title: Hexane extracts of Polygonum multiflorum improve tissue and functional outcome following focal cerebral ischemia in mice.
abstract: Polygonum multiflorum is a traditional Korean medicine that has been utilized widely in East Asian countries as a longevity agent. Clinical studies have demonstrated that Polygonum multiflorum improves hypercholesterolemia, coronary heart disease, neurosis and other diseases commonly associated with aging. However, scientific evidence defining the protective effects and mechanisms of Polygonum multiflorum against ischemic stroke is incomplete. In the present study, we investigated the cerebrovascular protective effects of Polygonum multiflorum against ischemic brain injury using an in vivo photothrombotic mouse model. To examine the underlying mechanism of action, we utilized an in vitro human brain microvascular endothelial cell (HBMEC) culture system. Hexane extracts (HEPM), ethyl acetate extracts (EAEPM) and methanol extracts (MEPM) of Polygonum multiflorum (100 mg/kg) were administered intraperitoneally 30 min prior to ischemic insult. Focal cerebral ischemia was induced in C57BL/6J mice and endothelial nitric oxide synthase knockout (eNOS KO) mice by photothrombotic cortical occlusion. We evaluated the infarct volume, as well as neurological and motor function, 24 h after ischemic brain injury. Following ischemic insult, HEPM induced a significant reduction in infarct volume and subsequent neurological deficits, compared with EAEPM and MEPM. HEPM significantly decreased infarct size and improved neurological and motor function, which was not observed in eNOS KO mice, suggesting that this cerebroprotective effect is primarily an eNOS-dependent mechanism. In vitro, HEPM effectively promoted NO production, however these effects were inhibited by the NOS inhibitor, L-NAME and the PI3K/Akt inhibitor, LY-294002. Furthermore, HEPM treatment resulted in increased phosphorylation-dependent activation of Akt and eNOS in HBMEC, suggesting that HEPM increased NO production via phosphorylation-dependent activation of Akt and eNOS. In conclusion, HEPM prevents cerebral ischemic damage through an eNOS-dependent mechanism, and thus may have clinical applications as a protective agent against neurological injury in stroke.
authors.affiliation: School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam 626-870, Republic of Korea.
authors.forename: Soo Vin
authors.initials: SV
authors.lastname: Lee
authors.affiliation: School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam 626-870, Republic of Korea.
authors.forename: Kyung Ha
authors.initials: KH
authors.lastname: Choi
authors.affiliation: College of Natural Resources and Life Sciences, Pusan National University, Gyeongnam 627-706, Republic of Korea.
authors.forename: Young Whan
authors.initials: YW
authors.lastname: Choi
authors.affiliation: School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam 626-870, Republic of Korea.
authors.forename: Jin Woo
authors.initials: JW
authors.lastname: Hong
authors.affiliation: School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam 626-870, Republic of Korea.
authors.forename: Jin Ung
authors.initials: JU
authors.lastname: Baek
authors.affiliation: School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam 626-870, Republic of Korea.
authors.forename: Byung Tae
authors.initials: BT
authors.lastname: Choi
authors.affiliation: School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam 626-870, Republic of Korea.
authors.forename: Hwa Kyoung
authors.initials: HK
authors.lastname: Shin
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D002544:Cerebral Infarction / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006586:Hexanes / Q000737:chemistry*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D055806:Microvessels / Q000473:pathology; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D009569:Nitric Oxide / Q000096:biosynthesis; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use*; D028502:Polygonum / Q000737:chemistry*; D020127:Recovery of Function / Q000187:drug effects*
chemical_list: D006586:Hexanes; D018696:Neuroprotective Agents; D010936:Plant Extracts; C026385:n-hexane; D009569:Nitric Oxide