Research On The Vasorelaxant Substances,novel Terpenoids From The Aerial Parts Of Pogostemon Cablin And Leonurus Japonicus

Objective:To investigate the terpenoid components and their vasodilation activities from traditional Chinese medicine Pogostemon cablin and Leonurus japonicus.In addition,we have evaluated the pharmacological activity and analyzed the structure-function relationship.Methods:1.The terpenes of P.cablin and L.japonicus were isolated and purified by various chromatographic methods including column chromatography over silica,Sephadex LH-20,and Rp C₁₈8 columns.Their structures were identified by physicochemical properties and spectroscopic analysis,including single-crystal X-ray diffraction,MS,IR,1D NMR,2D NMR.2.The pharmacodynamic effects of terpenes were evaluated by rat aortic rings.The effects of different compounds on the vessels under tension stimulated with potassium chloride（KCl）/phenylephrine（PHE）were collected and recorded by the tissue perfusion model and the PowerLab data analysis system.Results:1.Thirty compounds including 16 new ones（1^*–15^*,22^*）were isolated and identified from the extracts from P.cablin and L.japonicus.2.Compounds 9^*and 21 isolated from P.cablin,in a concentration-dependent manner,relaxed rat aorta rings precontracted with KCl（60 mmol/L）,with EC₅₀ values of24.17 and 6.83μmol/L.And the EC₅₀ value of positive drug methoxyverapamil was 0.58μmol/L.Four constituents（2^*,7^*,9^*and 21）showed vasorelaxant effects on rat aorta rings induced by PHE（1μmol/L）,with EC₅₀ values of 16.32,5.42,1.63 and 2.72μmol/L.And the EC₅₀ value of positive drug phentolamine mesylate was 66.02 nmol/L.By analyzing the activity of the compounds,we found that compounds 2^*and 7^*exhibited weak activities on KCl-indued vascular rings,but significantly inhibited the phenylephrine concentration-response curve,indicating that the active monomers might involved in receptor-operated channel.3.In the same way,the effects of terpenes from L.japonicus were observed on the rat aorta rings precontracted by PHE and KCl.Six constituents（22^*25,27,29）showed vasodilation activity with EC₅₀ values of 2.32,6.41,4.81,2.43,8.74 and 18.40μmol/L on the rat aorta rings precontracted by KCl.Compounds 23 and 29 exhibited vasodilation activity with EC₅₀ values of 2.39 and 1.65μmol/L on vessels precontracted by PHE.According to their structural features and structure-activity relationship,the compounds of novel skeleton and labdane diterpenes isolated from Motherwort were more active than the phytane,and furthermore,better than many types of sesquiterpene compounds.Conclusion:Thirty sesquiterpenes or diterpenoids were isolated and purified from the Chinese traditional medicine P.cablin and Motherwort.Among them,there were sixteen new ones,including three unprecedented carbon skeletons.The pharmacologica experiment results showed that compounds 2^*,7^*,9^*,21,22^*–25,27 and 29 had a good vasodilation in vitro.According to the structure activity relationship analysis,it was concluded that the bis-spirolabdane diterpenoids from L.japonicus were more potent vasodilator activity than the others.