Xyloketal B, a marine compound, acts on a network of molecular proteins and regulates the activity and expression of rat cytochrome P450 3a: a bioinformatic and animal study

Su, Junhui; Chang, Cui; Xiang, Qi; Zhou, Zhi-Wei; Luo, Rong; Yang, Lun; He, Zhi-Xu; Yang, Hongtu; Li, Jianan; Bei, Yu; Xu, Jinmei; Zhang, Minjing; Zhang, Qihao; Su, Zhijian; Huang, Yadong; Pang, Jiyan; Zhou, Shu-Feng

There is an increasing prevalence of natural products, including marine products, that are used to improve body function and manage various ailments due to their diverse is a novel marine compound isolated from the mangrove fungus Xylaria sp., and has potent antioxidative, neuroprotective, and cardioprotective effects. 19 , 20 We have found that XKB has a relaxing effect on blood vessels and protects endothelial cells against oxidative injury induced by oxidized low-density lipoprotein. 10 It directly scavenged the free radical-generating compound 1,1-diphenyl-2-picrylhydrazyl and protected PC12 cells against oxygen-glucose deprivation injury. 9 Further, it has a strong inhibitory effect on the L-calcium channel. 21 The potent antioxidative effect of XKB suggests that it is a promising agent in the treatment of oxidative stress-associated conditions, such as CVD. To establish the dose-response and dose-toxicity relationships of XKB, we investigated its metabolism and PKs in rats. In vivo, the plasma PKs of XKB followed a two-compartment model with a distribution phase and an elimination phase. 22 XKB showed a short elimination half-life (22-27 minutes) , suggesting that it was rapidly distributed in the body and also rapidly eliminated. However, the molecular targets in response to XKB treatment and the effect of XKB on regulation of drug-metabolizing enzymes are unknown.