Kushenol C

Re-evaluation of the antioxidant prenylated flavonoids from the roots of Sophora flavescens.[Pubmed:18451517]

Biol Pharm Bull. 2008 May;31(5):908-15.

The objective of this research was to re-evaluate the antioxidant effects of the prenylated flavonoids from Sophora flavescens via in vitro 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS), peroxynitrite (ONOO(-)), and total reactive oxygen species (ROS) assays. In addition, a further examination of kuraridinol, kurarinol, and kurarinone, also isolated from S. flavescens, was carried out by the inhibition of tert-butylhydroperoxide (t-BHP)-induced intracellular ROS generation and t-BHP-induced activation of nuclear factor-kappaB (NF-kappaB). Upon re-examination of the ethyl acetate (EtOAc) soluble fraction of S. flavescens, two major prenylated chalcones, including kuraridin and kuraridinol, along with a minor prenylated flavonol, Kushenol C, were isolated as good DPPH scavengers. This was in contrast to the prenylated flavanones, sophoraflavanone G and kurarinone, which were isolated from the methylene chloride (CH(2)Cl(2)) fraction of the same source. Five flavanones consisting of kushenol E, leachianone G, kurarinol, sophoraflavanone G, and kurarinone exhibited significant antioxidant potentials in the ABTS, ONOO(-), and total ROS assays; however, the prenylated chalcones and prenylated flavonol showed more potent scavenging/inhibitory activities than the prenylated flavanones. Therefore, the prenylated chalcones and prenylated flavonol, rather than the prenylated flavanones, may make important contributions toward the marked antioxidant capacities of S. flavescens. Furthermore, kuraridinol, kurarinol, and kurarinone showed significant inhibitory activities against intracellular ROS levels as well as NF-kappaB activation by t-BHP. Overall, the results indicate that S. flavescens and its prenylated flavonoids may possess good anti-inflammatory activity, which is implicated in their significant antioxidant activity.

Selective inhibition of prenylated flavonoids from Sophora flavescens against BACE1 and cholinesterases.[Pubmed:20387235]

Am J Chin Med. 2010;38(2):415-29.

It was previously reported that certain lavandulylated flavanones from Sophora flavescens are beta-site APP cleaving enzyme 1 (BACE1) inhibitors; however, based upon their levels within the extract, their inhibitory effects should be higher than expected. Moreover, chalcones and flavonols were reported to exert higher bioactivities than flavanones. These findings have led to a further search for other possible constituents potentially contributing to the strong inhibitory activity of the S. flavescens extract. In this study, BACE1 activities were significantly inhibited by 8-lavandulylkaempferol (IC(50) 7.29 microM), kuraridinol (IC(50) 7.10 microM), kuraridin (IC(50) 6.03 microM), and Kushenol C (IC(50) 5.45 microM) from the ethyl acetate fraction, along with desmethylanhydroicaritin (IC(50) 1.86 microM), xanthohumol (IC(50) 7.19 microM), and leachianone G (IC(50) 8.56 microM) from the dichloromethane fraction of the extract. The results indicate that the prenyl group, rather than the lavandulyl group, and the flavonols and chalcones, rather than flavanones, might make predominant contributions to BACE1 inhibition. In particular, 8-lavandulylkaempferol exhibited significant inhibitory effects with IC(50) values of 7.10 and 8.11 microM for butyrylcholinesterase and acetylcholinesterase, respectively, when compared to its counterpart, desmethylanhydroicaritin. This indicates that the lavandulyl group might play a predominant role in both cholinesterase inhibitions. This is the first study indicating that prenylated flavonoids exert varying degrees of inhibition primarily through their skeleton (flavonols, chalcones, flavanones), as well as their lipophilic chain length (prenyl and lavandulyl groups). Therefore, S. flavescens and its prenylated flavonoids, possessing low molecular weights and lipophilic moieties may be potent preventive and therapeutic candidates for Alzheimer's disease.