Anti-inflammatory and anticholinesterase activity of six flavonoids isolated from Polygonum and Dorstenia species.

This study was aimed at investigating the anti-inflammatory and anticholinesterase activity of six naturally occurring flavonoids: (-) pinostrobin (1), 2',4'-dihydroxy-3',6'-dimethoxychalcone (2), 6-8-diprenyleriodictyol (3), isobavachalcone (4), 4-hydroxylonchocarpin (5) and 6-prenylapigenin (6). These compounds were isolated from Dorstenia and Polygonum species used traditionally to treat pain. The anti-inflammatory activity was determined by using the Griess assay and the 15-lipoxygenase inhibitory activity was determined with the ferrous oxidation-xylenol orange assay. Acetylcholinesterase inhibition was determined by the Ellman's method. At the lowest concentration tested (3.12 µg/ml), compounds 2, 3 and 4 had significant NO inhibitory activity with 90.71, 84.65 and 79.57 % inhibition respectively compared to the positive control quercetin (67.93 %). At this concentration there was no significant cytotoxicity against macrophages with 91.67, 72.86 and 70.86 % cell viability respectively, compared to 73.1 % for quercetin. Compound 4 had the most potent lipoxygenase inhibitory activity (IC50 of 25.92 µg/ml). With the exception of (-) pinostrobin (1), all the flavonoids had selective anticholinesterase activity with IC50 values ranging between 5.93 and 8.76 µg/ml compared to the IC50 4.94 µg/ml of eserine the positive control. These results indicate that the studied flavonoids especially isobavachalcone are potential anti-inflammatory natural products that may have the potential to be developed as therapeutic agents against inflammatory conditions and even Alzheimer's disease.

Diprenylated chalcones and other constituents from the twigs of Dorstenia barteri var. subtriangularis.

The twigs of Dorstenia barteri var. subtriangularis yielded three diprenylated chalcones: (-)-3-(3,3-dimethylallyl)-5'-(2-hydroxy-3-methylbut-3-enyl)-4,2',4'-trihydroxychalcone, (+)-3-(3,3-dimethylallyl)-4',5'-[2'''-(1-hydroxy-1-methylethyl)-dihydrofurano]-4,2'-dihydroxychalcone and 3,4-(6",6"-dimethyldihydropyrano)-4',5'-[2''',-(1-hydroxy-1-methylethyl)-dihydrofurano]-2'-hydroxychalcone for which the names bartericins A, B and C, respectively, are proposed. Stipulin, beta-sitosterol and its 3-beta-D-glucopyranosyl derivative were also isolated. The structures of these secondary metabolites were determined on the basis of spectroscopic analysis, especially, NMR spectra in conjunction with 2D experiments, COSY, HMQC and HMBC. The structural relationship of bartericins B and C was further established by the chemical cyclization of one to the other.

Antimicrobial action mechanism of flavonoids from Dorstenia species.

Naturally occurring flavonoids have been reported to possess antimicrobial activity against a wide range of pathogens. However, the antimicrobial action mechanism of these compounds has not yet been elucidated. This study investigated the mechanism underlying the antibacterial activity of four flavonoids: 6,8-diprenyleriodictyol (1), isobavachalcone (2), 6-prenylapigenin (3) and 4-hydroxylonchocarpin (4). In addition, the toxicity of these compounds was evaluated. Determination of the minimum inhibitory concentrations (MICs) was performed by microbroth dilution method. Radiolabeled thymidine, uridine, and methionine were used to evaluate the effect of the compounds on the biosynthesis of DNA, RNA, and proteins while the sensitive cyanine dye DiS-C3-(5) (3,3'-dipropylthiadicarbocyanine iodide) was used for the effect on membrane potential. Bactericidal/bacteriolysis activities were performed by time-kill kinetic method. In the toxicity study, the numbers of survivors was recorded after injection of compounds into the hemolymph of silkworm larvae. Compounds showed significant antibacterial activity against Staphylococcus aureus including methicillin-resistant S. aureus (MRSA) strains with MICs values ranged between 0.5-128 µg/mL. Depolarization of membrane and inhibition of DNA, RNA, and proteins synthesis were observed in S. aureus when treated with those flavonoids. At 5-fold minimum inhibitory concentration, compounds reduced rapidly the bacterial cell density and caused lysis of S. aureus. Compounds 1, 2, and 4 did not show obvious toxic effects in silkworm larvae up to 625 µg/g of body weight. Flavonoids from Dorstenia species, 6,8-diprenyleriodictyol, isobavachalcone, and 4-hydroxylonchocarpin are bactericidal compounds. They cause damage of cell membrane, leading to the inhibition of macromolecular synthesis. Taking into account the in vivo safety and their significant antimicrobial potency, these flavonoids are promising leads for further drug development.