[Show abstract][Hide abstract] ABSTRACT: Advanced glycation end-products (AGE) play a pivotal role in the development of diabetic complications by inducing inflammation. We previously reported that the fresh roots of Rehmannia glutinosa Libosch., which have been used for the treatment of diabetes in traditional Korean medicine, also have the potential to suppress AGE-mediated inflammatory response in THP-1 cells. In the present study, we isolated catalpol from R. glutinosa, and examined whether it has anti-inflammatory effects on AGE-stimulated THP-1 cells. Catalpol reduced the expression of pro-inflammatory mediates, such as monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), inducible NO synthase (iNOS), and receptor for AGE (RAGE). Promoter and electromobility shift assays showed that transcriptional activation of NF-κB was significantly reduced by catalpol treatment, while AP-1 was not. Catalpol also suppressed AGE-induced phosphorylation of mitogen activated protein (MAP) kinases, degradation of IκBα and the nuclear localization of NF-κB. Moreover, the production of intracellular reactive oxygen species (ROS) elicited by AGE was also suppressed by catalpol treatment, through dual action of reducing ROS itself and inhibiting NADPH oxidase activity. Our findings indicate that catalpol suppresses AGE-mediated inflammation by inhibiting ROS production and NF-κB activity. We suggest that catalpol, a major constituent of the fresh roots of R. glutinosa, contributes to the prevention of AGE-mediated diabetic complications.
[Show abstract][Hide abstract] ABSTRACT: Codium fragile (CF) is an edible green alga consumed as a traditional food source in Korea. In this study, the ethanol extract of CF was evaluated to determine if it has anti-inflammatory activity. Lipopolysaccharide (LPS), a toxin from bacteria, is a potent inducer of inflammatory cytokines, such as tumor necrosis factor (TNF)- and interleukin (IL)-6. Therefore, we studied whether CF extracts have an anti-inflammatory effect in LPS-induced murine macrophage cell lines (RAW 264.7). In the present study, IL-6 production was measured using an enzyme-linked immunosorbent assay (ELISA), prostaglandin () production was measured using the EIA kit, and cyclooxygenase (COX)-2 and mitogen-activated protein kinase (MAPK) activation were determined by Western blot analysis. IL-6 mRNA, COX-2 mRNA and iNOS mRNA expression were measured using reverse transcription-polymerase chain reaction (RT-PCR). The results indicated that CF extracts inhibit LPS-induced IL-6, NO and PGE2 production in a dose-dependent manner, as well as expression of iNOS and COX-2. CF extracts significantly inhibited LPS-induced c-Jun N-terminal kinase (JNK) 1/2 phosphorylation. Taken together, these findings may help elucidate the mechanism by which CF modulates RAW 264.7 cell activation under inflammatory conditions.
[Show abstract][Hide abstract] ABSTRACT: Resveratrol is a phytoalexin polyphenolic compound found in various plants, including grapes, berries, and peanuts. Recently, studies have documented various health benefits of resveratrol including cardiovascular and cancer-chemopreventive properties. The aim of the present study was to demonstrate the effects of resveratrol on the expression of pro-inflammatory cytokines, as well as to elucidate its mechanism of action in the human mast cell line (HMC-1). Cells were stimulated with phorbol 12-myristate 13-acetate (PMA) plus A23187 in the presence or absence of resveratrol. To study the possible effects of resveratrol, ELISA, RT-PCR, real-time RT-PCR, Western blot analysis, fluorescence, and luciferase activity assays were used in this study. Resveratrol significantly inhibited the PMA plus A23187-induction of inflammatory cytokines such as tumour necrosis factor (TNF)-alpha, interleukin (IL)-6 and IL-8. Moreover, resveratrol attenuated cyclooxygenase (COX)-2 expression and intracellular Ca2+ levels. In activated HMC-1 cells, phosphorylation of extra-signal response kinase (ERK) 1/2 decreased after treatment with resveratrol. Resveratrol inhibited PMA plus A23187-induced nuclear factor (NF)-kappaB activation, IkappaB degradation, and luciferase activity. Resveratrol suppressed the expression of TNF-alpha, IL-6, IL-8 and COX-2 through a decrease in the intracellular levels of Ca2+ and ERK 1/2, as well as activation of NF-kappaB. These results indicated that resveratrol exerted a regulatory effect on inflammatory reactions mediated by mast cells.
Full-text · Article · Jun 2009 · Pharmacological Research
[Show abstract][Hide abstract] ABSTRACT: In this study, we evaluated the effect of 5-hydroxytryptophan on anti-inflammatory and analgesic activity in RAW 264.7 cells. Cells were treated with different concentrations of 5-hydroxytryptophan for either 1 h or for 24 h. The anti-inflammatory effect was then analyzed by enzyme-linked immunosorbent assay (ELISA), Western blotting and reverse transcription polymerase chain reaction (RT-PCR). In addition, the analgesic activity was evaluated by measuring the acetic acid-induced writhing response. We found that 5-hydroxytryptophan significantly reduced the acetic acid-induced writhing response. Moreover we evaluated the effects of 5-hydroxytryptophan on the release of several inflammatory mediators including nitric oxide (NO) and interleukin-6 (IL-6). Our results demonstrated that 5-hydroxytryptophan inhibited the lipopolysaccharide (LPS)-induced expression of NO and IL-6. Furthermore, we found that 5-hydroxytryptophan played a role in LPS induced inducible nitric oxide synthase (iNOS), cyclo oxygenase-2 (COX-2) and extracellular-signal regulated protein kinase (ERK) activation. Taken together, these results indicate that 5-hydroxytryptophan has the potential for use in the treatment of inflammatory disease and as an analgesic.
No preview · Article · May 2009 · Biological & Pharmaceutical Bulletin
[Show abstract][Hide abstract] ABSTRACT: Methyl gallate is a major component of Galla Rhois, as carvacrol is of oregano essential oils. Both have shown good antibacterial activity against intestinal bacteria. This study investigated the antibacterial activities of nalidixic acid in combination with methyl gallate and carvacrol against nalidixic acid resistant bacteria. The combined effect of nalidixic acid with methyl gallate and carvacrol was evaluated using the checkerboard method to obtain a fractional inhibitory concentration index. The results showed that the combinations of nalidixic acid + methyl gallate/carvacrol improved nalidixic acid resistant pathogenic bacteria inhibition with synergy or partial synergy activity. Thus, a strong bactericidal effect of the drug combinations was observed. In vitro data thus suggested that nalidixic acid combined with methyl gallate and carvacrol may be microbiologically beneficial, rather than antagonists.
[Show abstract][Hide abstract] ABSTRACT: We evaluated the in vivo anti-inflammatory and analgesic activities of orally administered paeonol in mice, and also investigated the anti-inflammatory activity of paeonol in a cell line. Paeonol significantly reduced the edema induced by arachidonic acid in rats. The analgesic effects were assayed using 2 different models, i.e., by acetic acid-induced writhing response and by formalin induced licking and biting time. Moreover, we examined the effects of paeonol on the release of inflammatory mediators such as NO, PGE(2) and IL-6. Our results demonstrated that paeonol inhibited LPS induced expression of NO, PGE(2) and IL-6. Paeonol prevented LPS induced iNOS, COX-2 and ERK activation. Therefore, paeonol appears to have potential as a treatment for inflammatory disease and analgesic.
No preview · Article · Feb 2009 · The American Journal of Chinese Medicine
[Show abstract][Hide abstract] ABSTRACT: Salmonella remains a primary cause of food poisoning worldwide, and massive outbreaks have been witnessed in recent years. Therefore, this study investigated the antimicrobial activity of methyl gallate (MG), which exhibited good antibacterial activity (MIC=3.9-125 mg/ml) against all the bacterial strains tested. In a checkerboard dilution test, MG markedly lowered the MICs of ciprofloxacin (CPFX) against Salmonella. The combined activity of CPFX and MG against Salmonella resulted in fractional inhibitory concentrations (FICs) ranging from 0.0037 to 0.015 and from 0.24 to 7.8 mg/ml, respectively. Meanwhile, the FIC index ranged from 0.31-0.37, indicating a marked synergistic relationship between CPFX and MG against Salmonella. Time-kill assays also showed a decrease in the CFU/ml between the combination and the more active compound. Therefore, this study demonstrated that MG and CPFX can act synergistically in inhibiting Salmonella in vitro.
No preview · Article · Dec 2008 · Journal of Microbiology and Biotechnology
[Show abstract][Hide abstract] ABSTRACT: Macrophages play central roles in the innate immune system. The roots of Aralia cordata are widely used in Oriental medicine as a remedy for arthritis. During our program to screen medicinal plants for potential anti-inflammatory compounds, ent-pimara-8(14), 15-dien-19-oic acid (pimaradienoic acid; PA) was isolated from the roots of A. cordata. We examined the effect of PA on pro-inflammatory mediators in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. PA was found to significantly inhibit the production of nitric oxide (NO), prostaglandin E(2) (PGE(2)), and interleukin-6 (IL-6), as well as the expressions of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), and IL-6. Furthermore, we examined whether mitogen-activated protein kinases (MAPKs) and phosphatidylinositol 3-kinase (PI3K) signaling pathways are involved in LPS-induced RAW 264.7 cells. We found that a p38 inhibitor (SB203580) and an ERK 1/2 inhibitor (PD98059) significantly affected LPS-induced IL-6 production. In contrast, a JNK 1/2 inhibitor (SP600125) and PI3K inhibitor (wortmannin or LY294002) did not block the induction of IL-6 production by LPS. The LPS-induced phosphorylation of p38 MAPK and extracellular signal-regulated kinase 1/2 (ERK1/2) was inhibited by PA, but not the phosphorylation of JNK 1/2 and AKT (Ser473). Moreover, PA suppressed I kappaB alpha degradation, NF-kappaB activation and luciferase activity. These results suggest that PA isolated from A. cordata has a potential regulatory effect on inflammatory iNOS, COX-2 and IL-6 expression through blockade of the phosphorylation of MAPKs following I kappaB alpha degradation and NF-kappaB activation.
No preview · Article · Nov 2008 · European journal of pharmacology
[Show abstract][Hide abstract] ABSTRACT: The extract of Angelicae dahuricae radix has traditionally been used as an anti-noceptive remedy in China. In this study, the methanol extract of Angelicae dahuricae radix (MEAD) was evaluated to determine if it has anti-noceptive and anti-inflammatory action. The anti-nociceptive activities of MEAD were evaluated by determining the writhing response and sleeping time, as well as by a formalin test. In addition, the anti-inflammatory activities of MEAD were evaluated by a vascular permeability test as well as by measuring the carrageenan-induced paw edema and conducting a myeloperoxidase (MPO) assay. MEAD (600 and 1200 mg/kg) exhibited anti-inflammatory effects on acetic acid-induced vascular permeability, carrageenan-induced paw edema, and MPO activity. Moreover, the results of the formalin test, the acetic acid-induced writhing response and the pentobarbital-induced sleeping time indicated that MEAD had anti-nociceptive effects that occurred in a concentration-dependent manner. To determine the mechanism by which MEAD exerted its effects on the expression of inducible nitric oxide synthase (iNOS) and the production of nitric oxide (NO) by treated murine macrophage RAW 264.7 cells was evaluated. Similar to the in vivo activities, both the iNOS expression and NO production were significantly suppressed by MEAD in a dose-dependent manner. Furthermore, MEAD inhibited the activating phosphorylation of ERK1/2. These results provide a scientific basis that explains the mechanism by which Angelicae dahuricae radix relieves inflammatory pain.
Full-text · Article · Feb 2008 · The American Journal of Chinese Medicine