Sdudies On The Chemical Constitutes And Biological Effect Of Melia Azedarach L.

Melia azedarach L. is a large tree of genus Melia L. and distributes in the most parts of China.The bark of Melia azedarach L.As a traditional Chinese medicine, the extract of M. azedarach L.showed a variety of biological effects, such as antiulcer, anti-diarrhea, anti-inflammatory, antiviral, anti-tumor and so on. From this plant, many kinds of compounds, including triterpenes, flavones, alkaloids and sterols were obtained in previous chemical research. In this study, seven tetracyclic triterpenoids with other compounds were isolated from the bark of M. azedarach L.and the cytotoxicity for six tetracyclic triterpenoids compounds were also evaluated. Meanwhile, Pharmacokinetic study for two activity compounds was carried out by HPLC/MS/MS.Objectives: To study the chemical constitutes of Melia azedarach L. and provide some basis to evaluted its effective components. To study the cytotoxicity studies and Pharmacokinetics on some constitutes of high quantity.Methods: The 95% ethanol extract of the bark of M. azedarach L.was partitioned into petroleum ether, chloroform ethyl acetate, n-butyl alcohol successively. Constituents were isolated and purified by silica gel column chromatography, TLC preparation and recry stallisation. Their structures were identified on the basis of their chemical and physical properties as well as the spectra data of IR, ESI-MS, 1H-NMR, 13C-NMR, HMBC et al. Meanwhile, a sensitive and specific LC/MS/MS method for determination of two activity compounds in rat plasma was developed to study their pharmacokinetic characterizations. Results: Sixteen compounds were obtained and identified form M. azedarach L., which were identified as melissic acid (I), fraxinellone(II), kulactone(III), methyl kulonate(IV), kulinone(V), dubione B(VI), isosclerone(VII),β-sitosterol(VIII), 5-(hydroxymethyl)-2- furaldehyde(IX), succinic(X), isotoosendanin(XI), azedarachol(XII), kulonic acid(XIII), octacosanol(XIV), daucosterol(XV), argyroside(XVI).Conclusions: Compound XVI was isolated from Melia for the first time, Compounds I, VII, X, XIV are isolated from Melia azedarach L.for the first time. Compounds V and XI had cytotoxic activities with the IC50 at 8.57 and 8.57μg/ml to cell of BEL7402, 6.29 and 4.1μg/ml to cell of H460, 6.08 and 9.25μg/ml to cell of SGC-7901, respectively. A rapid, sensitive LC/MS/MS method was developed to determine compounds IV and XI in rat plasma, and drawn a chart of the average plasma concentration-time successfully.