Generic placeholder image

Current Cancer Therapy Reviews

Editor-in-Chief

ISSN (Print): 1573-3947
ISSN (Online): 1875-6301

Research Article

A Study on Anti-oxidant and Anti-cancer Perspectives of Rutin

Author(s): Prashant Tiwari, Rakhi Mishra*, Rupa Mazumder, Avijit Mazumder and Ayushi Singh

Volume 20, Issue 2, 2024

Published on: 15 June, 2023

Page: [212 - 222] Pages: 11

DOI: 10.2174/1573394719666230519095551

Price: $65

Abstract

Introduction: The purpose of this study was to extract, isolate, and evaluate in vitro the antioxidant and anticancer properties of rutin from Citrus reticulata and Citrus limon.

Background: Bioflavonoids are a class of polyphenolic secondary metabolites that give plants their distinctive organoleptic properties. Rutin, also known as rutoside, is a citrus flavonoid that is found in a variety of plants, including citrus fruits, and has a wide range of pharmacological effects.

Objective: This investigation's goal was to extract, isolate, and test the antioxidant and anti-cancer properties of rutin in vitro.

Methods: By incorporating the appropriate solvent system, the Soxhlet apparatus was used to extract C. reticulata (R2) and C. limon (R3) from dried peel powder. Column chromatography was used in the isolation process. Various solvent systems on the basis of their polarity were used to isolate rutin, which further was evaluated for anti-oxidant and anti-cancer action by the use of in vitro tests.

Results: Successful extraction and isolation of rutin from two sources were achieved. Additionally, their antioxidant and anticancer activity was also evaluated by in vitro methods. Both isolated rutins (R2 and R3) possessed optimal antioxidants in the range of 31.64 to 76.28 g/ml and anticancer activity with IC50 values of 4 to 7 g/ml, when compared to standard doxorubicin with an IC50 value of 3g/ml. In the comparison of rutin isolated from C. reticulata with rutin isolated from C. limon, rutin isolated from C. reticulata was found to be more abundant and more potent in terms of yield and activity.

Conclusion: The study's findings are clear; Citrus reticulata species have a higher flavonoid and phenolic content, and the rutin extracted from them is an effective anti-oxidant and anti-cancer agent against lung cancer. The study can be used as a model for future studies on rutin’s role in cancer.

Keywords: Rutin, flavonoids, antioxidant, anti-cancer, Citrus reticulata, Citrus limon.

Graphical Abstract
[1]
Uba AI, Zengin G, Montesano D, et al. Antioxidant and enzyme inhibitory properties, and hplc–ms/ms profiles of different extracts of arabis carduchorum boiss.: An endemic plant to Turkey. Appl Sci 2022; 12(13): 6561.
[2]
Middleton E. Effect of plant flavonoids on immune and inflammatory cell function. Adv Exp Med Biol 1998; 439: 175-82.
[http://dx.doi.org/10.1007/978-1-4615-5335-9_13]
[3]
de Souza Farias SA, da Costa KS, Martins JBL. Analysis of conformational, structural, magnetic, and electronic properties related to anti-oxidant activity: Revisiting flavan, anthocyanidin, flavanone, flavonol, isoflavone, flavone, and flavan-3-ol. ACS Omega 2021; 6(13): 8908-18.
[http://dx.doi.org/10.1021/acsomega.0c06156] [PMID: 33842761]
[4]
Dias MC, Pinto DCGA, Silva AMS. Plant flavonoids: Chemical characteristics and biological activity. Molecules 2021; 26(17): 5377.
[http://dx.doi.org/10.3390/molecules26175377] [PMID: 34500810]
[5]
Liu Y, Qian J, Li J, et al. Hydroxylation decoration patterns of flavonoids in horticultural crops: Chemistry, bioactivity, and biosynthesis. Hortic Res 2022; 9: uhab068.
[http://dx.doi.org/10.1093/hr/uhab068] [PMID: 35048127]
[6]
Santos EL, Maia BH, Ferriani AP, Teixeira SD. Flavonoids: Classification, biosynthesis and chemical ecology Flavonoids - From Biosynthesis to Human Health. United Kingdom: IntechOpen 2017; pp. 1-18.
[7]
Aryal B, Raut BK, Bhattarai S, et al. Potential therapeutic applications of plant-derived alkaloids against inflammatory and neurodegenerative diseases. Evid Based Complement Alternat Med 2022; 2022: 1-18.
[http://dx.doi.org/10.1155/2022/7299778] [PMID: 35310033]
[8]
Tapas AR, Sakarkar DM, Kakde RB. Flavonoids as nutraceuticals: A review. Trop J Pharm Res 2008; 7(3): 1089-99.
[http://dx.doi.org/10.4314/tjpr.v7i3.14693]
[9]
Behr A, Seidensticker T. Vital amines-vitaminsChemistry of Renewables. Berlin, Heidelberg: Springer 2020; pp. 295-307.
[10]
Kumar S, Pandey AK. Chemistry and biological activities of flavonoids: An overview. Sci World J 2013; 2017: 162750.
[http://dx.doi.org/10.1155/2013/162750]
[11]
Yusha’u Y, Muhammad UA, Nze M, Egwuma JM, Igomu OJ, Abdulkadir M. Modulatory role of rutin supplement on open space forced swim test murine model of depression. Niger J Physiol Sci 2017; 32(2): 201-5.
[PMID: 29485642]
[12]
Patel K, Patel DK. The beneficial role of rutin, a naturally occurring flavonoid in health promotion and disease prevention: A systematic review and updateBioactive food as dietary interventions for arthritis and related inflammatory. Netherlands: Elsevier 2019; pp. 457-79.
[http://dx.doi.org/10.1016/B978-0-12-813820-5.00026-X]
[13]
Kreft I, Fabjan N, Yasumoto K. Rutin content in buckwheat (Fagopyrum esculentum Moench) food materials and products. Food Chem 2006; 98(3): 508-12.
[http://dx.doi.org/10.1016/j.foodchem.2005.05.081]
[14]
Negahdari R, Bohlouli S, Sharifi S, et al. Therapeutic benefits of rutin and its nanoformulations. Phytother Res 2021; 35(4): 1719-38.
[http://dx.doi.org/10.1002/ptr.6904] [PMID: 33058407]
[15]
Memar MY, Yekani M, Sharifi S, Dizaj SM. Antibacterial and biofilm inhibitory effects of rutin nanocrystals. Biointerface Res Appl Chem 2023; 13(2)
[16]
Masugi Y. The desmoplastic stroma of pancreatic cancer: Multilayered levels of heterogeneity, clinical significance, and therapeutic oppor-tunities. Cancers 2022; 14(13): 3293.
[http://dx.doi.org/10.3390/cancers14133293] [PMID: 35805064]
[17]
Zhu J, Chen M, Chen N, et al. Glycyrrhetinic acid induces G1-phase cell cycle arrest in human non-small cell lung cancer cells through endoplasmic reticulum stress pathway. Int J Oncol 2015; 46(3): 981-8.
[http://dx.doi.org/10.3892/ijo.2015.2819] [PMID: 25573651]
[18]
Satari A, Ghasemi S, Habtemariam S, Asgharian S, Lorigooini Z. Rutin: A flavonoid as an effective sensitizer for anticancer therapy; in-sights into multifaceted mechanisms and applicability for combination therapy. Evid Based Complement Alternat Med 2021; 2021: 1-10.
[http://dx.doi.org/10.1155/2021/9913179] [PMID: 34484407]
[19]
Prasad R, Prasad SB. A review on the chemistry and biological properties of Rutin, a promising nutraceutical agent. Asian J Pharm Pharmacol 2019; 5(S1): 1-20.
[http://dx.doi.org/10.31024/ajpp.2019.5.s1.1]
[20]
Ghasemzadeh A, Jaafar HZE, Rahmat A, Devarajan T. Evaluation of bioactive compounds, pharmaceutical quality, and anticancer activity of curry leaf (Murraya koenigii L.). Evid Based Complement Alternat Med 2014; 2014: 1-8.
[http://dx.doi.org/10.1155/2014/873803] [PMID: 24693327]
[21]
Makrane H, El Messaoudi M, Melhaoui A, El Mzibri M, Benbacer L, Aziz M. Cytotoxicity of the aqueous extract and organic fractions from Origanum majorana on human breast cell line MDA-MB-231 and human colon cell line HT-29. Adv Pharmacol Sci 2018; 2018: 1-9.
[http://dx.doi.org/10.1155/2018/3297193] [PMID: 30210537]
[22]
Pandey P, Khan F, Maurya P. Targeting Jab1 using hesperidin (dietary phytocompound) for inducing apoptosis in HeLa cervical cancer cells. J Food Biochem 2021; 45(7): e13800.
[http://dx.doi.org/10.1111/jfbc.13800] [PMID: 34047379]
[23]
Musial C, Siedlecka-Kroplewska K, Kmiec Z, Gorska-Ponikowska M. Modulation of autophagy in cancer cells by dietary polyphenols. Antioxidants 2021; 10(1): 123.
[http://dx.doi.org/10.3390/antiox10010123] [PMID: 33467015]
[24]
Nouri Z, Fakhri S, Nouri K, Wallace CE, Farzaei MH, Bishayee A. Targeting multiple signaling pathways in cancer: The rutin therapeutic approach. Cancers 2020; 12(8): 2276.
[http://dx.doi.org/10.3390/cancers12082276] [PMID: 32823876]
[25]
Kyung TW, Lee JE, Shin HH, Choi HS. Rutin inhibits osteoclast formation by decreasing reactive oxygen species and TNF-α by inhibiting activation of NF-κB. Exp Mol Med 2008; 40(1): 52-8.
[http://dx.doi.org/10.3858/emm.2008.40.1.52] [PMID: 18305398]
[26]
Forman HJ, Zhang H. Targeting oxidative stress in disease: Promise and limitations of antioxidant therapy. Nat Rev Drug Discov 2021; 20(9): 689-709.
[http://dx.doi.org/10.1038/s41573-021-00233-1] [PMID: 34194012]
[27]
Gupta J, Gupta A, Gupta AK. Flavonoids: Its working mechanism and various protective roles. Int J Chem Stud 2016; 4(4): 190-8.
[28]
Pisoschi AM, Pop A, Iordache F, Stanca L, Predoi G, Serban AI. Oxidative stress mitigation by antioxidants - An overview on their chem-istry and influences on health status. Eur J Med Chem 2021; 209: 112891.
[http://dx.doi.org/10.1016/j.ejmech.2020.112891] [PMID: 33032084]
[29]
Pandey P, Khan F, Qari HA, Oves M. Rutin (Bioflavonoid) as cell signaling pathway modulator: Prospects in treatment and chemoprevention. Pharmaceuticals 2021; 14(11): 1069.
[http://dx.doi.org/10.3390/ph14111069] [PMID: 34832851]
[30]
Choi SS, Park HR, Lee KA. A comparative study of rutin and rutin glycoside: Antioxidant activity, anti-inflammatory effect, effect on platelet aggregation and blood coagulation. Antioxidants 2021; 10(11): 1696.
[http://dx.doi.org/10.3390/antiox10111696] [PMID: 34829567]
[31]
Yu JS, Lim SH, Lee SR, Choi CI, Kim KH. Antioxidant and anti-inflammatory effects of white mulberry (Morus alba L.) fruits on lipopolysaccharide-stimulated RAW 264.7 macrophages. Molecules 2021; 26(4): 920.
[http://dx.doi.org/10.3390/molecules26040920] [PMID: 33572374]
[32]
Yu XL, Li YN, Zhang H, et al. Rutin inhibits amylin-induced neurocytotoxicity and oxidative stress. Food Funct 2015; 6(10): 3296-306.
[http://dx.doi.org/10.1039/C5FO00500K] [PMID: 26242245]
[33]
Enogieru AB, Haylett W, Hiss DC, Bardien S, Ekpo OE. Rutin as a potent antioxidant: Implications for neurodegenerative disorders. Oxid Med Cell Longev 2018; 2018: 1-17.
[http://dx.doi.org/10.1155/2018/6241017] [PMID: 30050657]
[34]
Fan X, Fan Z, Yang Z, et al. Flavonoids-Natural gifts to promote health and longevity. Int J Mol Sci 2022; 23(4): 2176.
[http://dx.doi.org/10.3390/ijms23042176] [PMID: 35216290]
[35]
Wang W, Xiong P, Zhang H, Zhu Q, Liao C, Jiang G. Analysis, occurrence, toxicity and environmental health risks of synthetic phenolic antioxidants: A review. Environ Res 2021; 201: 111531.
[http://dx.doi.org/10.1016/j.envres.2021.111531] [PMID: 34146526]
[36]
Ahmed SI, Hayat MQ, Tahir M, et al. Pharmacologically active flavonoids from the anticancer, antioxidant and antimicrobial extracts of Cassia angustifolia Vahl. BMC Complement Altern Med 2016; 16(1): 460.
[http://dx.doi.org/10.1186/s12906-016-1443-z] [PMID: 27835979]
[37]
Noman OM, Nasr FA, Alqahtani AS, et al. Comparative study of antioxidant and anticancer activities and HPTLC quantification of rutin in white radish (Raphanus sativus L.) leaves and root extracts grown in Saudi Arabia. Open Chem 2021; 19(1): 408-16.
[http://dx.doi.org/10.1515/chem-2021-0042]
[38]
Mammen D, Daniel M. A critical evaluation on the reliability of two aluminum chloride chelation methods for quantification of flavonoids. Food Chem 2012; 135(3): 1365-8.
[http://dx.doi.org/10.1016/j.foodchem.2012.05.109] [PMID: 22953867]
[39]
Savych A, Milian I. Total flavonoid content in the herbal mixture with antidiabetic activity. Pharmacologyonline 2021; 2: 68-75.
[40]
Shan S, Huang X, Shah MH, Abbasi AM. Evaluation of polyphenolics content and antioxidant activity in edible wild fruits. BioMed Res Int 2019; 2019: 1-11.
[http://dx.doi.org/10.1155/2019/1381989] [PMID: 30792989]
[41]
Suhartomi KN, Gulo AD, Saragih AR. Antioxidant properties of sweet orange peels in several fractions of methanolic extract. InProceedings of the International Conference on Health Informatics and Medical Application Technology 2020; 1: 371-8.
[42]
N Sharma G. Kaur H, Shrivastava B, Chander Arora S. Comparative in vitro antioxidant activity of ethyl acetate and ethanol extracts of callicarpa macrophylla. Asian J Pharm Clin Res 2021; 2021: 31-5.
[http://dx.doi.org/10.22159/ajpcr.2021.v14i5.41014]
[43]
Prieto P, Pineda M, Aguilar M. Spectrophotometric quantitation of antioxidant capacity through the formation of a phosphomolybdenum complex: Specific application to the determination of vitamin E. Anal Biochem 1999; 269(2): 337-41.
[http://dx.doi.org/10.1006/abio.1999.4019] [PMID: 10222007]
[44]
Untea A, Lupu A, Saracila M, Panaite T. Comparison of ABTS, DPPH, phosphomolybdenum assays for estimating antioxidant activity and phenolic compounds in five different plant extracts. Bull Univ Agric Sci Vet Med Cluj-Napoca Anim Sci Biotechnol 2018; 75(2): 110.
[http://dx.doi.org/10.15835/buasvmcn-asb:2018.0009]
[45]
Šafranko S, Ćorković I, Jerković I, et al. Green extraction techniques for obtaining bioactive compounds from mandarin peel (Citrus un-shiu var. Kuno): Phytochemical analysis and process optimization. Foods 2021; 10(5): 1043.
[http://dx.doi.org/10.3390/foods10051043] [PMID: 34064619]
[46]
Di Lorenzo C, Colombo F, Biella S, Stockley C, Restani P. Polyphenols and human health: The role of bioavailability. Nutrients 2021; 13(1): 273.
[http://dx.doi.org/10.3390/nu13010273] [PMID: 33477894]
[47]
Liu S, Xiao P, Kuang Y, Hao J, Huang T, Liu E. Flavonoids from sea buckthorn: A review on phytochemistry, pharmacokinetics and role in metabolic diseases. J Food Biochem 2021; 45(5): e13724.
[http://dx.doi.org/10.1111/jfbc.13724] [PMID: 33856060]
[48]
Sezgin-Bayindir Z, Losada-Barreiro S, Bravo-Díaz C, Sova M, Kristl J, Saso L. Nanotechnology-based drug delivery to improve the therapeutic benefits of NRF2 modulators in cancer therapy. Antioxidants 2021; 10(5): 685.
[http://dx.doi.org/10.3390/antiox10050685] [PMID: 33925605]
[49]
Abotaleb M, Samuel S, Varghese E, et al. Flavonoids in cancer and apoptosis. Cancers 2018; 11(1): 28.
[http://dx.doi.org/10.3390/cancers11010028] [PMID: 30597838]
[50]
Ferreyra MLF, Serra P, Casati P. Recent advances on the roles of flavonoids as plant protective molecules after UV and high light exposure. Physiol Plant 2021; 173(3): 736-49.
[http://dx.doi.org/10.1111/ppl.13543] [PMID: 34453749]
[51]
Li Z, Zhao T, Li J, et al. Nanomedicine based on natural products: Improving clinical application potential. J Nanomater 2022; 2022: 1-11.
[http://dx.doi.org/10.1155/2022/3066613]
[52]
Ullah A, Munir S, Badshah SL, et al. Important flavonoids and their role as a therapeutic agent. Molecules 2020; 25(22): 5243.
[http://dx.doi.org/10.3390/molecules25225243] [PMID: 33187049]
[53]
Wolfe KL, Kang X, He X, Dong M, Zhang Q, Liu RH. Cellular antioxidant activity of common fruits. J Agric Food Chem 2008; 56(18): 8418-26.
[http://dx.doi.org/10.1021/jf801381y] [PMID: 18759450]
[54]
Sánchez-Velázquez OA, Cortés-Rodríguez M, Milán-Carrillo J, et al. Anti-oxidant and anti-proliferative effect of anthocyanin enriched fractions from two Mexican wild blackberries (Rubus spp.) on HepG2 and glioma cell lines. J Berry Res 2020; 10(3): 513-29.
[http://dx.doi.org/10.3233/JBR-200566]
[55]
Fernandes I, Marques F, de Freitas V, Mateus N. Antioxidant and antiproliferative properties of methylated metabolites of anthocyanins. Food Chem 2013; 141(3): 2923-33.
[http://dx.doi.org/10.1016/j.foodchem.2013.05.033] [PMID: 23871042]

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