Preliminary Study On The Pharmacokinetics And Metabolism(In Vivo And In Vitro) Of Nigella A

Nigella glandulifera Freyn belongs to Nigella L.of Ranunculaceae.Its dry seeds are known as Uygur and Dai nationality's traditional medicine.A series of triterpenoid saponins,flavonoids,fatty oils,volatile oils and alkaloids have been isolated from Nigella glandulifera Freyn.In previous work,Nigella A has been isolated from Nigella glandulifera Freyn,which shows good anti-tumor activity.However,the absorption,distribution,metabolism and excretion of Nigella A in vivo are unknown,so this research will investigate the pharmacokinetic and metabolism of Nigella A in vivo and in vitro.1.The pharmacokinetic study of Nigella A in ratA reliable LC-MS/MS analysis method was developed for determinating Nigella A in rat plasma.This method shows good selectivity,linearity,sensitivity,accuracy,precision,extraction,recovery,matrix effect and stability.Experimental result revealed that the bioavailability of Nigella A in rat was very poor.2.The biotransformating study of Nigella A in vitro by rat intestinal microfloraNigella A was anaerobically cultured with rat intestinal microflora at 37?.The metabolites were qualitatively and quantitatively analysed by UPLC-Q/TOF-MS.As a result,two metabolites were detected.M1 is Nigella A's deglycosyl product(in 28-position),which was named Nigella B.M2 is M1's deglycosyl product(in 3-position),which was named Hederagenin.After 36 hours of incubation,a small amount of M1 and M2 were generated.C(M0)>C(M1)>C(M2)in whole reaction system.After 48 hours of incubation,a large amount of M2 and M1 were generated.C(M2)>C(M1)>C(M0)in whole reaction system.3.The metabolism of Nigella A in ratThe experimental rat was given Nigella A by oral administration,then collected the plasma,urine and feces samples.All samples were qualitatively and quantitatively analysed by UPLC-Q/TOF-MS.As a result,three metabolites were detected in urine samples and twenty-nine metabolites were detected in feces samples respectively.Nigella A's metabolic pathway in vivo mainly including deglycosylation,methylation,dehydrogenation and binding reaction and so on.There were no metabolites were detected in plasma samples,which may related to the sensitivity of the instrument.After 24 hours of administration,C(M0)>C(M1)in urine samples and C(M2)>C(Mi)>C(M0)in feces samples.After 48 hours of administration,C(M1)>C(M0)in urine samples and C(M2)>C(MO)>C(M1)in feces samples respectively.Synthesizing the results of the above three studies,help to reveal Nigella A's material base of antitumor activity.Laying foundation for the Nigella glandulifera Freyn's research and development of new saponins.