CHRYSIN: POTENTIAL PHARMACOLOGICAL and TOXICOLOGICAL EFFECTS

Year 2021, Volume: 12 Issue: 3, 151 - 160, 29.12.2021

Esra Zeybek Asım Kart

https://doi.org/10.38137/vftd.995966

Cited By: 1

Abstract

Recently, the use of pharmacotherapeutic agents of plant origin is increasing as an alternative to synthetic chemical drugs. Although quite a lot of plant-based bioactive ingredients have been reported, the bioactive molecule chyrisin, which is found in some products such as blue passionflower, honey and propolis, has become a remarkable phytochemical in recent years. Chrysin is an important flavonoid that stands out with its strong antioxidant, anticarcinogenic and anxiolytic properties as well as having many different pharmacological effects. In this review, it is aimed to give information about the physicochemical, pharmacokinetic, pharmacodynamic properties of chrysin and its protective and beneficial properties in various diseases.

Keywords

Chrysin, flavonoid, passiflora, Honey, Propolis

KRİSİN: POTANSİYEL FARMAKOLOJİK ve TOKSİKOLOJİK ETKİLERİ

Abstract

Günümüzde sentetik kimyasal ilaçlara alternatif olarak bitki kökenli farmakoterapötik ajanların kullanımı artmaktadır. Oldukça fazla bitki bazlı biyoaktif bileşen bildirilmiş olsa da mavi çarkıfelek, bal ve propolis gibi bazı ürünlerde bulunan biyoaktif molekül krisin, son yıllarda dikkat çekici bir fitokimyasal haline gelmiştir. Krisin, birçok farklı farmakolojik etkiye sahip olmasının yanı sıra güçlü antioksidan, antikanserojenik ve anksiyolitik özellikleri ile öne çıkan önemli bir flavonoiddir. Bu derlemede krisinin fizikokimyasal, farmakokinetik, farmakodinamik özellikleri ve çeşitli hastalıklarda koruyucu ve faydalı özellikleri hakkında bilgi verilmesi amaçlanmıştır.

Keywords

Chrysin, flavonoid, Bal, Propolis

References

• Bae, Y., Lee, S., & Kim, S. H. (2011). Chrysin suppresses mast cell-mediated allergic inflammation: involvement of calcium, caspase-1 and nuclear factor-κB. Toxicol Appl Pharm, 254(1), 56-64. Doi: 10.1016/j.taap.2011.04.008
• Boulton, D. W., Walle, U. K., & Walle, T. (1998). Extensive binding of the bioflavonoid quercetin to human plasma proteins. J Pharm Pharmacol, 50(2), 243-249. Doi: 10.1111/j.2042-7158.1998.tb06183.x.
• Brown, E., Hurd, N.S., McCall, S., & Ceremuga, T. E. (2007). Evaluation of the anxiolytic effects of chrysin, a Passiflora incarnata extract, in the laboratory rat. AANA Journal, 75(5), 333-7.
• Chang, H., Mi, M. T., Gu, Y. Y., Yuan, J. L., Ling, W. H., & Lin, H. (2007). Effects of flavonoids with different structures on proliferation of leukemia cell line HL-60.  Ai zheng, 26(12), 1309-1314.
• Cos, P., Ying, L., Calomme, M., Hu, J. P., Cimanga, K., Van Poel, B., & Berghe D. V. (1998). Structure− activity relationship and classification of flavonoids as inhibitors of xanthine oxidase and superoxide scavengers. J Nat Prod, 61(1), 71-76.
• Crespy, V., Morand, C., Besson, C., Cotelle, N., Vézin, H., Demigne, C., & Remesy, C. (2003). The splanchnic metabolism of flavonoids highly differed according to the nature of the compound. Am J Physiol Gastrointest Liver, 284(6), G980-G988. Doi.org/10.1152/ajpgi.00223.2002.
• Drago, L., De Vecchi, E., Nicola, L., & Gismondo, M. R. (2007). In vitro antimicrobial activity of a novel propolis formulation (Actichelated propolis).  J Appl Microbiol, 103(5), 1914-1921. Doi.10.1111/j.1365-2672.2007.03421.x.
• Elmore, M. R., Lee, R. J., West, B. L., & Green, K. N. (2015). Characterizing newly repopulated microglia in the adult mouse: impacts on animal behavior, cell morphology, and neuroinflammation. PLOS One, 10(4). Doi:org/10.1371/journal. pone. 0122912.
• Erlund, I. (2004). Review of the flavonoids quercetin, hesperetin, and naringenin. Dietary sources, bioactivities, bioavailability, and epidemiology. Nutr Res Rev, 24(10), 851-874. DOI: 10.1016/j.nutres.2004.07.005.
• Farkhondeh, T., Samarghandian, S., & Roshanravan, B. (2019). Impact of chrysin on the molecular mechanisms underlying diabetic complications. J Cell Physiol, 234(10), 17144-17158. DOI: 10.1002/jcp.28488.
• Filho, C. B., Jesse, C. R., Donato, F., Giacomeli, R., Del Fabbro, L., da Silva Antunes, M., de Gomes, M. G., Goes, A. T., Boeira, S. P., Prigol, M., & Souza, L. C. (2015). Chronic unpredictable mild stress decreases BDNF and NGF levels and Na(+), K(+)-ATPase activity in the hippocampus and prefrontal cortex of mice: antidepressant effect of chrysin. Neurosci., 19(289), 367-380. Doi: 10.1016/j.neuroscience.2014.12.048.
• Gresa‐Arribas, N., Serratosa, J., Saura, J., & Solà, C. (2010). Inhibition of CCAAT/enhancer binding protein δ expression by chrysin in microglial cells results in anti‐inflammatory and neuroprotective effects. J Neurochem, 115(2), 526-536. Doi: 10.1111/j.1471-4159.2010.06952.x.
• Guerrero, F. A., Medina, & G. M. (2017). Effect of a medicinal plant (Passiflora incarnata L) on Sleep Science, 10(3), 96. Doi: 10.5935/1984-0063.20170018.
• Ha, S. K., Moon, E., & Kim, S. Y. (2010). Chrysin suppresses LPS-stimulated proinflammatory responses by blocking NF-κB and JNK activations in microglia cells. Neurosci Lett, 485(3), 143-147. Doi: 10.1016/j.neulet.2010.08.064.
• Habtemariam, S. (1997). Flavonoids as inhibitors or enhancers of the cytotoxicity of tumor necrosis factor-α in L-929 tumor cells. J Nat Prod, 60(8), 775-778. Doi.org/10.1021/np960581z.
• Hadjmohammadi, M. R., & Nazari, S. S. S. (2010). Separation optimization of quercetin, hesperetin and chrysin in honey by micellar liquid chromatography and experimental design. J Sep Sci, 33(20), 3144-3151. DOI 10.1002/jssc.201000326.
• Hickey, M., & King, C. (1988). 100 families of flowering plants. Cambridge: Cambridge University Press, p: 42.
• Hougee, S., Sanders, A., Faber, J., Graus, Y. M., van den Berg, W. B., Garssen, J., & Oijer, M. A. (2005). Decreased pro-inflammatory cytokine production by LPS-stimulated PBMC upon in vitro incubation with the flavonoids apigenin, luteolin or chrysin, due to selective elimination of monocytes/macrophages. Biochem Pharmacol, 69(2), 241-248. DOI: 10.1016/j.bcp.2004.10.002.
• Ibrahim, S. O., Mada, S. B., Abarshi, M. M., Tanko, M. S., & Babangida, S. (2021). Chrysin alleviates alteration of bone-remodeling markers in ovariectomized rats and exhibits estrogen-like activity in silico. Hum Exp Toxicol, 40, 125-136. doi: 10.1177/09603271211033777. 
• Jesse, C. R., Donato, F., Giacomeli, R., Del Fabbro, L., da Silva Antunes, M., de Gomes, M. G., & Souza, L. C. (2015). Chronic unpredictable mild stress decreases BDNF and NGF levels and Na+, K+-ATPase activity in the hippocampus and prefrontal cortex of mice: Antidepressant effect of chrysin. Neuroscience, 289, 367-380. Doi: 10.1016/j.pbb.2015.04.010.
• Jiang, Y., Gong, F. L., Zhao, G. B., & Li, J. (2014). Chrysin suppressed inflammatory responses and the inducible nitric oxide synthase pathway after spinal cord injury in rats. Int J Mol Sci, 15(7), 12270-12279. Doi:10.3390/ijms150712270.
• Kalogeropoulos, N., Yanni, A. E., Koutrotsios, G., & Aloupi, M. (2013). Bioactive microconstituents and antioxidant properties of wild edible mushrooms from the island of Lesvos, Greece. Food Chem Toxicol, 55, 378-385.
• Kao, Y. C., Zhou, C., Sherman, M., Laughton, C. A., & Chen, S. (1998). Molecular basis of the inhibition of human aromatase (estrogen synthetase) by flavone and isoflavone phytoestrogens: A site-directed mutagenesis study. Environ Health Perspect, 106(2), 85-92.
• Karrari, P., Mehrpour, O., Afshari, R., & Keyler, D. (2013). Pattern of illicit drug use in patients referred to addiction treatment centres in Birjand, Eastern Iran. JPMA, 63(6), 711-6.
• Keppler, D. O., Rudigier, J. F., Bischoff, E., & Deckker, K. F. (1970). The trapping of uridine phosphates by d-galactosamine, d-glucosamine, and 2-deoxy-d-galactose: A study on the mechanism of galactosamine hepatitis. Eur j biochem, 17(2), 246-253.
• Khan, R., Khan, A. Q., Qamar, W., Lateef, A., Tahir, M., Rehman, M. U., & Sultana, S. (2012). Chrysin protects against cisplatin-induced colon toxicity via amelioration of oxidative stress and apoptosis: probable role of p38MAPK and p53. Toxicol Appl Pharmacol, 258(3), 315-329. Doi: 10.1016/j.taap.2011.11.013.
• Khan, R., & Sultana, S. (2011). Farnesol attenuates 1, 2-dimethylhydrazine induced oxidative stress, inflammation and apoptotic responses in the colon of Wistar rats. Chem Biol Interact, 192(3), 193-200. DOI: 10.1016/j.cbi.2011.03.009.
• Khoo, B. Y., Chua, S. L., & Balaram, P. (2010). Apoptotic effects of chrysin in human cancer cell lines. Int J Mol Sci, 11(5), 2188-2199. Doi:10.3390/ijms11052188.
• Koca, N., & Karadeniz, F. (2003). Serbest radikal oluşum mekanizmaları ve vücuttaki antioksidan savunma sistemleri. Gıda Mühendisliği Dergisi, 16, 32-37.
• Kozlowska, A., & Szostak-Wegierek, D. (2014). Flavonoids-food sources and health benefits. Roczniki Państwowego Zakładu Higieny, 65(2).
• Li. X., Huang, Q., Ong, C. N., Yang, X. F., & Shen, H. M. (2010). Chrysin sensitizes tumor necrosis factor-α-induced apoptosis in human tumor cells via suppression of nuclear factor-kappaB. Cancer Lett, 293(1), 109-116.
• Liu, G., Xie, W., He, A. D., Da, X. W., Liang, M. L., Yao, G. O., & Ming, Z. Y. (2016). Antiplatelet activity of chrysin via inhibiting platelet αIIbβ3-mediated signaling pathway. Mol Nutr Food Res, 60(9), 1984-1993. DOI 10.1002/mnfr.201500801.
• Manach, C., Scalbert, A., Morand, C., Rémésy, C., & Jiménez, L. (2004). Polyphenols: food sources and bioavailability. Am J Clin Nutr, 79(5), 727-747. Doi.org/10.1093/ajcn/79.5.727.
• Mani, R., & Natesan, V. (2018). Chrysin: Sources, beneficial pharmacological activities, and molecular mechanism of action. Phytochem Lett, 145, 187-196.  Doi: 10.1016/j.phytochem.
• Mantawy, E. M., El-Bakly, W. M., Esmat, A., Badr, A. M., & El-Demerdash, E. (2014). Chrysin alleviates acute doxorubicin cardiotoxicity in rats via suppression of oxidative stress, inflammation and apoptosis. Eur J Pharmacol, 728, 107-118. Doi: 10.1016/j.ejphar.
• Manzolli, E. S., Serpeloni, J. M., Grotto, D., Bastos, J. K., Antunes, L. M. G., Barbosa, F., & Barcelos, G. M. R. (2015). Protective effects of the flavonoid chrysin against methylmercury-induced genotoxicity and alterations of antioxidant status, in vivo. Oxid Med Cell Longev, 2015. Doi.org/10.1155/2015/602360.
• Medina, J. H., Paladini, A. C., Wolfman, C., de Stein, M. L., Calvo, D., Diaz, L. E., & Pena, C. (1990). Chrysin (5, 7-di-OH-flavone), a naturally-occurring ligand for benzodiazepine receptors, with anticonvulsant properties. Biochem Pharmacol, 40(10), 2227-2231.
• Metodiewa, D., Kochman, A., & Karolczak, S. (1997). Evidence for antiradical and antioxidant properties of four biologically active N, N-Diethylaminoethyl ethers of flavaone oximes: A comparison with natural polyphenolic flavonoid rutin action. IUBMB Life, 41(5), 1067-1075.
• Middleton, E., Kandaswami, C., & Theoharides, T.C. (2000). The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease, and cancer. Pharmacol Rev, 52(4), 673-751.
• Miroddi, M., Calapai, G., Navarra, M., Minciullo, P. L., & Gangemi, S. (2013). Passiflora incarnata L.: ethnopharmacology, clinical application, safety and evaluation of clinical trials. J Ethnopharmacol, 150(3), 791-804. Doi. 10.1016/j.jep.2013.09.047.
• Missassi, G., dos Santos Borges, C., de Lima Rosa, J., Villela e Silva, P., da Cunha Miyasaka, L. S., Atallah, A. N., & Soares, B. (2007). Passiflora for anxiety disorder. Cochrane Database Syst Rev, (1). Doi: 10.1002/14651858.CD004518.
• Monasterio, A., Urdaci, M. C., Pinchuk, I. V., Lopez-Moratalla, N., & Martinez-Irujo, J.J. (2004). Flavonoids induce apoptosis in human leukemia U937 cells through caspase-and caspase-calpain-dependent pathways. Nutr Cancer, 50(1), 90-100. DOI: 10.1207/s15327914nc5001_12.
• Muñoz, V. A., Ferrari, G. V., Sancho, M. I., & Montaña, M.P. (2016). Spectroscopic and thermodynamic study of chrysin and quercetin complexes with Cu (II). J Chem Eng Data, 61(2), 987-995. doi.org/10.1111/php.13213.
• Nabavi, S. F., Braidy, N., Habtemariam, S., Orhan, I. E., Daglia, M., Manayi, A., & Nabavi, S. M. (2015). Neuroprotective effects of chrysin: From chemistry to medicine. Neurochem Int, 90, 224-231. Doi: 10.1016/j.neuint.2015.09.006.
• Naz, S., Imran, M., Rauf, A., Orhan, I. E., Shariati, M. A., Shahbaz, M., & Heydari, M. (2019). Chrysin: Pharmacological and therapeutic properties. Life Sci, 116797.  Doi: 10.1016/j.lfs.
• Pusz, J., Nitka, B., Zielińska, A., & Wawer, I. (2000). Synthesis and physicochemical properties of the Al (III), Ga (III) and In (III) complexes with chrysin. Mıcrochem J, 65(3), 245-253.
• Rashno, M., Sarkaki, A., Farbood, Y., Rashno, M., Khorsandi, L., Naseri, M. K. G., & Dianat, M. (2019). Therapeutic effects of chrysin in a rat model of traumatic brain injury: A behavioral, biochemical, and histological study. Life Sci, 228, 285-294. DOI: 10.1016/j.lfs.2019.05.007.
• Rauf, A., Khan, R., Raza, M., Khan, H., Pervez, S., De Feo, V., & Mascolo, N. (2015). Suppression of inflammatory response by chrysin, a flavone isolated from Potentilla evestita Th. Wolf. In silico predictive study on its mechanistic effect. Fitoterapia, 103, 129-135. Doi: 10.1016/j.fitote.2015.03.019.
• Samarghandian, S., Farkhondeh, T., & Azimi-Nezhad, M. (2017). Protective effects of chrysin against drugs and toxic agents. Dose-Response, 15(2). Doi.org/10.1177/1559325817711782.
• Siess, M. H., Le Bon, A. M., Canivenc-Lavier, M. C., Amiot, M. J., Sabatier, S., Aubert, S. Y., & Suschetet, M. (1996). Flavonoids of Honey and Propolis: Characterization and Effects on Hepatic Drug-Metabolizing Enzymes and Benzo [a] pyrene− DNA Binding in Rats. J Agric Food Chem, 44(8). Doi.org/10.1021/jf9504733.
• Tsuji, P. A., & Walle, T. (2008). Cytotoxic effects of the dietary flavones chrysin and apigenin in a normal trout liver cell line. Chem Biol Interact, 171(1), 37-44. Doi: 10.1016/j.cbi.2007.08.007.
• Vedagiri, A., & Thangarajan, S. (2016). Mitigating effect of chrysin loaded solid lipid nanoparticles against Amyloid β25–35 induced oxidative stress in rat hippocampal region: An efficient formulation approach for Alzheimer’s disease. Neuropeptides, 58, 111-125.  Doi: 10.1016/j.npep.2016.03.002.
• Walle, T., Otake, Y., Brubaker, J.A., Walle, U.K., & Halushka, P.V. (2001). Disposition and metabolism of the flavonoid chrysin in normal volunteers. Br J Clin, 51(2), 143-146.
• Walle, U. K., Galijatovic, A., & Walle, T. (1999). Transport of the flavonoid chrysin and its conjugated metabolites by the human intestinal cell line Caco-2. Biochem Pharmacol, 58(3), 431-438.  DOI: 10.1016/s0006-2952(99)00133-1.
• Woo, K. J., Jeong, Y. J., Park, J. W., & Kwon, T. K. (2004). Chrysin-induced apoptosis is mediated through caspase activation and Akt inactivation in U937 leukemia cells. Biochem Biophys Res Commun, 325(4), 1215-1222. DOI: 10.1016/j.bbrc.
• Yao, J., Jiang, M., Zhang, Y., Liu, X., Du, Q., & Feng, G. (2016). Chrysin alleviates allergic inflammation and airway remodeling in a murine model of chronic asthma. Int Immunopharmacol, 32, 24-31. DOI: 10.1016/j.intimp.2016.01.005.
• Yao, Y., Chen, L., Xiao, J., Wang, C., Jiang, W., Zhang, R., & Hao, J. (2014). Chrysin protects against focal cerebral ischemia/reperfusion injury in mice through attenuation of oxidative stress and inflammation. Int J Mol Sci, 15(11), 20913-20926.  Doi: 10.3390/ijms151120913.
• Zanoli, P., Avallone, R., & Baraldi, M. (2000). Behavioral characterisation of the flavonoids apigenin and chrysin. Fitoterapia, 71, S117-S123. Doi: 10.1016/s0367-326x (00)00186-6.
• Zhang, T., Chen, X., Qu, L., Wu, J., Cui, R., & Zhao, Y. (2004). Chrysin and its phosphate ester inhibit cell proliferation and induce apoptosis in Hela cells. Bioorg Med Chem, 12(23), 6097-6105.  Doi: 10.1016/j.bmc.2004.09.013.