128
Views
10
CrossRef citations to date
0
Altmetric
Original Research

Investigating the effect of Crocus sativus L. petal hydroalcoholic extract on inflammatory and enzymatic indices resulting from alcohol use in kidney and liver of male rats

, , ORCID Icon, ORCID Icon, , ORCID Icon, , ORCID Icon & ORCID Icon show all
Pages 269-283 | Published online: 08 Oct 2019

References

  • Lim SS, Vos T, Flaxman AD, et al. A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990–2010: a systematic analysis for the global burden of disease study 2010. Lancet. 2012;380(9859):2224–2260. doi:10.1016/S0140-6736(12)61766-823245609
  • Grant BF, Goldstein RB, Saha TD, et al. Epidemiology of DSM-5 alcohol use disorder: results from the national epidemiologic survey on alcohol and related conditions III. JAMA Psychiatry. 2015;72(8):757–766. doi:10.1001/jamapsychiatry.2015.058426039070
  • Grant B, Chou SP, Saha TD, et al. Prevalence of 12-month alcohol use, high-risk drinking, and DSM-iv alcohol use disorder in the United States, 2001-2002 to 2012-2013: results from the national epidemiologic survey on alcohol and related conditions. JAMA Psychiatry. 2017;74(9):911–923. doi:10.1001/jamapsychiatry.2017.216128793133
  • World Health Organization (WHO). Global Status Report on Alcohol and Health 2014. Geneva: WHO; 2016 Available from: http://www.who.int/substance_abuse/publications/global_alcohol_report/msb_gsr_2014_1.pdf. Accessed December 31, 2016.
  • Molina PE, Gardner JD, Souza-Smith FM, Whitaker AM. Alcohol abuse: critical pathophysiological processes and contribution to disease burden. Physiology (Bethesda). 2014;29(3):203–215.24789985
  • Kirpich IA, McClain CJ, Vatsalya V, et al. Liver injury and endotoxemia in male and female alcohol-dependent individuals admitted to an alcohol treatment program. Alcohol Clin Exp Res. 2017;41(4):747–757. doi:10.1111/acer.1334628166367
  • Gao B, Tsukamoto H. Inflammation in alcoholic and nonalcoholic fatty liver disease: friend or foe? Gastroenterology. 2016;150(8):1704–1709. doi:10.1053/j.gastro.2016.01.02526826669
  • Testino G, Leone S. Acute alcoholic hepatitis: a literature review and proposal of treatment. Minerva Med. 2018;109(4):290–299. doi:10.23736/S0026-4806.17.05431-329115798
  • Stickel F, Datz C, Hampe J, Bataller R. Pathophysiology and management of alcoholic liver disease: update 2016. Gut Liver. 2017;11(12):173–188. doi:10.5009/gnl1647728274107
  • Varga ZV, Matyas C, Paloczi J, Pacher P. Alcohol misuse and kidney injury: epidemiological evidence and potential mechanisms. Alcohol Res. 2017;38(2):283–288.28988579
  • Egerod Israelsen M, Gluud LL, Krag A. Acute kidney injury and hepatorenal syndrome in cirrhosis. J Gastroenterol Hepatol. 2015;30(2):236–243. doi:10.1111/jgh.1270925160511
  • Ronksley PE, Brien SE, Turner BJ, Mukamal KJ, Ghali WA. Association of alcohol consumption with selected cardiovascular disease outcomes: a systematic review and meta-analysis. BMJ. 2011;342:d671. doi:10.1136/bmj.d67121343207
  • Schefold JC, Filippatos G, Hasenfuss G, Anker SD, von Haehling S. Heart failure and kidney dysfunction: epidemiology, mechanisms and management. Nat Rev Nephrol. 2016;12(10):610–623. doi:10.1038/nrneph.2016.11327573728
  • Husain K, Ansari RA, Ferder L. Alcohol-induced hypertension: mechanism and prevention. World J Cardiol. 2014;6(5):245–252. doi:10.4330/wjc.v6.i5.24524891935
  • Da Silva AL, Ruginsk SG, Uchoa ET, et al. Time-course of neuroendocrine changes and its correlation with hypertension induced by ethanol consumption. Alcohol Alcohol. 2013;48(8):495–504. doi:10.1093/alcalc/agt04023733506
  • Chow BS, Allen TJ. Angiotensin II type 2 receptor (AT2R) in renal and cardiovascular disease. Clin Sci (Lond). 2016;130(5):1307–1326. doi:10.1042/CS2016024327358027
  • Mennuni S, Rubattu S, Pierelli G, Tocci G, Fofi C, Volpe M. Hypertension and kidneys: unraveling complex molecular mechanisms underlying hypertensive renal damage. J Hum Hypertens. 2014;28(2):74–79. doi:10.1038/jhh.2013.5523803592
  • Liamis GL, Milionis HJ, Rizos EC, Siamopoulos KC, Elisaf MS. Mechanisms of hyponatraemia in alcohol patients. Alcohol Alcohol. 2000;35(6):612–616. doi:10.1093/alcalc/35.6.61211093969
  • Ragland G. Electrolyte abnormalities in the alcoholic patient. Emerg Med Clin North Am. 1990;8(4):761–773.2226285
  • Naranjo M, Lerma EV, Rangaswami J. Cardio-renal syndrome: a double edged sword. Dis Mon. 2017;63(4):92–100. doi:10.1016/j.disamonth.2017.02.00128302277
  • Souza-Smith FM, Lang CH, Nagy LE, Bailey SM, Parsons LH, Murray GJ. Physiological processes underlying organ injury in alcohol abuse. Am J Physiol Endocrinol Metab. 2016;311(3):605–619. doi:10.1152/ajpendo.00270.2016
  • Steiner JL, Lang CH. Etiology of alcoholic cardiomyopathy: mitochondria, oxidative stress and apoptosis. Int J Biochem Cell Biol. 2017;89:125–135. doi:10.1016/j.biocel.2017.06.00928606389
  • Christodoulou E, Kadoglou NP, Kostomitsopoulos N, Valsami G. Saffron: a natural product with potential pharmaceutical applications. J Pharm Pharmacol. 2015;67(12):1634–1649. doi:10.1111/jphp.1245626272123
  • Hosseini A, Razavi BM, Hosseinzadeh H. Saffron (Crocus sativus) petal as a new pharmacological target: a review. Iran J Basic Med Sci. 2018;21(11):1091–1099. doi:10.22038/IJBMS.2018.31243.752930483381
  • Zeka K, Ruparelia KC, Continenza MA, Stagos D, Vegliò F, Arroo RJ. Petals of Crocus sativus L. as a potential source of the antioxidants crocin and kaempferol. Fitoterapia. 2015;107:128–134. doi:10.1016/j.fitote.2015.05.01426012879
  • Akhondzadeh Basti A, Moshiri E, Noorbala AA, Jamshidi AH, Abbasi SH, Akhondzadeh S. Comparison of petal of Crocus sativus L. and fluoxetine in the treatment of depressed outpatients: a pilot double-blind randomized trial. Prog Neuropsychopharmacol Biol Psychiatry. 2007;31(2):439–442. doi:10.1016/j.pnpbp.2006.11.01017174460
  • Fatehi M, Rashidabady T, Fatehi- Hassanabad Z. Effects of Crocus sativus petals’ extract on rat blood pressure and on responses induced by electrical field stimulation in the rat isolated vas deferens and guinea-pig ileum. J Ethnopharmacol. 2003;84(2–3):199–203.12648816
  • Chen K, Wang XM, Chen F, Bai J. In vitro antimicrobial and free radical scavenging activities of the total flavonoid in petal and stamen of Crocus sativus. Indian J Pharm Sci. 2017;79(3):482–487. doi:10.4172/pharmaceutical-sciences.1000254
  • D’Archivio AA, Di Donato F, Foschi M, Maggi MA, Ruggieri F. UHPLC analysis of saffron (Crocus sativus L.): optimization of separation using chemometrics and detection of minor crocetin esters. Molecules. 2018;23(8):E1851. doi:10.3390/molecules2308185130044436
  • Khleifat K, Shakhanbeh J, Tarawneh K. The chronic effects of Teucrium polium on some blood parameters and histopathology of liver and kidney in the rat. Turk J Biol. 2002;26:65–71.
  • Amraei M, Ghorbani A, Seifinejad Y, Mousavi SF, Mohamadpour M, Shirzadpour E. The effect of hydroalcoholic extract of Teucrium polium L. on the inflammatory markers and lipid profile in hypercholesterolemic rats. J Inflamm Res. 2018;11:265–272. doi:10.2147/JIR.S16517229950880
  • Abu Sitta KH, Shomah MS, Salhab AS. Hepatotoxicity of Teucrium polium L tea: supporting evidence in mice models. Austr J Med Herb. 2009;21(4):106–108.
  • Krache I, Boussoualim N, Charef N, et al. Evaluation of acute and chronic toxic effects of Algerian germander in Swiss albino mice. J App Pharm Sci. 2015;5(Suppl 3):027–032.
  • Habib-ur-Rehman M, Tahir M, Lone KP, Sami W. Ethanol induced hepatotoxicity in albino rats. J Coll Physicians Surg Pak. 2011;21(10):642–643. doi:10.2011/JCPSP.64264322015132
  • Stockham SL, Scott MA. Fundamentals of Veterinary Clinical Pathology. Ames: Iowa State University Press; 2002:434–459.
  • Contreras-Zentella ML, Hernández-Muñoz R. Is liver enzyme release really associated with cell necrosis induced by oxidant stress? Oxid Med Cell Longev. 2016;2016:3529149. doi:10.1155/2016/352914926798419
  • Afshar M, Richards S, Mann D, et al. Acute immunomodulatory effects of binge alcohol ingestion. Alcohol. 2015;49(1):57–64. doi:10.1016/j.alcohol.2014.10.00225572859
  • Ki SH, Park O, Zheng M, et al. Interleukin-22 treatment ameliorates alcoholic liver injury in a murine model of chronic-binge ethanol feeding: role of signal transducer and activator of transcription 3. Hepatology. 2010;52(4):1291–1300. doi:10.1002/hep.2383720842630
  • Marmier S, Dentin R, Daujat-Chavanieu M, et al. Novel role for carbohydrate responsive element binding protein in the control of ethanol metabolism and susceptibility to binge drinking. Hepatology. 2015;62(4):1086–1100. doi:10.1002/hep.2777825761756
  • Masarone M, Rosato V, Dallio M, et al. Epidemiology and natural history of alcoholic liver disease. Rev Recent Clin Trials. 2016;11(3):167–174.27515957
  • Sheron N. Alcohol and liver disease in Europe–simple measures have the potential to prevent tens of thousands of premature deaths. J Hepatol. 2016;64:957–967. doi:10.1016/j.jhep.2015.11.00626592352
  • Livero FA, Acco A. Molecular basis of alcoholic fatty liver disease: from incidence to treatment. Hepatol Res. 2016;46:111–123. doi:10.1111/hepr.1259426417962
  • Rehm J, Taylor B, Mohapatra S, et al. Alcohol as a risk factor for liver cirrhosis: a systematic review and metaanalysis. Drug Alcohol Rev. 2010;29(4):437–445. doi:10.1111/j.1465-3362.2009.00153.x20636661
  • Sid B, Verrax J, Calderon PB. Role of oxidative stress in the pathogenesis of alcohol-induced liver disease. Free Radic Res. 2013;47(11):894–904. doi:10.3109/10715762.2013.82883623800214
  • Teplova VV, Belosludtsev KN, Belosludtseva NV, Holmuhamedov EL. Role of mitochondria in hepatotoxicity of ethanol. Biophysics (Russia). 2010;55(6):1038–1047.
  • Tilg H, Moschen AR, Kaneider NC. Pathways of liver injury in alcoholic liver disease. J Hepatol. 2011;55(5):1159–1161. doi:10.1016/j.jhep.2011.05.01521723837
  • Auger C, Alhasawi A, Contavadoo M, Appanna VD. Dysfunctional mitochondrial bioenergetics and the pathogenesis of hepatic disorders. Front Cell Dev Biol. 2015;3:40. doi:10.3389/fcell.2015.0004026161384
  • Song BJ, Abdelmegeed MA, Henderson LE, et al. Increased nitroxidative stress promotes mitochondrial dysfunction in alcoholic and nonalcoholic fatty liver disease. Oxid Med Cell Longev. 2013;2013:781050.23691267
  • Mantena KS, King AL, Andringa KK, Eccleston HB, Bailey SM. Mitochondrial dysfunction and oxidative stress in the pathogenesis of alcohol and obesity induced fatty liver diseases. Free Radic Biol Med. 2008;44(7):1259–1272. doi:10.1016/j.freeradbiomed.2007.12.03218242193
  • Manzo-Avalos S, Saavedra-Molina A. Cellular and mitochondrial effects of alcohol consumption. Int J Environ Res Public Health. 2010;7(12):4281–4304. doi:10.3390/ijerph712428121318009
  • Zhong Z, Ramshesh VK, Rehman H, et al. Acute ethanol causes hepatic mitochondrial depolarization in mice: role of ethanol metabolism. PLoS One. 2014;9(3):e91308. doi:10.1371/journal.pone.009130824618581
  • Bailey SM, Cunningham CC. Acute and chronic ethanol increases reactive oxygen species generation and decreases viability in fresh, isolated rat hepatocytes. Hepatology. 1998;28(5):1318–1326. doi:10.1002/hep.5102806249794917
  • Hoyt LR, Randall MJ, Ather JL, DePuccio DP, Landry CC, Qian X. Mitochondrial ROS induced by chronic ethanol exposure promotes hyper-activation of the NLRP3 inflammasome. Redox Biol. 2017;12:883–896. doi:10.1016/j.redox.2017.04.02028463821
  • El-Beshbishy HA, Hassan MH, Aly H, Doghish A, Alghaithy A. Crocin “saffron” protects against beryllium chloride toxicity in rats through diminution of oxidative stress and enhancing gene expression of antioxidant enzymes. Ecotoxicol Environ Saf. 2012;83:47–54. doi:10.1016/j.ecoenv.2012.06.00322766413
  • Lari P, Abnous K, Imenshahidi M, Rashedinia M, Razavi M, Hosseinzadeh H. Evaluation of diazinon-induced hepatotoxicity and protective effects of crocin. Toxicol Ind Health. 2015;31(4):367–376. doi:10.1177/074823371347551923406950
  • Shati A, Alamri S. Role of saffron (Crocus sativus L.) and honey syrup on aluminium induced hepatotoxicity. Saudi Med J. 2010;31(10):1106–1113.20953525
  • Jnaneshwaria S, Hemshekhara M, Santhosha S, et al. Crocin, a dietary colorant mitigates cyclophosphamide-induced organ toxicity by modulating antioxidant status and inflammatory cytokines. J Pharm Pharmacol. 2013;65(4):604–614. doi:10.1111/jphp.1201623488790
  • Nair SC, Panikkar KR, Parthod RK. Protective effects of crocetin on the bladder toxicity induced by cyclophosphamide. Cancer Biother. 1993;8(4):339–344. doi:10.1089/cbr.1993.8.3397804375
  • Lin JK, Wang CJ. Protection of crocin dyes on the acute hepatic damage induced by aflatoxin B1 and dimethylnitrosamine in rats. Carcinogenesis. 1986;7(4):595–599. doi:10.1093/carcin/7.4.5952870820
  • Wang CJ, Shiow SJ, Lin JK. Effects of crocetin on the hepatotoxicity and hepatic DNA binding of aflatoxin B1 in rats. Carcinogenesis. 1991;12(3):459–462. doi:10.1093/carcin/12.3.4591672627
  • EL-Maraghy SA, Rizk SM, El-Sawalhi MM. Hepatoprotective potential of crocin and curcumin against iron overload-induced biochemical alterations in rat. Afr J Biochem Res. 2009;3(5):215–221.
  • Yousefsani B, Mehri S, Pourahmad J, Hosseinzadeh H. Crocin prevents sub-cellular organelle damage, proteolysis and apoptosis in rat hepatocytes: a justification for its hepatoprotection. Iranian J Pharm Res. 2018;17(2):553–562.
  • Iranshahi M, Khoshangosht M, Mohammadkhani Z, Karimi G. Protective effects of aqueous and ethanolic of saffron stigma and petal on liver toxicity induced by carbon tetrachloride in mice. Pharmacologyonline. 2011;1:203–212.
  • Omidi A, Riahinia N, Montazer Torbati M, Behdani M. Hepatoprotective effect of Crocus sativus (saffron) petals extract against acetaminophen toxicity in male Wistar rats. Avicenna J Phytome. 2014;4(5):330–336.
  • Mohajeri Dariush DY. Protective effects of Crocus sativus petal against cisplatin-induced hepatotoxicity in rats. Med Sci J Islamic Azad Univ. 2011;21(4):251–261.
  • Rezaee Khorasany AR, Hosseinzadeh H. Therapeutic effects of saffron (Crocus sativus L.) in digestive disorders: a review. Iran J Basic Med Sci. 2016;19(5):455–469.27403251
  • Donohue TM. Alcohol-induced steatosis in liver cells. World J Gastroenterol. 2007;13(37):4974–4978. doi:10.3748/wjg.v13.i37.497417854140
  • Sozio M, Crabb DW. Alcohol and lipid metabolism. Am J Physiol Endocrinol Metabol. 2008;295(1):10–16. doi:10.1152/ajpendo.00011.2008
  • You M, Matsumoto M, Pacold CM, Cho WK, Crabb DW. The role of AMP-activated protein kinase in the action of ethanol in the liver. Gastroenterology. 2004;127(6):1798–1808. doi:10.1053/j.gastro.2004.09.04915578517
  • You M, Rogers CQ. Adiponectin: a key adipokine in alcoholic fatty liver. Exp Biol Med (Maywood). 2009;234(8):850–859. doi:10.3181/0902-MR-6119491377
  • Zhong W, Zhao Y, Tang Y, et al. Chronic alcohol exposure stimulates adipose tissue lipolysis in mice: role of reverse triglyceride transport in the pathogenesis of alcoholic steatosis. Am J Pathol. 2012;180(3):998–1007. doi:10.1016/j.ajpath.2011.11.01722234172
  • Shi Y, Sheng L, Qian ZY, Chen Z. Beneficial effects of crocetin on alcoholic fatty liver in rats and the mechanism. Chin J New Drugs. 2008;17:2115–2118.
  • Asdaq SMB, Inamdar MN. Potential of Crocus sativus (saffron) and its constituent, crocin, as hypolipidemic and antioxidant in rats. Appl Biochem Biotech. 2010;162(2):358–372. doi:10.1007/s12010-009-8740-7
  • Hoshyar R, Hosseinian M, Naghandar MR, et al. Anti-dyslipidemic properties of saffron: reduction in the associated risks of atherosclerosis and insulin resistance. Iran Red Cres Med J. 2016;18(2):e36266. doi:10.5812/ircmj.36226
  • Nordman R. Alcohol and antioxidant system. Alcohol Alcohol. 1994;29(5):513–522.7811335
  • Wu D, Cederbaum I. Alcohol, oxidative stress, and free radical damage. Alcohol Res Health. 2003;27(4):277–284.15540798
  • Wilce MC, Parker MW. Structure and function of glutathione Stransferases. Biochim Biophys Acta. 1994;1205(1):1–18. doi:10.1016/0167-4838(94)90086-88142473
  • Alin P, Danielson HU, Mannervik B. 4- Hydroxyalk-2-enals are substrates for glutathione transferase. FEBS Lett. 1985;179(2):267–270. doi:10.1016/0014-5793(85)80532-93838159
  • Rahbani M, Mohajeri D, Rezaie A, Nazeri M. Protective effect of ethanolic extract of saffron (dried stigmas of Crocus sativus L.) on hepatic tissue injury in streptozotocin-induced diabetic rats. J Anim Vet Adv. 2012;11(12):1985–1994. doi:10.3923/javaa.2012.1985.1994
  • Farahmand SK, Samini F, Samini M, Samarghandian S. Safranal ameliorates antioxidant enzymes and suppresses lipid peroxidation and nitric oxide formation in aged male rat liver. Biogerontology. 2013;14(1):63–71. doi:10.1007/s10522-012-9409-023179288
  • Ramadan A, Soliman G, Mahmoud SS, Nofal SM, Abdel-Rahman RF. Evaluation of the safety and antioxidant activities of Crocus sativus and Propolis ethanolic extracts. J Saudi Chem Soc. 2012;16(1):13–21. doi:10.1016/j.jscs.2010.10.012
  • Chen Y, Yang T, Huang J, et al. Comparative evaluation of the antioxidant capacity of crocetin and crocin in vivo. Chin Pharm Bull. 2010;26:248–251.
  • Bandegi AR, Vafaei Abbas A, Ghaderdoost B, Rashidy-Pour A. Protective effects of Crocus sativus L. extract and crocin against chronic-stress induced oxidative damage of brain, liver and kidneys in rats. Adv Pharm Bull. 2014;4(Suppl 2):493–499. doi:10.5681/apb.2014.07325671180
  • Lari P, Rashedinia M, Abnous K, Hosseinzadeh H. Crocin improves lipid dysregulation in subacute diazinon exposure through ERK1/2 pathway in rat liver. Drug Res (Stuttg). 2014;64(6):301–305. doi:10.1055/s-0033-135719624132704
  • Ardalan T, Ardalan P, Heravi M. Kinetic study of free radicals scavenging by saffron petal extracts. J Chem Health Risks. 2012;2(4):29–36.
  • Termentzi A, Kokkalou E. LC-DAD-MS (ESI+) analysis and antioxidant capacity of Crocus sativus petal extracts. Planta Med. 2008;74(5):573–581. doi:10.1055/s-0028-108831918401844
  • Zeng T, Zhang CL, Xiao M, Yang R, Xie KQ. Critical roles of Kupffer cells in the pathogenesis of alcoholic liver disease: from basic science to clinical trials. Front Immunol. 2016;7:538. doi:10.3389/fimmu.2016.0053827965666
  • An L, Wang X, Cederbaum AI. Cytokines in alcoholic liver disease. Arch Toxicol. 2012;86(9):1337–1348. doi:10.1007/s00204-011-0763-522367091
  • Kawaratani H, Tsujimoto T, Douhara A, et al. The effect of inflammatory cytokines in alcoholic liver disease. Mediators Inflamm. 2013;2013:495156. doi:10.1155/2013/49515624385684
  • Louvet A, Mathurin P. Alcoholic liver disease: mechanisms of injury and targeted treatment. Nat Rev Gastroenterol Hepatol. 2015;12(4):231–242. doi:10.1038/nrgastro.2015.3525782093
  • Amin B, Abnous K, Motamedshariaty V, Hosseinzadeh H. Attenuation of oxidative stress, inflammation and apoptosis by ethanolic and aqueous extracts of Crocus sativus L. stigma after chronic constriction injury of rats. An Acad Bras Cienc. 2014;86(4):1821–1832.25590719
  • Hosseinzadeh H, Younesi HM. Antinociceptive and anti-inflammatory effects of Crocus sativus L. stigma and petal extracts in mice. BMC Pharmacol. 2002;2:7. doi:10.1186/1471-2210-2-711914135
  • Zhang C, Ma J, Fan L, et al. Neuroprotective effects of safranal in a rat model of traumatic injury to the spinal cord by anti-apoptotic, anti-inflammatory and edema-attenuating. Tissue Cell. 2015;47(3):291–300. doi:10.1016/j.tice.2015.03.00725891268
  • Hariri AT, Moallem SA, Mahmoudi M, Memar B, Hosseinzadeh H. Sub-acute effects of diazinon on biochemical indices and specific biomarkers in rats: protective effects of crocin and safranal. Food Chem Toxicol. 2010;48(10):2803–2808. doi:10.1016/j.fct.2010.07.01020637253
  • Gholamnezhad Z, Koushyar H, Byrami G, Boskabady MH. The extract of Crocus sativus and its constituent safranal, affect serum levels of endothelin and total protein in sensitized guinea pigs. Iran J Basic Med Sci. 2013;16(9):1022–1026.24175050
  • Boskabady MH, Farkhondeh T. Anti-inflammatory, antioxidant, and immunomodulatory effects of Crocus sativus L. and its main constituents. Phytother Res. 2016;30(7):1072–1094. doi:10.1002/ptr.562227098287
  • Boskabady MH, Rahbardar MG, Jafari Z. The effect of safranal on histamine (H1) receptors of guinea pig tracheal chains. Fitoterapia. 2011;82(2):162–167. doi:10.1016/j.fitote.2010.08.01720804826
  • Xu GL, Li G, Ma HP, Zhong H, Liu F, Ao GZ. Preventive effect of crocin in inflamed animals and in LPS-challenged RAW 264.7 cells. J Agric Food Chem. 2009;57(18):8325–8330. doi:10.1021/jf901752f19754168
  • Surh YJ, Chun KS, Cha HH, Han SS, Keum YS, Park KK. Molecular mechanisms underlying chemopreventive activities of anti-inflammatory phytochemicals: down-regulation of COX-2 and iNOS through suppression of NF kappa B activation. Mutat Res. 2001;480–481:243–268. doi:10.1016/S0027-5107(01)00183-X
  • Lappas M, Permezel M, Georgiou HM, Rice GE. Nuclear factor kappa B regulation of proinflammatory cytokines in human gestational tissues in vitro. Biol Reprod. 2002;67(2):668–673. doi:10.1095/biolreprod67.2.66812135912
  • Kim JH, Park GY, Bang SY, Park SY, Bae SK, Kim Y. Crocin suppresses LPS-stimulated expression of inducible nitric oxide synthase by upregulation of heme oxygenase-1 via calcium/calmodulin-dependent protein kinase 4. Mediators Inflamm. 2014;2014:728709. doi:10.1155/2014/72870924839356
  • El-Maraghy SA, Rizk SM, Shahin NN. Gastroprotective effect of crocin in ethanol-induced gastric injury in rats. Chem Biol Interact. 2015;229:26–35. doi:10.1016/j.cbi.2015.01.01525637687
  • Calixto JB, Beirith A, Ferreira J, Santos AR, Cechinel Filho V, Yunes RA. Naturally occurring antinociceptive substances from plants. Phytother Res. 2000;14(6):401–418.10960893
  • Galati EM, Monforte MT, Kirjavainen S, Forestieri AM, Trovato A, Tripodo MM. Biological effects of hesperidin, a citrus flavonoid. (Note I): anti-inflammatory and analgesic activity. Farmaco. 1994;40(11):709–712.7832973
  • Ramesh M, Rao YN, Rao AV, et al. Antinociceptive and anti-inflammatory activity of a flavonoid isolated from Caralluma attenuata. J Ethnopharmacol. 1998;62(1):63–66.9720613