3-methylquercetin and Edema

Previously, we reported that isorhamnentin, a 3'-O-methylated metabolite of quercetin, reduced inducible nitric oxide synthase (iNOS) expression and NO production. The present study further investigated the underlying mechanism of anti-inflammatory and antioxidant effects of isorhamnentin. Administration of isorhamnetin decreased the number of cyclooxygenase-2 (COX-2) positive cells in rats with carrageenan-induced paw edema. Isorhamnetin also suppressed lipopolysaccharide (LPS)-induced expression of COX-2 in cells. It is well known that LPS-induced reactive oxygen species (ROS) production leads to COX-2 induction. Isorhamnetin decreased LPS-induced ROS production and apoptosis. In addition, the basal expression of heme oxygenase-1 (HO-1) was increased by isorhamnetin treatment in agreement with the increase in nuclear translocation of NF-E2-related factor-2 (Nrf2), an essential transcription factor for the regulation of HO-1 expression. Moreover, pretreatment of tin protoporphyrin IX (SnPP), a chemical inhibitor of HO-1, reversed the ability of isothamnetin to inhibit COX-2 expression. These results demonstrate that induction of HO-1 by isorhamnetin leads to a reduction in ROS production and its antioxidant property might contribute to the inhibition of COX-2 expression in response to inflammation.

Topics: Active Transport, Cell Nucleus; Animals; Anti-Inflammatory Agents; Antioxidants; Apoptosis; Cell Line; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Edema; Heme Oxygenase (Decyclizing); Inflammation; L-Lactate Dehydrogenase; Lipopolysaccharides; Macrophages; Metalloporphyrins; Mice; NF-E2-Related Factor 2; Nitric Oxide; Nitric Oxide Synthase Type II; Protoporphyrins; Quercetin; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species

Here, we isolated isorhamnetin, a natural 3'-O-methylated flavonoid, from water dropwort (Oenanthe javanica, Umbelliferae) and investigated its ability to protect against acute inflammation in vivo and in vitro. To induce paw swelling, the hind paw of each rat was injected with a carrageenan 1h after vehicle or isorhamnetin treatment. In vitro effect and mechanism studies were performed in lipopolysaccharide (LPS)-activated macrophages. Administration of isorhamnetin markedly inhibited the swelling volume and the thickness of hind paws. Moreover, isorhamnetin significantly reduced inflammatory cell infiltration and pro-inflammatory gene expression in rats. Isorhamnetin pretreatment inhibited inducible nitric oxide synthase (iNOS) expression and NO release in LPS-stimulated cells. Activation of nuclear factor-kappa B (NF-κB) and activating protein-1 (AP-1) is the key step in the iNOS gene induction. Isorhamnetin specifically inhibited NF-κB luciferase activity, but not AP-1. Pretreatment with isorhamnetin suppressed NF-κB nuclear translocation in accordance with decreased phosphorylation and degradation of inhibitory-κB. Consistently, TNF-α, IL-1β and IL-6 expression, representative NF-κB target genes, were almost completely prohibited by isorhamnetin. Furthermore, isorhamnetin inhibited LPS-induced JNK and AKT/IKKα/β phosphorylation. Our results suggest that isorhamnetin inhibited JNK, and AKT/IKKα/β activation, leading to NF-κB inactivation, which might contribute to the inhibition of the acute inflammatory response.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cell Line, Transformed; Cell Nucleus; Disease Models, Animal; Edema; Ethnopharmacology; Lymphocyte Activation; Macrophage Activation; Macrophages; Male; Medicine, East Asian Traditional; Mice; NF-kappa B; Oenanthe; Protein Transport; Quercetin; Random Allocation; Rats; Rats, Sprague-Dawley; Republic of Korea; Skin

Extracts obtained from the leaves and branches of various Cistus species have been used worldwide as folk remedy for the treatment of various inflammatory ailments including rheumatism and renal inflammations. Effects of the extracts and fractions from the leaves with non-woody branches of Cistus laurifolius L. (Cistaceae) were studied using two in vivo models of inflammation in mice. Model one was based on observed potent inhibitory activity against carrageenan-induced hind paw oedema and the second model used was acetic acid-induced, increased vascular permeability model. Through bioassay-guided fractionation and isolation procedures three flavonoids; 3-O-methylquercetin (1), 3,7-O-dimethylquercetin (2) and 3,7-O-dimethylkaempferol (3) were isolated as the main active ingredients from the ethanol extract. Later on, these flavonoids were shown to possess potent antinociceptive activity, which was assessed through inhibition of p-benzoquinone-induced writhing reflex. Results of the present study have clearly supported the utilization of Cistus laurifolius in Turkish traditional medicine. Subsequently, three flavonoids were shown to have strong antinociceptive and anti-inflammatory activities, per os without inducing any apparent acute toxicity as well as gastric damage.

Topics: Acetic Acid; Analgesics; Animals; Anti-Inflammatory Agents; Aspirin; Biological Assay; Carrageenan; Chemical Fractionation; Cistus; Edema; Flavonoids; Hindlimb; Indomethacin; Injections; Kaempferols; Male; Mice; Molecular Structure; Plant Extracts; Plant Leaves; Quercetin; Turkey

The aqueous and ethanol extracts from the leaves of Gochnatia polymorpha and further fractions obtained from the latter extract using solvents with increasing polarity, including its aqueous residue and the amino acid, 4-hydroxy-N-methyl-proline were investigated by carrageenin-induced pedal oedema formation. It was shown that the aqueous and ethanol extracts and the ethyl acetate fraction demonstrated significant antiinflammatory activity. The chemical investigation of the latter fraction revealed the presence of caffeic acid, chlorogenic acid, 3-0-methylquercetin, hyperosid and rutin. The amino acid 4-hydroxy-N-methyl-proline, a nonprotein amino acid that has not been reported before in the Asteraceae was isolated as a major compound and identified by spectroscopic methods.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Antioxidants; Antiviral Agents; Brazil; Caffeic Acids; Chlorogenic Acid; Chromatography, Gel; Chromatography, Thin Layer; Edema; Flavonols; Plant Extracts; Plant Leaves; Plants, Medicinal; Proline; Quercetin; Rats; Rutin