Study On The Chemical Constituents And Bioactivities Of Penicillium Commune

We studied on the chemical constituents and bioactivities of endophytic fungus Penicillium commune, and a total of 15 compounds, including 3 new compounds, have been isolated and identified depending on chromatography methods, spectroscopic and single crystal X-ray diffraction analysis. The chemical type involved two new phenone derivatives penicophenones, a new cyclic tetrapeptide and other type components. In addition, the 11?-HSD1 inhibitory activity have been investigated.The fungus of penicillium sp. often grow on the surface and deep inside of rotten fruits, vegtables and meat. Many Penicillium sp. fungus could decomposed agricultural byproducts, and a few are pathogenic fungus to humen and animals. Moreover, some species like P. notatum and P. chrysogenum were used to produced penicillin, which was the first antibiotics in the world and has been widely used. P. commume is a family of penicillium sp., we studied on the chemical constituents of P. commume and investigated the chemical components of the rice fermentation products of this fungus, 15 compounds have been isolated from the solid fermentation products compounds, among these two new phenone derivatives penicophenones 1 and 2, a new cyclic tetrapeptide 3, and 12 known compounds were isolated from the culture broth of P. commune, an endophytic fungus derived from Vitis vinifera. In the bioactivity assay, we test the 11?-HSD1 inhibitory activity compound 1,2,3,5,6,7,15,16, and compound 3 exhibited significant inhibition activities against 11?-hydroxysteroid dehydrogenase type 1(11?-HSD1) in vitro and showed strong binding affinity to 11?-HSD1. Moreover, compound 3 treatments decreased the lipid droplet accumulation associate with the inhibition of 11?-HSD1 expression in differentiate-induced 3T3-L1 preadipocytes. Furthermore, the molecular docking demonstrated that compound 3 coordinated in the active site of 11?-HSD1 is essential for the ability of diminishing the enzyme activity.Glucocorticoids influence a wide variety of physiologic processes, including lipid and glucose metabolism, immune modulation, cell growth, and anti-inflammatory responses. Excessive activation of glucocorticoid hormones(GCs) can result in metabolic syndromes with multiple clinical features, including insulin resistant diabetes, obesity, dyslipidemia, and hypertension1. 11?-hydroxysteroid dehydrogenase type 1(11?-HSD1), which converts inactive glucocorticoid into active glucocorticoid, such as cortisol in humans can amplify the local levels and activities of GCs2. Given that 11?-HSD1 is abundantly expressed in metabolically important tissues which become resistant to insulin action in type 2 diabetes, such as adipose, muscle, and liver tissue, the inhibition of 11?-HSD1 offers the ability to restore the metabolic action of insulin in these tissues3. Consequently, the developments of 11?-HSD1 inhibitor drugs are urgently demanded.