TY - JOUR T1 - Low cerebral exposure cannot hinder the neuroprotective effects of panax notoginsenosides JF - Drug Metabolism and Disposition JO - Drug Metab Dispos DO - 10.1124/dmd.117.078436 SP - dmd.117.078436 AU - Haofeng Li AU - Jingcheng Xiao AU - Xinuo Li AU - Huimin Chen AU - Dian Kang AU - Yuhao Shao AU - Boyu Shen AU - Zhangpei Zhu AU - Xiaoxi Yin AU - Lin Xie AU - Guangji Wang AU - Yan Liang Y1 - 2017/01/01 UR - http://dmd.aspetjournals.org/content/early/2017/10/23/dmd.117.078436.abstract N2 - A bidirectional route of communication between the gastrointestinal tract and the central nervous system, termed the "gut-brain axis", is becoming increasingly relevant to treatment of cerebral damage. Panax Notoginsenoside extract (PNE) is extremely popular for prevention and treatment of cardio-cerebrovascular ischemic diseases although their plasma and cerebral exposure levels were extremely low. To date, the mechanisms underlying the neuroprotective effects of PNE remain largely unknown. In the present study, the neuroprotective effects of PNE are systematically studied via investigating the regulation of PNE on gastrointestinal microbial community and gamma aminobutyric acid (GABA) receptors. The results demonstrated that pretreatment with PNE exerted a remarkable neuroprotective effect from focal cerebral ischemia / reperfusion (I/R) injury in rats, and the efficiency was attenuated in germ-free rats. Pretreatment with PNE could significantly prevent down-regulation of Bifidobacterium longum (B.L) caused by I/R surgery, and colonization of B.L could also exert neuroprotective effects. Both PNE and B.L could up-regulate the expression of GABA receptors in the hippocampus of I/R rats, and co-administration of a GABA-B receptor antagonist could significantly attenuate the neuroprotective effects of PNE and B.L. The study above suggests that the neuroprotective effects of PNE may be largely attributable to its regulation of intestinal flora, and oral treatment of B.L was also useful in therapy of I/R by up-regulating GABA-B receptors. ER -