Study On The Anti-inflammatory Active Components Of Lignans From Trachelospermum Jasminoides

To treat for inflammation,the current anti-inflammatory drugs such as steroidal anti-inflammatory drugs and non-steroidal anti-inflammatory drugs,they can only relieve symptoms,with side effects.Therefore,they can’t be used for a long time.The market vacancy of anti-inflammatory drugs is relatively large.According to the literatures,nortracheloside,tracheloside,nortrachelogenin,matairesinol,trachelogenin and arctigenin from the lignans of Trachelospermum jasminoides had different intensities of anti-inflammatory activity.We intended to synthesize the anti-inflammatory active monomers and derivatives from the lignans of Trachelospermum jasminoides,and built the screening model to screen activities.Using enzyme reaction kinetics and the Lineweaver-Burk double reciprocal method,we obtained IC₅₀ value and inhibition constant K_ivalue of the monomers and their derivatives,and simulated the interaction between the elastase and activity monomers with their derivatives by molecular docking.The results were as followed:Several monomeric compounds which were separated from the lignans of Trachelospermum jasminoides and defined the structure,and used as the basic structural units.The monomer compound and its derivative:matairesinol and7-hydroxymatairesinol have been synthesized.The method which synthesized the dibenzylbutyrolactone lignans was designed.The target product was got by Stobbe’s condensation,choosing the conjugated double bond,dehydration,ring condensation,aldol condensation reaction,catalytic hydrogenation debenzylation to restore.Their chemical structures were confirmed by MS,¹H NMR and ¹³C NMR.Excessive expression or activity of elastase can lead to a variety of chronic inflammatory diseases.The use of elastase inhibitors can reduce elastase expression and prevent the development of inflammation.The screening model has made to screen activities by elastase used as target enzyme and N-Suc-Ala-Ala-Ala-p NA used as substrate.The results showed that nortrachelogenin,matairesinol,trachelogenin,arctigenin and 7-hydroxymatairesinol all had inhibitory effects on the catalytic activity of elastase.By using the enzyme reaction kinetics,the IC₅₀ values of nortrachelogenin,matairesinol,trachelogenin,arctigenin and 7-hydroxymatairesinol were 1.7 mmol/L,1.5mmol/L,1.2 mmol/L,0.8 mmol/L and 0.3 mmol/L.According to the Lineweaver-Burk double reciprocal method,the inhibition types of the five inhibitors were all competitive inhibition,the inhibition constant K_i values of nortrachelogenin,matairesinol,trachelogenin,arctigenin and 7-hydroxymatairesinol were 1.9×10^-3 mol/L,1.5×10^-3mol/L,1.1×10^-3 mol/L,6.0×10^-4 mol/L and 1.5×10^-4 mol/L.By comparing their IC₅₀values and inhibition constant K_i values of the five inhibitors,it can be concluded that their inhibition ability from small to large was followed:nortrachelogenin,matairesinol,trachelogenin,arctigenin and 7-hydroxymatairesinol.Nortrachelogenin,matairesinol,trachelogenin,arctigenin,7-hydroxymatairesinol were used to simulate the interaction with elastase by molecular docking.Several monomer compounds had hydrogen bonding,hydrophobic interaction andπ-cation interaction with elastase.The strength of the interaction depended on the functional group.From the results of molecular docking and enzyme reaction kinetics,several monomer compounds with methoxy group and 7-hydroxyl group were favorable for the inhibitory activity of elastase inhibitors,and the 8’-hydroxyl group had no significant effect on the inhibitory activity of elastase inhibitors.