Isolation of potential liver x receptor alpha agonist and antioxidant compounds from Hypericum microcalycinum Boiss. & Heldr.

Year 2021, Volume: 51 Issue: 1, 98 - 104, 30.04.2021

Seçil Sarıkaya Aydın Vahap Murat Kutluay Toshiaki Makino Makoto Inoue Ümmühan Şebnem Harput İclal Saraçoğlu

Abstract

Background and Aims: Hypericum microcalycinum Boiss. & Heldr. is used for inflammatory diseases in Anatolia. The involvement of liver X receptors (LXRs) and free radicals in inflammatory diseases, activation of LXRs, and high radical contents in cancerous tissue and organs prompted us to determine the radical scavenging and LXRα agonist activity of aqueous fraction of methanol extract and fractions of H. microcalycinum along with the isolation studies from active fractions. Methods: Isolation studies were carried out on chromatographic techniques. DPPH, NO, and SO radical scavenging activity methods were used for the determination of antioxidant activity, and a LXRE reporter gene assay was used for the determination of LXRα agonist activity. Results: While the extract showed weak LXRα agonist activity, phenolic compounds- rich fractions showed moderate activity. DPPH radical scavenging capacities of the extract and some fractions seemed to be very high as well as some isolated compounds. Bioactivity- guided studies resulted in the isolation of catechin (1), epicatechin (2), apigenin-8-C-(2-O-acetyl)- glucopyranoside (3), quercetin-3-O-β-glucopyranoside (4), quercetin-3-O-β-arabinopyranoside (5), kaempferol-3-O-β- arabinopyranoside (6), luteolin-8-C-β-glucopyranoside (orientin) (7). Conclusion: According to our results, compounds 1, 2, 4, and 5 may be responsible for the anti-inflammatory effects of H. microcalycinum as a function of LXRα agonist and free radical scavenging effects.

Keywords

Hypericum microcalycinum, phenolic compounds, free radical scavenging, LXRα agonist activity

References

• • Aktas, N., Genc, Y., Gozcelioglu, B., Konuklugil, B., & Harput, U. S. (2013). Radical scavenging effect of different marine sponges from mediterranean coasts. Records of Natural Products, 7(2), 96- 104.
• • Almahy, H. A., & Fouda, H. A. R. (2013). Isolation of Luteolin-8-C- β-D-glucopyranoside from the roots of Salvadora persica (Rutaceae). Journal of Current Chemical and Pharmaceutical Sciences, 3, 49-53. • Baytop, T. (1999). Türkiye’de Bitkilerle Tedavi: Geçmişte ve Bugün, (pp. 166-167). Istanbul, Turkey: İstanbul Üniversitesi Yayınları.
• • Boga, M., Ertas, A., Eroglu-Ozkan, E., Kizil, M., Ceken, B., & Topcu, G. (2016). Phytochemical analysis, antioxidant, antimicrobial, anticholinesterase and DNA protective effects of Hypericum capitatum var. capitatum extracts. South African Journal of Botany, 104, 249-257. doi: 10.1016/j.sajb.2016.02.204
• • Donovan, J. L., Luthria, D. L., Stremple, P., & Waterhouse, A. L. (1999). Analysis of (+)-catechin, (-)-epicatechin and their 3 ‘- and 4 ‘-O-methylated analogs - A comparison of sensitive methods. Journal of Chromatography B-Analytical Technologies in the Biomedical and Life Sciences, 726(1-2), 277-283. doi: 10.1016/S0378- 4347(99)00019-5
• • Eroglu, E., Aksu, B. Z., & Mat, A. (2008). An overview on Hypericum species of Turkey. Planta Medica, 74(9), 1139-1139.
• • Fessler, M. B. (2018). The challenges and promise of targeting the Liver X Receptors for treatment of inflammatory disease. Pharmacology & Therapeutics, 181, 1-12. doi: 10.1016/j.pharmthera. 2017.07.010
• • Fobofou, S. A., Franke, K., Sanna, G., Porzel, A., Bullita, E., La Colla, P., & Wessjohann, L. A. (2015). Isolation and anticancer, anthelminthic, and antiviral (HIV) activity of acylphloroglucinols, and regioselective synthesis of empetrifranzinans from Hypericum roeperianum. Bioorganic & Medicinal Chemistry, 23(19), 6327-6334. doi: 10.1016/j.bmc.2015.08.028
• • Fouache, A., Zabaiou, N., De Joussineau, C., Morel, L., Silvente- Poirot, S., Namsi, A., . . . Trousson, A. (2019). Flavonoids differentially modulate liver X receptors activity—Structure-function relationship analysis. The Journal of Steroid Biochemistry and Molecular Biology, 190, 173-182. doi: https://doi.org/10.1016/j.jsbmb. 2019.03.028
• • Francisco, V., Figueirinha, A., Costa, G., Liberal, J., Ferreira, I., Lopes, M. C., . . . Batista, M. T. (2016). The flavone luteolin inhibits liver X receptor activation. Journal of Natural Products, 79(5), 1423-1428. doi: 10.1021/acs.jnatprod.6b00146
• • Gong, H., He, J., Lee, J. H., Mallick, E., Gao, X., Li, S., . . . Xie, W. (2009). Activation of the liver X receptor prevents lipopolysaccharideinduced lung injury. The Journal of Biological Chemistry, 284(44), 30113-30121. doi: 10.1074/jbc.M109.047753
• • Hatano, T., Edamatsu, R., Hiramatsu, M., Mori, A., Fujita, Y., Yasuhara, T., . . . Okuda, T. (1989). Effects of the interaction of tannins with coexisting substances .6. Effects of tannins and related polyphenols on superoxide anion radical, and on 1,1-diphenyl-2-picrylhydrazyl radical. Chemical & Pharmaceutical Bulletin, 37(8), 2016-2021.
• • Hiebl, V., Ladurner, A., Latkolik, S., & Dirsch, V. M. (2018). Natural products as modulators of the nuclear receptors and metabolic sensors LXR, FXR and RXR. Biotechnology Advances, 36(6), 1657- 1698. doi: https://doi.org/10.1016/j.biotechadv.2018.03.003
• • Islam, M., Al-Amin, M. D., Siddiqi, M. M. A., Akter, S., Haque, M. M., Sultana, N., & Chowdhury, S. (2012). Isolation of quercetin-3-O-β- D-glucopyranoside from the leaves of Azadirachta indica and antimicrobial and cytotoxic screening of the crude extracts. Dhaka University Journal of Science, 60, 11-14.
• • Jensen, S. R., Gotfredsen, C. H., Harput, U. S., & Saracoglu, I. (2010). Chlorinated iridoid glucosides from Veronica longifolia and their antioxidant activity. Journal of Natural Products, 73(9), 1593-1596. doi: 10.1021/np100366k
• • Joseph, S. B., Castrillo, A., Laffitte, B. A., Mangelsdorf, D. J., & Tontonoz, P. (2003). Reciprocal regulation of inflammation and lipid metabolism by liver X receptors. Nature Medicine, 9(2), 213-219. doi: 10.1038/nm820
• • Kadota, S., Takamori, Y., Nyein, K. N., Kikuchi, T., Tanaka, K., & Ekimoto, H. (1990). Constituents of the leaves of Woodfordia fruticosa Kurz. I. Isolation, structure, and proton and carbon-13 nuclear magnetic resonance signal assignments of woodfruticosin (woodfordin C), an inhibitor of deoxyribonucleic acid topoisomerase II. Chem Pharm Bull (Tokyo), 38(10), 2687-2697. doi: 10.1248/ cpb.38.2687
• • Kotani, H., Tanabe, H., Mizukami, H., Makishima, M., & Inoue, M. (2010). Identification of a naturally occurring rexinoid, honokiol, that activates the retinoid X receptor. Journal of Natural Products, 73(8), 1332-1336. doi: 10.1021/np100120c
• • Kunchandy, E., & Rao, M. N. A. (1990). Oxygen radical scavenging activity of curcumin. International Journal of Pharmaceutics, 58(3), 237-240. doi: 10.1016/0378-5173(90)90201-E
• • Nakashima, K., Murakami, T., Tanabe, H., & Inoue, M. (2014). Identification of a naturally occurring retinoid X receptor agonist from Brazilian green propolis. Biochimica et Biophysica Acta-General Subjects, 1840(10), 3034-3041. doi: 10.1016/j.bbagen.2014.06.011
• • Nicollier, G., & Thompson, A. C. (1983). Flavonoids of Desmanthus illinoensis. Journal of Natural Products, 46(1), 112-117. doi: 10.1021/np50025a011
• • Nunez, A. R. (1985). Taxonomia de Hypericum hyssopifolium Chaix Y Especies Relacionadas. Lagascalia, 13(2), 173-185.
• • Ohara, K., Wakabayashi, H., Taniguchi, Y., Shindo, K., Yajima, H., & Yoshida, A. (2013). Quercetin-3-O-glucuronide induces ABCA1 expression by LXRα activation in murine macrophages. Biochemical and Biophysical Research Communications, 441(4), 929-934. doi: https://doi.org/10.1016/j.bbrc.2013.10.168
• • Prochazkova, D., Bousova, I., & Wilhelmova, N. (2011). Antioxidant and prooxidant properties of flavonoids. Fitoterapia, 82(4), 513- 523. doi: 10.1016/j.fitote.2011.01.018
• • Razavi, S. M., Zahri, S., Zarrini, G., Nazemiyeh, H., & Mohammadi, S. (2009). Biological activity of quercetin-3-O-glucoside, a known plant flavonoid. Russian Journal of Bioorganic Chemistry, 35(3), 376-378. doi: 10.1134/S1068162009030133
• • Robson, N. K. B. (1980). Hypericum L. . In P. H. Davis (Ed.), Flora of Turkey and East Aegean Islands (pp. 355-401). Edinburgh: Edinburgh University.
• • Sarian, M. N., Ahmed, Q. U., So’ad, S. Z. M., Alhassan, A. M., Murugesu, S., Perumal, V., . . . Latip, J. (2017). Antioxidant and Antidiabetic Effects of Flavonoids: A Structure-Activity Relationship Based Study. Biomed Research International, 2017. doi: Artn 8386065 doi: 10.1155/2017/8386065
• • Srinivasan, R., Chandrasekar, M. J. N., Nanjan, M. J., & Suresh, B. (2007). Antioxidant activity of Caesalpinia digyna root. Journal of Ethnopharmacology, 113(2), 284-291. doi: 10.1016/j. jep.2007.06.006
• • Szondy, Z., Garabuczi, E., Joos, G., Tsay, G. J., & Sarang, Z. (2014). Impaired clearance of apoptotic cells in chronic inflammatory diseases: therapeutic implications. Frontiers in Immunology, 5, 354. doi: 10.3389/fimmu.2014.00354
• • Tsai, P. J., Tsai, T. H., Yu, C. H., & Ho, S. C. (2007). Comparison of NOscavenging and NO-suppressing activities of different herbal teas with those of green tea. Food Chemistry, 103(1), 181-187. doi: 10.1016/j.foodchem.2006.08.013
• • Vedin, L. L., Gustafsson, J. A., & Steffensen, K. R. (2013). The oxysterol receptors LXRalpha and LXRbeta suppress proliferation in the colon. Molecular Carcinogenesis, 52(11), 835-844. doi: 10.1002/ mc.21924
• • Viennois, E., Mouzat, K., Dufour, J., Morel, L., Lobaccaro, J. M., & Baron, S. (2012). Selective liver X receptor modulators (SLiMs): What use in human health? Molecular and Cellular Endocrinology, 351(2), 129-141. doi: 10.1016/j.mce.2011.08.036
• • Wang, W., Nakashima, K., Hirai, T., & Inoue, M. (2019). Anti-inflammatory effects of naturally occurring retinoid X receptor agonists isolated from Sophora tonkinensis Gagnep. via retinoid X receptor/ liver X receptor heterodimers. Journal of Natural Medicines, 73(2), 419-430. doi: 10.1007/s11418-018-01277-1
• • Willy, P. J., Umesono, K., Ong, E. S., Evans, R. M., Heyman, R. A., & Mangelsdorf, D. J. (1995). Lxr, a Nuclear Receptor That Defines a Distinct Retinoid Response Pathway. Genes & Development, 9(9), 1033-1045. doi: 10.1101/gad.9.9.1033
• • Zhang, P. C., & Xu, S. X. (2003). C-glucoside flavonoids from the leaves of Crataegus pinnatifida Bge. var. major N.E.Br. Journal of Asian Natural Products Research, 5(2), 131-136. doi: 10.1080/1028602021000054982
• • Zhang, X. F., Thuong, P. T., Jin, W., Su, N. D., Sok, D. E., Bae, K., & Kang, S. S. (2005). Antioxidant activity of anthraquinones and flavonoids from flower of Reynoutria sachalinensis. Archives of Pharmacal Research, 28(1), 22-27. doi: 10.1007/Bf02975130
• • Zorzetto, C., Sanchez-Mateo, C. C., Rabanal, R. M., Lupidi, G., Petrelli, D., Vitali, L. A., . . . Maggi, F. (2015). Phytochemical analysis and in vitro biological activity of three Hypericum species from the Canary Islands (Hypericum reflexum, Hypericum canariense and Hypericum grandifolium). Fitoterapia, 100, 95-109.