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http://dx.doi.org/10.3831/KPI.2021.24.1.1

Biological and Therapeutic Effects of Troxerutin: Molecular Signaling Pathways Come into View  

Ahmadi, Zahra (Department of Basic Science, Faculty of Veterinary Medicine, Islamic Azad Branch, University of Shushtar)
Mohammadinejad, Reza (Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences)
Roomiani, Sahar (Department of Basic Science, Faculty of Veterinary Medicine, Islamic Azad Branch, University of Shushtar)
Afshar, Elham Ghasemipour (Department of Microbiology, Faculty of Science, Islamic Azad University)
Ashrafizadeh, Milad (Department of Basic Science, Faculty of Veterinary Medicine, University of Tabriz)
Publication Information
Journal of Pharmacopuncture / v.24, no.1, 2021 , pp. 1-13 More about this Journal
Abstract
Flavonoids consist a wide range of naturally occurring compounds which are exclusively found in different fruits and vegetables. These medicinal herbs have a number of favourable biological and therapeutic activities such as antioxidant, neuroprotective, renoprotective, anti-inflammatory, anti-diabetic and anti-tumor. Troxerutin, also known as vitamin P4, is a naturally occurring flavonoid which is isolated from tea, coffee and cereal grains as well as vegetables. It has a variety of valuable pharmacological and therapeutic activities including antioxidant, anti-inflammatory, anti-diabetic and anti-tumor. These pharmacological impacts have been demonstrated in in vitro and in vivo studies. Also, clinical trials have revealed the efficacy of troxerutin for management of phlebocholosis and hemorrhoidal diseases. In the present review, we focus on the therapeutic effects and biological activities of troxerutin as well as its molecular signaling pathways.
Keywords
troxerutin; flavonoid; herbal medicine; biological activity; therapeutic effect;
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1 Badalzadeh R, Baradaran B, Alihemmati A, Yousefi B, Abbaszadeh A. Troxerutin preconditioning and ischemic postconditioning modulate inflammatory response after myocardial ischemia/ reperfusion injury in rat model. Inflammation. 2017;40(1):136-43.   DOI
2 Zamanian M, Hajizadeh MR, Esmaeili Nadimi A, Shamsizadeh A, Allahtavakoli M. Antifatigue effects of troxerutin on exercise endurance capacity, oxidative stress and matrix metalloproteinase-9 levels in trained male rats. Fundam Clin Pharmacol. 2017;31(4):447-55.   DOI
3 Xu P, Zhang WB, Cai XH, Qiu PY, Hao MH, Lu DD. Activating AKT to inhibit JNK by troxerutin antagonizes radiation-induced PTEN activation. Eur J Pharmacol. 2017;795:66-74.   DOI
4 Geetha R, Sathiya Priya C, Anuradha CV. Troxerutin abrogates mitochondrial oxidative stress and myocardial apoptosis in mice fed calorie-rich diet. Chem Biol Interact. 2017;278:74-83.   DOI
5 Rajagopalan G, Chandrasekaran SP, Carani Venkatraman A. Troxerutin attenuates diet-induced oxidative stress, impairment of mitochondrial biogenesis and respiratory chain complexes in mice heart. Clin Exp Pharmacol Physiol. 2017;44(1):103-13.   DOI
6 Mokhtari B, Badalzadeh R, Alihemmati A, Mohammadi M. Phosphorylation of GSK-3β and reduction of apoptosis as targets of troxerutin effect on reperfusion injury of diabetic myocardium. Eur J Pharmacol. 2015;765:316-21.   DOI
7 Zhang Z, Wang X, Zheng G, Shan Q, Lu J, Fan S, et al. Troxerutin attenuates enhancement of hepatic gluconeogenesis by inhibiting NOD activation-mediated inflammation in high-fat diet-treated mice. Int J Mol Sci. 2017;18(1):31.   DOI
8 Zhang ZF, Zhang YQ, Fan SH, Zhuang J, Zheng YL, Lu J, et al. Troxerutin protects against 2,2',4,4'-tetrabromodiphenyl ether (BDE-47)-induced liver inflammation by attenuating oxidative stress-mediated NAD+-depletion. J Hazard Mater. 2015;283:98-109.   DOI
9 Zhang ZF, Fan SH, Zheng YL, Lu J, Wu DM, Shan Q, et al. Troxerutin improves hepatic lipid homeostasis by restoring NAD(+)-depletion-mediated dysfunction of lipin 1 signaling in high-fat diet-treated mice. Biochem Pharmacol. 2014;91(1):74-86.   DOI
10 Zhang ZF, Shan Q, Zhuang J, Zhang YQ, Wang X, Fan SH, et al. Troxerutin inhibits 2,2',4,4'-tetrabromodiphenyl ether (BDE-47)-induced hepatocyte apoptosis by restoring proteasome function. Toxicol Lett. 2015;233(3):246-57.   DOI
11 Mintz KJ, Mercado G, Zhou Y, Ji Y, Hettiarachchi SD, Liyanage PY, et al. Tryptophan carbon dots and their ability to cross the blood-brain barrier. Colloids Surf B Biointerfaces. 2019;176:488-93.   DOI
12 Yaribeygi H, Atkin SL, Sahebkar A. Interleukin-18 and diabetic nephropathy: a review. J Cell Physiol. 2019;234(5):5674-82.   DOI
13 Yaribeygi H, Butler AE, Atkin SL, Katsiki N, Sahebkar A. Sodium-glucose cotransporter 2 inhibitors and inflammation in chronic kidney disease: possible molecular pathways. J Cell Physiol. 2018;234(1):223-30.   DOI
14 Yang X, Xu W, Huang K, Zhang B, Wang H, Zhang X, et al. Precision toxicology shows that troxerutin alleviates ochratoxin Ainduced renal lipotoxicity. FASEB J. 2019;33(2):2212-27.   DOI
15 Yaribeygi H, Katsiki N, Butler AE, Atkin SL, Sahebkar A. A response to "In response to 'Sodium-glucose cotransporter 2 inhibitors and inflammation in chronic kidney disease: possible molecular pathways'". J Cell Physiol. 2019;234(7):9908-9.   DOI
16 Yaribeygi H, Simental-Mendia LE, Butler AE, Sahebkar A. Protective effects of plant-derived natural products on renal complications. J Cell Physiol. 2019;234(8):12161-72.   DOI
17 Salama SA, Arab HH, Maghrabi IA. Troxerutin down-regulates KIM-1, modulates p38 MAPK signaling, and enhances renal regenerative capacity in a rat model of gentamycin-induced acute kidney injury. Food Funct. 2018;9(12):6632-42.   DOI
18 Shan Q, Zheng GH, Han XR, Wen X, Wang S, Li MQ, et al. Troxerutin protects kidney tissue against BDE-47-induced inflammatory damage through CXCR4-TXNIP/NLRP3 signaling. Oxid Med Cell Longev. 2018;2018:9865495.   DOI
19 Elangovan P, Ramakrishnan R, Amudha K, Jalaludeen AM, Sagaran GK, Babu FR, et al. Beneficial protective effect of troxerutin on Nickel-induced renal dysfunction in Wistar Rats. J Environ Pathol Toxicol Oncol. 2018;37(1):1-14.   DOI
20 Dehnamaki F, Karimi A, Pilevarian AA, Fatemi I, Hakimizadeh E, Kaeidi A, et al. Treatment with troxerutin protects against cisplatin-induced kidney injury in mice. Acta Chir Belg. 2019;119(1):31-7.   DOI
21 Shan Q, Zhuang J, Zheng G, Zhang Z, Zhang Y, Lu J, et al. Troxerutin reduces kidney damage against BDE-47-induced apoptosis via inhibiting NOX2 activity and increasing Nrf2 activity. Oxid Med Cell Longev. 2017;2017:6034692.   DOI
22 Najafi H, Changizi Ashtiyani S, Madani SH, Fakhri S, Mohamadi Yarijani Z, Hazem M. Therapeutic effects of curcumin on renal tissue damages induced by ischemia reperfusion in rat. Koomesh. 2014;16(2):273-81.
23 Ambati RR, Phang SM, Ravi S, Aswathanarayana RG. Astaxanthin: sources, extraction, stability, biological activities and its commercial applications--a review. Mar Drugs. 2014;12(1):128-52.   DOI
24 Edge R, McGarvey DJ, Truscott TG. The carotenoids as antioxidants--a review. J Photochem Photobiol B. 1997;41(3):189-200.   DOI
25 Heidari Khoei H, Fakhri S, Parvardeh S, Shams Mofarahe Z, Ghasemnejad-Berenji H, Nazarian H, et al. Testicular toxicity and reproductive performance of streptozotocin-induced diabetic male rats: the ameliorating role of silymarin as an antioxidant. Toxin Rev. 2019;38(3):223-33.   DOI
26 Najafi H, Changizi Ashtiyani S, Sayedzadeh SA, Mohamadi Yarijani Z, Fakhri S. Therapeutic effects of curcumin on the functional disturbances and oxidative stress induced by renal ischemia/reperfusion in rats. Avicenna J Phytomed. 2015;5(6):576-86.
27 Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol. 2007;39(1):44-84.   DOI
28 Wu H, Niu H, Shao A, Wu C, Dixon BJ, Zhang J, et al. Astaxanthin as a potential neuroprotective agent for neurological diseases. Mar Drugs. 2015;13(9):5750-66.   DOI
29 Raja B, Saranya D, Prabhu R. Role of flavonoid troxerutin on blood pressure, oxidative stress and regulation of lipid metabolism. Front Biosci (Elite Ed). 2019;11:121-9.   DOI
30 Xin X, Zhang M, Li X, Lai F, Zhao G. Biocatalytic synthesis of acylated derivatives of troxerutin: their bioavailability and antioxidant properties in vitro. Microb Cell Fact. 2018;17(1):130.   DOI
31 Bahreyni A, Rezaei M, Bahrami A, Khazaei M, Fiuji H, Ryzhikov M, et al. Diagnostic, prognostic, and therapeutic potency of microRNA 21 in the pathogenesis of colon cancer, current status and prospective. J Cell Physiol. 2019;234(6):8075-81.   DOI
32 Elangovan P, Jalaludeen AM, Ramakrishnan R, Pari L. Protective effect of troxerutin on Nickel-induced testicular toxicity in Wistar Rats. J Environ Pathol Toxicol Oncol. 2016;35(2):133-46.   DOI
33 Panat NA, Maurya DK, Ghaskadbi SS, Sandur SK. Troxerutin, a plant flavonoid, protects cells against oxidative stress-induced cell death through radical scavenging mechanism. Food Chem. 2016;194:32-45.   DOI
34 Bahreyni A, Ghorbani E, Fuji H, Ryzhikov M, Khazaei M, Erfani M, et al. Therapeutic potency of oncolytic virotherapy-induced cancer stem cells targeting in brain tumors, current status, and perspectives. J Cell Biochem. 2019;120(3):2766-73.   DOI
35 Barati Bagherabad M, Afzaljavan F, ShahidSales S, Hassanian SM, Avan A. Targeted therapies in pancreatic cancer: promises and failures. J Cell Biochem. 2019;120(3):2726-41.   DOI
36 Ghobadi N, Mehramiz M, ShahidSales S, Rezaei Brojerdi A, Anvari K, Khazaei M, et al. A genetic variant in CDKN2A/2B locus was associated with poor prognosis in patients with esophageal squamous cell carcinoma. J Cell Physiol. 2019;234(4):5070-6.   DOI
37 Mahdavi M, Nassiri M, Kooshyar MM, Vakili-Azghandi M, Avan A, Sandry R, et al. Hereditary breast cancer; genetic penetrance and current status with BRCA. J Cell Physiol. 2019;234(5):5741-50.   DOI
38 Marjaneh RM, Khazaei M, Ferns GA, Avan A, Aghaee-Bakhtiari SH. The role of microRNAs in 5-FU resistance of colorectal cancer: possible mechanisms. J Cell Physiol. 2019;234(3):2306-16.   DOI
39 Jose J, Sudhakaran S, Sumesh Kumar TM, Jayaraman S, Jayadevi Variyar E. A comparative evaluation of anticancer activities of flavonoids isolated from Mimosa pudica, Aloe vera and Phyllanthus niruri against human breast carcinoma cell line (MCF-7) using MTT assay. Int J Pharm Pharm Sci. 2014;6(2):319-22.
40 Ghosh D, Dey SK, Saha C. Antagonistic effects of black tea against gamma radiation-induced oxidative damage to normal lymphocytes in comparison with cancerous K562 cells. Radiat Environ Biophys. 2014;53(4):695-704.   DOI
41 Erdman JW Jr, Balentine D, Arab L, Beecher G, Dwyer JT, Folts J, et al. Flavonoids and heart health: proceedings of the ILSI North America Flavonoids Workshop, May 31-June 1, 2005, Washington, DC. J Nutr. 2007;137(3 Suppl 1):718S-37S.   DOI
42 Mahomoodally MF, Gurib-Fakim A, Subratty AH. Antimicrobial activities and phytochemical profiles of endemic medicinal plants of Mauritius. Pharm Biol. 2005;43(3):237-42.   DOI
43 Scalbert A, Williamson G. Dietary intake and bioavailability of polyphenols. J Nutr. 2000;130(8S Suppl):2073S-85S.   DOI
44 Williamson G, Clifford MN. Colonic metabolites of berry polyphenols: the missing link to biological activity? Br J Nutr. 2010;104 Suppl 3:S48-66.   DOI
45 Badalzadeh R, Layeghzadeh N, Alihemmati A, Mohammadi M. Beneficial effect of troxerutin on diabetes-induced vascular damages in rat aorta: histopathological alterations and antioxidation mechanism. Int J Endocrinol Metab. 2015;13(2):e25969.   DOI
46 Cha HJ, Lee KS, Lee GT, Lee KK, Hong JT, Lee SN, et al. Altered miRNA expression profiles are involved in the protective effects of troxerutin against ultraviolet B radiation in normal human dermal fibroblasts. Int J Mol Med. 2014;33(4):957-63.   DOI
47 Taghizadeh Kermani A, Hosseini S, Fanipakdel A, Joudi Mashhad M, Akhavan Rezayat K, Zardadi M, et al. A randomized clinical trial on the antitumoral effects of low molecular weight heparin in the treatment of esophageal cancer. J Cell Physiol. 2019;234(4):4191-9.   DOI
48 Moradi-Marjaneh R, Hassanian SM, Hasanzadeh M, Rezayi M, Maftouh M, Mehramiz M, et al. Therapeutic potential of tolllike receptors in treatment of gynecological cancers. IUBMB Life. 2019;71(5):549-64.   DOI
49 Parizadeh SM, Jafarzadeh-Esfehani R, Ghandehari M, Goldani F, Parizadeh SMR, Hassanian SM, et al. MicroRNAs as potential diagnostic and prognostic biomarkers in hepatocellular carcinoma. Curr Drug Targets. 2019;20(11):1129-40.   DOI
50 Parizadeh SM, Jafarzadeh-Esfehani R, Hassanian SM, Parizadeh SMR, Vojdani S, Ghandehari M, et al. Targeting cancer stem cells as therapeutic approach in the treatment of colorectal cancer. Int J Biochem Cell Biol. 2019;110:75-83.   DOI
51 Thomas NS, George K, Selvam AAA. Anticancer mechanism of troxerutin via targeting Nrf2 and NF-κB signalling pathways in hepatocarcinoma cell line. Toxicol In Vitro. 2019;54:317-29.   DOI
52 Thomas NS, George K, Selvam AAA. Troxerutin subdues hepatic tumorigenesis via disrupting the MDM2-p53 interaction. Food Funct. 2018;9:5336-49.   DOI
53 Subastri A, Suyavaran A, Preedia Babu E, Nithyananthan S, Barathidasan R, Thirunavukkarasu C. Troxerutin with copper generates oxidative stress in cancer cells: its possible chemotherapeutic mechanism against hepatocellular carcinoma. J Cell Physiol. 2018;233(3):1775-90.   DOI
54 Xu GY, Tang XJ. Troxerutin (TXN) potentiated 5-Fluorouracil (5-Fu) treatment of human gastric cancer through suppressing STAT3/NF-κB and Bcl-2 signaling pathways. Biomed Pharmacother. 2017;92:95-107.   DOI
55 Vinothkumar R, Vinoth Kumar R, Sudha M, Viswanathan P, Balasubramanian T, Nalini N. Modulatory effect of troxerutin on biotransforming enzymes and preneoplasic lesions induced by 1,2-dimethylhydrazine in rat colon carcinogenesis. Exp Mol Pathol. 2014;96(1):15-26.   DOI
56 Geetha R, Radika MK, Priyadarshini E, Bhavani K, Anuradha CV. Troxerutin reverses fibrotic changes in the myocardium of high-fat high-fructose diet-fed mice. Mol Cell Biochem. 2015; 407(1-2):263-79.   DOI
57 Lee KS, Cha HJ, Lee GT, Lee KK, Hong JT, Ahn KJ, et al. Troxerutin induces protective effects against ultraviolet B radiation through the alteration of microRNA expression in human HaCaT keratinocyte cells. Int J Mol Med. 2014;33(4):934-42.   DOI
58 Sampath S, Karundevi B. Effect of troxerutin on insulin signaling molecules in the gastrocnemius muscle of high fat and sucrose-induced type-2 diabetic adult male rat. Mol Cell Biochem. 2014;395(1-2):11-27.   DOI
59 Thomas NS, George K, Arivalagan S, Mani V, Siddique AI, Namasivayam N. The in vivo antineoplastic and therapeutic efficacy of troxerutin on rat preneoplastic liver: biochemical, histological and cellular aspects. Eur J Nutr. 2017;56(7):2353-66.   DOI
60 Subastri A, Harikrishna K, Sureshkumar M, Alshammari GM, Aristatile B, Thirunavukkarasu C. Effect of troxerutin on 2-aminoanthracene and DNA interaction and its anti-mutagenic property. Biomed Pharmacother. 2017;88:325-34.   DOI
61 Panat NA, Singh BG, Maurya DK, Sandur SK, Ghaskadbi SS. Troxerutin, a natural flavonoid binds to DNA minor groove and enhances cancer cell killing in response to radiation. Chem Biol Interact. 2016;251:34-44.   DOI
62 Azarfarin M, Farajdokht F, Babri S, Salehpour F, Taghizadeh M, Mohaddes G. Effects of troxerutin on anxiety- and depressive-like behaviors induced by chronic mild stress in adult male rats. Iran J Basic Med Sci. 2018;21(8):781-6.
63 Diba R, Mohaddes G, Mirzaie Bavil F, Farajdokht F, Bayandor P, Hosseindoost M, et al. Protective effects of troxerutin on maternal high-fat diet-induced impairments of spatial memory and apelin in the male offspring. Iran J Basic Med Sci. 2018;21(7):682-7.
64 Zhao H, Liu Y, Zeng J, Li D, Huang Y. Troxerutin cerebroprotein hydrolysate injection ameliorates neurovascular injury induced by traumatic brain injury- via endothelial nitric oxide synthase pathway regulation. Int J Neurosci. 2018;128(12):1118-27.   DOI
65 Bayandor P, Farajdokht F, Mohaddes G, Diba R, Hosseindoost M, Mehri K, et al. The effect of troxerutin on anxiety- and depressive-like behaviours in the offspring of high-fat diet fed dams. Arch Physiol Biochem. 2019;125(2):156-62.   DOI
66 Farajdokht F, Amani M, Mirzaei Bavil F, Alihemmati A, Mohaddes G, Babri S. Troxerutin protects hippocampal neurons against amyloid beta-induced oxidative stress and apoptosis. EXCLI J. 2017;16:1081-9.
67 Yaribeygi H, Atkin SL, Ramezani M, Sahebkar A. A review of the molecular pathways mediating the improvement in diabetes mellitus following caloric restriction. J Cell Physiol. 2019;234(6):8436-42.   DOI
68 Baluchnejadmojarad T, Jamali-Raeufy N, Zabihnejad S, Rabiee N, Roghani M. Troxerutin exerts neuroprotection in 6-hydroxy-dopamine lesion rat model of Parkinson's disease: possible involvement of PI3K/ERβ signaling. Eur J Pharmacol. 2017;801:72-8.   DOI
69 Zhang S, Li H, Zhang L, Li J, Wang R, Wang M. Effects of troxerutin on cognitive deficits and glutamate cysteine ligase subunits in the hippocampus of streptozotocin-induced type 1 diabetes mellitus rats. Brain Res. 2017;1657:355-60.   DOI
70 Gui Y, Li A, Chen F, Zhou H, Tang Y, Chen L, et al. Involvement of AMPK/SIRT1 pathway in anti-allodynic effect of troxerutin in CCI-induced neuropathic pain. Eur J Pharmacol. 2015;769:234-41.   DOI
71 Yaribeygi H, Atkin SL, Sahebkar A. Natural compounds with DPP-4 inhibitory effects: implications for the treatment of diabetes. J Cell Biochem. 2019;120(7):10909-13.   DOI
72 Yaribeygi H, Atkin SL, Simental-Mendia LE, Barreto GE, Sahebkar A. Anti-inflammatory effects of resolvins in diabetic nephropathy: mechanistic pathways. J Cell Physiol. 2019;234(9):14873-82.   DOI
73 Yaribeygi H, Bo S, Ruscica M, Sahebkar A. Ceramides and diabetes mellitus: an update on the potential molecular relationships. Diabet Med. 2020;37(1):11-9.   DOI
74 Zavvari Oskuye Z, Mirzaei Bavil F, Hamidian GR, Mehri K, Qadiri A, Ahmadi M, et al. Troxerutin affects the male fertility in prepubertal type 1 diabetic male rats. Iran J Basic Med Sci. 2019;22(2):197-205.
75 Shu L, Zhang W, Huang G, Huang C, Zhu X, Su G, et al. Troxerutin attenuates myocardial cell apoptosis following myocardial ischemia-reperfusion injury through inhibition of miR-146a-5p expression. J Cell Physiol. 2019;234(6):9274-82.   DOI
76 Zhang W, Wang R, Liu W, Wang X, Li P, Zhang W, et al. Tecontaining carbon dots for fluorescence imaging of superoxide anion in mice during acute strenuous exercise or emotional changes. Chem Sci. 2017;9(3):721-7.   DOI
77 Yu Y, Zheng G. Troxerutin protects against diabetic cardiomyopathy through NF-κB/AKT/IRS1 in a rat model of type 2 diabetes. Mol Med Rep. 2017;15(6):3473-8.   DOI
78 Yavari R, Badalzadeh R, Alipour MR, Tabatabaei SM. Modulation of hippocampal gene expression of microRNA-146a/microRNA-155-nuclear factor-kappa B inflammatory signaling by troxerutin in healthy and diabetic rats. Indian J Pharmacol. 2016;48(6):675-80.   DOI
79 Kheirollahi A, Abbaszadeh A, Anbari K, Rostami B, Ahangari A, Hasanvand A, et al. Troxerutin protect sperm, seminiferous epithelium and pituitary-gonadal axis from torsion-detorsion injury: an experimental study. Int J Reprod Biomed. 2018;16(5):315-22.   DOI
80 Zhao H, Liu Y, Zeng J, Li D, Zhang W, Huang Y. Troxerutin and cerebroprotein hydrolysate injection protects neurovascular units from oxygen-glucose deprivation and reoxygenation-induced injury in vitro. Evid Based Complement Alternat Med. 2018;2018:9859672.
81 Najafi M, Noroozi E, Javadi A, Badalzadeh R. Anti-arrhythmogenic and anti-inflammatory effects of troxerutin in ischemia/ reperfusion injury of diabetic myocardium. Biomed Pharmacother. 2018;102:385-91.   DOI
82 Shu L, Zhang W, Huang C, Huang G, Su G. Troxerutin protects against myocardial ischemia/reperfusion injury via Pi3k/Akt pathway in rats. Cell Physiol Biochem. 2017;44(5):1939-48.   DOI