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Endocrine, Metabolic & Immune Disorders - Drug Targets

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ISSN (Online): 2212-3873

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Review Article

Molecular and Immunological Mechanisms Underlying the Various Pharmacological Properties of the Potent Bioflavonoid, Rutin

Author(s): David O.C. Yong, Sanggetha R. Saker, Dinesh K. Chellappan*, Thiagarajan Madheswaran, Jithendra Panneerselvam, Hira Choudhury, Manisha Pandey, Yik L. Chan, Trudi Collet, Gaurav Gupta, Brian G. Oliver, Peter Wark, Nicole Hansbro, Alan Hsu, Philip M. Hansbro, Kamal Dua* and Farrukh Zeeshan

Volume 20, Issue 10, 2020

Page: [1590 - 1596] Pages: 7

DOI: 10.2174/1871530320666200503053846

Price: $65

Abstract

The application of medicinal plants has captured the interest of researchers in recent times due to their potent therapeutic properties and a better safety profile. The prominent role of herbal products in treating and preventing multiple diseases dates back to ancient history and most of the modern drugs today originated from their significant sources owing to their ability to control multiple targets via different signalling pathways. Among them, flavonoids consist of a large group of polyphenols, which are well known for their various therapeutic benefits. Rutin is considered one of the attractive phytochemicals and important flavonoids in the pharmaceutical industry due to its diverse pharmacological activities via various underlying molecular mechanisms. It is usually prescribed for various disease conditions such as varicosities, haemorrhoids and internal haemorrhage. In this review, we have discussed and highlighted the different molecular mechanisms attributed to the various pharmacological activities of rutin, such as antioxidant, anti-inflammatory, anticancer, anti-allergic and antidiabetic. This review will be beneficial to herbal, biological and molecular scientists in understanding the pharmacological relevance of rutin at the molecular level.

Keywords: Rutin, molecular mechanisms, antioxidant, anti-inflammatory, anticancer, anti-allergic, anti-diabetic.

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Graphical Abstract

[1]
Gupta, G.; Tiwari, J.; Dahiya, R.; Kumar Sharma, R.; Mishra, A.; Dua, K. Recent updates on neuropharmacological effects of luteolin. EXCLI J., 2018, 17, 211-214.
[PMID: 29743859]
[2]
Ng, Z.Y.; Wong, J.Y.; Panneerselvam, J.; Madheswaran, T.; Kumar, P.; Pillay, V.; Hsu, A.; Hansbro, N.; Bebawy, M.; Wark, P.; Hansbro, P.; Dua, K.; Chellappan, D.K. Assessing the potential of liposomes loaded with curcumin as a therapeutic intervention in asthma. Colloids Surf. B Biointerfaces, 2018, 172, 51-59.
[http://dx.doi.org/10.1016/j.colsurfb.2018.08.027] [PMID: 30134219]
[3]
Chellappan, D.K.; Ng, Z.Y.; Wong, J.Y.; Hsu, A.; Wark, P.; Hansbro, N.; Taylor, J.; Panneerselvam, J.; Madheswaran, T.; Gupta, G.; Bebawy, M.; Hansbro, P.M.; Dua, K. Immunological axis of curcumin-loaded vesicular drug delivery systems. Future Med. Chem., 2018, 10(8), 839-844.
[http://dx.doi.org/10.4155/fmc-2017-0245] [PMID: 29620416]
[4]
Gupta, G.; Sharma, R.K.; Dahiya, R.; Mishra, A.; Tiwari, J.; Sharma, G.N.; Sharma, S.; Dua, K. Aphrodisiac activity of an aqueous extract of wood ear mushroom, Auricularia polytricha (Heterobasidiomycetes), in male rats. Int. J. Med. Mushrooms, 2018, 20(1), 81-88.
[http://dx.doi.org/10.1615/IntJMedMushrooms.2018025303] [PMID: 29604915]
[5]
Gupta, G.; Chellappan, D.K.; Kikuchi, I.S.; Pinto, T.J.A.; Pabreja, K.; Agrawal, M.; Singh, Y.; Tiwari, J.; Dua, K. Nephrotoxicity in rats exposed to paracetamol: the protective role of moralbosteroid, a steroidal glycoside. J. Environ. Pathol. Toxicol. Oncol., 2017, 36(2), 113-119.
[http://dx.doi.org/10.1615/JEnvironPatholToxicolOncol.2017019457] [PMID: 29199592]
[6]
Das, P.; Kumar, K.; Nambiraj, A.; Rajan, R.; Awasthi, R.; Dua, K.M,H. Potential therapeutic activity of Phlogacanthus thyrsiformis Hardow (Mabb) flower extract and its biofabricated silver nanoparticles against chemically induced urolithiasis in male Wistar rats. Int. J. Biol. Macromol., 2017, 103, 621-629.
[http://dx.doi.org/10.1016/j.ijbiomac.2017.05.096] [PMID: 28528955]
[7]
Sharma, S.; Pathak, S.; Gupta, G.; Sharma, S.K.; Singh, L.; Sharma, R.K.; Mishra, A.; Dua, K. Pharmacological evaluation of aqueous extract of syzigium cumini for its antihyperglycemic and antidyslipidemic properties in diabetic rats fed a high cholesterol diet-Role of PPARγ and PPARα. Biomed. Pharmacother., 2017, 89, 447-453.
[http://dx.doi.org/10.1016/j.biopha.2017.02.048] [PMID: 28249245]
[8]
Dua, K.; Sheshala, R.; Ling, T.Y.; Hui, Ling S.; Gorajana, A. Anti-inflammatory, antibacterial and analgesic potential of cocos nucifera linn.: a review. Antiinflamm. Antiallergy Agents Med. Chem., 2013, 12(2), 158-164.
[http://dx.doi.org/10.2174/1871523011312020007] [PMID: 23286236]
[9]
Sheshala, R.; Ying, L.T.; Hui, L.S.; Barua, A.; Dua, K. Development and anti-microbial potential of topical formulations containing Cocos nucifera Linn. Antiinflamm. Antiallergy Agents Med. Chem., 2013, 12(3), 253-264.
[http://dx.doi.org/10.2174/18715230113129990012] [PMID: 23746224]
[10]
Chellappan, D.K.; Ganasen, S.; Batumalai, S.; Candasamy, M.; Krishnappa, P.; Dua, K.; Chellian, J.; Gupta, G. The protective action of the aqueous extract of Auricularia polytricha in paracetamol induced hepatotoxicity in rats. Recent Pat. Drug Deliv. Formul., 2016, 10(1), 72-76.
[http://dx.doi.org/10.2174/1872211309666151030110015] [PMID: 26517821]
[11]
Gullón, B.; Lú-Chau, T.A.; Moreira, M.T.; Lema, J.; Eibes, G. Rutin: A review on extraction, identification and purification methods, biological activities and approaches to enhance its bioavailability. Trends Food Sci. Technol., 2017, 67, 220-235.
[http://dx.doi.org/10.1016/j.tifs.2017.07.008]
[12]
Patil, S.L.; Rao, N.B.; Somashekarappa, H.M.; Rajashekhar, K.P. Antigenotoxic potential of rutin and quercetin in Swiss mice exposed to gamma radiation. Biomed. J., 2014, 37(5), 305-313.
[http://dx.doi.org/10.4103/2319-4170.132880] [PMID: 25179701]
[13]
Chua, L.S. A review on plant-based rutin extraction methods and its pharmacological activities. J. Ethnopharmacol., 2013, 150(3), 805-817.
[http://dx.doi.org/10.1016/j.jep.2013.10.036] [PMID: 24184193]
[14]
Shayne, C.D. Combining NMR spectral information. Drug Discovery Handbook; John Wiley & Sons, Wiley-Interscience: Canada, 2005, p. 278.
[15]
Ahmad, M. Sahabjada.; Akhtar, J.; Hussain, A.; Badaruddeen.; Arshad, M.; Mishra, A. Development of a new rutin nanoemulsion and its application on prostate carcinoma PC3 cell line. EXCLI J., 2017, 16, 810-823.
[PMID: 28694767]
[16]
Sharma, S.; Ali, A.; Ali, J.; Sahni, J.K.; Baboota, S. Rutin: Therapeutic potential and recent advances in drug delivery. Expert Opin. Investig. Drugs, 2013, 22(8), 1063-1079.
[http://dx.doi.org/10.1517/13543784.2013.805744] [PMID: 23795677]
[17]
Dwyer, J.T.; Saldanha, L.G.; Bailen, R.; Bailey, R.L.; Costello, R.; Betz, J.M.; Chang, F.F.; Goshorn, J.; Andrews, K.W.; Pehrsson, P.R.; Milner, J.A.; Burt, V.L.; Gahche, J.J.; Hardy, C.J.; Emenaker, N.J. A free new dietary supplement label database for dietitians. J. Acad. Nutr. Diet., 2014, 114(10), 1512-1517.
[http://dx.doi.org/10.1016/j.jand.2014.04.015] [PMID: 24928780]
[18]
Dzoyem, J.P.; Hamamoto, H.; Ngameni, B.; Ngadjui, B.T.; Sekimizu, K. Antimicrobial action mechanism of flavonoids from Dorstenia species. Drug Discov. Ther., 2013, 7(2), 66-72.
[PMID: 23715504]
[19]
Ou-yang, Z.; Cao, X.; Wei, Y.; Zhang, W.W. Qi.; Zhao, M.; Duan, J. Pharmacokinetic study of rutin and quercetin in rats after oral administration of total flavones of mulberry leaf extract. Rev. Bras. Farmacogn., 2013, 23(5), 776-782.
[http://dx.doi.org/10.1590/S0102-695X2013000500009]
[20]
Alfadda, A.A.; Sallam, R.M. Reactive oxygen species in health and disease. J. Biomed. Biotechnol., 2012.2012936486
[http://dx.doi.org/10.1155/2012/936486] [PMID: 22927725]
[21]
Mohammed, A.A.; Ibrahim, A.A. Pathological roles of reactive oxygen species and their defence mechanism. Saudi Pharm. J., 2004, 12(6), 1-8.
[22]
Nikfarjam, B.A.; Adineh, M.; Hajiali, F.; Nassiri-Asl, M. Treatment with Rutin - A therapeutic strategy for neutrophil-mediated inflammatory and autoimmune diseases - Anti-inflammatory effects of rutin on neutrophils. J. Pharmacopuncture, 2017, 20(1), 52-56.
[http://dx.doi.org/10.3831/KPI.2017.20.003] [PMID: 28392963]
[23]
Sun, C.L.; Wei, J.; Bi, L.Q. Rutin attenuates oxidative stress and proinflammatory cytokine level in adjuvant induced rheumatoid arthritis via inhibition of NF-kappaB. Pharmacology, 2017, 100(1-2), 40-49.
[http://dx.doi.org/10.1159/000451027] [PMID: 28467992]
[24]
Xianchu, L.; Lan, Z.; Ming, L.; Yanzhi, M. Protective effects of rutin on lipopolysaccharide-induced heart injury in mice. J. Toxicol. Sci., 2018, 43(5), 329-337.
[http://dx.doi.org/10.2131/jts.43.329] [PMID: 29743444]
[25]
Na, J.Y.; Song, K.; Kim, S.; Kwon, J. Rutin protects rat articular chondrocytes against oxidative stress induced by hydrogen peroxide through SIRT1 activation. Biochem. Biophys. Res. Commun., 2016, 473(4), 1301-1308.
[http://dx.doi.org/10.1016/j.bbrc.2016.04.064] [PMID: 27086847]
[26]
Su, S.; Li, X.; Li, S.; Ming, P.; Huang, Y.; Dong, Y.; Ding, H.; Feng, S.; Li, J.; Wang, X.; Li, Y.; Wu, J. Rutin protects against lip-opolysaccharide-induced mastitis by inhibiting the activation of the NF-κB signaling pathway and attenuating endoplasmic reticulum stress. Inflammopharmacology, 2019, 27(1), 77-88.
[http://dx.doi.org/10.1007/s10787-018-0521-x] [PMID: 30099676]
[27]
Han, Y.; Lu, J.S.; Xu, Y.; Zhang, L.; Hong, B.F. Rutin ameliorates renal fibrosis and proteinuria in 5/6-nephrectomized rats by anti-oxidation and inhibiting activation of TGFβ1-smad signaling. Int. J. Clin. Exp. Pathol., 2015, 8(5), 4725-4734.
[PMID: 26191162]
[28]
You, K.M.; Jong, H.G.; Kim, H.P. Inhibition of cyclooxygenase/lipoxygenase from human platelets by polyhydroxylated/methoxylated flavonoids isolated from medicinal plants. Arch. Pharm. Res., 1999, 22(1), 18-24.
[http://dx.doi.org/10.1007/BF02976430] [PMID: 10071954]
[29]
Liu, L.L.; Zhang, Y.; Zhang, X.F.; Li, F.H. Influence of rutin on the effects of neonatal cigarette smoke exposure-induced exacerbated MMP-9 expression, Th17 cytokines and NF-κB/iNOS-mediated inflammatory responses in asthmatic mice model. Korean J. Physiol. Pharmacol., 2018, 22(5), 481-491.
[http://dx.doi.org/10.4196/kjpp.2018.22.5.481] [PMID: 30181695]
[30]
Gul, A.; Kunwar, B.; Mazhar, M.; Faizi, S.; Ahmed, D.; Shah, M.R.; Simjee, S.U. Rutin and rutin-conjugated gold nanoparticles ameliorate collagen-induced arthritis in rats through inhibition of NF-κB and iNOS activation. Int. Immunopharmacol., 2018, 59, 310-317.
[http://dx.doi.org/10.1016/j.intimp.2018.04.017] [PMID: 29679855]
[31]
Khajevand-Khazaei, M.R.; Mohseni-Moghaddam, P.; Hosseini, M.; Gholami, L.; Baluchnejadmojarad, T.; Roghani, M. Rutin, a quercetin glycoside, alleviates acute endotoxemic kidney injury in C57BL/6 mice via suppression of inflammation and up-regulation of antioxidants and SIRT1. Eur. J. Pharmacol., 2018, 833, 307-313.
[http://dx.doi.org/10.1016/j.ejphar.2018.06.019] [PMID: 29920283]
[32]
Amin, M.U.; Khurram, M.; Khattak, B.; Khan, J. Antibiotic additive and synergistic action of rutin, morin and quercetin against methicillin resistant Staphylococcus aureus. BMC Complement. Altern. Med., 2015, 15(1), 59.
[http://dx.doi.org/10.1186/s12906-015-0580-0] [PMID: 25879586]
[33]
Yeh, C.H.; Yang, J.J.; Yang, M.L.; Li, Y.C.; Kuan, Y.H. Rutin decreases lipopolysaccharide-induced acute lung injury via inhibition of oxidative stress and the MAPK-NF-κB pathway. Free Radic. Biol. Med., 2014, 69, 249-257.
[http://dx.doi.org/10.1016/j.freeradbiomed.2014.01.028] [PMID: 24486341]
[34]
Yoo, H.; Ku, S.K.; Baek, Y.D.; Bae, J.S. Anti-inflammatory effects of rutin on HMGB1-induced inflammatory responses in vitro and in vivo. Inflamm. Res., 2014, 63(3), 197-206.
[http://dx.doi.org/10.1007/s00011-013-0689-x] [PMID: 24292859]
[35]
Ramos, S. Cancer chemoprevention and chemotherapy: dietary polyphenols and signalling pathways. Mol. Nutr. Food Res., 2008, 52(5), 507-526.
[http://dx.doi.org/10.1002/mnfr.200700326] [PMID: 18435439]
[36]
Soobrattee, M.A.; Bahorun, T.; Aruoma, O.I. Chemopreventive actions of polyphenolic compounds in cancer. Biofactors, 2006, 27(1-4), 19-35.
[http://dx.doi.org/10.1002/biof.5520270103] [PMID: 17012761]
[37]
Ben Sghaier, M.; Pagano, A.; Mousslim, M.; Ammari, Y.; Kovacic, H.; Luis, J. Rutin inhibits proliferation, attenuates superoxide pro-duction and decreases adhesion and migration of human cancerous cells. Biomed. Pharmacother., 2016, 84, 1972-1978.
[http://dx.doi.org/10.1016/j.biopha.2016.11.001] [PMID: 27829548]
[38]
Lin, J.P.; Yang, J.S.; Lin, J.J.; Lai, K.C.; Lu, H.F.; Ma, C.Y.; Sai-Chuen Wu, R.; Wu, K.C.; Chueh, F.S.; Gibson Wood, W.; Chung, J.G. Rutin inhibits human leukemia tumor growth in a murine xenograft model in vivo. Environ. Toxicol., 2012, 27(8), 480-484.
[http://dx.doi.org/10.1002/tox.20662] [PMID: 21254320]
[39]
Memariani, T.; Hosseini, T.; Kamali, H.; Mohammadi, A.; Ghorbani, M.; Shakeri, A.; Spandidos, D.A.; Tsatsakis, A.M.; Shahsavand, S. Evaluation of the cytotoxic effects of Cyperus longus extract, fractions and its essential oil on the PC3 and MCF7 cancer cell lines. Oncol. Lett., 2016, 11(2), 1353-1360.
[http://dx.doi.org/10.3892/ol.2015.4050] [PMID: 26893742]
[40]
Guon, T.E.; Chung, H.S. Hyperoside and rutin of Nelumbo nucifera induce mitochondrial apoptosis through a caspase-dependent mechanism in HT-29 human colon cancer cells. Oncol. Lett., 2016, 11(4), 2463-2470.
[http://dx.doi.org/10.3892/ol.2016.4247] [PMID: 27073499]
[41]
Chen, H.; Miao, Q.; Geng, M.; Liu, J.; Hu, Y.; Tian, L.; Pan, J.; Yang, Y. Anti-tumor effect of rutin on human neuroblastoma cell lines through inducing G2/M cell cycle arrest and promoting apoptosis. ScientificWorldJournal, 2013, 2013269165
[http://dx.doi.org/10.1155/2013/269165.]
[42]
Karakurt, S. Modulatory effects of rutin on the expression of cytochrome P450s and antioxidant enzymes in human hepatoma cells. Acta Pharm., 2016, 66(4), 491-502.
[http://dx.doi.org/10.1515/acph-2016-0046] [PMID: 27749250]
[43]
Failli, A.; Legitimo, A.; Orsini, G.; Castagna, M.; Spisni, R.; Miccoli, P.; Consolini, R. Antiproliferative effects of 5-fluorouracil and oxaliplatin in colon cancer cell lines: Comparison of three different cytotoxicity assays. J. Biol. Regul. Homeost. Agents, 2013, 27(1), 275-284.
[PMID: 23489708]
[44]
Chen, S.; Gong, J.; Liu, F.; Mohammed, U. Naturally occurring polyphenolic antioxidants modulate IgE-mediated mast cell activation. Immunology, 2000, 100(4), 471-480.
[http://dx.doi.org/10.1046/j.1365-2567.2000.00045.x] [PMID: 10929074]
[45]
Kim, H.Y.; Nam, S.Y.; Hong, S.W.; Kim, M.J.; Jeong, H.J.; Kim, H.M. Protective effects of rutin through regulation of vascular endothelial growth factor in allergic rhinitis. Am. J. Rhinol. Allergy, 2015, 29(3), e87-e94.
[http://dx.doi.org/10.2500/ajra.2015.29.4195] [PMID: 25975244]
[46]
Choi, J.K.; Kim, S.H. Rutin suppresses atopic dermatitis and allergic contact dermatitis. Exp. Biol. Med. (Maywood), 2013, 238(4), 410-417.
[http://dx.doi.org/10.1177/1535370213477975] [PMID: 23760007]
[47]
Jung, C.H.; Lee, J.Y.; Cho, C.H.; Kim, C.J. Anti-asthmatic action of quercetin and rutin in conscious guinea-pigs challenged with aerosolized ovalbumin. Arch. Pharm. Res., 2007, 30(12), 1599-1607.
[http://dx.doi.org/10.1007/BF02977330] [PMID: 18254248]
[48]
Sattanathan, K.; Dhanapal, C.K.; Manavalan, R. LDL lowering properties of rutin in diabetic patients. Int. J. Pharma Bio Sci., 2010, 1(4), 468-473.
[49]
Jung, U.J.; Lee, M.K.; Park, Y.B.; Kang, M.A.; Choi, M.S. Effect of citrus flavonoids on lipid metabolism and glucose-regulating enzyme mRNA levels in type-2 diabetic mice. Int. J. Biochem. Cell Biol., 2006, 38(7), 1134-1145.
[http://dx.doi.org/10.1016/j.biocel.2005.12.002] [PMID: 16427799]
[50]
Niture, N.T.; Ansari, A.A.; Naik, S.R. Anti-hyperglycemic activity of rutin in streptozotocin-induced diabetic rats: An effect mediated through cytokines, antioxidants and lipid biomarkers. Indian J. Exp. Biol., 2014, 52(7), 720-727.
[PMID: 25059040]
[51]
Jeong Lee, Y.; Hee Jeune, K. The Effect of Rutin on Antioxidant and Anti-inflammation in Streptozotocin-induced Diabetic Rats. Appl. Microsc, 2013, 43(2), 54-64.
[http://dx.doi.org/10.9729/AM.2013.43.2.54]
[52]
Hsu, C.Y.; Shih, H.Y.; Chia, Y.C.; Lee, C.H.; Ashida, H.; Lai, Y.K.; Weng, C.F. Rutin potentiates insulin receptor kinase to enhance insulin-dependent glucose transporter 4 translocation. Mol. Nutr. Food Res., 2014, 58(6), 1168-1176.
[http://dx.doi.org/10.1002/mnfr.201300691] [PMID: 24668568]
[53]
Kappel, V.D.; Zanatta, L.; Postal, B.G.; Silva, F.R. Rutin potentiates calcium uptake via voltage-dependent calcium channel associated with stimulation of glucose uptake in skeletal muscle. Arch. Biochem. Biophys., 2013, 532(2), 55-60.
[http://dx.doi.org/10.1016/j.abb.2013.01.008] [PMID: 23395857]
[54]
Saklani, R.; Gupta, S.K.; Mohanty, I.R.; Kumar, B.; Srivastava, S.; Mathur, R. Cardioprotective effects of rutin via alteration in TNF-α, CRP, and BNP levels coupled with antioxidant effect in STZ-induced diabetic rats. Mol. Cell. Biochem., 2016, 420(1-2), 65-72.
[http://dx.doi.org/10.1007/s11010-016-2767-1] [PMID: 27443845]

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