Izalpinin from fruits of Alpinia oxyphylla with antagonistic activity against the rat bladder contractility.
BACKGROUND
Alpinia oxyphylla (Zingiberaceae), an herbaceous perennial plant, its capsular fruit is commonly used in traditional Chinese medicine for the treatment of different urinary incontinence symptoms including frequency, urgency and nocturia. These symptoms are similar to the overactive bladder syndrome. In our lab, we found that the 95% ethanol extract of the capsular fruits exhibited significant anti-muscarinic activity. Some constituents in capsular fruits including flavonoids (e.g., izalpinin and tectochrysin), diarylheptanoids (e.g., yakuchinone A and yakuchinone B) and sesquiterpenes (e.g., nootkatone), are regarded as representative chemicals with putative pharmacological activities.


OBJECTIVE
This study aimed to evaluate the in vitro antagonistic actions of izalpinin on carbachol-induced contraction of the rat detrusor muscle.


METHODS
In vitro inhibition of rat detrusor contractile response to carbachol was used to study the functional activity of izalpinin. The isolated detrusor strips of rats were mounted in organ baths containing oxygenated Krebs' solution. The cumulative consecutive concentration-response curves to carbachol-evoked contractions in strips of rat bladder were obtained.


RESULTS
Carbachol induced concentration-dependent contractions of isolated rat bladder detrusor strips. The vehicle DMSO had no impact on the contraction response. The contraction effects were concentration-dependently antagonized by izalpinin, with a mean EC50 value of 0.35 µM. The corresponding cumulative agonist concentration-response curves shifted right-ward.


CONCLUSIONS
Izalpinin exhibits inhibitory role of muscarinic receptor-related detrusor contractile activity, and it may be a promising lead compound to treat overactive bladder.
School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China ; Hainan Normal Universities, Haikou 571158, China.
Yuan
Y
Yuan
School of Pharmacy, Hainan Medical University, Haikou 571101, China ; Hainan Provincial Key Laboratory of R&D of Tropical Herbs, Haikou 571101, China ; Haikou Municipal Key Laboratory of R&D of Li nationality Herbs, Haikou 571101, China.
Yin-Feng
YF
Tan
School of Pharmacy, Hainan Medical University, Haikou 571101, China ; Hainan Provincial Key Laboratory of R&D of Tropical Herbs, Haikou 571101, China ; Haikou Municipal Key Laboratory of R&D of Li nationality Herbs, Haikou 571101, China.
Peng
P
Xu
School of Pharmacy, Hainan Medical University, Haikou 571101, China ; Hainan Provincial Key Laboratory of R&D of Tropical Herbs, Haikou 571101, China ; Haikou Municipal Key Laboratory of R&D of Li nationality Herbs, Haikou 571101, China.
Hailong
H
Li
School of Pharmacy, Hainan Medical University, Haikou 571101, China ; Hainan Provincial Key Laboratory of R&D of Tropical Herbs, Haikou 571101, China ; Haikou Municipal Key Laboratory of R&D of Li nationality Herbs, Haikou 571101, China.
Yong-Hui
YH
Li
School of Pharmacy, Hainan Medical University, Haikou 571101, China.
Wen-Ya
WY
Chen
School of Pharmacy, Hainan Medical University, Haikou 571101, China ; Hainan Provincial Key Laboratory of R&D of Tropical Herbs, Haikou 571101, China ; Haikou Municipal Key Laboratory of R&D of Li nationality Herbs, Haikou 571101, China.
Jun-Qing
JQ
Zhang
School of Pharmacy, Hainan Medical University, Haikou 571101, China ; Hainan Provincial Key Laboratory of R&D of Tropical Herbs, Haikou 571101, China ; Haikou Municipal Key Laboratory of R&D of Li nationality Herbs, Haikou 571101, China.
Feng
F
Chen
School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
Guo-Jun
GJ
Huang
D032429:Alpinia / Q000737:chemistry*; D002217:Carbachol / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology* / Q000627:therapeutic use; D005638:Fruit / Q000737:chemistry; D018727:Muscarinic Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D001743:Urinary Bladder / Q000187:drug effects* / Q000502:physiology; D053201:Urinary Bladder, Overactive / Q000188:drug therapy
D018679:Cholinergic Agonists; D005419:Flavonoids; D018727:Muscarinic Antagonists; D010936:Plant Extracts; D002217:Carbachol
Izalpinin; antagonistic action; muscarinic receptor; rat bladder