@article {Lidmd.117.078436, author = {Haofeng Li and Jingcheng Xiao and Xinuo Li and Huimin Chen and Dian Kang and Yuhao Shao and Boyu Shen and Zhangpei Zhu and Xiaoxi Yin and Lin Xie and Guangji Wang and Yan Liang}, title = {Low cerebral exposure cannot hinder the neuroprotective effects of panax notoginsenosides}, elocation-id = {dmd.117.078436}, year = {2017}, doi = {10.1124/dmd.117.078436}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {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.}, issn = {0090-9556}, URL = {https://dmd.aspetjournals.org/content/early/2017/10/23/dmd.117.078436}, eprint = {https://dmd.aspetjournals.org/content/early/2017/10/23/dmd.117.078436.full.pdf}, journal = {Drug Metabolism and Disposition} }