019; 1(1): 48-52.
[5]
Zhu YX, Hu HQ, Zuo ML, et al. Effect of oxymatrine on liver gluconeogenesis is associated with the regulation of PEPCK and G6Pase expression and AKT phosphorylation. Biomed Rep 2021; 15(1): 56.
[http://dx.doi.org/10.3892/br.2021.1432] [PMID: 34007449]
[6]
Seenappa V, Joshi MB, Satyamoorthy K. Intricate regulation of phosphoenolpyruvate carboxykinase (PEPCK) isoforms in normal physiology and disease. Curr Mol Med 2019; 19(4): 247-72.
[http://dx.doi.org/10.2174/1566524019666190404155801] [PMID: 30947672]
[7]
Choi JM, Seo MH, Kyeong HH, Kim E, Kim HS. Molecular basis for the role of glucokinase regulatory protein as the allosteric switch for glucokinase. Proc Natl Acad Sci 2013; 110(25): 10171-6.
[http://dx.doi.org/10.1073/pnas.1300457110] [PMID: 23733961]
[8]
Thorens B. GLUT2, glucose sensing and glucose homeostasis. Diabetologia 2015; 58(2): 221-32.
[http://dx.doi.org/10.1007/s00125-014-3451-1] [PMID: 25421524]
[9]
Chandrashekar J, Hoon MA, Ryba NJP, Zuker CS. The receptors and cells for mammalian taste. Nature 2006; 444(7117): 288-94.
[http://dx.doi.org/10.1038/nature05401] [PMID: 17108952]
[10]
Doblado M, Moley KH. Facilitative glucose transporter 9, a unique hexose and urate transporter. Am J Physiol Endocrinol Metab 2009; 297(4): E831-5.
[http://dx.doi.org/10.1152/ajpendo.00296.2009] [PMID: 19797240]
[11]
Doege H, Bocianski A, Joost HG, Schürmann A. Activity and genomic organization of human glucose transporter 9 (GLUT9), a novel member of the family of sugar-transport facilitators predominantly expressed in brain and leucocytes. Biochem J 2000; 350(3): 771-6.
[http://dx.doi.org/10.1042/bj3500771] [PMID: 10970791]
[12]
Li S, Sanna S, Maschio A, et al. The GLUT9 gene is associated with serum uric acid levels in Sardinia and Chianti cohorts. PLoS Genet 2007; 3(11): e194.
[http://dx.doi.org/10.1371/journal.pgen.0030194] [PMID: 17997608]
[13]
Keembiyehetty C, Augustin R, Carayannopoulos MO, et al. Mouse glucose transporter 9 splice variants are expressed in adult liver and kidney and are up-regulated in diabetes. Mol Endocrinol 2006; 20(3): 686-97.
[http://dx.doi.org/10.1210/me.2005-0010] [PMID: 16293642]
[14]
Dandona P, Aljada A, Bandyopadhyay A. Inflammation: The link between insulin resistance, obesity and diabetes. Trends Immunol 2004; 25(1): 4-7.
[http://dx.doi.org/10.1016/j.it.2003.10.013] [PMID: 14698276]
[15]
Dandona P, Aljada A, Chaudhuri A, Bandyopadhyay A. The potential influence of inflammation and insulin resistance on the pathogenesis and treatment of atherosclerosis-related complications in type 2 diabetes. J Clin Endocrinol Metab 2003; 88(6): 2422-9.
[http://dx.doi.org/10.1210/jc.2003-030178] [PMID: 12788837]
[16]
Moller DE. Potential role of TNF-α in the pathogenesis of insulin resistance and type 2 diabetes. Trends Endocrinol Metab 2000; 11(6): 212-7.
[http://dx.doi.org/10.1016/S1043-2760(00)00272-1] [PMID: 10878750]
[17]
Akash MSH, Rehman K, Liaqat A. Tumor necrosis factor‐alpha: Role in development of insulin resistance and pathogenesis of type 2 diabetes mellitus. J Cell Biochem 2018; 119(1): 105-10.
[http://dx.doi.org/10.1002/jcb.26174] [PMID: 28569437]
[18]
Swaroop J, Naidu JN, Rajarajeswari D. Association of TNF-α with insulin resistance in type 2 diabetes mellitus. Indian J Med Res 2012; 135(1): 127-30.
[http://dx.doi.org/10.4103/0971-5916.93435] [PMID: 22382194]
[19]
Pradhan AD, Manson JE, Rifai N, Buring JE, Ridker PM. C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA 2001; 286(3): 327-34.
[http://dx.doi.org/10.1001/jama.286.3.327] [PMID: 11466099]
[20]
Pickup JC, Chusney GD, Thomas SM, Burt D. Plasma interleukin-6, tumour necrosis factor α and blood cytokine production in type 2 diabetes. Life Sci 2000; 67(3): 291-300.
[http://dx.doi.org/10.1016/S0024-3205(00)00622-6] [PMID: 10983873]
[21]
Illig T, Bongardt F, Schöpfer A, et al. Significant association of the interleukin-6 gene polymorphisms C-174G and A-598G with type 2 diabetes. J Clin Endocrinol Metab 2004; 89(10): 5053-8.
[http://dx.doi.org/10.1210/jc.2004-0355] [PMID: 15472205]
[22]
Rehman K, Akash MSH, Liaqat A, Kamal S, Qadir MI, Rasul A. Role of interleukin-6 in development of insulin resistance and type 2 diabetes mellitus. Crit Rev Eukaryot Gene Expr 2017; 27(3): 229-36.
[http://dx.doi.org/10.1615/CritRevEukaryotGeneExpr.2017019712]
[23]
Karković Marković A, Torić J, Barbarić M, Jakobušić Brala C. Hydroxytyrosol, tyrosol and derivatives and their potential effects on human health. Molecules 2019; 24(10): 2001.
[http://dx.doi.org/10.3390/molecules24102001] [PMID: 31137753]
[24]
Covas MI, Miró-Casas E, Fitó M, et al. Bioavailability of tyrosol, an antioxidant phenolic compound present in wine and olive oil, in humans. Drugs Exp Clin Res 2003; 29(5-6): 203-6.
[PMID: 15134375]
[25]
Cañuelo A, Gilbert-López B, Pacheco-Liñán P, Martínez-Lara E, Siles E, Miranda-Vizuete A. Tyrosol, a main phenol present in extra virgin olive oil, increases lifespan and stress resistance in Caenorhabditis elegans. Mech Ageing Dev 2012; 133(8): 563-74.
[http://dx.doi.org/10.1016/j.mad.2012.07.004] [PMID: 22824366]
[26]
Lee H, Im SW, Jung CH, Jang YJ, Ha TY, Ahn J. Tyrosol, an olive oil polyphenol, inhibits ER stress-induced apoptosis in pancreatic β-cell through JNK signaling. Biochem Biophys Res Commun 2016; 469(3): 748-52.
[http://dx.doi.org/10.1016/j.bbrc.2015.12.036] [PMID: 26692476]
[27]
Kwon Y-I, Jang H-D, Shetty K. Evaluation of Rhodiola crenulata and Rhodiola rosea for management of type II diabetes and hypertension. Asia Pac J Clin Nutr 2006; 15(3): 425-32.
[PMID: 16837437]
[28]
Kendall M, Batterham M, Prenzler P, Ryan D, Robards K. Absorption, metabolism and excretion of phenols derived from olive products. Funct Plant Sci Biotechnol 2009; 3(S1): 81-91.
[29]
Uchegbu IF, Vyas SP. Non-ionic surfactant based vesicles (niosomes) in drug delivery. Int J Pharm 1998; 172(1-2): 33-70.
[http://dx.doi.org/10.1016/S0378-5173(98)00169-0]
[30]
Marianecci C, Di Marzio L, Rinaldi F, et al. Niosomes from 80s to present: The state of the art. Adv Colloid Interface Sci 2014; 205: 187-206.
[http://dx.doi.org/10.1016/j.cis.2013.11.018] [PMID: 24369107]
[31]
Sahin NO. Niosomes as nanocarrier systems. In: Nanomaterials and Nanosystems for Biomedical Applications. Dordrecht: Springer 2007; pp. 67-81.
[http://dx.doi.org/10.1007/978-1-4020-6289-6_4]
[32]
Rinaldi F, Hanieh P, Chan L, et al. Chitosan glutamate-coated niosomes: A proposal for nose-to-brain delivery. Pharmaceutics 2018; 10(2): 38.
[http://dx.doi.org/10.3390/pharmaceutics10020038] [PMID: 29565809]
[33]
Pourseif T, Ghafelehbashi R, Abdihaji M, et al. Chitosan -based nanoniosome for potential wound healing applications: Synergy of controlled drug release and antibacterial activity. Int J Biol Macromol 2023; 230: 123185.
[http://dx.doi.org/10.1016/j.ijbiomac.2023.123185] [PMID: 36623618]
[34]
Chandramohan R, Pari L, Rathinam A, Sheikh BA. Tyrosol, a phenolic compound, ameliorates hyperglycemia by regulating key enzymes of carbohydrate metabolism in streptozotocin induced diabetic rats. Chem Biol Interact 2015; 229: 44-54.
[http://dx.doi.org/10.1016/j.cbi.2015.01.026] [PMID: 25641191]
[35]
Ashkezari S, Abtahi MS, Sattari Z, et al. Antibiotic and inorganic nanoparticles co-loaded into carboxymethyl chitosan-functionalized niosome: Synergistic enhanced antibacterial and anti-biofilm activities. J Drug Deliv Sci Technol 2023; 83: 104386.
[http://dx.doi.org/10.1016/j.jddst.2023.104386]
[36]
Mansouri M, Khayam N, Jamshidifar E, et al. Streptomycin sulfate–loaded niosomes enables increased antimicrobial and anti-biofilm activities. Front Bioeng Biotechnol 2021; 9: 745099.
[http://dx.doi.org/10.3389/fbioe.2021.745099] [PMID: 34778226]
[37]
Magliano DJ, Sacre JW, Harding JL, Gregg EW, Zimmet PZ, Shaw JE. Young-onset type 2 diabetes mellitus - implications for morbidity and mortality. Nat Rev Endocrinol 2020; 16(6): 321-31.
[http://dx.doi.org/10.1038/s41574-020-0334-z] [PMID: 32203408]
[38]
Zatterale F, Longo M, Naderi J, et al. Chronic adipose tissue inflammation linking obesity to insulin resistance and type 2 diabetes. Front Physiol 2020; 10: 1607.
[http://dx.doi.org/10.3389/fphys.2019.01607] [PMID: 32063863]
[39]
Gasmi A, Noor S, Menzel A, Doşa A, Pivina L, Bjørklund G. Obesity and insulin resistance: Associations with chronic inflammation, genetic and epigenetic factors. Curr Med Chem 2021; 28(4): 800-26.
[http://dx.doi.org/10.2174/1875533XMTA57NDQgz] [PMID: 32838708]
[40]
Yu JH, Kim HY, Kim SR, Ko E, Jin HY. Factors influencing psychological insulin resistance in type 2 diabetes patients. Int J Nurs Pract 2019; 25(3): e12733.
[http://dx.doi.org/10.1111/ijn.12733] [PMID: 30945437]
[41]
Sutherland C, O’Brien RM, Granner DK, Marshall CJ. New connections in the regulation of PEPCK gene expression by insulin. Philos Trans R Soc Lond B Biol Sci 1996; 351(1336): 191-9.
[http://dx.doi.org/10.1098/rstb.1996.0016] [PMID: 8650266]
[42]
Xu L, Zheng D, Wang L, Jiang D, Liu H, Xu L, et al. GCK gene-body hypomethylation is associated with the risk of coronary heart disease. BioMed Res Int 2014; 2014
[43]
Mueckler M, Thorens B. The SLC2 (GLUT) family of membrane transporters. Mol Aspects Med 2013; 34(2-3): 121-38.
[http://dx.doi.org/10.1016/j.mam.2012.07.001] [PMID: 23506862]
[44]
Nieto-Vazquez I, Fernández-Veledo S, Krämer DK, Vila-Bedmar R, Garcia-Guerra L, Lorenzo M. Insulin resistance associated to obesity: The link TNF-alpha. Arch Physiol Biochem 2008; 114(3): 183-94.
[http://dx.doi.org/10.1080/13813450802181047] [PMID: 18629684]
[45]
Rotter V, Nagaev I, Smith U. Interleukin-6 (IL-6) induces insulin resistance in 3T3-L1 adipocytes and is, like IL-8 and tumor necrosis factor-α overexpressed in human fat cells from insulin-resistant subjects. J Biol Chem 2003; 278(46): 45777-84.
[http://dx.doi.org/10.1074/jbc.M301977200] [PMID: 12952969]
[46]
Paneni F, Costantino S, Cosentino F. Insulin resistance, diabetes, and cardiovascular risk. Curr Atheroscler Rep 2014; 16(7): 419.
[http://dx.doi.org/10.1007/s11883-014-0419-z] [PMID: 24781596]
[47]
Orgel E, Mittelman SD. The links between insulin resistance, diabetes, and cancer. Curr Diab Rep 2013; 13(2): 213-22.
[http://dx.doi.org/10.1007/s11892-012-0356-6] [PMID: 23271574]
[48]
Kahn SE, Hull RL, Utzschneider KM. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 2006; 444(7121): 840-6.
[http://dx.doi.org/10.1038/nature05482] [PMID: 17167471]
[49]
Chandramohan R, Saravanan S, Pari L. Beneficial effects of tyrosol on altered glycoprotein components in streptozotocin-induced diabetic rats. Pharm Biol 2017; 55(1): 1631-7.
[http://dx.doi.org/10.1080/13880209.2017.1315603] [PMID: 28427293]
[50]
Zhang J, Nugrahaningrum DA, Marcelina O, et al. Tyrosol facilitates neovascularization by enhancing skeletal muscle cells viability and paracrine function in diabetic hindlimb ischemia mice. Front Pharmacol 2019; 10: 909.
[http://dx.doi.org/10.3389/fphar.2019.00909] [PMID: 31474865]
[51]
Anghore D, Kulkarni GT. Development of novel nano niosomes as drug delivery system of Spermacoce hispida extract and in vitro antituberculosis activity. Curr Nanomater 2017; 2(1): 17-23.
[http://dx.doi.org/10.2174/2405461502666170314151949]
[52]
Moghassemi S, Hadjizadeh A. Nano-niosomes as nanoscale drug delivery systems: An illustrated review. J Control Release 2014; 185: 22-36.
[http://dx.doi.org/10.1016/j.jconrel.2014.04.015] [PMID: 24747765]
[53]
Varshosaz J, Taymouri S. Effect of different types of surfactants on the physical properties and stability of carvedilol nano-niosomes. Adv Biomed Res 2016; 5(1): 48.
[http://dx.doi.org/10.4103/2277-9175.178781] [PMID: 27110545]
[54]
Jafari-Rastegar N, Hosseininia HS, Jalilvand E, Naseroleslami M, Khakpai F, Mousavi-Niri N. Oral administration of nano-tyrosol reversed the diabetes-induced liver damage in streptozotocin-induced diabetic rats. J Diabetes Metab Disord 2022; 22(1): 297-305.
[http://dx.doi.org/10.1007/s40200-022-01133-w] [PMID: 37255797]
[55]
Rizza RA, Gerich JE, Haymond MW, et al. Control of blood sugar in insulin-dependent diabetes: Comparison of an artificial endocrine pancreas, continuous subcutaneous insulin infusion, and intensified conventional insulin therapy. N Engl J Med 1980; 303(23): 1313-8.
[http://dx.doi.org/10.1056/NEJM198012043032301] [PMID: 7001229]
[56]
Rajas F, Croset M, Zitoun C, Montano S, Mithieux G. Induction of PEPCK gene expression in insulinopenia in rat small intestine. Diabetes 2000; 49(7): 1165-8.
[http://dx.doi.org/10.2337/diabetes.49.7.1165] [PMID: 10909974]
[57]
Quinn PG, Yeagley D. Insulin regulation of PEPCK gene expression: A model for rapid and reversible modulation. Curr Drug Targets Immune Endocr Metabol Disord 2005; 5(4): 423-37.
[http://dx.doi.org/10.2174/156800805774912962] [PMID: 16375695]
[58]
Samuel VT, Beddow SA, Iwasaki T, et al. Fasting hyperglycemia is not associated with increased expression of PEPCK or G6Pc in patients with Type 2 Diabetes. Proc Natl Acad Sci USA 2009; 106(29): 12121-6.
[http://dx.doi.org/10.1073/pnas.0812547106] [PMID: 19587243]
[59]
Osbak KK, Colclough K, Saint-Martin C, et al. Update on mutations in glucokinase (GCK), which cause maturity-onset diabetes of the young, permanent neonatal diabetes, and hyperinsulinemic hypoglycemia. Hum Mutat 2009; 30(11): 1512-26.
[http://dx.doi.org/10.1002/humu.21110] [PMID: 19790256]
[60]
Gloyn AL. Glucokinase (GCK) mutations in hyper- and hypoglycemia: Maturity-onset diabetes of the young, permanent neonatal diabetes, and hyperinsulinemia of infancy. Hum Mutat 2003; 22(5): 353-62.
[http://dx.doi.org/10.1002/humu.10277] [PMID: 14517946]
[61]
Cuesta-Muñoz AL, Tuomi T, Cobo-Vuilleumier N, et al. Clinical heterogeneity in monogenic diabetes caused by mutations in the glucokinase gene (GCK-MODY). Diabetes Care 2010; 33(2): 290-.
[http://dx.doi.org/10.2337/dc09-0681] [PMID: 19903754]
[62]
Stanirowski PJ, Szukiewicz D, Pyzlak M, Abdalla N, Sawicki W, Cendrowski K. Impact of pre-gestational and gestational diabetes mellitus on the expression of glucose transporters GLUT-1, GLUT-4 and GLUT-9 in human term placenta. Endocrine 2017; 55(3): 799-808.
[http://dx.doi.org/10.1007/s12020-016-1202-4] [PMID: 27981520]
[63]
Guillam MT, Hümmler E, Schaerer E, et al. Early diabetes and abnormal postnatal pancreatic islet development in mice lacking Glut-2. Nat Genet 1997; 17(3): 327-30.
[http://dx.doi.org/10.1038/ng1197-327] [PMID: 9354799]
[64]
Behrouz V, Sohrab G, Hedayati M, Sedaghat M. Inflammatory markers response to crocin supplementation in patients with type 2 diabetes mellitus: A randomized controlled trial. Phytother Res 2021; 35(7): 4022-31.
[http://dx.doi.org/10.1002/ptr.7124] [PMID: 33856733]
[65]
Mirza S, Hossain M, Mathews C, et al. Type 2-diabetes is associated with elevated levels of TNF-alpha, IL-6 and adiponectin and low levels of leptin in a population of Mexican Americans: A cross-sectional study. Cytokine 2012; 57(1): 136-42.
[http://dx.doi.org/10.1016/j.cyto.2011.09.029] [PMID: 22035595]
[66]
Jacob CO, Aiso S, Michie SA, McDevitt HO, Acha-Orbea H. Prevention of diabetes in nonobese diabetic mice by tumor necrosis factor (TNF): Similarities between TNF-alpha and interleukin 1. Proc Natl Acad Sci 1990; 87(3): 968-72.
[http://dx.doi.org/10.1073/pnas.87.3.968] [PMID: 2405400]
[67]
Zegeye MM, Lindkvist M, Fälker K, et al. Activation of the JAK/STAT3 and PI3K/AKT pathways are crucial for IL-6 trans-signaling-mediated pro-inflammatory response in human vascular endothelial cells. Cell Commun Signal 2018; 16(1): 55.
[http://dx.doi.org/10.1186/s12964-018-0268-4] [PMID: 30185178]
[68]
Harder-Lauridsen NM, Krogh-Madsen R, Holst JJ, et al. Effect of IL-6 on the insulin sensitivity in patients with type 2 diabetes. Am J Physiol Endocrinol Metab 2014; 306(7): E769-78.
[http://dx.doi.org/10.1152/ajpendo.00571.2013] [PMID: 24473436]
[69]
Jahandideh B, Derakhshani M, Abbaszadeh H, et al. The pro-Inflammatory cytokines effects on mobilization, self-renewal and differentiation of hematopoietic stem cells. Hum Immunol 2020; 81(5): 206-17.
[http://dx.doi.org/10.1016/j.humimm.2020.01.004] [PMID: 32139091]
[70]
Yun JH, Lee DH, Jeong HS, Kim SH, Ye SK, Cho CH. STAT3 activation in microglia increases pericyte apoptosis in diabetic retinas through TNF-ɑ/AKT/p70S6 kinase signaling. Biochem Biophys Res Commun 2022; 613: 133-9.
[http://dx.doi.org/10.1016/j.bbrc.2022.05.004] [PMID: 35561580]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy