医药导报2026，Vol.45Issue(4)：588-596,9.DOI:10.3870/j.issn.1004-0781.2026.04.005
蛇床子素调控钙通道抑制磷酸二酯酶抗腹泻双重机制
Dual Mechanisms of Osthole in Antidiarrheal Action:Regulation of Calcium Channels and Inhibition of Phosphodiesterase
摘要
Abstract
Objective To investigate the dual molecular mechanisms of osthole(OST)against diarrhea.Methods An experimental diarrhea model was established in mice induced by castor oil(20 mL•kg-1).Mice were randomly divided into model control group,low-dose(37.5 mg•kg-1),medium-dose(75 mg•kg-1)and high-dose(150 mg•kg-1)OST groups and loperamide group(4 mg•kg-1).The antidiarrheal effect and intestinal motility/secretion function were evaluated using fecal morphology,excretion index(EI),ink propulsion test,and intestinal fluid accumulation test.The inhibitory effects of OST on spontaneous contraction and contractions induced by carbachol(CCh),high/low potassium were analyzed using an ex vivo jejunum experiment.The calcium channel blocking effect was detected using a calcium depletion-reperfusion model.The activities of cyclic adenosine monophosphate(cAMP)and phosphodiesterase(PDE)were determined via enzyme-linked immunosorbent assay(ELISA).The interaction between OST and PDE4B/4D was analyzed using molecular docking(Autodock Vina).Results Compared with model control group,OST significantly delayed the initial appearance time of semi-solid(high-dose:97.67±6.93 vs.60.25±6.51 min,P<0.01)and reduced EI(2.69±2.66 vs.13.56±1.81,P<0.01),with efficacy comparable to loperamide.OST inhibited the small intestinal propulsion rate,intestinal fluid secretion,and jejunal contractions,showing a concentration-dependent manner,and right-shifted the Ca2+concentration-response curve.OST up-regulated cAMP and inhibited PDE activity.Molecular docking confirmed OST’s binding affinity to PDE4B/4D(-33.05 kJ•mol-1),involving Asn567 hydrogen bonds and Phe586 π-π stacking.Conclusions OST exerts antidiarrheal effects through dual mechanisms:inhibiting calcium channels(reducing Ca2+influx)and blocking PDE4 activity(elevating cAMP).Its multi-target properties provide scientific insights for developing plant-based antidiarrheal drugs.关键词
蛇床子素/腹泻/肠平滑肌/钙通道/磷酸二酯酶Key words
Osthole/Diarrhea/Intestinal smooth muscle/Calcium channels/Phosphodiesterase分类
医药卫生引用本文复制引用
董俊芳,张建武,彭清秀,杨兰,张成华,文静,李阳友,艾正毅,代荔君,侯宇洁..蛇床子素调控钙通道抑制磷酸二酯酶抗腹泻双重机制[J].医药导报,2026,45(4):588-596,9.基金项目
南充市政府-高校合作科研项目(19SXHZ0242) （19SXHZ0242）
南充市政府-高校合作科研项目(22SXQT0163) （22SXQT0163）
川北医学院博士启动基金资助项目(CBY19-QD07). （CBY19-QD07）
