Login Register Cart 0
Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

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

Recent Progress in the Hesperetin Delivery Regimes: Significance of Pleiotropic Actions and Synergistic Anticancer Efficacy

Author(s): Parth Malik, Manju Bernela, Mahima Seth, Priya Kaushal and Tapan Kumar Mukherjee*

Volume 29, Issue 37, 2023

Published on: 13 November, 2023

Page: [2954 - 2976] Pages: 23

DOI: 10.2174/0113816128253609231030070414

Price: $65

Abstract

Background: In the plant kingdom, flavonoids are widely distributed with multifunctional immunomodulatory actions. Hesperetin (HST) remains one of the well-studied compounds in this domain, initially perceived in citrus plants as an aglycone derivative of hesperidin (HDN).

Observations: Natural origin, low in vivo toxicity, and pleiotropic functional essence are the foremost fascinations for HST use as an anticancer drug. However, low aqueous solubility accompanied with a prompt degradation by intestinal and hepatocellular enzymes impairs HST physiological absorption.

Motivation: Remedies attempted herein comprise the synthesis of derivatives and nanocarrier (NC)-mediated delivery. As the derivative synthesis aggravates the structural complexity, NC-driven HST delivery has emerged as a sustainable approach for its sustained release. Recent interest in HST has been due to its significant anticancer potential, characterized via inhibited cell division (proliferation), new blood vessel formation (angiogenesis), forceful occupation of neighboring cell’s space (invasion), migration to erstwhile physiological locations (metastasis) and apoptotic induction. The sensitization of chemotherapeutic drugs (CDs) by HST is driven via stoichiometrically regulated synergistic actions.

Purpose and Conclusion: This article sheds light on HST structure-function correlation and pleiotropic anticancer mechanisms, in unaided and NC-administered delivery in singular and with CDs synergy. The discussion could streamline the HST usefulness and long-term anticancer efficacy.

Keywords: Hesperetin, hesperidin, aglycone derivative, phytochemical, chemotherapeutic drugs, nanocarrier, structure-function correlation.

« Previous Next »
[1]
Baena Ruiz R, Salinas Hernández P. Diet and cancer: Risk factors and epidemiological evidence. Maturitas 2014; 77(3): 202-8.
[http://dx.doi.org/10.1016/j.maturitas.2013.11.010] [PMID: 24374225]
[2]
Calaf GM, Crispin LA, Muñoz JP, Aguayo F, Narayan G, Roy D. Cell adhesion molecules affected by ionizing radiation and estrogen in an experimental breast cancer model. Int J Mol Sci 2022; 23(20): 12674.
[http://dx.doi.org/10.3390/ijms232012674] [PMID: 36293530]
[3]
Hanika C, Porter N, Blick K, Mendis J. Lifestyle choices following head and neck cancer treatment: A qualitative study. Nutr Health 2022.
[http://dx.doi.org/10.1177/02601060221106624] [PMID: 35726202]
[4]
Reiche EMV, Nunes SOV, Morimoto HK. Stress, depression, the immune system, and cancer. Lancet Oncol 2004; 5(10): 617-25.
[http://dx.doi.org/10.1016/S1470-2045(04)01597-9] [PMID: 15465465]
[5]
Reuter S, Gupta SC, Chaturvedi MM, Aggarwal BB. Oxidative stress, inflammation, and cancer: How are they linked? Free Radic Biol Med 2010; 49(11): 1603-16.
[http://dx.doi.org/10.1016/j.freeradbiomed.2010.09.006] [PMID: 20840865]
[6]
Hayes JD, Dinkova-Kostova AT, Tew KD. Oxidative stress in cancer. Cancer Cell 2020; 38(2): 167-97.
[http://dx.doi.org/10.1016/j.ccell.2020.06.001] [PMID: 32649885]
[7]
Varghese R, Dalvi YB. Natural products as anticancer agents. Curr Drug Targets 2021; 22(11): 1272-87.
[http://dx.doi.org/10.2174/1389450121999201230204526] [PMID: 33390130]
[8]
Li B, Shao H, Gao L, Li H, Sheng H, Zhu L. Nano-drug co-delivery system of natural active ingredients and chemotherapy drugs for cancer treatment: A review. Drug Deliv 2022; 29(1): 2130-61.
[http://dx.doi.org/10.1080/10717544.2022.2094498] [PMID: 35815678]
[9]
Demain AL, Vaishnav P. Natural products for cancer chemotherapy. Microb Biotechnol 2011; 4(6): 687-99.
[http://dx.doi.org/10.1111/j.1751-7915.2010.00221.x] [PMID: 21375717]
[10]
Yun BD, Son SW, Choi SY, Kuh HJ, Oh TJ, Park JK. Anti-cancer activity of phytochemicals targeting hypoxia-inducible factor-1 alpha. Int J Mol Sci 2021; 22(18): 9819.
[http://dx.doi.org/10.3390/ijms22189819] [PMID: 34575983]
[11]
Zheng Z, Zhang L, Hou X. Potential roles and molecular mechanisms of phytochemicals against cancer. Food Funct 2022; 13(18): 9208-25.
[http://dx.doi.org/10.1039/D2FO01663J] [PMID: 36047380]
[12]
Banudevi S, Swaminathan S, Maheswari KU. Pleiotropic role of dietary phytochemicals in cancer: Emerging perspectives for combinational therapy. Nutr Cancer 2015; 67(7): 1021-48.
[http://dx.doi.org/10.1080/01635581.2015.1073762] [PMID: 26359767]
[13]
Turrini E, Ferruzzi L, Fimognari C. Natural compounds to overcome cancer chemoresistance: Toxicological and clinical issues. Expert Opin Drug Metab Toxicol 2014; 10(12): 1677-90.
[http://dx.doi.org/10.1517/17425255.2014.972933] [PMID: 25339439]
[14]
Ko YH, Kim SK, Lee SY, Jang CG. Flavonoids as therapeutic candidates for emotional disorders such as anxiety and depression. Arch Pharm Res 2020; 43(11): 1128-43.
[http://dx.doi.org/10.1007/s12272-020-01292-5] [PMID: 33225387]
[15]
Pandey P, Khan F. A mechanistic review of the anticancer potential of hesperidin, a natural flavonoid from citrus fruits. Nutr Res 2021; 92: 21-31.
[http://dx.doi.org/10.1016/j.nutres.2021.05.011] [PMID: 34273640]
[16]
Jin MJ, Kim U, Kim IS, et al. Effects of gut microflora on pharmacokinetics of hesperidin: A study on non-antibiotic and pseudogerm-free rats. J Toxicol Environ Health A 2010; 73(21-22): 1441-50.
[http://dx.doi.org/10.1080/15287394.2010.511549] [PMID: 20954071]
[17]
Justesen U, Arrigoni E, Larsen BR, Amado R. Degradation of flavonoid glycosides and aglycones during in vitro fermentation with human faecal flora. Lebensm Wiss Technol 2000; 33(6): 424-30.
[http://dx.doi.org/10.1006/fstl.2000.0681]
[18]
Parhiz H, Roohbakhsh A, Soltani F, Rezaee R, Iranshahi M. Antioxidant and anti-inflammatory properties of the citrus flavonoids hesperidin and hesperetin: An updated review of their molecular mechanisms and experimental models. Phytother Res 2015; 29(3): 323-31.
[http://dx.doi.org/10.1002/ptr.5256] [PMID: 25394264]
[19]
Sugasawa N, Katagi A, Kurobe H, et al. Inhibition of atherosclerotic plaque development by oral administration of α-glucosyl hesperidin and water-dispersible hesperetin in apolipoprotein E knockout mice. J Am Coll Nutr 2019; 38(1): 15-22.
[http://dx.doi.org/10.1080/07315724.2018.1468831] [PMID: 30321103]
[20]
Sivagami G, Vinothkumar R, Preethy CP, et al. Role of hesperetin (a natural flavonoid) and its analogue on apoptosis in HT-29 human colon adenocarcinoma cell line – A comparative study. Food Chem Toxicol 2012; 50(3-4): 660-71.
[http://dx.doi.org/10.1016/j.fct.2011.11.038] [PMID: 22142698]
[21]
Yang Y, Wolfram J, Boom K, Fang X, Shen H, Ferrari M. Hesperetin impairs glucose uptake and inhibits proliferation of breast cancer cells. Cell Biochem Funct 2013; 31(5): 374-9.
[http://dx.doi.org/10.1002/cbf.2905] [PMID: 23042260]
[22]
Zhang J, Song J, Wu D, Wang J, Dong W. Hesperetin induces the apoptosis of hepatocellular carcinoma cells via mitochondrial pathway mediated by the increased intracellular reactive oxygen species, ATP and calcium. Med Oncol 2015; 32(4): 101.
[http://dx.doi.org/10.1007/s12032-015-0516-z] [PMID: 25737432]
[23]
Shirzad M, Heidarian E, Beshkar P, Gholami-Arjenaki M. Biological effects of hesperetin on interleukin-6/phosphorylated signal transducer and activator of transcription 3 pathway signaling in prostate cancer PC3 cells. Pharmacognosy Res 2017; 9(2): 188-94.
[http://dx.doi.org/10.4103/0974-8490.204655] [PMID: 28539744]
[24]
Kanaze FI, Bounartzi MI, Georgarakis M, Niopas I. Pharmacokinetics of the citrus flavanone aglycones hesperetin and naringenin after single oral administration in human subjects. Eur J Clin Nutr 2007; 61(4): 472-7.
[http://dx.doi.org/10.1038/sj.ejcn.1602543] [PMID: 17047689]
[25]
Ersoz M, Erdemir A, Duranoglu D, et al. Comparative evaluation of hesperetin loaded nanoparticles for anticancer activity against C6 glioma cancer cells. Artif Cells Nanomed Biotechnol 2019; 47(1): 319-29.
[http://dx.doi.org/10.1080/21691401.2018.1556213] [PMID: 30688095]
[26]
du Preez BVP, de Beer D, Joubert E. By-product of honeybush (Cyclopia maculata) tea processing as source of hesperidin-enriched nutraceutical extract. Ind Crops Prod 2016; 87: 132-41.
[http://dx.doi.org/10.1016/j.indcrop.2016.04.012]
[27]
Soares MS, da Silva DF, Forim MR, et al. Quantification and localization of hesperidin and rutin in Citrus sinensis grafted on] C. limonia after Xylella fastidiosa infection by HPLC-UV and MALDI imaging mass spectrometry. Phytochemistry 2015; 115: 161-70.
[http://dx.doi.org/10.1016/j.phytochem.2015.02.011] [PMID: 25749617]
[28]
Alam P, Alam A, Anwer MK, Alqasoumi SI. Quantitative estimation of hesperidin by HPTLC in different varieties of citrus peels. Asian Pac J Trop Biomed 2014; 4(4): 262-6.
[http://dx.doi.org/10.12980/APJTB.4.2014C1007] [PMID: 25182548]
[29]
Jokić S, Šafranko S, Jakovljević M, et al. Sustainable green procedure for extraction of hesperidin from selected croatian mandarin peels. Processes 2019; 7(7): 469.
[http://dx.doi.org/10.3390/pr7070469]
[30]
Najafian S, Moradi M, Sepehrimanesh M. Polyphenolic contents and antioxidant activities of two medicinal plant species, Mentha piperita and Stevia rebaudiana, cultivated in Iran. Comp Clin Pathol 2016; 25(4): 743-7.
[http://dx.doi.org/10.1007/s00580-016-2258-5]
[31]
Gu H, Chen F, Zhang Q, Zang J. Application of ionic liquids in vacuum microwave-assisted extraction followed by macroporous resin isolation of three flavonoids rutin, hyperoside and hesperidin from Sorbus tianschanica leaves. J Chromatogr B Analyt Technol Biomed Life Sci 2016; 1014: 45-55.
[http://dx.doi.org/10.1016/j.jchromb.2016.01.045] [PMID: 26874229]
[32]
Hamdan DI, Mahmoud MF, Wink M, El-Shazly AM. Effect of hesperidin and neohesperidin from bittersweet orange (Citrus aurantium var. Bigaradia) peel on indomethacin-induced peptic ulcers in rats. Environ Toxicol Pharmacol 2014; 37(3): 907-15.
[http://dx.doi.org/10.1016/j.etap.2014.03.006] [PMID: 24691249]
[33]
Damián-Reyna AA, González-Hernández JC, Maya-Yescas R, de Jesús Cortés-Penagos C, del Carmen Chávez-Parga M. Polyphenolic content and bactericidal effect of Mexican Citrus limetta and Citrus reticulata. J Food Sci Technol 2017; 54(2): 531-7.
[http://dx.doi.org/10.1007/s13197-017-2498-7] [PMID: 28242952]
[34]
Man MQ, Yang B, Elias PM. Benefits of hesperidin for cutaneous functions. Evidence-Based Compl Alt Med 2019; 2019: 2676307.
[http://dx.doi.org/10.1155/2019/2676307]
[35]
Mun GI, Kim S, Choi E, Kim CS, Lee YS. Pharmacology of natural radioprotectors. Arch Pharm Res 2018; 41(11): 1033-50.
[http://dx.doi.org/10.1007/s12272-018-1083-6] [PMID: 30361949]
[36]
Selim NM, Elgazar AA, Abdel-Hamid NM, et al. Chrysophanol, physcion, hesperidin and curcumin modulate the gene expression of pro-inflammatory mediators induced by LPS in HepG2: In silico and molecular studies. Antioxidants 2019; 8(9): 371.
[http://dx.doi.org/10.3390/antiox8090371] [PMID: 31484451]
[37]
Pyrzynska K. Hesperidin: A review on extraction methods, stability and biological activities. Nutrients 2022; 14(12): 2387.
[http://dx.doi.org/10.3390/nu14122387] [PMID: 35745117]
[38]
Kuntić V, Pejić N, Mićić S. Direct spectrophotometric determination of hesperidin in pharmaceutical preparations. Acta Chim Slov 2012; 59(2): 436-41.
[PMID: 24061264]
[39]
Li Y, Li X, Li G, et al. In vivo pharmacokinetics of hesperidin are affected by treatment with glucosidase-like BglA protein isolated from yeasts. J Agric Food Chem 2008; 56(14): 5550-7.
[http://dx.doi.org/10.1021/jf800105c] [PMID: 18570429]
[40]
Németh K, Plumb GW, Berrin J-G, et al. Deglycosylation by small intestinal epithelial cell beta-glucosidases is a critical step in the absorption and metabolism of dietary flavonoid glycosides in humans. Eur J Nutr 2003; 42(1): 29-42.
[http://dx.doi.org/10.1007/s00394-003-0397-3] [PMID: 12594539]
[41]
Mahyuni S. The production of flavonoids (quercetin and hesperetin) from callus culture of Citrus aurantifolia (Christm & Panzer) Swingle (Doctoral dissertation). Universiti Putra Malaysia 1999.
[42]
Prakash S, Elavarasan N, Subashini K, et al. Isolation of hesperetin - A flavonoid from Cordia sebestena flower extract through antioxidant assay guided method and its antibacterial, anticancer effect on cervical cancer via in vitro and in silico molecular docking studies. J Mol Struct 2020; 1207: 127751.
[http://dx.doi.org/10.1016/j.molstruc.2020.127751]
[43]
Tong L, Zhou D, Gao J, Zhu Y, Sun H, Bi K. Simultaneous determination of naringin, hesperidin, neohesperidin, naringenin and hesperetin of Fractus aurantii extract in rat plasma by liquid chromatography tandem mass spectrometry. J Pharm Biomed Anal 2012; 58: 58-64.
[http://dx.doi.org/10.1016/j.jpba.2011.05.001] [PMID: 22018980]
[44]
Grohmann K, Manthey JA, Cameron RG. Acid-catalyzed hydrolysis of hesperidin at elevated temperatures. Carbohydr Res 2000; 328(2): 141-6.
[http://dx.doi.org/10.1016/S0008-6215(00)00081-1] [PMID: 11028782]
[45]
5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)-3,4-dihydro-2H-1-benzopyran-4-one. Available From: https://pubchem.ncbi.nlm.nih.gov/compound/3593 (Accessed 20 June 2021).
[46]
Garg A, Garg S, Zaneveld LJD, Singla AK. Chemistry and pharmacology of the citrus bioflavonoid hesperidin. Phytother Res 2001; 15(8): 655-69.
[http://dx.doi.org/10.1002/ptr.1074] [PMID: 11746857]
[47]
Chen L. Dietary phenolic compound with the presence of C2= C3 double bond take the pre-emptive opportunities to enhance its biological effects. J Food Microbiol 2018; 2: 4-6.
[48]
Majo DD, Giammanco M, Guardia ML, Tripoli E, Giammanco S, Finotti E. Flavanones in citrus fruit: Structure-antioxidant activity relationships. Food Res Int 2005; 38(10): 1161-6.
[http://dx.doi.org/10.1016/j.foodres.2005.05.001]
[49]
Hwang SL, Yen GC. Modulation of Akt, JNK, and p38 activation is involved in citrus flavonoid-mediated cytoprotection of PC12 cells challenged by hydrogen peroxide. J Agric Food Chem 2009; 57(6): 2576-82.
[http://dx.doi.org/10.1021/jf8033607] [PMID: 19222219]
[50]
Sambantham S, Radha M, Paramasivam A, et al. Molecular mechanism underlying hesperetin-induced apoptosis by in silico analysis and in prostate cancer PC-3 cells. Asian Pac J Cancer Prev 2013; 14(7): 4347-52.
[http://dx.doi.org/10.7314/APJCP.2013.14.7.4347] [PMID: 23992001]
[51]
Sak K. Cytotoxicity of dietary flavonoids on different human cancer types. Pharmacogn Rev 2014; 8(16): 122-46.
[http://dx.doi.org/10.4103/0973-7847.134247] [PMID: 25125885]
[52]
Curti V, Di Lorenzo A, Rossi D, et al. Enantioselective modulatory effects of naringenin enantiomers on the expression levels of miR-17-3p involved in endogenous antioxidant defenses. Nutrients 2017; 9(3): 215.
[http://dx.doi.org/10.3390/nu9030215] [PMID: 28264488]
[53]
Famurewa AC, Renu K, Eladl MA, et al. Hesperidin and hesperetin against heavy metal toxicity: Insight on the molecular mechanism of mitigation. Biomed Pharmacother 2022; 149: 112914.
[http://dx.doi.org/10.1016/j.biopha.2022.112914] [PMID: 36068775]
[54]
Prasanna S, Doerksen R. Topological polar surface area: A useful descriptor in 2D-QSAR. Curr Med Chem 2009; 16(1): 21-41.
[http://dx.doi.org/10.2174/092986709787002817] [PMID: 19149561]
[55]
Rawson NE, Ho CT, Li S. Efficacious anti-cancer property of flavonoids from citrus peels. Food Sci Hum Wellness 2014; 3(3-4): 104-9.
[http://dx.doi.org/10.1016/j.fshw.2014.11.001]
[56]
Sohel M, Sultana H, Sultana T, et al. Chemotherapeutic potential of hesperetin for cancer treatment, with mechanistic insights: A comprehensive review. Heliyon 2022; 8(1): e08815.
[http://dx.doi.org/10.1016/j.heliyon.2022.e08815] [PMID: 35128104]
[57]
Nurhayati IP, Khumaira A, Ilmawati GPN, Meiyanto E, Hermawan A. Cytotoxic and antimetastatic activity of hesperetin and doxorubicin combination toward Her2 expressing breast cancer cells. Asian Pac J Cancer Prev 2020; 21(5): 1259-67.
[http://dx.doi.org/10.31557/APJCP.2020.21.5.1259] [PMID: 32458631]
[58]
Yunita E, Muflikhasari HA, Ilmawati GPN, Meiyanto E, Hermawan A. Hesperetin alleviates doxorubicin-induced migration in 4T1 breast cancer cells. Future J Pharm Sci 2020; 6(1): 23.
[http://dx.doi.org/10.1186/s43094-020-00036-y]
[59]
Wang Y, Liu S, Dong W, et al. Combination of hesperetin and platinum enhances anticancer effect on lung adenocarcinoma. Biomed Pharmacother 2019; 113: 108779.
[http://dx.doi.org/10.1016/j.biopha.2019.108779] [PMID: 30889488]
[60]
Malik P, Hoidal JR, Mukherjee TK. Recent advances in curcumin treated non-small cell lung cancers: An impetus of pleiotropic traits and nanocarrier aided delivery. Curr Med Chem 2020; 27: 1-45.
[http://dx.doi.org/10.2174/0929867327666200824110332] [PMID: 32838707]
[61]
Gupta SC, Patchva S, Aggarwal BB. Therapeutic roles of curcumin: Lessons learned from clinical trials. AAPS J 2013; 15(1): 195-218.
[http://dx.doi.org/10.1208/s12248-012-9432-8] [PMID: 23143785]
[62]
Ferreira O, Pinho SP. Solubility of flavonoids in pure solvents. Ind Eng Chem Res 2012; 51(18): 6586-90.
[http://dx.doi.org/10.1021/ie300211e]
[63]
Lucas-Abellán C, Pérez-Abril M, Castillo J, et al. Effect of temperature, pH, β- and HP-β-cds on the solubility and stability of flavanones: Naringenin and hesperetin. Lebensm Wiss Technol 2019; 108: 233-9.
[http://dx.doi.org/10.1016/j.lwt.2019.03.059]
[64]
Ferreira O, Schröder B, Pinho SP. Solubility of hesperetin in mixed solvents. J Chem Eng Data 2013; 58(9): 2616-21.
[http://dx.doi.org/10.1021/je400513s]
[65]
Chamundeeswari M, Jeslin J, Verma ML. Nanocarriers for drug delivery applications. Environ Chem Lett 2019; 17(2): 849-65.
[http://dx.doi.org/10.1007/s10311-018-00841-1]
[66]
Patra JK, Das G, Fraceto LF, et al. Nano based drug delivery systems: Recent developments and future prospects. J Nanobiotechnol 2018; 16(1): 71.
[http://dx.doi.org/10.1186/s12951-018-0392-8] [PMID: 30231877]
[67]
Yeh CH, Shen ZQ, Wang TW, et al. Hesperetin promotes longevity and delays aging via activation of Cisd2 in naturally aged mice. J Biomed Sci 2022; 29(1): 53.
[http://dx.doi.org/10.1186/s12929-022-00838-7] [PMID: 35871686]
[68]
Wu D, Zhang J, Wang J, Li J, Liao F, Dong W. Hesperetin induces apoptosis of esophageal cancer cells via mitochondrial pathway mediated by the increased intracellular reactive oxygen species. Tumour Biol 2016; 37(3): 3451-9.
[http://dx.doi.org/10.1007/s13277-015-4176-6] [PMID: 26449828]
[69]
Zhang J, Wu D, Vikash , et al. Hesperetin induces the apoptosis of gastric cancer cells via activating mitochondrial pathway by increasing reactive oxygen species. Dig Dis Sci 2015; 60(10): 2985-95.
[http://dx.doi.org/10.1007/s10620-015-3696-7] [PMID: 25972151]
[70]
He S, Wang X, Zhong Y, et al. Hesperetin post-treatment prevents rat cardiomyocytes from hypoxia/reoxygenation injury in vitro via activating PI3K/Akt signaling pathway. Biomed Pharmacother 2017; 91: 1106-12.
[http://dx.doi.org/10.1016/j.biopha.2017.05.003] [PMID: 28531921]
[71]
Choi EJ. Hesperetin induced G1-phase cell cycle arrest in human breast cancer MCF-7 cells: Involvement of CDK4 and p21. Nutr Cancer 2007; 59(1): 115-9.
[http://dx.doi.org/10.1080/01635580701419030] [PMID: 17927510]
[72]
Nel A, Ruoslahti E, Meng H. New insights into “permeability” as in the enhanced permeability and retention effect of cancer nanotherapeutics. ACS Nano 2017; 11(10): 9567-9.
[http://dx.doi.org/10.1021/acsnano.7b07214] [PMID: 29065443]
[73]
Bertrand N, Wu J, Xu X, Kamaly N, Farokhzad OC. Cancer nanotechnology: The impact of passive and active targeting in the era of modern cancer biology. Adv Drug Deliv Rev 2014; 66: 2-25.
[http://dx.doi.org/10.1016/j.addr.2013.11.009] [PMID: 24270007]
[74]
Roger E, Lagarce F, Garcion E, et al. Biopharmaceutical parameters to consider in order to alter the fate of nanocarriers after oral delivery. Nanomedicine 2010; 5(2): 287-306.
[http://dx.doi.org/10.2217/nnm.09.110]
[75]
Perrigue PM, Murray RA, Mielcarek A, Henschke A, Moya SE. Degradation of drug delivery nanocarriers and payload release: A review of physical methods for tracing nanocarrier biological fate. Pharmaceutics 2021; 13(6): 770.
[http://dx.doi.org/10.3390/pharmaceutics13060770] [PMID: 34064155]
[76]
Malik P, Mukherjee TK. Recent advances in gold and silver nanoparticle based therapies for lung and breast cancers. Int J Pharm 2018; 553(1-2): 483-509.
[http://dx.doi.org/10.1016/j.ijpharm.2018.10.048] [PMID: 30394284]
[77]
Lu Q, Lai Y, Zhang H, et al. Hesperetin inhibits TGF-β1-induced migration and invasion of triple negative breast cancer MDA-MB-231 cells via suppressing Fyn/Paxillin/RhoA pathway. Integr Cancer Ther 2022; 21.
[http://dx.doi.org/10.1177/15347354221086900] [PMID: 35297710]
[78]
Yang Y, Wolfram J, Shen H, Fang X, Ferrari M. Hesperetin: An inhibitor of the transforming growth factor-β (TGF-β) signaling pathway. Eur J Med Chem 2012; 58: 390-5.
[http://dx.doi.org/10.1016/j.ejmech.2012.10.028] [PMID: 23153811]
[79]
Abdallah RM, Elkhouly AM, Soliman RA, et al. Hindering the synchronization between mir-486-5p and H19 Lncrna by hesperetin halts breast cancer aggressiveness through tuning ICAM-1. Anti-Cancer Agents Med Chem 2022; 22: 586-95.
[http://dx.doi.org/10.2174/1871520621666210419093652]
[80]
Abdallah R, Elkhouly A, Soliman R, Motaal A, Assal R, Youness RA. 59P Hesperitin halts metastatic breast cancer through tweaking the interplay between the tumour suppressor miR-486-5p and the oncogenic lncRNA H19. Ann Oncol 2020; 31: S1235.
[http://dx.doi.org/10.1016/j.annonc.2020.08.2218]
[81]
Abdallah RM, Youness RA, El Meckawy N, El Sebaaei A, Abdelmotaal AA, Assal RA. Crosstalk between hesperetin and miR-486-5p in triple-negative breast cancer (TNBC): An approach towards precision medicine. Ann Oncol 2018; 29: vi28-9.
[http://dx.doi.org/10.1093/annonc/mdy314.028]
[82]
Mukhopadhyay S, Malik P, Arora SK, Mukherjee TK. Intercellular adhesion molecule-1 as a drug target in asthma and rhinitis. Respirology 2014; 19(4): 508-13.
[http://dx.doi.org/10.1111/resp.12285] [PMID: 24689994]
[83]
Elango R, Athinarayanan J, Subbarayan VP, Lei DKY, Alshatwi AA. Hesperetin induces an apoptosis-triggered extrinsic pathway and a p53- independent pathway in human lung cancer H522 cells. J Asian Nat Prod Res 2018; 20(6): 559-69.
[http://dx.doi.org/10.1080/10286020.2017.1327949] [PMID: 28537448]
[84]
Park JH, Ku HJ, Park JW. Hesperetin mitigates acrolein-induced apoptosis in lung cells in vitro and in vivo. Redox Rep 2018; 23(1): 188-93.
[http://dx.doi.org/10.1080/13510002.2018.1535640] [PMID: 30325253]
[85]
Tanaka M, Endo H, Sakusa K, Yano M. Hesperetin induces apoptosis in A549 cells via the Hsp70-mediated activation of Bax. Int J Oncol 2022; 61(6): 143.
[http://dx.doi.org/10.3892/ijo.2022.5433] [PMID: 36196892]
[86]
Wang S, Sheng H, Zheng F, Zhang F. Hesperetin promotes DOT1L degradation and reduces histone H3K79 methylation to inhibit gastric cancer metastasis. Phytomedicine 2021; 84: 153499.
[http://dx.doi.org/10.1016/j.phymed.2021.153499] [PMID: 33667841]
[87]
Cheng Q, Mao L, Huang H, et al. Hesperetin ameliorates glioblastoma by inhibiting proliferation, inducing apoptosis, and suppressing metastasis. Transl Cancer Res 2022; 11(6): 1781-94.
[http://dx.doi.org/10.21037/tcr-22-1497] [PMID: 35836521]
[88]
Li Q, Miao Z, Wang R, et al. Hesperetin induces apoptosis in human glioblastoma cells via p38 MAPK activation. Nutr Cancer 2019; 72(3): 538-45.
[http://dx.doi.org/10.1080/01635581.2019.1638424]
[89]
Wang J, Chen H, Hu Z, Ma K, Wang H. Hesperetin regulates transforming growth factor-β1/Smads pathway to suppress epithelial-mesenchymal transition-mediated invasion and migration in cervical cancer cell. Anticancer Drugs 2021; 32(9): 930-8.
[http://dx.doi.org/10.1097/CAD.0000000000001085] [PMID: 34016833]
[90]
Lee J, Lee J, Kim M, Kim JH. Fermented extraction of Citrus unshiu peel inhibits viability and migration of human pancreatic cancers. J Med Food 2018; 21(1): 5-12.
[http://dx.doi.org/10.1089/jmf.2017.3984] [PMID: 29346059]
[91]
Ban C, Park SJ, Lim S, Choi SJ, Choi YJ. Improving flavonoid bioaccessibility using an edible oil-based lipid nanoparticle for oral delivery. J Agric Food Chem 2015; 63(21): 5266-72.
[http://dx.doi.org/10.1021/acs.jafc.5b01495] [PMID: 25976277]
[92]
Latifi S, Tamayol A, Habibey R, et al. Natural lecithin promotes neural network complexity and activity. Sci Rep 2016; 6(1): 25777.
[http://dx.doi.org/10.1038/srep25777] [PMID: 27228907]
[93]
Meena J, Singh M. Hydrophobics and double bond of Tweens affecting water interactions estimated with physicochemical properties at T = 298.15 K. J Mol Liq 2016; 220: 671-80.
[http://dx.doi.org/10.1016/j.molliq.2016.04.114]
[94]
Malik P, Inwati GK, Mukherjee TK, Singh S, Singh M. Green silver nanoparticle and Tween-20 modulated pro-oxidant to antioxidant curcumin transformation in aqueous CTAB stabilized peanut oil emulsions. J Mol Liq 2019; 291: 111252.
[http://dx.doi.org/10.1016/j.molliq.2019.111252]
[95]
Menezes P, Frank LA, Lima B, et al. Hesperetin-loaded lipid-core nanocapsules in polyamide: A new textile formulation for topical drug delivery. Int J Nanomedicine 2017; 12: 2069-79.
[http://dx.doi.org/10.2147/IJN.S124564] [PMID: 28352176]
[96]
Zeng F, Wang D, Tian Y, et al. Nanoemulsion for improving the oral bioavailability of hesperetin: Formulation optimization and absorption mechanism. J Pharm Sci 2021; 110(6): 2555-61.
[http://dx.doi.org/10.1016/j.xphs.2021.02.030] [PMID: 33652015]
[97]
Lazer LM, Kesavan Y, Gor R, et al. Targeting colon cancer stem cells using novel doublecortin like kinase 1 antibody functionalized folic acid conjugated hesperetin encapsulated chitosan nanoparticles. Colloids Surf B Biointerfaces 2022; 217: 112612.
[http://dx.doi.org/10.1016/j.colsurfb.2022.112612] [PMID: 35738074]
[98]
Mary Lazer L, Sadhasivam B, Palaniyandi K, et al. Chitosan-based nano-formulation enhances the anticancer efficacy of hesperetin. Int J Biol Macromol 2018; 107(Pt B): 1988-98.
[http://dx.doi.org/10.1016/j.ijbiomac.2017.10.064] [PMID: 29032208]
[99]
Wolfram J, Scott B, Boom K, et al. Hesperetin liposomes for cancer therapy. Curr Drug Deliv 2016; 13(5): 711-9.
[http://dx.doi.org/10.2174/1567201812666151027142412] [PMID: 26502889]
[100]
Sheokand S, Navik U, Bansal AK. Nanocrystalline solid dispersions (NSD) of hesperetin (HRN) for prevention of 7,12-dimethylbenz[a]anthracene (DMBA)-induced breast cancer in Sprague-Dawley (SD) rats. Eur J Pharm Sci 2019; 128: 240-9.
[http://dx.doi.org/10.1016/j.ejps.2018.12.006] [PMID: 30553062]
[101]
Wang J, Li Q, Chen Z, et al. Improved bioavailability and anticancer efficacy of Hesperetin on breast cancer via a self-assembled rebaudioside A nanomicelles system. Toxicol Appl Pharmacol 2021; 419: 115511.
[http://dx.doi.org/10.1016/j.taap.2021.115511] [PMID: 33819459]
[102]
Simão DO, Honorato TD, Gobo GG, et al. Preparation and cytotoxicity of lipid nanocarriers containing a hydrophobic flavanone. Colloids Surf A Physicochem Eng Asp 2020; 601: 124982.
[http://dx.doi.org/10.1016/j.colsurfa.2020.124982]
[103]
Gokuladhas K, Jayakumar S, Rajan B, et al. Exploring the potential role of chemopreventive agent, hesperetin conjugated PEGylated gold nanoparticles in diethylnitrosamine-induced hepatocellular carcinoma in male wistar albino rats. Indian J Clin Biochem 2016; 31(2): 171-84.
[http://dx.doi.org/10.1007/s12291-015-0520-2] [PMID: 27069325]
[104]
Gokuladhas K, Jayakumar S, Madankumar A, et al. Synthesis and characterization of biocompatible gold nanoparticles stabilized with hydrophilic polymer coated hesperetin drug for sustained drug delivery to treat hepatocellular carcinoma-derived cancer cells. Int J Pharm Res 2014; 8: 98-105.
[105]
Zare M, Norouzi Sarkati M, Tashakkorian H, et al. Dextran-hesperetin conjugate as a novel biocompatible medicine for antimicrobial and anticancer applications. J Polym Environ 2021; 29(3): 811-20.
[http://dx.doi.org/10.1007/s10924-020-01922-5]
[106]
Kong W, Ling X, Chen Y, et al. Hesperetin reverses P-glycoprotein-mediated cisplatin resistance in DDP-resistant human lung cancer cells via modulation of the nuclear factor-κB signaling pathway. Int J Mol Med 2020; 45(4): 1213-24.
[http://dx.doi.org/10.3892/ijmm.2020.4485] [PMID: 32124932]
[107]
Go RS, Adjei AA. Review of the comparative pharmacology and clinical activity of cisplatin and carboplatin. J Clin Oncol 1999; 17(1): 409-22.
[http://dx.doi.org/10.1200/JCO.1999.17.1.409] [PMID: 10458260]
[108]
He P, Ma J, Liu Y, Deng H, Dong W. Hesperetin promotes cisplatin-induced apoptosis of gastric cancer in vitro and in vivo by upregulating PTEN expression. Front Pharmacol 2020; 11: 1326.
[http://dx.doi.org/10.3389/fphar.2020.01326] [PMID: 32973533]
[109]
Lee J, Kim DH, Kim JH. Combined administration of naringenin and hesperetin with optimal ratio maximizes the anti-cancer effect in human pancreatic cancer via down regulation of FAK and p38 signaling pathway. Phytomedicine 2019; 58: 152762.
[http://dx.doi.org/10.1016/j.phymed.2018.11.022] [PMID: 31005717]
[110]
Adan A, Baran Y. Fisetin and hesperetin induced apoptosis and cell cycle arrest in chronic myeloid leukemia cells accompanied by modulation of cellular signaling. Tumour Biol 2016; 37(5): 5781-95.
[http://dx.doi.org/10.1007/s13277-015-4118-3] [PMID: 26408178]
[111]
Aboismaiel MG, El-Mesery M, El-Karef A, El-Shishtawy MM. Hesperetin upregulates Fas/FasL expression and potentiates the antitumor effect of 5-fluorouracil in rat model of hepatocellular carcinoma. Egypt J Basic Appl Sci 2020; 7(1): 20-34.
[http://dx.doi.org/10.1080/2314808X.2019.1707627]
[112]
Wu D, Li J, Hu X, Ma J, Dong W. Hesperetin inhibits Eca-109 cell proliferation and invasion by suppressing the PI3K/AKT signaling pathway and synergistically enhances the anti-tumor effect of 5-fluorouracil on esophageal cancer in vitro and in vivo. RSC Advances 2018; 8(43): 24434-43.
[http://dx.doi.org/10.1039/C8RA00956B] [PMID: 35539191]
[113]
Coutinho L, Oliveira H, Pacheco AR, et al. Hesperetin-etoposide combinations induce cytotoxicity in U2OS cells: Implications on therapeutic developments for osteosarcoma. DNA Repair (Amst) 2017; 50: 36-42.
[http://dx.doi.org/10.1016/j.dnarep.2016.12.006] [PMID: 28063664]
[114]
Edis Z, Wang J, Waqas MK, Ijaz M, Ijaz M. Nanocarriers-mediated drug delivery systems for anticancer agents: An overview and perspectives. Int J Nanomedicine 2021; 16: 1313-30.
[http://dx.doi.org/10.2147/IJN.S289443] [PMID: 33628022]
[115]
Gaber M, Hany M, Mokhtar S, Helmy MW, Elkodairy KA, Elzoghby AO. Boronic-targeted albumin-shell oily-core nanocapsules for synergistic aromatase inhibitor/herbal breast cancer therapy. Mater Sci Eng C 2019; 105: 110099.
[http://dx.doi.org/10.1016/j.msec.2019.110099] [PMID: 31546395]
[116]
Zhen L, Ma T, Tang J, et al. Hesperitin enhances the ability of daunorubicin by co-loading with MPEG-PCL nanoparticles to induce apoptosis in gastric cancer. Oncotarget 2014; 5.
[http://dx.doi.org/10.18632/oncotarget.22182]
[117]
Arya A, Ahmad H, Tulsankar S, et al. Bioflavonoid hesperetin overcome bicalutamide induced toxicity by co-delivery in novel SNEDDS formulations: Optimization, in vivo evaluation and uptake mechanism. Mater Sci Eng C 2017; 71: 954-64.
[http://dx.doi.org/10.1016/j.msec.2016.11.006] [PMID: 27987794]
[118]
Hodaei M, Varshosaz J. Cationic okra gum coated nanoliposomes as a pH-sensitive carrier for co-delivery of hesperetin and oxaliplatin in colorectal cancers. Pharm Dev Technol 2022; 27(7): 773-84.
[http://dx.doi.org/10.1080/10837450.2022.2119249] [PMID: 36040153]
[119]
de Araújo Andrade T, Heimfarth L, dos Santos DM, et al. Hesperetin-based hydrogels protect the skin against UV radiation-induced damage. AAPS PharmSciTech 2022; 23(6): 170.
[http://dx.doi.org/10.1208/s12249-022-02323-8] [PMID: 35729366]
[120]
Li J, Wang T, Liu P, et al. Hesperetin ameliorates hepatic oxidative stress and inflammation via the PI3K/AKT-Nrf2-ARE pathway in oleic acid-induced HepG2 cells and a rat model of high-fat diet-induced NAFLD. Food Funct 2021; 12(9): 3898-918.
[http://dx.doi.org/10.1039/D0FO02736G] [PMID: 33977953]
[121]
Jiang S, Wang S, Zhang L, et al. Hesperetin as an adjuvant augments protective anti‐tumour immunity responses in B16F10 melanoma by stimulating cytotoxic CD8 + T cells. Scand J Immunol 2020; 91(4): e12867.
[http://dx.doi.org/10.1111/sji.12867] [PMID: 31975405]
[122]
Chen X, Wei W, Li Y, Huang J, Ci X. Hesperetin relieves cisplatin-induced acute kidney injury by mitigating oxidative stress, inflammation and apoptosis. Chem Biol Interact 2019; 308: 269-78.
[http://dx.doi.org/10.1016/j.cbi.2019.05.040] [PMID: 31153982]
[123]
Jo SH, Kim ME, Cho JH, et al. Hesperetin inhibits neuroinflammation on microglia by suppressing inflammatory cytokines and MAPK pathways. Arch Pharm Res 2019; 42(8): 695-703.
[http://dx.doi.org/10.1007/s12272-019-01174-5] [PMID: 31327152]
[124]
Sak K, Lust H, Kase M, Saar M, Jaal J. Suppression of taxanes cytotoxicity by citrus flavonoid hesperetin in PPC-1 human prostate cancer cells. Anticancer Res 2018; 38(11): 6209-15.
[http://dx.doi.org/10.21873/anticanres.12975] [PMID: 30396939]

Rights & Permissions Print Cite
Article Metrics
19
2
Wayfinder Image
© 2024 Bentham Science Publishers | Privacy Policy