title: Ginkgo biloba L. extract protects against chronic cerebral hypoperfusion by modulating neuroinflammation and the cholinergic system.
abstract: BACKGROUND
  Ginkgo biloba extract (GBE)-a widely used nutraceutical-is reported to have diverse functions, including positive effects on memory and vasodilatory properties. Although numerous studies have assessed the neuroprotective properties of GBE in ischemia, only a few studies have investigated the neuro-pharmacological mechanisms of action of GBE in chronic cerebral hypoperfusion (CCH).
  
  
  OBJECTIVE
  In the present study, we sought to determine the effects of GBE on CCH-induced neuroinflammation and cholinergic dysfunction in a rat model of bilateral common carotid artery occlusion (BCCAo).
  
  
  METHODS
  Chronic BCCAo was induced in adult male Wistar rats to reflect the CCH conditions. On day 21 after BCCAo, the animals were treated orally with saline or GBE (5, 10, 20, and 40mg/kg) daily for 42 days. After the final treatment, brain tissues were isolated for the immunohistochemical analysis of glial markers and choline acetyltransferase (ChAT), as well as for the western blot analysis of proinflammatory cytokines, toll-like receptor (TLR)-related pathway, receptor for advanced glycation end products (RAGE), angiotensin-II (Ang-II), and phosphorylated mitogen-activated protein kinases (MAPKs).
  
  
  RESULTS
  BCCAo increased glial proliferation in the hippocampus and white matter, whereas proliferation was significantly attenuated by GBE treatment. GBE also attenuated the BCCAo-related increases in the hippocampal expression of proinflammatory cytokines (TNF-α, IL-1β, and IL-6), TLR4, myeloid differentiation primary response gene 88, RAGE, Ang-II, and phosphorylated MAPKs (ERK, p38, and JNK). Furthermore, GBE treatment restored the ChAT expression in the basal forebrain following BCCAo.
  
  
  CONCLUSIONS
  These findings suggest that GBE has specific neuroprotective effects that may be useful for the treatment of CCH. The pharmacological mechanism of GBE partly involves the modulation of inflammatory mediators and the cholinergic system.
authors.affiliation: Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, The Republic of Korea; Convergence Research Center for Diagnosis, Treatment and Care System of Dementia, Korea Institute of Science and Technology, Seoul 02792, The Republic of Korea.
authors.forename: Min-Soo
authors.initials: MS
authors.lastname: Kim
authors.affiliation: Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, The Republic of Korea.
authors.forename: Ji Hye
authors.initials: JH
authors.lastname: Bang
authors.affiliation: Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, The Republic of Korea; Convergence Research Center for Diagnosis, Treatment and Care System of Dementia, Korea Institute of Science and Technology, Seoul 02792, The Republic of Korea.
authors.forename: Jun
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Biological Science, Konkuk University, Seoul 05029, The Republic of Korea.
authors.forename: Jung-Soo
authors.initials: JS
authors.lastname: Han
authors.affiliation: Central Research Center, Yuyu Pharma. Inc., Seoul 04598, The Republic of Korea.
authors.forename: Tae Gon
authors.initials: TG
authors.lastname: Baik
authors.affiliation: Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, The Republic of Korea; Convergence Research Center for Diagnosis, Treatment and Care System of Dementia, Korea Institute of Science and Technology, Seoul 02792, The Republic of Korea. Electronic address: wkjeon@kiom.re.kr.
authors.forename: Won Kyung
authors.initials: WK
authors.lastname: Jeon
mesh_terms: D000818:Animals; D001342:Autonomic Nervous System Diseases / Q000188:drug therapy* / Q000503:physiopathology; D017536:Carotid Artery, Common; D016893:Carotid Stenosis / Q000188:drug therapy / Q000503:physiopathology; D049109:Cell Proliferation / Q000187:drug effects; D002561:Cerebrovascular Disorders / Q000188:drug therapy* / Q000503:physiopathology; D016207:Cytokines / Q000378:metabolism; D020441:Ginkgo biloba; D007249:Inflammation / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010275:Parasympathetic Nervous System / Q000187:drug effects*; D010936:Plant Extracts / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D016207:Cytokines; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D010936:Plant Extracts
keywords: Choline acetyltransferase; Chronic cerebral hypoperfusion; Ginkgo biloba; Neuroinflammation; Toll-like receptor