Possible therapeutic effects of Crocus sativus stigma and its petal flavonoid, kaempferol, on respiratory disorders

References

• Abo-Salem OM. 2014. Kaempferol attenuates the development of diabetic neuropathic pain in mice: Possible anti-inflammatory and anti-oxidant mechanisms. Open Access Maced J Med Sci. 2(3):424–430.
   Google Scholar
• Abrishami MH. 1987. Understanding of Iranian saffron. 1st ed. Tehran (Iran): Tous.
   Google Scholar
• Amin A, Hamza AA, Daoud S, Khazanehdari K, Hrout AA, Baig B, Chaiboonchoe A, Adrian TE, Zaki N, Salehi-Ashtiani K, et al. 2016. Saffron-based crocin prevents early lesions of liver cancer: in vivo, in vitro and network analyses. Recent Pat Anticancer Drug Discov. 11(1):121–133.
   PubMed Web of Science ®Google Scholar
• Amin B, Abnous K, Motamedshariaty V, Hosseinzadeh H. 2014. 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. 86(4):1821–1832.
   PubMed Web of Science ®Google Scholar
• Anderson GP, Coyle AJ. 1994. TH2 and ‘TH2-like’cells in allergy and asthma: pharmacological perspectives. Trend Pharm Sci. 15(9):324–332.
   PubMed Web of Science ®Google Scholar
• Barnes PJ. 2006. Corticosteroids: the drugs to beat. Eur J Pharmacol. 533(1-3):2–14.
   PubMed Web of Science ®Google Scholar
• Barnes PJ. 2014. Cellular and molecular mechanisms of chronic obstructive pulmonary disease. Clin Chest Med. 35(1):71–86.
   PubMed Web of Science ®Google Scholar
• Bayrami G, Boskabady M. 2012. The potential effect of the extract of Crocus sativus and safranal on the total and differential white blood cells of ovalbumin-sensitized guinea pigs. Res Pharm Sci. 7:249–255.
   PubMedGoogle Scholar
• Belal SA, Choe HS, Shin DK, Shim KS. 2018. Effect of kaempferol on cyclooxygenase 2 (Cox2) and cytosolic phospholipase A2 (cPLA2) protein expression in BALB/c mice. Iran J All Asthma Immunol. 17:428–435.
   PubMed Web of Science ®Google Scholar
• Boskabady M, Aslani M. 2006. Relaxant effect of Crocus sativus (saffron) on guinea‐pig tracheal chains and its possible mechanisms. J Pharm Pharmacol. 58(10):1385–1390.
   PubMed Web of Science ®Google Scholar
• Boskabady MH, Gholamnezhad Z, Ghorani V, Saadat S. 2019. The effect of Crocus sativus (daffron) on the respiratory system: traditional and experimental evidence. Sci Spices Culinary Herbs-Latest Lab Pre-Clin Clin Stud. 1:30–54.
   Google Scholar
• Boskabady MH, Rahbardar MG, Nemati H, Esmaeilzadeh M. 2010. Inhibitory effect of Crocus sativus (saffron) on histamine (H1) receptors of guinea pig tracheal chains. Die Pharm An Int J Pharm Sci. 65:300–305.
   Google Scholar
• Boskabady MH, Seyedhosseini Tamijani SM, Rafatpanah H, Rezaei A, Alavinejad A. 2011. The effect of Crocus sativus extract on human lymphocytes’ cytokines and T helper 2/T helper 1 balance. J Med Food. 14(12):1538–1545.
   PubMed Web of Science ®Google Scholar
• Boskabady MH, Shafei MN, Shakiba A, Sefidi HS. 2008. Effect of aqueous-ethanol extract from Crocus sativus (saffron) on guinea-pig isolated heart. Phytother. Res. 22(3):330–334.
   PubMed Web of Science ®Google Scholar
• Boskabady M, Tabatabaee A, Byrami G. 2012. The effect of the extract of Crocus sativus and its constituent safranal, on lung pathology and lung inflammation of ovalbumin sensitized guinea-pigs. Phytomedicine. 19(10):904–911.
   PubMed Web of Science ®Google Scholar
• Boulet L-P, Lemière C, Archambault F, Carrier G, Descary MC, Deschesnes F. 2006. Smoking and asthma: clinical and radiologic features, lung function, and airway inflammation. Chest. 129(3):661–668.
   PubMed Web of Science ®Google Scholar
• Bousquet J, Jeffery PK, Busse WW, Johnson M, Vignola AM. 2000. Asthma. From bronchoconstriction to airways inflammation and remodeling. Am J Respir Crit Care Med. 161(5):1720–1745.
   PubMed Web of Science ®Google Scholar
• Bukhari SI, Pattnaik B, Rayees S, Kaul S, Dhar MK. 2015. Safranal of Crocus sativus L. inhibits inducible nitric oxide synthase and attenuates asthma in a mouse model of asthma. Phytother Res. 29(4):617–627.
   PubMed Web of Science ®Google Scholar
• Byrami G, Boskabady MH, Jalali S, Farkhondeh T. 2013. The effect of the extract of Crocus sativus on tracheal responsiveness and plasma levels of IL-4, IFN-γ, total NO and nitrite in ovalbumin sensitized Guinea-pigs. J Ethnopharmacol. 147(2):530–535.
   PubMed Web of Science ®Google Scholar
• Chen X, Yang X, Liu T, Guan M, Feng X, Dong W, Chu X, Liu J, Tian X, Ci X, et al. 2012. Kaempferol regulates MAPKs and NF-κB signaling pathways to attenuate LPS-induced acute lung injury in mice. Int Immunopharmacol. 14(2):209–216.
   PubMed Web of Science ®Google Scholar
• Cohn L, Elias JA, Chupp GL. 2004. Asthma: mechanisms of disease persistence and progression. Annu Rev Immunol. 22:789–815.
   PubMed Web of Science ®Google Scholar
• Devi KP, Malar DS, Nabavi SF, Sureda A, Xiao J, Nabavi SM, Daglia M. 2015. Kaempferol and inflammation: from chemistry to medicine. Pharmacol Res. 99:1–10.
   PubMed Web of Science ®Google Scholar
• Duarte J, Pérez FV, Utrilla P, Jiménez J, Tamargo J, Zarzuelo A. 1993. Vasodilatory effects of flavonoids in rat aortic smooth muscle. Structure-activity relationships. General Pharmacol. 24(4):857–862.
   PubMedGoogle Scholar
• El-Maraghy SA, Rizk SM, Shahin NN. 2015. Gastroprotective effect of crocin in ethanol-induced gastric injury in rats. Chem Biol Interact. 229:26–35.
   PubMed Web of Science ®Google Scholar
• Fatehi M, Rashidabady T, Fatehi-Hassanabad Z. 2003. 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. 84(2-3):199–203.
   PubMed Web of Science ®Google Scholar
• Ghazavi A, Mosayebi G, Salehi H, Abtahi H. 2009. Effect of ethanol extract of saffron (Crocus sativus L.) on the inhibition of experimental autoimmune encephalomyelitis in C57bl/6 mice. Pak J Biol Sci. 12(9):690–695.
   PubMedGoogle Scholar
• Gholamnezhad Z, Boskabady MH, Khazdair MR, Hosseini M, Abbasnejad M. 2014. Effect of fluticasone and salmeterol on tracheal responsiveness to ovalbumin and lung inflammation, administrated during and after sensitization. Sci World J. 2014:865292.
   Google Scholar
• Gholamnezhad Z, Koushyar H, Byrami G, Boskabady MH. 2013. 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. 16:1022–1026.
   PubMed Web of Science ®Google Scholar
• Gong J-H, Shin D, Han S-Y, Park S-H, Kang M-K, Kim J-L, Kang Y-H. 2013. Blockade of airway inflammation by kaempferol via disturbing Tyk-STAT signaling in airway epithelial cells and in asthmatic mice. Evid-Based Complement Alternat Med. 2013:250725.
   PubMed Web of Science ®Google Scholar
• Gong JH, Cho IH, Shin D, Han SY, Park SH, Kang YH. 2014. Inhibition of airway epithelial-to-mesenchymal transition and fibrosis by kaempferol in endotoxin-induced epithelial cells and ovalbumin-sensitized mice. Lab Invest. 94(3):297–308.
   PubMed Web of Science ®Google Scholar
• Greenberger PA. 2003. Therapy in the management of the rhinitis/asthma complex. Allergy Asthma Proc. 6:403–407.
   Google Scholar
• Hadizadeh F, Khalili N, Hosseinzadeh H, Khair-Aldine R. 2010. Kaempferol from saffron petals. Iran J Pharm Res. 2:251–252.
   Google Scholar
• Hämäläinen M, Nieminen R, Vuorela P, Heinonen M, Moilanen E. 2007. Anti-inflammatory effects of flavonoids: genistein, kaempferol, quercetin, and daidzein inhibit STAT-1 and NF-kappaB activations, whereas flavone, isorhamnetin, naringenin, and pelargonidin inhibit only NF-kappaB activation along with their inhibitory effect on iNOS expression and NO production in activated macrophages. Mediators Inflamm. 2007:45673.
   PubMed Web of Science ®Google Scholar
• Ho HM, Chen R, Huang Y, Chen ZY. 2002. Vascular effects of a soy leaves (Glycine max) extract and kaempferol glycosides in isolated rat carotid arteries. Planta Med. 68(6):487–491.
   PubMed Web of Science ®Google Scholar
• Hoogsteden H, Verhoeven G, Lambrecht B, Prins JB. 1999. Airway inflammation in asthma and chronic obstructive pulmonary disease with special emphasis on the antigen‐presenting dendritic cell: influence of treatment with fluticasone propionate. Clin Exp All. 29:116–124.
   PubMed Web of Science ®Google Scholar
• Hosseinzadeh H, Ghenaati J. 2006. Evaluation of the antitussive effect of stigma and petals of saffron (Crocus sativus) and its components, safranal and crocin in guinea pigs. Fitoterapia. 77(6):446–448.
   PubMed Web of Science ®Google Scholar
• Hosseinzadeh H, Younesi HM. 2002. Antinociceptive and anti-inflammatory effects of Crocus sativus L. stigma and petal extracts in mice. BMC Pharmacol. 2:1–8.
   PubMedGoogle Scholar
• Imenshahidi M, Hosseinzadeh H, Javadpour Y. 2010. Hypotensive effect of aqueous saffron extract (Crocus sativus L.) and its constituents, safranal and crocin, in normotensive and hypertensive rats. Phytother Res. 24(7):990–994.
   PubMed Web of Science ®Google Scholar
• Imenshahidi M, Razavi BM, Faal A, Gholampoor A, Mousavi SM, Hosseinzadeh H. 2013. The effect of chronic administration of saffron (Crocus sativus) stigma aqueous extract on systolic blood pressure in rats. Jundishapur J Nat Pharm Prod. 8(4):175–179.
   PubMedGoogle Scholar
• Imran M, Rauf A, Shah ZA, Saeed F, Imran A, Arshad MU, Ahmad B, Bawazeer S, Atif M, Peters DG, et al. 2019. Chemo-preventive and therapeutic effect of the dietary flavonoid kaempferol: a comprehensive review. Phytother Res. 33(2):263–275.
   PubMed Web of Science ®Google Scholar
• Janssen LJ, Killian K. 2006. Airway smooth muscle as a target of asthma therapy: history and new directions. Resp Res. 7:1–12.
   PubMed Web of Science ®Google Scholar
• Jo E, Park SJ, Choi YS, Jeon W-K, Kim B-C. 2015. Kaempferol suppresses transforming growth factor-β1-induced epithelial-to-mesenchymal transition and migration of A549 lung cancer cells by inhibiting Akt1-mediated phosphorylation of Smad3 at threonine-179. Neoplasia. 17(7):525–537.
   PubMed Web of Science ®Google Scholar
• Khazdair M, Boskabady M, Tabatabaee A, Hosseini M, Abbasnejad M. 2013. Effect of inhaled fluticasone and salmeterol on tracheal responsiveness and lung inflammation: influence of administration time and allergen-free period. India J Med Sci. 67:78–88.
   PubMedGoogle Scholar
• Khazdair MR, Anaeigoudari A, Hashemzehi M, Mohebbati R. 2019a. Neuroprotective potency of some spice herbs, a literature review. J Tradit Complement Med. 9(2):98–105.
   PubMedGoogle Scholar
• Khazdair MR, Anaeigoudari A, Kianmehr M. 2019b. Anti-asthmatic effects of Portulaca oleracea and its constituents, a review. J Pharmacopunct. 22:122–130.
   PubMed Web of Science ®Google Scholar
• Khazdair MR, Boskabady MH, Hosseini M, Rezaee R, Tsatsakis AM. 2015. The effects of Crocus sativus (saffron) and its constituents on nervous system: a review. Avicenna J Phytomed. 5(5):376–391.
   PubMed Web of Science ®Google Scholar
• Kim M, Lim SJ, Kang SW, Um B-H, Nho CW. 2014. Aceriphyllum rossii extract and its active compounds, quercetin and kaempferol inhibit IgE-mediated mast cell activation and passive cutaneous anaphylaxis. J Agric Food Chem. 62(17):3750–3758.
   PubMed Web of Science ®Google Scholar
• Komi DE, Bjermer L. 2019. Mast cell-mediated orchestration of the immune responses in human allergic asthma: current insights. Clin Rev Allergy Immunol. 56(2):234–247.
   PubMed Web of Science ®Google Scholar
• Kong L, Luo C, Li X, Zhou Y, He H. 2013. The anti-inflammatory effect of kaempferol on early atherosclerosis in high cholesterol fed rabbits. Lipid Health Dis. 12:1.
   PubMed Web of Science ®Google Scholar
• Kowalski J, Samojedny A, Paul M, Pietsz G, Wilczok T. 2005. Effect of apigenin, kaempferol and resveratrol on the expression of interleukin-1beta and tumor necrosis factor-alpha genes in J774. 2 macrophages. Pharmacol Rep. 57(3):390–394.
   PubMed Web of Science ®Google Scholar
• Lin C-W, Chen P-N, Chen M-K, Yang W-E, Tang C-H, Yang S-F, Hsieh Y-S. 2013. Kaempferol reduces matrix metalloproteinase-2 expression by down-regulating ERK1/2 and the activator protein-1 signaling pathways in oral cancer cells. PLoS One. 8(11):e80883.
   PubMed Web of Science ®Google Scholar
• Luo H, Rankin GO, Liu L, Daddysman MK, Jiang B-H, Chen YC. 2009. Kaempferol inhibits angiogenesis and VEGF expression through both HIF dependent and independent pathways in human ovarian cancer cells. Nutr Cancer. 61(4):554–563.
   PubMed Web of Science ®Google Scholar
• Mahmoudabady M, Neamati A, Vosooghi S, Aghababa H. 2013. Hydroalcoholic extract of Crocus sativus effects on bronchial inflammatory cells in ovalbumin sensitized rats. Avicenna J Phytomed. 3(4):356–363.
   PubMedGoogle Scholar
• Mahobiya A, Singh TU, Rungsung S, Kumar T, Chandrasekaran G, Parida S, Kumar D. 2018. Kaempferol-induces vasorelaxation via endothelium-independent pathways in rat isolated pulmonary artery. Pharmacol Rep. 70(5):863–874.
   Web of Science ®Google Scholar
• Maleki SJ, Crespo JF, Cabanillas B. 2019. Anti-inflammatory effects of flavonoids. Food Chem. 299:125124.
   PubMed Web of Science ®Google Scholar
• Medeiros K, Faustino L, Borduchi E, Nascimento R, Silva T, Gomes E, Piuvezam M, Russo M. 2009. Preventive and curative glycoside kaempferol treatments attenuate the TH2-driven allergic airway disease. Int Immunopharmacol. 9(13–14):1540–1548.
   PubMed Web of Science ®Google Scholar
• Mohebbati R, Khazdair MR, Hedayati M. 2017. Neuroprotective effects of medicinal plants and their constituents on different induced neurotoxicity methods: a review. J Rep Pharm Sci. 6:34–50.
   Google Scholar
• Mokhtari-Zaer A, Khazdair MR, Boskabady MH. 2015. Smooth muscle relaxant activity of Crocus sativus (saffron) and its constituents: possible mechanisms. Avicenna J Phytomed. 5(5):365–375.
   PubMed Web of Science ®Google Scholar
• Mousavi B, Bathaie SZ, Fadai F, Ashtari Z, Ali Beigi N, Farhang S, Hashempour S, Shahhamzei N, Heidarzadeh H. 2015. Safety evaluation of saffron stigma (Crocus sativus L.) aqueous extract and crocin in patients with schizophrenia. Avicenna J Phytomed. 5(5):413–419.
   PubMed Web of Science ®Google Scholar
• Neamati N, Boskabady MH. 2010. Effect of Crocus sativus (saffron) on muscarinic receptors of guinea pig tracheal chains. Func Plant Sci Biotec. 4:128–131.
   Google Scholar
• Nemati H, Boskabady M, Vostakolaei HA. 2008. Stimulatory effect of Crocus sativus (saffron) on β2-adrenoceptors of guinea pig tracheal chains. Phytomedicine. 15(12):1038–1045.
   PubMed Web of Science ®Google Scholar
• Park MJ, Lee EK, Heo H-S, Kim M-S, Sung B, Kim MK, Lee J, Kim ND, Anton S, Choi JS, et al. 2009. The anti-inflammatory effect of kaempferol in aged kidney tissues: the involvement of nuclear factor-kappaB via nuclear factor-inducing kinase/IkappaB kinase and mitogen-activated protein kinase pathways. J Med Food. 12(2):351–358.
   PubMed Web of Science ®Google Scholar
• Qian J, Chen X, Chen X, Sun C, Jiang Y, Qian Y, Zhang Y, Khan Z, Zhou J, Liang G, et al. 2019. Kaempferol reduces K63-linked polyubiquitination to inhibit nuclear factor-κB and inflammatory responses in acute lung injury in mice. Toxicol Lett. 306:53–60.
   PubMed Web of Science ®Google Scholar
• Rabha DJ, Singh TU, Rungsung S, Kumar T, Parida S, Lingaraju MC, Paul A, Sahoo M, Kumar D. 2018. Kaempferol attenuates acute lung injury in caecal ligation and puncture model of sepsis in mice. Exp Lung Res. 44(2):63–78.
   PubMed Web of Science ®Google Scholar
• Razavi BM, Alyasin A, Hosseinzadeh H, Imenshahidi M. 2018. Saffron induced relaxation in isolated rat aorta via endothelium dependent and independent mechanisms. Iran J Pharm Res. 17(3):1018–1025.
   PubMed Web of Science ®Google Scholar
• Revuelta M, Cantabrana B, Hidalgo A. 1997. Depolarization-dependent effect of flavonoids in rat uterine smooth muscle contraction elicited by CaCl2. General Pharmacol Vasc Syst. 29(5):847–857.
   PubMedGoogle Scholar
• Revuelta M, Cantabrana B, Hidalgo A. 2000. Mechanisms involved in kaempferol-induced relaxation in rat uterine smooth muscle. Life Sci. 67(3):251–259.
   PubMed Web of Science ®Google Scholar
• Revuelta MP, Hidalgo A, Cantabrana B. 1999. Involvement of cAMP and beta-adrenoceptors in the relaxing effect elicited by flavonoids on rat uterine smooth muscle. J Auton Pharmacol. 19(6):353–358.
   PubMedGoogle Scholar
• Sears MR, Taylor DR, Print CG, Lake DC, Li Q, Flannery EM, Yates DM, Lucas MK, Herbison GP. 1990. Regular inhaled beta-agonist treatment in bronchial asthma. Lancet. 336(8728):1391–1396.
   PubMed Web of Science ®Google Scholar
• Shin D, Park S-H, Choi Y-J, Kim Y-H, Antika L, Habibah N, Kang M-K, Kang Y-H. 2015. Dietary compound kaempferol inhibits airway thickening induced by allergic reaction in a bovine serum albumin-induced model of asthma. Int J Mol Sci. 16(12):29980–29995.
   PubMed Web of Science ®Google Scholar
• Sun Z, Li Q, Hou R, Sun H, Tang Q, Wang H, Hao Z, Kang S, Xu T, Wu S. 2019. Kaempferol-3-O-glucorhamnoside inhibits inflammatory responses via MAPK and NF-κB pathways in vitro and in vivo. Toxicol Appl Pharmacol. 364:22–28.
   PubMed Web of Science ®Google Scholar
• Tiribuzi R, Crispoltoni L, Chiurchiù V, Casella A, Montecchiani C, Del Pino AM, Maccarrone M, Palmerini CA, Caltagirone C, Kawarai T, et al. 2017. Trans-crocetin improves amyloid-β degradation in monocytes from Alzheimer’s disease patients. J Neurol Sci. 372:408–412.
   PubMed Web of Science ®Google Scholar
• Vosooghi S, Mahmoudabady M, Neamati A, Aghababa H. 2013. Preventive effects of hydroalcoholic extract of saffron on hematological parameters of experimental asthmatic rats. Avicenna J Phytomed. 3:279–287.
   PubMedGoogle Scholar
• Xu G, Yu S, Gong Z, Zhang S. 2005. Study of the effect of crocin on rat experimental hyperlipemia and the underlying mechanisms. Zhongguo Zhong Yao Za Zhi. 30:369–372.
   PubMedGoogle Scholar
• Xu YC, Yeung DK, Man RY, Leung SW. 2006. Kaempferol enhances endothelium-independent and dependent relaxation in the porcine coronary artery. Mol Cell Biochem. 287(1-2):61–67.
   PubMed Web of Science ®Google Scholar
• Yoon HY, Lee EG, Lee H, Cho IJ, Choi YJ, Sung MS, Yoo HG, Yoo WH. 2013. Kaempferol inhibits IL-1β-induced proliferation of rheumatoid arthritis synovial fibroblasts and the production of COX-2, PGE2 and MMPs . Int J Mol Med. 32(4):971–977.
   PubMed Web of Science ®Google Scholar
• Zeka K, Arroo RRJ. 2016. Saffron Crocus (Crocus sativus L.) as a source of kaempferol. In: Garde-Cerdán T, Gonzalo-Diago A, editors. Kaempferol: biosynthesis, food sources and therapeutic uses. Nova Science Publishers Inc.; p. 197–215.
   Google Scholar