Actinomycetes 04-4776 Active Metabolite Of The Isolation And Purification, Structure And Identification Of Anti-atherosclerosis-related Activity And Preliminary Molecular Pharmacology

Atherosclerosis is one of the common diseases that damage human health. Although multiple epidemiological, experimental, and genetic studies have supported that the elevated level of HDL-C is very important for protection against atherogenesis, the effective therapeutic methods aiming at selectively elevated HDL-C level in patients are not currently available. In 1996, the scavenger receptor class B, type I (SR-B I) was reported as the first molecularly well-defined and functionally active cell-surface HDL receptor (HDL-R) which can mediate the selective uptake of HDL-CE by cells through taking part in reverse cholesterol transport. So new compounds which elevate SR-B I expression level may become the leading compounds of new anti-atherosclerosis drugs.With the SR-B I expression upregulators screening model established in our laboratory, the microbial fermentation broths were screened. Among them, the fermentation broth of Actinomyces 04-4776 showed good upregulatory effect on CLA-1 expression. After cultivation of the strain, two positive compounds, 4776B and 4776C were isolated and purified from the fermentation. Their chemical structures were identified by means of UV, MS and NMR. 4776B was identified as 4'-methoxyl-3',5,7-hydroxyl isoflavone which is firstly reported from microorganisms. 4776C was identified as 7-Deoxy-13-dihydrodaunomycinone by comparison with literature data. Molecular pharmacological tests have been done to confirm these two compounds effect. In mRNA and protein level, both compounds show upregultory effect on CLA-1 expression. Flow cytometry assay showed that the lipids in HepG2 cell were highly increased after treatment with the compounds.