Creat New Nucleoside Microbial Transformation And The Study Of Metabolism In Rats

Chuanxinlian is the dried aerial parts of Andrographispaniculata (Burm.f.) Nees, which is a Chinese herbal medicine used as an anti-inflammatory and antipyretic drug for treatment of fever, cold, laryngitis and diarrhea. And it was specified in the Pharmacopoeia of the P. R. China (2000) as an anti-virus and anti-bacterial remedy. Neoandrographolide is one of the main anti-virus components isolated from Andrographis paniculata (Burm.f.) Nees. The pharmacology research indicated that neoandrographolide has lots of activities, such as anti-inflammatory, antibiosis, blood pressure lowering, hepatoprotective and so on.The microorganism Mucor spinosus AS 3.2450 was selected to transform the substrate—neoandrographolide, ten products were isolated and purified from the fermented broth, and the structures of these products were elucidated on the basis of chemical evidences and spectral analyses. They are 14-deoxyandrographolide (1),17,19-dihydroxy-8,13-ent-labdadien-16,15-olide (2)*,3,14-dideoxyandrographolide (3),7β-hydroxy-3,14-dideoxyandrographolide (4)*, 17,19-dihydroxy-7,13-ent-labdadien-16,15-olide (5)*,8(17),13-ent-labdadien-16,15-olid-19-oic acid (6),8,17β-epoxy-3,14-dideoxyandrographolide (7)*,8β,17,19-trihydroxy-ent-labd-13-en-16,15-olide (8)*, phlogantholide-A (9),19-[(β-D-glucopyranosyl)oxy]-19-oxo-ent-labda-8(17),13-dien-16,15-olide (10), respectively. Among these ten products,2,4,5,7 and 8 are new compounds.This study provided more diterpenoid lactones derivatives to elucidate the antiviral constituents of Andrographis paniculata (Burm.f.) Nees., and further investigating antiviral structure-activity relationship. Meanwhile, as a vitro-model for mammalian metabolic research in vivo, microbial transformation can provide a new study route to obtain metabolites in vivo.The metabolic investigation of neoandrographolide in rats was also conducted in this study. The main metabolite—3,14-dideoxyandrographolide was detected and isolated, the aglycone of neoandrographolide, The result should provide information and reference for the further metabolism and pharmacokinetics investigation of neoandrographolide in humans.