Catalpol suppresses advanced glycation end-products-induced inflammatory responses through inhibition of reactive oxygen species in human monocytic THP-1 cells.

Advanced glycation end-products (AGEs) 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.

Quality of life, upper extremity function and the effect of lymphedema treatment in breast cancer related lymphedema patients.

OBJECTIVE: To evaluate quality of life (QOL), upper extremity function and the effect of lymphedema treatment in patients with breast cancer related lymphedema. METHOD: The basic data comprised medical records (detailing age, sex, dominant side, location of tumor, cancer stage, operation record, cancer treatment and limb circumferences) and questionnaires (lymphedema duration, satisfaction, self-massage). Further to this, we measured upper extremity function and QOL, administered the DASH (Disabilities of Arm Shoulder and Hand outcome measure) and used the EORTC (European Organization for Research and Treatment of Cancer)-QLQ-C30 and the EORTC-QLQ-Br23. Results of these were calculated as main outcome variables. RESULTS: The questionnaire responses and arm circumferences of 59 patients with breast cancer related lymphedema were analyzed. In the DASH questionnaire, it was found that the older the lymphedema patient was, the lower their upper extremity function. On the EORTC-QLQ, patients with metastasis had significantly lower scores in physical functioning and role functioning. In terms of upper extremity circumference, there was a significant upper extremity size reduction after lymphedema treatment. CONCLUSION: There were several dissociations between some subscales of quality of life questionnaires and those of upper extremity functions. Upper extremity function was correlated with the age of breast cancer patients and QOL was influenced by M-stage. Lymphedema treatment was found to be effective in reducing edema in patients with breast cancer related lymphedema.

Effects of transcranial direct current stimulation (tDCS) on post-stroke dysphagia.

PURPOSE: Transcranial direct current stimulation (tDCS) combined with swallowing training might improve swallowing function in patients with post-stroke dysphagia. We investigate the effects of transcranial direct current stimulation (tDCS) combined with swallowing training on post-stroke dysphagia. METHODS: Sixteen patients with post-stroke dysphagia, diagnosed using video fluoroscopic swallowing (VFSS), were randomly assigned into two groups: (1) anodal tDCS group (1 mA for 20 min), or (2) sham group (1 mA for 30 s). Patients received anodal tDCS or sham over the pharyngeal motor cortex of the affected hemisphere during 30 min of conventional swallowing training for 10 days. Functional dysphagia scale (FDS) scores based on VFSS were measured at baseline and immediately and 3 months after the intervention. The effect of tDCS on dysphagia was analyzed using a generalized linear model (GLM) with repeated measures. RESULTS: After the intervention, FDS scores improved in both groups without significant differences. However, 3 months after the intervention, anodal tDCS elicited greater improvement in terms of FDS compared to the sham group (ß = -7.79, p = 0.041) after controlling for age, National Institutes of Health Stroke Scale (NIHSS) score, lesion size, baseline FDS score, and time from stroke onset. CONCLUSIONS: Anodal tDCS applied over the affected pharyngeal motor cortex can enhance the outcome of swallowing training in post-stroke dysphagia. Our results suggest that non-invasive cortical stimulation has a potential role as an adjuvant strategy during swallowing training in patients with post-stroke dysphagia.

Antibacterial activity of methyl gallate isolated from Galla Rhois or carvacrol combined with nalidixic acid against nalidixic acid resistant bacteria.

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.

Inhibition of LPS-induced iNOS, COX-2 and inflammatory mediator expression by paeonol through the MAPKs inactivation in RAW 264.7 cells.

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.

In vitro activity of methyl gallate isolated from galla rhois alone and in combination with ciprofloxacin against clinical isolates of salmonella.

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.

Anti-nociceptive and anti-inflammatory effects of Angelicae dahuricae radix through inhibition of the expression of inducible nitric oxide synthase and NO production.

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.

Ent-pimara-8(14), 15-dien-19-oic acid isolated from the roots of Aralia cordata inhibits induction of inflammatory mediators by blocking NF-kappaB activation and mitogen-activated protein kinase pathways.

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.