Study On The Anti Tuberculosis Activity And Metabolism In Rats Of Ranunculi Ternati Radix

Objective:Study on the in vitro anti tuberculosis activity of 4-[formyl-5-(hydroxymethyl)-1H-pyrrol-1-yl]butanoic acid and their derivatives 4-[2-carboxyl-5-(hydroxymethyl)-1H-pyrrol-l-yl]butanoic acid.And The pharmacokinetics of the two drugs in rats were studied.Methods:The inhibitory activity of RanuncuLi Ternati Radix monomer compositio n and its homologous object was investigated by bacteriostatic test of Mycobacteri um tuberculosis.Method for determining content of 4-[formyl-5-(hydroxymethyl)-1 H-pyrrol-l-yl]butanoic acid and their derivatives 4-[2-carboxyl-5-(hydroxymethyl)-1H-pyrrol-l-yl]butanoic acid in rat plasma by UHPLC-MS/MS.The quantitative analy sis of MRM negative ion mode was used to study the pharmacokinetics of 4-[for myl-5-(hydroxymethyl)-1H-pyrrol-1-yl]butanoic acid and their derivatives 4-[2-carbox yl-5-(hydroxymethyl)-1H-pyrrol-1-yl]butanoic acid in rats after intravenous injection and intragastric administration.Results:The minimum inhibitory concentration of anti tuberculosis was 31.25 μg·mL-1.The pharmacokinetic parameters showed that the bioavailability of 4-[formyl-5-(hydroxymethyl)-1H-pyrrol-1-yl]butanoic acid was 73.81%,and the 4-[2-carbox yl-5-(hydroxymethyl)-1H-pyrrol-1-yl]butanoic acid was 35.94%.The total excretion rates of 4-[formyl-5-(hydroxymethyl)-1H-pyrrol-1-yl]butanoic acid in the urine and feces of rats were 6.37%and 4.05%after intravenous injection and intragastric ad ministration.Conclusion:4-[formyl-5-(hydroxymethyl)-1H-pyrrol-1-yl]butanoic acid and their der ivatives 4-[2-carboxyl-5-(hydroxymethyl)-1H-pyrrol-1-yl]butanoic acid has good anti bacterial activity against Mycobacterium tuberculosis,and thier have higher bioavai lability,excretion experiments indicated that 4-[formyl-5-(hydroxymethyl)-1H-pyrrol-1-yl]butanoic acid aldehyde pyrrole occurred widely butyric acid metabolism in rats.