4',5-Dihydroxyflavone

Discovery of New Microbial Collagenase Inhibitors

Bacterial virulence factors are mediating bacterial pathogenesis and infectivity. Collagenases are virulence factors secreted by several bacterial stains, such as Clostridium, Bacillus, Vibrio and Pseudomonas. These enzymes are among the most efficient degraders of collagen, playing a crucial role in host colonization. Thus, they are an important target for developing new anti-infective agents because of their pivotal roles in the infection process. A primary screening using a fluorescence resonance energy-transfer assay was used to experimentally evaluate the inhibitory activity of 77 compounds on collagenase A. Based on their inhibitory activity and chemical diversity, a small number of compounds was selected to determine the corresponding half maximal inhibitory con-centration (IC50). Additionally, we used molecular docking to get a better understanding of the enzyme-compound interaction. Several natural compounds (capsaicin, 4',5-dihydroxyflavone, curcumin, dihydrorobinetin, palmatine chloride, biochanin A, 2'-hydroxychalcone, and juglone) were identified as promising candidates for further development into useful anti-infective agents against infections caused by multi-drug-resistant bacterial pathogens which include collagenase A in their enzymatic set.

Study of chemical composition and antimicrobial activity of leaves and roots of Scrophularia ningpoensis

Two saponins: scrokoelziside A (1), scrokoelziside B (2), one iridoid glycoside, eurostoside (3), and two flavonoids: nepitrin (4) and homoplantaginin (5), were isolated from the leaves of Scrophularia ningpoensis for the first time. Moreover, eight known compounds: cane sugar (6), harpagide (7), aucubin (8), 6-O-methylcatalpol (9), harpagoside (10), angoroside C (11), beta-sitosterol (12) and beta-sitosterol glucoside (13) were isolated from the roots of S. ningpoensis. Furthermore, the antimicrobial activity of the extracts of the leaves of S. ningpoensis and the 10 compounds (1, 2, 3, 4, 5, 7, 8, 9, 10, 11) was studied in vitro against eight reference strains of bacteria by using the disc-diffusion method and micro-well dilution assay. The extracts of leaves and scrokoelziside A are effective against beta-haemolytic streptococci but had no effect against other strains. The extract of roots and other compounds showed no activity against all bacterial strains at the test concentration.

Dihydrohomoplantagin and Homoplantaginin, Major Flavonoid Glycosides from Salvia plebeia R. Br. Inhibit oxLDL-Induced Endothelial Cell Injury and Restrict Atherosclerosis via Activating Nrf2 Anti-Oxidation Signal Pathway

Oxidized low-density lipoprotein (oxLDL)-induced endothelium injury promotes the development of atherosclerosis. It has been reported that homoplantaginin, a flavonoid glycoside from the traditional Chinese medicine Salvia plebeia R. Br., protected vascular endothelial cells by inhibiting inflammation. However, it is undetermined whether homoplantaginin affects atherosclerosis. In this study, we evaluated the effect of homoplantaginin and its derivative dihydrohomoplantagin on oxLDL-induced endothelial cell injury and atherosclerosis in apoE-/- mice. Our results showedthat both dihydrohomoplantagin and homoplantaginin inhibited apoptosis and the increased level of ICAM-1 and VCAM-1 in oxLDL-stimulated HUVECs and the plaque endothelium of apoE-/- mice. Additionally, both of them restricted atherosclerosis development of apoE-/- mice. Mechanistic studies showed that oxLDL-induced the increase in ROS production, phosphorylation of ERK and nuclear translocation of NF-κB in HUVECs was significantly inhibited by the compounds. Meanwhile, these two compounds promoted Nrf2 nuclear translocation and increased the anti-oxidation downstream HO-1 protein level in HUVECs and plaque endothelium. Notably, knockdown of Nrf2 by siRNA abolished the cell protective effects of compounds and antagonized the inhibition effects of them on ROS production and NF-κB activation in oxLDL-stimulated HUVECs. Collectively, dihydrohomoplantagin and homoplantaginin protected VECs by activating Nrf2 and thus inhibited atherosclerosis in apoE-/- mice.

Pharmacokinetics of homoplantaginin in rats following intravenous, peritoneal injection and oral administration

The purpose of the present paper was to study the pharmacokinetic characteristics of homoplantaginin, a major active ingredient of Salvia plebeia R.Br. In this study, the effective partition coefficient, in situ absorption in rat intestinal segments and in vitro biotransformation of homoplantaginin by rat intestinal bacteria were determined. In addition, homoplantaginin was administered to rats by intravenous, peritoneal injection and oral administration. The concentrations of homoplantaginin and hispidulin, a metabolite of homoplantaginin, were determined by a validated highperformance liquid chromatographic (HPLC) assay. After intravenous, peritoneal injection, the concentration of hispidulin could not be determined. In contrast, after oral administration, hispidulin and homoplantaginin were simultaneous quantified, homoplantaginin was rapidly absorbed (Tmax=16.00±8.94min), reaching a mean Cmax between 0.77 and 1.27nmol/mL. The absolute oral bioavailability was calculated to be only 0.75%, and the area under curve (AUC) of hispidulin was about 5.4 times than that of homoplantaginin. The poor oral bioavailability may be attributed to the biotransformation of homoplantaginin by rat intestinal bacteria.

Characterization of natural aryl hydrocarbon receptor agonists from cassia seed and rosemary

Many recent studies have suggested that activation of the aryl hydrocarbon receptor (AhR) reduces immune responses, thus suppressing allergies and autoimmune diseases. In our continuing study on natural AhR agonists in foods, we examined the influence of 37 health food materials on the AhR using a reporter gene assay, and found that aqueous ethanol extracts of cassia seed and rosemary had particularly high AhR activity. To characterize the AhR-activating substances in these samples, the chemical constituents of the respective extracts were identified. From an active ethyl acetate fraction of the cassia seed extract, eight aromatic compounds were isolated. Among these compounds, aurantio-obtusin, an anthraquinone, elicited marked AhR activation. Chromatographic separation of an active ethyl acetate fraction of the rosemary extract gave nine compounds. Among these compounds, cirsimaritin induced AhR activity at 10-10? μM, and nepitrin and homoplantagenin, which are flavone glucosides, showed marked AhR activation at 10-10? μM.