ABSTRACT
Paeonol, quercetin, -sitosterol, and gallic acid extracted from MoutanCortex had been reported to possess anti-oxidative, anti-inflammatory, and antitumoractivities. This work aimed to illustrate the potential anti-oxidative mechanismof monomers in human liver hepatocellular carcinoma (HepG2) cells-induced byhydrogen peroxide (H2O2) and to evaluate whether the hepatoprotective effect ofmonomers was independence or synergy in mice stimulated by carbon tetrachloride(CCl4). Monomers protected against oxidative stress in HepG2 cells in a doseresponsemanner by inhibiting the generation of reactive oxygen species, increasingtotal antioxidant capacity, catalase and superoxide dismutase (SOD) activities, andactivating the antioxidative pathway of nuclear factor E2-related factor 2/KelchlikeECH-associated protein 1 (Nrf2/Keap1) signaling pathway. We found that thein vitro antioxidant capacities of paeonol and quercetin were better than those of-sitosterol and gallic acid. Furthermore, paeonol apparently diminished the levelsof alanine transaminase and aspartate aminotransferase, augmented the contentsof glutathione and SOD, promoted the expressions of Nrf2 and heme oxygenase-1proteins in mice stimulated by CCl4. In HepG2 cells, paeonol, quercetin, -sitosterol,and gallic acid play a defensive role against H2O2-induced oxidative stress throughactivating Nrf2/Keap1 pathway, indicating that these monomers have anti-oxidativeproperties. Totally, paeonol and quercetin exerted anti-oxidative and hepatoprotectiveeffects, which is independent rather than synergy.
ABSTRACT
Paeonol, quercetin, -sitosterol, and gallic acid extracted from MoutanCortex had been reported to possess anti-oxidative, anti-inflammatory, and antitumoractivities. This work aimed to illustrate the potential anti-oxidative mechanismof monomers in human liver hepatocellular carcinoma (HepG2) cells-induced byhydrogen peroxide (H2O2) and to evaluate whether the hepatoprotective effect ofmonomers was independence or synergy in mice stimulated by carbon tetrachloride(CCl4). Monomers protected against oxidative stress in HepG2 cells in a doseresponsemanner by inhibiting the generation of reactive oxygen species, increasingtotal antioxidant capacity, catalase and superoxide dismutase (SOD) activities, andactivating the antioxidative pathway of nuclear factor E2-related factor 2/KelchlikeECH-associated protein 1 (Nrf2/Keap1) signaling pathway. We found that thein vitro antioxidant capacities of paeonol and quercetin were better than those of-sitosterol and gallic acid. Furthermore, paeonol apparently diminished the levelsof alanine transaminase and aspartate aminotransferase, augmented the contentsof glutathione and SOD, promoted the expressions of Nrf2 and heme oxygenase-1proteins in mice stimulated by CCl4. In HepG2 cells, paeonol, quercetin, -sitosterol,and gallic acid play a defensive role against H2O2-induced oxidative stress throughactivating Nrf2/Keap1 pathway, indicating that these monomers have anti-oxidativeproperties. Totally, paeonol and quercetin exerted anti-oxidative and hepatoprotectiveeffects, which is independent rather than synergy.
ABSTRACT
OBJECTIVE:To study the interaction mechanism between flavonoids and human serum albumin (HSA),and to compare the effects of different B-ring substitutions(hydroxyl,methoxyl group)of flavonoids on macromolecular receptor. METH-ODS:The interaction regularity between three flavonoids with different B-ring substitutions(quercetin,hesperetin,methyl hespere-tin) and HSA was studied with fluorescence spectroscopy,the fluorescence quenching types between 3 flavonoids and HSA were determined and analyzed,and the velated binding constant,binding site and thermodynamic parameters were calculated. RE-SULTS:The quenching constants (Ksv) and binding constants (KA) were decreased with the increase of temperatures. The number of binding site(n)was approximately equal to one,and the thermodynamic parameters ΔH0,the binding interaction of these compounds with macromolecules was influenced because of the difference of the B-ring substituents. CONCLUSIONS:The quenching mechanism between three flavonoids and HSA was static quenching;the number of binding site was one;the interaction force of the three compounds with HSA was mainly static electricity,and hydroxyl group in the B-ring was likely the major active group and exerted stronger binding force than methoxyl group to connect with macromolecules.
ABSTRACT
To investigate the relationship between the structures of methylhesperetin-7-alkyl ether analogues and their anti-inflammatory activities, nine new compounds, methyl-hesperetin (2), methylhesperetin-7-ethyl ether (3), 7-n-butyl ether (4), 7-n-hexyl ether (5), 7-n-octyl ether (6), 7-n-decyl ether (7), 7-n-dodecyl ether (8), 7-n-tetradecyl ether (9) and 7-n-hexadecyl ether (10), were synthesized with the lead compound of methylhesperidin (1). Their structures were confirmed by UV, 1H NMR, MS and HR-MS spectral data. The in vivo antiinflammatory activities of these compounds were tested on mouse paw edema induced by Freund's complete adjuvant (FCA) and mouse capillary permeability induced by acetic acid with po dose of 300 mg x kg(-1) x d(-1). The result indicated that the anti-inflammatory activities of the synthetic compounds increased firstly and then decreased with the elongating of the length of alkyl chain. After 25-day oral administration of compounds 6, 7 and 8, the inhibitory rates on mouse paw edema of adjuvant arthritis (AA) were 31.9%, 38.5%, 39.1%, respectively. They showed the concentrations of COX-2 in serum of AA mice respectively were 79.3, 75.4, 73.9 ng x L(-1) and the concentrations of PGE2 were in correspondence with 275.4, 258.9, 242.6 ng x L(-1). The inhibitory rates of compounds 6 and 7 on mouse capillary permeability induced by acetic acid were, respectively, 42.4% and 41.5% after 5-day oral administration. Compared with the lead compound of methylhesperidin, the anti-inflammatory activities of compounds 6, 7 and 8 were increased and showed an effective inhibition on the symptom of adjuvant arthritis and capillary permeability in mice.