Production of Bioactive Substances to Alleviates Hangover and Ethanol-Induced Liver Damage through Fermentation of Oenanthe javanica Using Lactiplantibacillus plantarum.

The purpose of this study is to evaluate the effect of the bioconversion products of Oenanthe javanica extract fermented by Lactiplantibacillus plantarum (OEFL) on relieving hangovers and improving liver function. In addition, the bioactive substance of the OEFL, which alleviates hangover and ethanol-induced liver damage, was identified and its bioactive property was verified through in vivo experiments. In major substances analysis using high-performance liquid chromatography, OEFL produced 9.5-fold higher p-coumaric acid than the O. Javanica extract (OE). In addition, considering that quinic acid, which is not present in the OE, was produced in the OEFL it was confirmed that chlorogenic acid was decomposed into quinic acid by bioconversion. In the in vivo experiment using Sprague-Dawley rats, the OEFL and p-coumaric acid diets reduced blood ethanol, acetaldehyde, GPT, and ALP concentrations, increasing blood albumin concentrations compared to ethanol-administered groups, demonstrating that OEFL and p-coumaric acid, the main substance in the OEFL, improved ethanol-induced liver damage. Furthermore, the OEFL and its main bioactive substance, p-coumaric acid, alleviated liver fibrosis by downregulating TGF-ß, SMAD-2, SMAD-4, α-SMA, and upregulating MMP-1. Therefore, OEFL is expected to be used as a functional food or pharmaceutical material as it has been confirmed to effectively relieve hangovers, prevent liver damage, and delay liver fibrosis in ethanol-induced liver damages.

Hyaluronidase and degranulation inhibitors from the edible roots of Oenanthe javanica including seric acids F and G that were obtained by heating.

Oenanthe javanica is a vegetable grown in East Asia and Australia in which the roots and aerial parts are boiled together to make certain traditional dishes. Nineteen compounds (1-19) were isolated from O. javanica roots and the chemical structures of 2 new norlignans were determined. The inhibitory effects of the compounds on hyaluronidase and degranulation in RBL-2H3 cells were evaluated to determine antiallergic and antiinflammation activities. Saponins (2-4) and the new norlignan seric acid G (12) were among the active compounds identified. Seric acid G (12), a methoxy derivative of seric acid F (11), was obtained as an interconverting mixture of 3:1 trans-cis isomers. Seric acids F and G (11, 12) were derived from seric acids C (10) and E, respectively, by decarboxylation and dehydration reactions that occurred during heating. It was confirmed by HPLC analysis that all eleven of the O. javanica cultivars contained seric acid C (10).

Effect of the pyrolysis duration and the addition of zeolite powder on the leaching toxicity of copper and cadmium in biochar produced from four different aquatic plants.

The study aimed to determine the biochar yield of four aquatic plants, the leaching toxicity of copper (Cu) and cadmium (Cd) in the biochar, and the stabilization characteristics of the biochar produced under different pyrolysis conditions (at 350 °C for 1, 2, and 3 h and absence/presence of zeolite powder). The results showed that different plant species required a different pyrolysis duration and the presence or absence of zeolite powder. The stabilization of Cu and Cd was significantly affected by the pyrolysis duration and the external materials for different plant species and different types of admixtures. Pyrolysis temperatures over 350 °C for 1 h without zeolite powder generated stable Cu and Cd in goldfish algae (Ceratophyllum demersum L.), foxtail algae (Myriophyllum verticillatum L.), and penny grass (Hydrocotyle vulgaris). Pyrolysis temperatures over 350 °C for 1 h with zeolite powder made Cu and Cd stable in water celery (Oenanthe javanica (Bl.) DC). The addition of zeolite powder during pyrolysis was possible due to the weight reduction efficiency in plants with Cu and Cd. Furthermore, the surface of the biochar with the zeolite powder showed honeycombs and a spongy porous structure. The duration of the pyrolysis had little effect on the honeycomb pore structure.

Inhibitory Effects of Phenylpropanoid Derivatives from Oenanthe javanica on Antigen-Stimulated Degranulation in RBL-2H3 Cells.

Two diacyldaucic acids (1 and 2), an α,ß-unsaturated γ-lactone-type lignan (3) and its derivatives (4-6), and 12 known compounds were isolated from a traditional East Asian vegetable, Oenanthe javanica. The absolute configuration of 1 was validated by obtaining (+)-osbeckic acid through acid hydrolysis. The absolute configurations of 3-5 were determined by comparing their experimental and computed ECD data. The conclusion was supported by applying the phenylglycine methyl ester method to 3. Compound 6 was obtained as an interconverting mixture of isomers in a 3:1 trans- cis ratio. Several water-soluble components (1, 3, and 6) showed concentration-dependent inhibitory effects on antigen-stimulated degranulation in RBL-2H3 cells without producing any direct cytotoxicity against RBL-2H3 or HeLa cells.

Oenanthe Javanica Extract Protects Mouse Skin from UVB Radiation via Attenuating Collagen Disruption and Inflammation.

In recent years, the use of botanical agents to prevent skin damage from solar ultraviolet (UV) irradiation has received considerable attention. Oenanthe javanica is known to exert anti-inflammatory and antioxidant activities. This study investigated photoprotective properties of an Oenanthe javanica extract (OJE) against UVB-induced skin damage in ICR mice. The extent of skin damage was evaluated in three groups: control mice with no UVB, UVB-exposed mice treated with vehicle (saline), and UVB-exposed mice treated with 1% extract. Photoprotective properties were assessed in the dorsal skin using hematoxylin and eosin staining, Masson trichrome staining, immunohistochemical staining, quantitative real-time polymerase chain reaction, and western blotting to analyze the epidermal thickness, collagen expression, and mRNA and protein levels of type I collagen, type III collagen, and interstitial collagenases, including matrix metalloproteinase (MMP)-1 and MMP-3. In addition, tumor necrosis factor (TNF)-α and cyclooxygenase (COX)-2 protein levels were also assessed. In the UVB-exposed mice treated with extract, UV-induced epidermal damage was significantly ameliorated. In this group, productions of collagen types I and III were increased, and expressions of MMP-1 and MMP-3 were decreased. In addition, TNF-α and COX-2 expressions were reduced. Based on these findings, we conclude that OJE displays photoprotective effects against UVB-induced collagen disruption and inflammation and suggest that Oenanthe javanica can be used as a natural product for the treatment of photodamaged skin.

Biphenyl Derivatives from the Aerial Parts of Oenanthe javanica and Their COX-2 Inhibitory Activities.

Four new biphenyl derivatives (1-4), along with six known biphenyl derivatives (5-10) were isolated and elucidated by their detailed analyses of spectroscopic data and references from the aerial parts of Oenanthe javanica for the first time. Compounds (1-10) were assayed for their activities about the inhibition of COX-2 enzyme in vitro for the first time. Compounds 1, 2, 4, and 6 showed inhibitory activities against COX-2 with IC50 values ranging from 22.18±0.29 to 108.54±0.42 µm.

Isorhamnetin and hyperoside derived from water dropwort inhibits inflammasome activation.

BACKGROUND: Water dropwort (Oenanthe javanica), an umbelliferous plant, has been reported as hypolipidemic, antiplatelet, antitumor, or immune-stimulating agents and it has been suggested to cure cardiovascular disease and cancer. PURPOSE: Present study aimed to evaluate the effect of the extracts of water dropwort (EWD) and its pharmacological molecules, hyperoside and isorhamnetin, on inflammatory response, especially inflammasome activation. STUDY DESIGN/METHODS: The anti-inflammasome properties of EWD, isorhamnetin, and hyperoside were elucidated by human and mouse macrophages. RESULTS: EWD attenuated secretion of interleukin (IL)-1ß and formation of Asc pyroptosome resulting from NLRP3, NLRC4, and AIM2 inflammasome activation without interruption of cytokine transcription. Isorhamnetin selectively inhibited NLRP3 and AIM2 inflammasome activation and down-regulated expression of pro-inflammatory cytokines. Hyperoside selectively interrupted NLRC4 and AIM2 inflammasome activation but did not alter cytokine expression. In addition, EWD, isorhamnetin, and hyperoside inhibited caspase-1. CONCLUSION: Isorhamnetin and hyperoside, a key molecule of water dropwort, have been suggested as candidates to attenuate inflammasome inhibition.

Heavy metals in sediments, soils, and aquatic plants from a secondary anabranch of the three gorges reservoir region, China.

We investigated the occurrence of cadmium (Cd), copper (Cu), chromium (Cr), nickel (Ni), lead (Pb), Znic (Zn), iron (Fe), manganese (Mn), and magnesium (Mg) in sediments, as well as in related soils and aquatic plants in the Liangtan River, a typical secondary anabranch of the Yangtze River in the Three Gorges Reservoir Region (TGRR) of China. We found that sediments accumulated more metals than soils and aquatic plants. Concentrations of the nine metals in sediments and soils followed the same sequence, while their concentrations in aquatic plants followed a different sequence. Potential adverse effects of contaminated sediments on benthic fauna were evaluated, and the results showed that the toxic effect on benthic organisms followed the sequence Zn > Ni > Cr > Cu > Cd > Pb. The potential ecological risk index analysis indicated that Cd in sediments had considerable ecological risk, whereas Cr, Cu, Zn, Ni, and Pb had low ecological risk. The potential ecological risk index (RI) of the heavy metals in sediments of the Liangtan River was 174.9, indicating moderate ecological risk. The transfer factor trend of metals for aquatic plants showed that Cd and Ni had the most and least accumulation, respectively. For Cu, Cd, Mg, Pb, and Cr, a significant positive correlation of the metal concentrations was observed between sediments and soils, but no correlations (excluding Cr) were detected between sediments and aquatic plants. Our study indicated that anthropogenic input may be the primary source of metal contamination in the Liangtan River, and that Zn and Cd pollution in the Liangtan River should be further explored.

Identification and evaluation of antioxidants in Japanese parsley.

Two cultivars of Japanese parsley were harvested in different seasons; their antioxidant capacities were evaluated by oxygen radical absorbance capacity (ORAC) methods, and the contents of hydrophilic and lipophilic antioxidants were compared. Japanese parsley possessed potent antioxidant capacities both in hydrophilic and lipophilic extracts when evaluated by ORAC methods. LC/MS/MS analyses revealed that chlorogenic acid and four kinds of quercetin glycosides were major antioxidants in the hydrophilic extract. Lutein was the main contributor to the antioxidant capacity of the lipophilic extract. Antioxidant capacities of the hydrophilic extracts of both cultivars tended to be higher in winter because of the increase in the contents of chlorogenic acid and quercetin glycosides. An obvious trend in the lipophilic antioxidant capacities or lutein contents was not observed irrespective of the cultivar.

The protective effect of total phenolics from Oenanthe Javanica on acute liver failure induced by D-galactosamine.

ETHNOPHARMACOLOGY RELEVANCE: Water dropwort [Oenanthe javanica (O. javanica)] is an aquatic perennial herb cultivated in East Asian countries. It has been popularly used in traditional Chinese medicine which is beneficial for the treatment of many diseases, including jaundice and various types of chronic and acute hepatitis. In the present study, we investigated the hepatoprotective effect of total phenolics from O. javanica (TPOJ) against D-galactosamine (D-GalN) induced liver injury in mice. MATERIAL AND METHODS: The hepatoprotective activity of TPOJ (125, 250 and 500mg/kg) was investigated on D-GalN (800mg/kg)-induced liver damages in mice. Blood and liver were collected for biochemical and microscopic analysis. RT-PCR was used to determine the changes in hepatic nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression. Protein levels of iNOS, COX-2, superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) were determined by western blotting. RESULTS: In the animal studies, TPOJ could improve the survival of acute liver failure model significantly and prevente the D-GalN-induced elevation of the serum enzymatic markers and nonenzymatic markers levels significantly. Meanwhile, TPOJ-treatment decreased the malondialdehyde (MDA) level and elevated the content of glutathione (GSH) in the liver as compared to those in the D-GalN group. Hepatic activities and protein expressions of antioxidative enzymes, including SOD, GPx, and CAT were enhanced dose dependently with TPOJ. At the same time, application of TPOJ effectively suppressed the D-GalN-induced proinflammatory mRNA and protein expression of iNOS and COX-2. Subsequently, the serum levels of proinflammatory mediators, nitric oxide (NO) and prostaglandin E2 (PGE2) were reduced. Additionally, histological analyses also showed that TPOJ reduced the extent of liver lesions induced by D-GalN. CONCLUSION: Our investigation demonstrated the hepatoprotective activity of TPOJ and revealed that TPOJ attributed its significance in the traditional use for treating liver diseases.

Oenanthe Javanica Extract Protects Against Experimentally Induced Ischemic Neuronal Damage via its Antioxidant Effects.

BACKGROUND: Water dropwort (Oenanthe javanica) as a popular traditional medicine in Asia shows various biological properties including antioxidant activity. In this study, we firstly examined the neuroprotective effect of Oenanthe javanica extract (OJE) in the hippocampal cornus ammonis 1 region (CA1 region) of the gerbil subjected to transient cerebral ischemia. METHODS: Gerbils were established by the occlusion of common carotid arteries for 5 min. The neuroprotective effect of OJE was estimated by cresyl violet staining. In addition, 4 antioxidants (copper, zinc superoxide dismutase [SOD], manganese SOD, catalase, and glutathione peroxidase) immunoreactivities were investigated by immunohistochemistry. RESULTS: Pyramidal neurons in the CA1 region showed neuronal death at 5 days postischemia; at this point in time, all antioxidants immunoreactivities disappeared in CA1 pyramidal neurons and showed in many nonpyramidal cells. Treatment with 200 mg/kg, not 100 mg/kg, OJE protected CA1 pyramidal neurons from ischemic damage. In addition, 200 mg/kg OJE treatment increased or maintained antioxidants immunoreactivities. Especially, among the antioxidants, glutathione peroxidase immunoreactivity was effectively increased in the CA1 pyramidal neurons of the OJE-treated sham-operated and ischemia-operated groups. CONCLUSION: Our present results indicate that treatment with OJE can protect neurons from transient ischemic damage and that the neuroprotective effect may be closely associated with increased or maintained intracellular antioxidant enzymes by OJE.

Effect of Oenanthe Javanica Extract on Antioxidant Enzyme in the Rat Liver.

BACKGROUND: Oenanthe javanica (O. javanica) has been known to have high antioxidant properties via scavenging reactive oxygen species. We examined the effect of O. javanica extract (OJE) on antioxidant enzymes in the rat liver. METHODS: We examined the effect of the OJE on copper, zinc-superoxide dismutase (SOD1), manganese superoxide dismutase (SOD2), catalase (CAT), and glutathione peroxidase (GPx) in the rat liver using immunohistochemistry and western blot analysis. Sprague-Dawley rats were randomly assigned to three groups; (1) normal diet fed group (normal-group), (2) diet containing ascorbic acid (AA)-fed group (AA-group) as a positive control, (3) diet containing OJE-fed group (OJE-group). RESULTS: In this study, no histopathological finding in the rat liver was found in all the experimental groups. Numbers of SOD1, SOD2, CAT, and GPx immunoreactive cells and their protein levels were significantly increased in the AA-fed group compared with those in the normal-group. On the other hand, in the OJE-group, numbers of SOD1, SOD2, CAT, and GPx immunoreactive cells in the liver were significantly increased by about 190%, 478%, 685%, and 346%, respectively, compared with those in the AA-group. In addition, protein levels of SOD1, SOD2, CAT, and GPx in the OJE-group were also significantly much higher than those in the AA-group. CONCLUSION: OJE significantly increased expressions of SOD1 and SOD2, CAT, and GPx in the liver cells of the rat, and these suggests that significant enhancements of endogenous enzymatic antioxidants by OJE might be a legitimate strategy for decreasing oxidative stresses in the liver.

Oenanthe javanica extract increases immunoreactivities of antioxidant enzymes in the rat kidney.

BACKGROUND: Oenanthe javanica is an aquatic perennial herb originated from East Asia. Nowadays, the effects of Oenanthe javanica have been proven in various disease models. Studies regarding the antioxidant effect of Oenanthe javanica in the kidney are still unclear. METHODS: This study was therefore performed to investigate the effect of the Oenanthe javanica extract (OJE) in the rat kidney using immunohistochemistry for antioxidant enzymes, copper, zinc-superoxide dismutase (SOD1), manganese superoxide dismutase (SOD2), catalase (CAT) and glutathione peroxidase (GPx). Sprague-Dawley rats were randomly assigned to three groups: (1) normal diet fed-group (normal-group), (2) diet containing ascorbic acid (AA)-fed group (AA-group) as a positive control, (3) diet containing OJE-fed group (OJE-group). AA and OJE were supplied during 28 days. RESULTS: The side-effects were not observed in all the groups. Immunoreactivities of SOD1, SOD2, CAT and GPx were easily detected in the distal tubules of the kidney, and their immunoreactivities in the AA-and OJE-groups were increased to about 1.4-1.5 times and 2 times, respectively, compared with those in the normal-group. CONCLUSION: OJE significantly increased expressions of SOD1 & 2, CAT and GPx immunoreactivities in the distal tubules of the rat kidney, and this finding suggests that significant enhancements of endogenous enzymatic antioxidants by OJE treatment may be a legitimate strategy for decreasing oxidative stresses in the kidney.

Hepatoprotective effects of fermented field water-dropwort (Oenanthe javanica) extract and its major constituents.

Dropwort (Oenanthe javanica) has been used for many years for the treatment of inflammatory conditions, including hepatitis. We investigated the protective effects of fermented field water-dropwort extract (FDE) on tert-butyl hydroperoxide (t-BHP)-induced hepatotoxicity in HepG2 cells and carbon tetrachloride (CCl4)-induced liver damage in rats. Pretreatment with FDE prior to the t-BHP treatment of HepG2 cells inhibited cell death and lactate dehydrogenase (LDH) leakage in a dose-dependent manner. In addition FDE significantly prevented the increase of hepatic enzyme markers (ALT, AST) in vivo. Moreover, FDE administration for 7 days significantly affected CYP2E1, CYP4A2, and PPARγ gene expressions. CYP2E1 and CYP4A2 gene expression in the liver, increased 2 and 22-fold by CCl4 administration, respectively, was attenuated to normal levels by pretreatment with FDE. PPARγ gene expression, completely blocked by CCl4 treatment, was increased by FDE pretreatment compared to normal control group. Histopathological examination of the livers also revealed that FDE reduced the incidence of liver lesions. Caffeic acid and chlorogenic acid were identified as major constituents of FDE. These results demonstrate the protective effects of FDE against hepatocytotoxicity induced by CCl4 and t-BHP in rats and HepG2 cells, thus indicating the potential of FDE as a therapeutic for acute liver diseases.

Antifungal, antioxidant and anti-inflammatory activities of Oenanthe crocata L. essential oil.

The present study reports the chemical composition, antifungal, antioxidant and anti-inflammatory properties as well as the cytotoxicity of Oenanthe crocata essential oil and one of its main compounds. The essential oil was obtained from the aerial parts of the plant by hydrodistillation and analysed by GC and GC/MS. The oil was predominantly composed of monoterpene hydrocarbons (85.8%), being the main compounds trans-ß-ocimene (31.3%), sabinene (29.0%) and cis-ß-ocimene (12.3%). For the antifungal activity, the minimal inhibitory and minimal lethal concentrations (MICs and MLCs) were determined. The oil was particularly active against dermatophytes and Cryptococcus neoformans, with MIC values ranging from 0.08 to 0.16 µL/mL. Regarding the anti-inflammatory activity, both the oil and sabinene demonstrated strong anti-inflammatory activity through nitric oxide (NO) production inhibition in lipopolysaccharide (LPS) plus interferon gamma (IFN-γ)-triggered macrophages. Furthermore, the essential oil showed a potent NO scavenging effect and inhibited inducible NO synthase expression. Interestingly, and although we detected a cytotoxic effect in macrophages and keratinocytes for the highest concentrations tested of the oil and sabinene, we also disclosed bioactive and safe concentrations to be further explored for therapeutic proposes. Taking together, these results support the use of the oil and sabinene for the management of dermatophytosis and/or inflammatory-related diseases.

Selective inhibition of the cytochrome P450 isoform by hyperoside and its potent inhibition of CYP2D6.

Hyperoside, quercetin-3-O-galactoside, is a flavonoid isolated from Oenanthe javanica. In the present study, we investigated potential herb-drug inhibitory effects of hyperoside on nine cytochrome P450 (CYP) isoforms in pooled human liver microsomes (HLMs) and human recombinant cDNA expressed CYP using a cocktail probe assay. Hyperoside strongly inhibited CYP2D6-catalyzed dextromethorphan O-demethylation, with IC50 values of 1.2 and 0.81 µM after 0 and 15 min of preincubation, and a Ki value of 2.01 µM in HLMs, respectively. Hyperoside strongly decreased CYP2D6 activity dose-, but not time-, dependently in HLMs. In addition, the Lineweaver-Burk and Secondary plots for the inhibition of CYP2D6 in HLMs fitted a competitive inhibition mode. Furthermore, hyperoside decreased CYP2D6-catalyzed dextromethorphan O-demethylation activity of human recombinant cDNA-expressed CYP2D6, with an IC50 value of 3.87 µM. However, other CYPs were not inhibited significantly by hyperoside. In conclusion, our data demonstrate that hyperoside is a potent selective CYP2D6 inhibitor in HLMs, and suggest that hyperoside might cause herb-drug interactions when co-administrated with CYP2D substrates.

Inhibition of glycogen synthase kinase-3ß by falcarindiol isolated from Japanese Parsley (Oenanthe javanica).

A new biological activity of falcarindiol isolated from Japanese parsley (Oenanthe javanica) using the mutant yeast YNS17 strain (zds1Δ erg3Δ pdr1Δ pdr3Δ) was discovered as an inhibitor of glycogen synthase kinase-3ß (GSK-3ß). Falcarindiol inhibited GSK-3ß in an ATP noncompetitive manner with a Ki value of 86.9 µM using a human enzyme and luminescent kinase assay platform. Falcarindiol also both suppressed gene expression of glucose-6-phosphatase (G6Pase) in rat hepatoma H4IIE cells and protected mouse neuroblastoma HT22 cells from glutamate-induced oxidative cell death at 10 µM. During an oral glucose tolerance test (OGTT), the blood glucose level was significantly decreased in the rats treated with oral administration of O. javanica extract containing falcarindiol (15 mg/kg). These findings indicate that Japanese parsley could be a useful food ingredient against type-2 diabetes and Alzheimer's disease.

Down-regulation of endothelial protein C receptor shedding by persicarin and isorhamnetin-3-O-galactoside.

Increasing evidence has shown that beyond its role in coagulation, endothelial protein C receptor (EPCR) plays an important role in the cytoprotective pathway. Previous reports have shown that EPCR can be shed from the cell surface, and that this is mediated by tumor necrosis factor-α converting enzyme (TACE) and that sEPCR levels are increased in patients with systemic inflammatory diseases. Persicarin and isorhamnetin-3-O-galactoside (I3G) are active compounds from Oenanthe javanica, which has been widely studied for its neuroprotective, antioxidant, and barrier protective activities. However, little is known of the effects of persicarin on EPCR shedding. Here, we investigated this issue by monitoring the effects of persicarin and I3G on phorbol-12-myristate 13-acetate (PMA) and on cecal ligation and puncture (CLP)-mediated EPCR shedding and underlying mechanisms. According to the results, persicarin and I3G induced potent inhibition of PMA and CLP-induced EPCR shedding by suppressing expression of TACE. In addition, persicarin and I3G reduced PMA-stimulated phosphorylation of p38MAPK, extracellular regulated kinases (ERK) 1/2, and c-Jun N-terminal kinase (JNK). Given these results, persicarin and I3G could be used as a candidate therapeutic for treatment of severe vascular inflammatory diseases.

O-Methylated flavonol isorhamnetin prevents acute inflammation through blocking of NF-κB activation.

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-1ß and IL-6 expression, representative NF-κB target genes, were almost completely prohibited by isorhamnetin. Furthermore, isorhamnetin inhibited LPS-induced JNK and AKT/IKKα/ß phosphorylation. Our results suggest that isorhamnetin inhibited JNK, and AKT/IKKα/ß activation, leading to NF-κB inactivation, which might contribute to the inhibition of the acute inflammatory response.

Anticoagulant activities of persicarin and isorhamnetin.

Persicarin and isorhamnetin were isolated from Oenanthe javanica and their anticoagulant activities were examined by monitoring activated partial thromboplastin time (aPTT), prothrombin time (PT), and the activities of cell-based thrombin and activated factor X (FXa). In addition, the effects of persicarin and isorhamnetin on the expressions of plasminogen activator inhibitor type 1 (PAI-1) and tissue-type plasminogen activator (t-PA) were tested in tumor necrosis factor-α (TNF-α) activated human umbilical vein endothelial cells (HUVECs). The data obtained showed that persicarin and isorhamnetin both prolonged aPTT and PT significantly and inhibited the activities of thrombin and FXa. In addition, they both inhibited the generations of thrombin and FXa in HUVECs. In accordance with these anticoagulant activities, persicarin and isorhamnetin prolonged in vivo bleeding time and inhibited TNF-α induced PAI-1 production. Furthermore, PAI-1/t-PA ratio was significantly decreased by persicarin. Interestingly, the anticoagulant and profibrinolytic effects of persicarin were greater than those of isorhamnetin, which suggest that the sulfonate group of persicarin positively regulates its anticoagulatory function. Accordingly, our results suggest that persicarin and isorhamnetin possess antithrombotic activities and that they could provide bases for the development of new anticoagulant agents.