Natural Product Sciences

The Korean Society of Pharmacognosy (한국생약학회)
권호 표지
DOI QR코드

DOI QR Code

Sophora flavescens Extracts Have Therapeutic Effects on Overactive Bladder Syndrome by Potentiation of Large-Conductance Calcium-Activated Potassium Channel

  • Jo, Heeji (School of Life Sciences and Center for AI-applied High Efficiency Drug Discovery, Gwangju Institute of Science and Technology (GIST)) ;
  • Lee, Hyun Jun (Uimyung Research Institute for Neuroscience, Department of Pharmacy, Sahmyook University) ;
  • Jang, Sung Joo (Anti-Aging Research Institute, BIO-FD&C Co., Ltd.) ;
  • Moh, Sang Hyun (Anti-Aging Research Institute, BIO-FD&C Co., Ltd.) ;
  • Cheong, Jae Hoon (School of Pharmacy, Jeonbuk National University) ;
  • Park, Chul-Seung (School of Life Sciences and Center for AI-applied High Efficiency Drug Discovery, Gwangju Institute of Science and Technology (GIST))
  • Received : 2021.06.22
  • Accepted : 2021.09.12
  • Published : 2021.09.30
Download PDF
⟨ Previous Next ⟩

Abstract

Sophora flavescens Ait. (Fabaceae) is a medicinal plant widely founded in Northeast Asia, and its dried root (Kushen) has been used as a traditional Chinese herbal medicine. The therapeutic effects of Kushen in micturition disorder was not investigated comprehensively yet. In the present study, we examined and compared the efficacy of three batches of Kushen extract using different ethanol content through an in vitro cell-based assay. Among them, we chose the batch with the highest efficacy and augmented the volume of extract for industrial purpose. The bulk extract was examined in its efficacy in the in vitro cell-based assay, and the therapeutic effects through an in vivo behavioral assay of OAB rats. The main components of the extracts were analyzed by liquid chromatography. Cytotoxicity of the extracts was investigated by MTT assay. The overall efficacy of the extract was as much as, or more than, kurarinone, a potent BKCa channel activator. Thus, the extract was a potent relaxant of urinary smooth muscle by upregulating the activity of BKCa channel. The Kushen extract could be explored as an alternative medicine against overactive bladder patients indicating severe dysfunction of BKCa channel.

Keywords

Acknowledgement

This study was supported by a grant from the Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry (IPET) through the AgriBioindustry Technology Development Program, funded by the Ministry of Agriculture, Food and Rural Affairs (MAFRA) [317070-4] to CSP.

References

  1. Pallotta, B. S.; Magleby, K. L.; Barrett, J. N. Nature 1981, 293, 471-474. https://doi.org/10.1038/293471a0
  2. Barrett, J. N.; Magleby, K. L.; Pallotta, B. S. J. Physiol. 1982, 331, 211-230. https://doi.org/10.1113/jphysiol.1982.sp014370
  3. Yang, H.; Zhang, G.; Cui, J. Front Physiol. 2015, 6, 29. https://doi.org/10.3389/fphys.2015.00029
  4. Salkoff, L.; Butler, A.; Ferreira, G.; Santi, C.; Wei, A. Nat. Rev. Neurosci. 2006, 7, 921-931. https://doi.org/10.1038/nrn1992
  5. Cui, J.; Yang, H.; Lee, U. S. Cell Mol. Life Sci. 2009, 66, 852-875. https://doi.org/10.1007/s00018-008-8609-x
  6. Raffaelli, G.; Saviane, C.; Mohajerani, M. H.; Pedarzani, P.; Cherubini, E. J. Physiol. 2004, 557, 147-157. https://doi.org/10.1113/jphysiol.2004.062661
  7. Lu, R.; Alioua, A.; Kumar, Y.; Eghbali, M.; Stefani, E.; Toro, L. J. Physiol. 2006, 570, 65-72. https://doi.org/10.1113/jphysiol.2005.098913
  8. Ghatta, S.; Nimmagadda, D.; Xu, X.; O'Rourke, S. T. Pharmacol. Ther. 2006, 110, 103-116. https://doi.org/10.1016/j.pharmthera.2005.10.007
  9. Petkov, G. V. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2014, 307, R571- R584. https://doi.org/10.1152/ajpregu.00142.2014
  10. Hristov, K. L.; Afeli, S. A.; Parajuli, S. P.; Cheng, Q.; Rovner, E. S.; Petkov, G. V. PLoS One. 2013, 8, e68052. https://doi.org/10.1371/journal.pone.0068052
  11. Cerruto, M. A.; Asimakopoulos, A. D.; Artibani, W.; Del Popolo, G.; La Martina, M.; Carone, R.; Finazzi-Agro, E. Urol. Int. 2012, 89, 1-8. https://doi.org/10.1159/000339251
  12. Hristov, K. L.; Parajuli, S. P.; Provence, A.; Petkov, G. V. Am. J. Physiol. Renal. Physiol. 2016, 311, F1253-F1259. https://doi.org/10.1152/ajprenal.00238.2016
  13. Bentzen, B. H.; Olesen, S. P.; Ronn, L. C.; Grunnet, M. Front Physiol. 2014, 5, 389. https://doi.org/10.3389/fphys.2014.00389
  14. Oger, S.; Behr-Roussel, D.; Gorny, D.; Bernabe, J.; Comperat, E.; Chartier-Kastler, E.; Denys, P.; Giuliano, F. BJU Int. 2011, 108, 604-611. https://doi.org/10.1111/j.1464-410X.2010.09935.x
  15. Lee, S.; Chae, M. R.; Lee, B. C.; Kim, Y. C.; Choi, J. S.; Lee, S. W.; Cheong, J. H.; Park, C. S. Mol. Pharmacol. 2016, 90, 140-150. https://doi.org/10.1124/mol.115.102939
  16. Lee, S; Choi, J. S.; Park, C. S. Biol. Pharm. Bull. 2018, 41, 1295-1298. https://doi.org/10.1248/bpb.b18-00250
  17. He, X.; Fang, J.; Huang, L.; Wang, J.; Huang, X. J. Ethnopharmacol. 2015, 172, 10-29. https://doi.org/10.1016/j.jep.2015.06.010
  18. Hillerns, P. I.; Wink, M. Planta Med. 2005, 71, 1065-1068. https://doi.org/10.1055/s-2005-871302
  19. Chang, C.; Liu, S. P.; Fang, C. H.; He, R. S.; Wang, Z.; Zhu, Y. Q.; Jiang, S. W. Oncol. Lett. 2013, 6, 699-704. https://doi.org/10.3892/ol.2013.1449
  20. Shi, L. J.; Shi, L.; Song, G. Y.; Zhang, H. F.; Hu, Z. J.; Wang, C.; Zhang, D. H. Eur. J. Pharmacol. 2013, 714, 89-95. https://doi.org/10.1016/j.ejphar.2013.06.013
  21. Lee, B. C.; Kim, H. J.; Park, S. H.; Phuong, T. T.; Kang, T. M.; Park, C. S. J. Biotechnol. 2013, 167, 41-46. https://doi.org/10.1016/j.jbiotec.2013.06.007
  22. Clemow, D. B.; Steers, W. D.; McCarty, R.; Tuttle, J. B. Am. J. Physiol. 1998, 275, R1279-R1286.
  23. Zhang, L.; Xu, L.; Xiao, S. S.; Liao, Q. F.; Li, Q.; Liang, J.; Chen, X. H.; Bi, K. S. J. Pharm. Biomed. Anal. 2007, 44, 1019-1028. https://doi.org/10.1016/j.jpba.2007.04.019
  24. Chen, L.; Shao, J.; Luo, Y.; Zhao, L.; Zhao, K.; Gao, Y.; Wang, S.; Liu, Y. J. Pharm. Biomed. Anal. 2020, 186, 113306. https://doi.org/10.1016/j.jpba.2020.113306
  25. Zakharov, S. I.; Morrow, J. P.; Liu, G.; Yang, L.; Marx, S. O. J. Biol. Chem. 2005, 280, 30882-30887. https://doi.org/10.1074/jbc.M505302200
  26. Bentzen, B. H.; Nardi, A.; Calloe, K.; Madsen, L. S.; Olesen, S. P.; Grunnet, M. Mol. Pharmarol. 2007, 72, 1033-1044. https://doi.org/10.1124/mol.107.038331
  27. Ryu, Y. B.; Curtis-Long, M. J.; Kim, J. H.; Jeong, S. H.; Yang, M. S.; Lee, K. W.; Lee, W. S.; Park, K. H. Bioorg. Med. Chem. Lett. 2008, 18, 6046-6049. https://doi.org/10.1016/j.bmcl.2008.10.033
  28. Jung, H. A.; Yoon, N. Y.; Kang, S. S.; Kim, Y. S.; Choi, J. S. J. Pharm. Pharmacol. 2008, 60, 1227-1236. https://doi.org/10.1211/jpp.60.9.0016
  29. Quang, T. H.; Ngan, N. T. T.; Minh, C. V.; Kiem, P. V.; Tai, B. H.; Nhiem, N. X.; Thao, N. P.; Luyen, B. T. T.; Yang, S. Y.; Kim, Y. H. Phytother. Res. 2013, 27, 1300-1307. https://doi.org/10.1002/ptr.4871
  30. Hwang, E. M.; Ryu, Y. B.; Kim, H. Y.; Kim, D. G.; Hong, S. G.; Lee, J. H.; Curtis-Long, M. J.; Jeong, S. H.; Park, J. Y.; Park, K. H. Bioorg. Med. Chem. 2008, 16, 6669-6674. https://doi.org/10.1016/j.bmc.2008.05.080
  31. Lee, H. S.; Ko, H. R.; Ryu, S. Y.; Oh, W. K.; Kim, B. Y.; Ahn, S. C.; Mheen, T. I.; Ahn, J. S. Planta Med. 1997, 63, 266-268. https://doi.org/10.1055/s-2006-957670
  32. Kim, S. J.; Son, K. H.; Chang, H. W.; Kang, S. S.; Kim, H. P. Biol. Pharm. Bull. 2003, 26, 1348-1350. https://doi.org/10.1248/bpb.26.1348