title: Muscarinic, Ca(++) antagonist and specific butyrylcholinesterase inhibitory activity of dried ginger extract might explain its use in dementia.
abstract: Ginger rhizome (Zingiber officinale) has been used for centuries to treat dementia in South Asia. This study was undertaken to possibly justify its use. A 70% aqueous/methanolic extract of dried ginger (Zo.Cr) was used. Zo.Cr tested positive for the presence of terpenoids, flavonoids, secondary amines, phenols, alkaloids and saponins. When tested on isolated rat stomach fundus, Zo.Cr showed a spasmogenic effect (0.03-5.00 mg mL(-1)); it relaxed the tissue at concentrations > or =5 mg mL(-1). The stimulant effect was resistant to blockade by hexamethonium and methysergide, but sensitive to atropine, indicating activity via muscarinic receptors. In atropinized (0.1 microM) preparations, Zo.Cr (0.3-3.0 mg mL(-1)) relaxed high K(+) (80 mM)-induced contractions, indicating Ca(++) antagonism in addition to the muscarinic effect. This possible Ca(++) antagonist activity was investigated in Ca(++)-free conditions, with the inhibitory effect of the extract tested against contractions induced by externally administered Ca(++). Zo.Cr (0.1-0.3 mg mL(-1)), similar to verapamil (0.03-0.10 microM), shifted the contractions induced by externally administered Ca(++) to the right, thus suggesting an inhibitory interaction between Zo.Cr and voltage-operated Ca(++) channels. Zo.Cr (0.1-3.0 microg mL(-1)) also potentiated acetylcholine peak responses in stomach fundus, similar to physostigmine, a cholinesterase inhibitor. Zo.Cr, in an in-vitro assay, showed specific inhibition of butyrylcholinesterase (BuChE) rather than acetylcholinesterase enzyme. Different pure compounds of ginger also showed spasmolytic activity in stomach fundus, with 6-gingerol being the most potent. 6-Gingerol also showed a specific anti-BuChE effect. This study shows a unique combination of muscarinic, possible Ca(++) antagonist and BuChE inhibitory activities of dried ginger, indicating its benefit in dementia, including Alzheimer's disease.
authors.affiliation: Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan.
authors.forename: Muhammad N
authors.initials: MN
authors.lastname: Ghayur
authors.forename: Anwarul H
authors.initials: AH
authors.lastname: Gilani
authors.forename: Touqeer
authors.initials: T
authors.lastname: Ahmed
authors.forename: Asaad
authors.initials: A
authors.lastname: Khalid
authors.forename: Sarfraz A
authors.initials: SA
authors.lastname: Nawaz
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Agbedahunsi
authors.forename: Muhammad I
authors.initials: MI
authors.lastname: Choudhary
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Houghton
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000544:Alzheimer Disease / Q000188:drug therapy / Q000503:physiopathology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002091:Butyrylcholinesterase / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000737:chemistry / Q000494:pharmacology*; D002396:Catechols / Q000737:chemistry / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005233:Fatty Alcohols / Q000737:chemistry / Q000494:pharmacology; D005748:Gastric Fundus / Q000187:drug effects / Q000502:physiology; D020939:Zingiber officinale / Q000737:chemistry*; D066298:In Vitro Techniques; D015394:Molecular Structure; D018721:Muscarinic Agonists / Q000737:chemistry / Q000494:pharmacology*; D010276:Parasympatholytics / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology; D010830:Physostigmine / Q000494:pharmacology; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D027343:Rhizome / Q000737:chemistry; D014700:Verapamil / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D002396:Catechols; D002800:Cholinesterase Inhibitors; D005233:Fatty Alcohols; D018721:Muscarinic Agonists; D010276:Parasympatholytics; D010936:Plant Extracts; D001285:Atropine; C040115:shogaol; C007845:gingerol; D010830:Physostigmine; D014700:Verapamil; D002091:Butyrylcholinesterase; C534464:8-gingerol; D000109:Acetylcholine; D002118:Calcium