Relaxant Action Of Lotus Leaves Alkaloid On Mouse Airway Smooth Muscle

Asthma is a life-threatening chronic inflammatory disorder of the airway,often characterized by pathological changes such as reversible constrain of airflow,enhanced contraction of airway smooth muscle cells,and excitable airway response.Lotus leafis a traditional Chinese herbal medicine,it is widely used in the world because it has many biological activities,such as detoxication,antihypertension,bacteriostatic and antiviral.However,the role of Lotus leaf on modulation of airway smooth muscle function remains unknown.The purpose of this study is to explore potential roles of AELL on airway smooth muscle function and the mechanism.Firstly,we used 80 mM KCl as agonist to precontract airway smooth muscle.Then,the precontract airway smooth muscle was treated with AELL(0.316 mg/mL ~ 17.8 mg/mL)cumulatively.Our results showed that:(1)AELL inhibited high K+-induced pre-contraction of mouse tracheal rings in a dose-dependent manner;(2)AELL-induced smooth muscle relaxation was mediated partially by blocking voltage-dependent L-type Ca2+ channels(VDLCCs)and thus inhibiting inflow of Ca2+.Secondly,we choosed 100 μM ACh as agonistto precontract airway smooth muscle.Then,the precontract airway smooth muscle was treated with AELL(0.001 mg/mL ~ 100 mg/mL)cumulatively.Our results showed that:(1)AELL inhibited ACh-induced pre-contraction of mouse tracheal rings in a dose-dependent manner;(2)Blocking VDLCCs using nifedipine did not fully reverse AELL-induced smooth muscle relaxation,suggesting that additional mechanism might be involved;(3)AELLpartially reversed ACh-induced pre-contraction of mouse tracheal rings via blocking VDLCCs and non-selective cation channels(NSCCs).Nuciferine is one of the most important composition of the Lotus leaf alkaloids.We used nuciferine to treat ASM as above experiment,and we found that: nuciferine can completely relax high K+-induced pre-contraction of mouse tracheal rings and partiallyinhibited ACh-induced pre-contraction of mouse tracheal rings in a dose-dependent manner.The mechanisms of relaxing pre-contraction mouse tracheal rings are via blocking VDLCCs andNSCCs.Our results showed thatAELL and nuciferine can inhibit ASM contraction induced by K+ or ACh.The relaxant effect is mediated in part by lowering the intracellular Ca2+ concentration via blocking the channels of VDLCCs and NSCCs.This finding suggests that AELL and nuciferine might benew drugs to treat abnormal contractions oftrachea and asthma.