RT Journal Article
SR Electronic
T1 Low Cerebral Exposure Cannot Hinder the Neuroprotective Effects of Panax Notoginsenosides
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 53
OP 65
DO 10.1124/dmd.117.078436
VO 46
IS 1
A1 Haofeng Li
A1 Jingcheng Xiao
A1 Xinuo Li
A1 Huimin Chen
A1 Dian Kang
A1 Yuhao Shao
A1 Boyu Shen
A1 Zhangpei Zhu
A1 Xiaoxi Yin
A1 Lin Xie
A1 Guangji Wang
A1 Yan Liang
YR 2018
UL http://dmd.aspetjournals.org/content/46/1/53.abstract
AB 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 popular for prevention and treatment of cardio-cerebrovascular ischemic diseases although plasma and cerebral exposure levels are extremely low. To date, the mechanisms underlying the neuroprotective effects of PNE remain largely unknown. In the present study, the neuroprotective effects of PNE were systematically studied via investigation of the regulation by PNE of the gastrointestinal microbial community and γ aminobutyric acid (GABA) receptors. The results demonstrated that pretreatment with PNE exerted a remarkable neuroprotective effect on focal cerebral ischemia/reperfusion (I/R) injury in rats, and the efficiency was attenuated in germ-free rats. Pretreatment with PNE could significantly prevent downregulation of Bifidobacterium longum (B.L) caused by I/R surgery, and colonization by B.L could also exert neuroprotective effects. More importantly, both PNE and B.L could upregulate the expression of GABA receptors in the hippocampus of I/R rats, and coadministration 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 with B.L was also useful in therapy of ischemia/reperfusion injury (I/R) by upregulating GABA-B receptors.