TY - JOUR
T1 - Muscarinic, Ca++ antagonist and specific butyrylcholinesterase inhibitory activity of dried ginger extract might explain its use in dementia
AU - Ghayur, Muhammad N.
AU - Gilani, Anwarul H.
AU - Ahmed, Touqeer
AU - Khalid, Asaad
AU - Nawaz, Sarfraz A.
AU - Agbedahunsi, Joseph M.
AU - Choudhary, Muhammad I.
AU - Houghton, Peter J.
PY - 2008/10
Y1 - 2008/10
N2 - 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 ≥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 μm) 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 μm), 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 μg 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.
AB - 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 ≥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 μm) 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 μm), 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 μg 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.
UR - http://www.scopus.com/inward/record.url?scp=52949143061&partnerID=8YFLogxK
U2 - 10.1211/jpp/60.10.0014
DO - 10.1211/jpp/60.10.0014
M3 - Article
C2 - 18812031
AN - SCOPUS:52949143061
SN - 0022-3573
VL - 60
SP - 1375
EP - 1383
JO - Journal of Pharmacy and Pharmacology
JF - Journal of Pharmacy and Pharmacology
IS - 10
ER -