Taurine Supplementation Inhibits the Expression of Atrogin-1 and MURF-1, Protein Degradation Marker Genes, in Skeletal Muscle of C26-Induced Cachexia Mouse Model.

This study was designed to investigate the therapeutic effects of taurine in attenuating muscle atrophy. C26 carcinoma cells were cultured and injected into the scapulae of Balb/c mice with 1 × 106 cells. Taurine (200 µl suspension) was orally administered at the concentration of 200 mg/kg of body weight for 2 weeks. Femur muscle tissue, spleen, and gonadal fat tissue were collected and weighed. Muscle tissue was stained by H&E for histopathological analysis. The transcriptional expression of atrogin-1 and MuRF-1 gene was checked by real-time PCR. C26 cells, which induced tumor growth, caused a loss in muscle mass and gonadal fat tissue mass. Simultaneously, there was an increase in spleen and tumor tissue mass. In contrast, taurine supplementation showed a downregulatory effect on the transcriptional expression profile of muscle degradative factors atrogin-1 and MuRF-1. Our findings suggest that taurine has the potential to inhibit muscle atrophy and can be developed as a safe treatment option against muscle loss in sarcopenia patients.

Taurine Stimulates Thermoregulatory Genes in Brown Fat Tissue and Muscle without an Influence on Inguinal White Fat Tissue in a High-Fat Diet-Induced Obese Mouse Model.

This study was conducted to investigate if taurine supplementation stimulates the induction of thermogenic genes in fat tissues and muscles and decipher the mechanism by which taurine exerts its anti-obesity effect in a mildly obese ICR (CD-1®) mouse model. Three groups of ICR mice were fed a normal chow diet, a high-fat diet (HFD), or HFD supplemented with 2% taurine in drinking water for 28 weeks. The expression profiles of various genes were analyzed by real time PCR in interscapular brown adipose tissue (BAT), inguinal white adipose tissue (iWAT), and the quadriceps muscles of the experimental groups. Genes that are known to regulate thermogenesis like PGC-1α, UCP-1, Cox7a1, Cox8b, CIDE-A, and ß1-, ß2-, and ß3-adrenergic receptors (ß-ARs) were found to be differentially expressed in the three tissues. These genes were expressed at a very low level in iWAT as compared to BAT and muscle. Whereas, HFD increased the expression of these genes. Taurine supplementation stimulated the expression of UCP-1, Cox7a1, and Cox8b in BAT and only Cox7a1 in muscle, while there was a decrease in iWAT. In contrast, fat deposition-related genes, monoamine oxidases (MAO)-A, and -B, and lipin-1, were decreased by taurine supplementation only in iWAT and not in BAT or muscle. In conclusion, the potential anti-obesity effects of taurine may be partly due to upregulated thermogenesis in BAT, energy metabolism of muscle, and downregulated fat deposition in iWAT.

Analysis of Sasang Constitutional Medicine as an Optimal Preventive Care Strategy for Hemophilia Patients.

Introduction. Medical improvements have allowed hemophilia patients to anticipate an increased quality of life and life expectancy similar to that of the general population. Analysis of the potential disease symptoms of hemophilia patients based on a survey of Sasang Constitutional Medicine (SCM) is important for optimal preventive care and adjunctive therapy to avoid life-threating complications. AIM: To predict potential disease symptoms from the viewpoint of SCM as a preventive care strategy for hemophilia patients. METHODS: Sixty-one hemophilia patients responded to a survey on Sasang constitutional classification, hemophilia disease pattern, and original symptoms. RESULTS: In terms of SCM type, the 61 of hemophilia patients included 37 Tae-Eum (60.7%), 18 So-Yang (29.5%), and 6 So-Eum (12.5%). Hemophilia was found to be higher in Tae-Eum type and lower in So-Yang and So-Eum types, while considering the distributional rate of Korean Sasang types. Most of the patients with Tae-Eum type had Joyeol or Ganyeol. Furthermore, the incidences of diabetes and high blood pressure were greater in Tae-Eum type than in those of other types. CONCLUSION: In order to increase the quality of life and overall life expectancy, hemophilia patients with Tae-Eum type should be treated through management according to SCM along with medicine against hemophilia as long-term preventive care. Diabetes and high blood pressure should be regularly monitored in patients with Tae-Eum type.

Continentalic Acid Rather Than Kaurenoic Acid Is Responsible for the Anti-Arthritic Activity of Manchurian Spikenard In Vitro and In Vivo.

The aim of this study was to identify the active compound responsible for the pharmacological activities of Manchurian spikenard (Aralia continentalis Kitag.). Interleukin (IL)-1ß-stimulated human chondrocytes and monoiodoacetate (MIA)-induced osteoarthritic rats were treated with the 50% ethanolic extract of spikenard or its major components, such as continentalic acid (ent-pimara-8(14),15-diene-19-oic acid) and kaurenoic acid (ent-kaura-16-en-19-oic acid). The spikenard extract significantly inhibited IL-1ß-stimulated production of IL-6, IL-8, metalloproteinase (MMP)-1, MMP-13, cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS) and prostaglandin(PG)E2 in a dose-dependent manner but not MMP-3 production. The extract also inhibited the IL-1ß-induced translocation of NF-κB/p65 into the nucleus and dose-dependent phosphorylation levels of extracellular signal-regulated kinase (ERK), Jun amino-terminal kinase (JNK) and p38 mitogen-activated protein (MAP) kinase. Continentalic acid exhibited significant anti-arthritic activity corresponding exactly to that of the extract containing an equivalent amount of continentalic acid. On the other hand, kaurenoic acid exhibited a compatible activity at about a 10-times higher molar concentration than that of continentalic acid. In vitro anti-arthritic activities of the spikenard extract and continentalic acid were also confirmed in MIA-induced osteoarthritic rats. The 50% ethanolic extract of Manchurian spikenard exhibited promising anti-arthritic activities in the in vitro and in vivo osteoarthritis models, and continentalic acid, not kaurenoic acid, was most probably responsible for those activities.

Effects of Chronic Intake of a Low Concentration of Taurine on Physical Strength and Body Composition in Mice.

Most studies of taurine on athletic performance have been conducted at acute and high doses in rodents. These doses and duration of administration are not reasonable for normal human life. Thus, it is not valid to extrapolate these animal results to people. Dose and duration that mimic human use of taurine in normal life can help to clarify the taurine effect in humans. This study investigated whether long-term, low-dose taurine (2% taurine drinking water for 25 weeks), similar to normal taurine intake in humans, can affect endurance exercise and body composition. Twenty ICR mice were divided into two groups. The control group received normal drinking water, and the taurine treated group received 2% taurine drinking water for 25 weeks. The mice were evaluated for body composition by mass and for physical strength by treadmill exhaustion and suspension tests. The supply of chronic 2% taurine drinking water has a slight effect on weight gain. In body composition analysis, a slight increase in body weight was due to an increase in muscle mass, not an increase in body fat. However, taurine ingestion did not increase endurance exercise. In conclusion, these results indirectly suggest that acute, high-dose taurine treatment is better than long-term, low-dose treatment to increase athletic performance.

Anti-obesity effect of taurine through inhibition of adipogenesis in white fat tissue but not in brown fat tissue in a high-fat diet-induced obese mouse model.

This study was conducted to evaluate the anti-obesity effects of long-term taurine supplementation in a mild obese ICR mouse model and to study the mechanism by which taurine induces weight loss. Three groups of male ICR mice were fed a normal chow diet, a high-fat diet (HFD), or an HFD supplemented with 2% taurine in drinking water for 28 weeks. Body weight was measured every week. Metabolic, behavioral, and physiological monitoring were carried out using PhenoMaster at 28 weeks. Interscapular brown fat (BAT), inguinal white fat tissue (WAT), and quadriceps muscle were analyzed and compared to assess the change of gene expression related to adipogenesis. Taurine supplementation showed the trend of anti-obesity effect in ICR mice fed an HFD for 28 weeks. HFD-fed mice did not show significant difference of oxygen consumption (VO2), energy expenditure (EE), respiratory exchange rate (RER), and locomotive activity compared with those of normal chow diet fed mice. The expression of adipogenesis-related genes such as PPAR-α, PPAR-γ, C/EBP-α, C/EBP-ß, and AP2 increased in BAT and WAT, but not in muscle tissue. Taurine supplementation showed the downregulation of these genes in WAT but not in BAT or muscle. Consistently, the expression of taurine transporter (TauT) and adipocyte-specific genes such as adiponectin, leptin, and IL-6 was regulated in a similar pattern by taurine supplementation. Long-term taurine supplementation causes weight loss, most likely by inhibiting adipogenesis in WAT. TauT expression may be involved in the expression of various genes regulated by taurine supplementation.

Anti-inflammatory and anti-arthritic effects of the ethanolic extract of Aralia continentalis Kitag. in IL-1ß-stimulated human fibroblast-like synoviocytes and rodent models of polyarthritis and nociception.

BACKGROUND: Blocking the formation and invasive growth of pannus and its secretion of inflammatory cytokines and MMPs is important for treating rheumatoid arthritis. HYPOTHESIS/PURPOSE: Anti-arthritic activity of Aralia continentalis Kitag., an oriental herbal medicine, and the underlying mechanisms involved were investigated. STUDY DESIGN: Anti-inflammatory and anti-nocicpetive activities of the ethanolic extract (50% v/v) of Aralia continentalis Kitag. harvested from Imsil, Korea (ACI) were investigated in IL-1ß-stimulated human fibroblast-like synoviocyte (FLS) cells and rodent models of collagen-induced polyarthritis and carrageenan-induced acute paw pain. METHODS: In IL-1ß-stimulated FLS cells derived from rheumatoid arthritis patients, the anti-inflammatory activity of ACI was examined by analyzing the expression levels of inflammatory mediators such as TNF-α, IL-6, IL-8, MMP-1, MMP-3, MMP-13, PGE2, and COX-2 using ELISA and RT-PCR analysis. The anti-arthritic activity of ACI was investigated by measuring body weight, squeaking score, paw volume, and arthritis index in collagen-induced polyarthritis mice. The anti-nociceptive activity of ACI was examined in the paw-pressure test and Tail-flick latency test in rats. RESULTS: The ethanolic extract (50% v/v) of ACI reduced the levels of TNF-α, IL-6, IL-8, MMP-1, and MMP-13 secreted by IL-1ß-stimulated FLS cells, whereas MMP-3, COX-2, and PGE2 were not significantly affected. ACI inhibited the migration of NF-κB into the nucleus through the inhibition of ERK- and JNK-dependent MAP kinase pathways in IL-1ß-stimulated FLS cells. In collagen-induced polyarthritis mice, oral administration of ACI extract (200 mg/kg) significantly alleviated arthritic behaviors. Histological observations of arthritic mouse knees were consistent with their behaviors. The anti-arthritic and anti-inflammatory activities of 200 mg/kg ACI extract were comparable to those of 10 mg/kg prednisolone when administered to mice. However, ACI administration did not significantly affect carrageenan-induced hyperalgesia or thermal nociception in rats. CONCLUSION: These results suggest that the ethanolic extract of ACI have significant anti-inflammatory and anti-arthritic effects in a rodent arthritis model and in IL-1ß-stimulated FLS cells. Thus, ACI may be a useful candidate for developing pharmaceuticals or dietary supplements for the treatment of inflammatory arthritis.

Metabolomics Profiling of the Effects of Taurine Supplementation on Dyslipidemia in a High-Fat-Diet-Induced Rat Model by 1H NMR Spectroscopy.

Metabolomics, the comprehensive study of metabolites, has merged as a potent tool for analyzing complex phenotypes and identifying biomarkers of specific physiological responses and has the potential to lead to innovative therapeutic and diagnostic schemes for many diseases. In a former report, we showed that taurine supplementation considerably ameliorated dyslipidemia in rats fed a high-caloric diet. In this work, we examined the metabolic changes that occur in rat serum after they were fed a normal diet, a high-fat diet, and a high-fat diet containing 2% taurine (tau) by NMR spectroscopy combined with a multivariate statistical analysis containing PCA, PLS-DA, and OPLS-DA. We obtained 1H-NMR spectra of rat serum and used pattern recognition to identify key metabolites related to taurine supplementation. We found significant changes in creatine, methionine, glutamine, and threonine as well as in lipids, all of which decreased in the Tau group. To use these changes in metabolites as novel therapeutic and diagnostic markers, it should first be investigated whether these results are reproducible in future experiments. Next, researchers should determine how these changes affect serum lipid changes. This study identified some changes in serum metabolites and demonstrated the possibility of using an NMR-based metabolomics method to explore the effects of a taurine supplement on dyslipidemia in a high-fat-diet-induced rat model.

Low level light therapy modulates inflammatory mediators secreted by human annulus fibrosus cells during intervertebral disc degeneration in vitro.

Intervertebral disc degeneration (IVD) is one of the important causes of low back pain and is associated with inflammation induced by interaction between macrophages and the human annulus fibrosus (AF) cells. Low-level light therapy (LLLT) has been widely known to regulate inflammatory reaction. However, the effect of LLLT on macrophage-mediated inflammation in the AF cells has not been studied till date. The aim of this study is to mimic the inflammatory microenvironment and to investigate the anti-inflammatory effect of LLLT at a range of wavelengths (405, 532 and 650 nm) on the AF treated with macrophage-like THP-1 cells conditioned medium (MCM) containing proinflammatory cytokines and chemokines (interleukin-1beta, tumor necrosis factor-alpha, interleukin-6 and 8). We observed that AF cells exposed to MCM secrete significantly higher concentrations of IL-6, IL-8, IL-1ß and TNF-α. LLLT markedly inhibited secretion of IL-6 at 405 nm in a time-dependent manner. Level of IL-8 was significantly decreased at all wavelengths in a time-dependent manner. We showed that MCM can induce the inflammatory microenvironment in AF cells and LLLT selectively suppressed IL-6 and 8 levels. The results indicate that LLLT is a potential method of IVD treatment and provide insights into further investigation of its anti-inflammation effect on IVD.

Increased expression of endocan in arthritic synovial tissues: effects of adiponectin on the expression of endocan in fibroblast-like synoviocytes.

This study was performed to evaluate whether endocan expression, which is known to be involved in tumor angiogenesis, was increased in rheumatoid arthritic tissues. In addition, the involvement of adiponectin in the regulation of endocan expression in arthritic joints was examined. Arthritic synovial tissues from patients with rheumatoid arthritis (RA) or osteoarthritis (OA) were immunostained with antibodies to endocan and vascular endothelial growth factor (VEGF). Subsequently, synovial cells and human umbilical vein endothelial cells were cultured and stimulated with interleukin-1 ß (IL-1ß) or adiponectin. The mRNA and protein levels of endocan were evaluated by polymerase chain reaction and ELISA, respectively. Endocan expression was markedly increased in the inflammatory sites of RA synovial tissues. In OA tissues, endocan expression was higher in tissues displaying moderate and severe inflammation than in those with mild inflammation. In vitro expression levels of endocan and VEGF in endothelial and synovial cells were differentially increased in response to IL-1ß stimulation. Adiponectin was a more potent stimulant of endocan than IL-1ß at their respective physiological concentrations in synovial cells. Endocan silencing by small interfering RNA transfection of synovial cells decreased in vitro cell migration and invasion. In conclusion, adiponectin is an important factor in the stimulation of endocan expression in synovial cells. Adiponectin-induced endocan expression in synovial cells may stimulate cell migration and invasion as well as angiogenesis in the pannus of arthritic joints.

Ethanol extract of lotus (Nelumbo nucifera) root exhibits an anti-adipogenic effect in human pre-adipocytes and anti-obesity and anti-oxidant effects in rats fed a high-fat diet.

Lotus (Nelumbo Nucifera) root, a well-known medicinal plant in Asia, is reported to have various therapeutic benefits, including anti-diabetes, anti-hypertension, and anti-hyperlipidaemia. We hypothesized that the ethanol extract of lotus root (ELR) would exhibit an anti-adipogenic effect in human pre-adipocytes as well as anti-obesity and anti-oxidant effects in rats fed a high-fat diet. Treatment with ELR in human pre-adipocytes resulted in inhibition of lipid accumulation and attenuated expression of adipogenic transcription factors such as peroxisome proliferator-activated receptor gamma and adipocyte marker genes, such as glucose transporter 4 and leptin. Administration of ELR resulted in a significant decrease in relative weights of adipose tissues in rats fed a high-fat diet. Consumption of a high-fat diet resulted in an increase in serum total cholesterol (TC) and triglyceride (TG) levels; however, administration of ELR resulted in a decrease in the levels of TC and TG. Administration of ELR resulted in a decrease in the level of serum leptin and insulin. Administration of ELR in rats fed a high-fat diet resulted in a decrease in hepatic thiobarbituric acid reactive substance content, elevated by a high-fat diet and an increase in superoxide dismutase activity and hepatic glutathione content. These results suggest that lotus root exerts anti-oxidant and anti-obesity effects and could be used as a functional and nutraceutical ingredient in combatting obesity-related diseases.

Postprandial glucose and NF-κB responses are regulated differently by monounsaturated fatty acid and dietary fiber in impaired fasting glucose subjects.

Recently, much attention has been paid to observational studies that have linked postprandial glycemic response with the risk of cardiovascular disease. In this study, we investigated whether the nutrient composition of dietary formula might affect the postprandial inflammation in impaired fasting glucose (IFG) subjects. Eight subjects underwent three trials in a double-blind, randomized, crossover study with a 1-week washout period. The subjects were given three formulas according to serving size: (1) high-fiber formula (FF); (2) high-monounsaturated fatty acid formula (MF); and (3) control formula (CF). The area under the curves (AUCs) for glucose decreased 0.65- and 0.54-fold in the FF and MF trials, respectively, when compared with CF. A similar pattern was observed for the postprandial insulin response. However, as observed by the phosphorylation of proteolytic degradation product IκB, the AUC for activation of nuclear transcription factor κB (NF-κB) in peripheral blood mononuclear cells was significantly decreased in the FF trial, but not with MF (P=.0114). These findings demonstrated that postprandial glucose and inflammatory responses might be regulated differently by the nutrient composition of dietary formulas in IFG subjects.

Phosphatidylserine inhibits inflammatory responses in interleukin-1ß-stimulated fibroblast-like synoviocytes and alleviates carrageenan-induced arthritis in rat.

Recently, phosphatidylserine (PS) has received attention for its anti-inflammatory effect; however, the molecular mechanisms of its action have not been fully understood. Thus, we hypothesized that PS might have antiarthritic and anti-inflammatory effects. To test this hypothesis, the in vitro anti-inflammatory effect of soybean-derived PS was tested on interleukin (IL)-1ß-stimulated fibroblast-like synoviocytes from rheumatoid arthritis patients (RA-FLS) by measuring the levels of IL-6, IL-8, prostaglandin E(2), and vascular endothelial growth factor by enzyme-linked immunosorbent assay. The analgesic and antiarthritic activities of PS were investigated in rat models of carrageenan-induced acute paw pain and arthritis. The former was evaluated with a paw pressure test; the latter, by measuring paw volume and weight distribution ratio. In addition, the participation of mitogen-activated protein kinase signaling in the anti-inflammatory and antiarthritic effects of PS was investigated in RA-FLS. Phosphatidylserine inhibited the production of inflammatory mediators IL-6; IL-8; vascular endothelial growth factor; and, in particular, prostaglandin E(2) in IL-1ß-stimulated RA-FLS. These effects were associated with abrogation of inhibitor of nuclear factor-κBα phosphorylation and suppression of p38 and c-jun amino terminal kinase but not extracellular signal-regulated kinase 1/2 phosphorylation. In rats, PS also showed a significant inhibitory effect on arthritic and nociceptive symptoms induced by carrageenan. These findings suggest that PS has anti-inflammatory and antiarthritic effects in vitro and in in vivo animal models; thus, PS should be further studied to determine its potential use as either a pharmaceutical or dietary supplement for alleviating arthritic symptoms.

Taurine ameliorates hyperglycemia and dyslipidemia by reducing insulin resistance and leptin level in Otsuka Long-Evans Tokushima fatty (OLETF) rats with long-term diabetes.

This study aimed to determine whether taurine supplementation improves metabolic disturbances and diabetic complications in an animal model for type 2 diabetes. We investigated whether taurine has therapeutic effects on glucose metabolism, lipid metabolism, and diabetic complications in Otsuka Long- Evans Tokushima fatty (OLETF) rats with long-term duration of diabetes. Fourteen 50-week-old OLETF rats with chronic diabetes were fed a diet supplemented with taurine (2%) or a non-supplemented control diet for 12 weeks. Taurine reduced blood glucose levels over 12 weeks, and improved OGTT outcomes at 6 weeks after taurine supplementation, in OLETF rats. Taurine significantly reduced insulin resistance but did not improve ß-cell function or islet mass. After 12 weeks, taurine significantly decreased serum levels of lipids such as triglyceride, cholesterol, high density lipoprotein cholesterol, and low density lipoprotein cholesterol. Taurine significantly reduced serum leptin, but not adiponectin levels. However, taurine had no therapeutic effect on damaged tissues. Taurine ameliorated hyperglycemia and dyslipidemia, at least in part, by improving insulin sensitivity and leptin modulation in OLETF rats with long-term diabetes. Additional study is needed to investigate whether taurine has the same beneficial effects in human diabetic patients.

Analgesic and anti-inflammatory effects in animal models of an ethanolic extract of Taheebo, the inner bark of Tabebuia avellanedae.

Taheebo, the purple inner bark of the Bignoniaceae tree Tabebuia avellanedae Lorentz ex Griseb, which is found in tropical rain forests in northeastern Brazil, has been used as a traditional medicine for various diseases for more than 1,500 years. In the current study, various animal models were used to demonstrate the analgesic and anti-inflammatory properties of its ethanolic extract, thereby investigating its potential as a therapeutic treatment for diseases with pain and inflammation. In the hot plate and writhing tests for the in vivo analgesic effect test of Taheebo, a 200 mg/kg dose of the extract induced a significant anti-nociceptive effect and increased the pain threshold by approximately 30% compared with the control. In vascular permeability and tetradecanoylphorbol acetate (TPA)­, arachidonic acid- and carrageenan-induced paw edema tests for anti-inflammatory effects, treatment with 200 mg/kg Taheebo led to significant anti-inflammatory effects and inhibited inflammation by 30-50% compared with the control. At 100 mg/kg, the extract decreased the levels of pain and inflammation in all tested models, but the degree of inhibition was not statistically significant. The results suggest that the ethanolic extract of the inner bark of Tabebuia avellanedae has the potential to be developed as a therapeutic or supportive drug against diseases with accompanying pain and inflammation, including osteoarthritis.

Taurine chloramine inhibits osteoclastogenesis and splenic lymphocyte proliferation in mice with collagen-induced arthritis.

Taurine chloramine (TauCl) is produced by activated neutrophils in the inflammatory joint cavities of rheumatoid arthritis and is known to have anti-inflammatory and anti-arthritic effects. However, the mechanisms underlying the anti-arthritic effect of TauCl have not been elucidated. Here, we investigated that mechanism using a collagen-induced arthritis (CIA) mouse model. DBA/1J mice were immunized with bovine type II collagen to induce CIA and were given daily subcutaneous injections of TauCl from the day of first collagen immunization. Severity of arthritis was scored by paw swelling and the arthritis score system. At the 8th week, mice were sacrificed for histological examination using hematoxylin and eosin, safranin-O and tartrate-resistant acid phosphatase (TRAP) staining. Effects of TauCl on osteoclastogenesis from bone marrow-derived preosteoclasts and proliferation of the lymphocytes obtained from spleens of CIA mice were determined. TauCl significantly attenuated the severity of paw swelling and reduced arthritis score in CIA mice. TauCl treated CIA mice showed significant reductions of synovial inflammation, cartilage damage and bone erosion. The number of TRAP-positive cells in the joints of TauCl treated CIA mice was reduced. TauCl inhibited osteoclastogenesis from the RANKL treated bone marrow-derived preosteoclasts in a dose-dependent manner. TauCl also inhibited the proliferation of splenic lymphocytes obtained from CIA mice. In conclusion, TauCl attenuated the severity of CIA by inhibiting lymphocyte proliferation and osteoclastogenesis. Combined our results suggest that TauCl produced endogenously in inflamed joints may suppress the development of rheumatoid arthritis and that TauCl may be used for therapeutic treatment of rheumatoid arthritis.

The analgesic and anti-inflammatory effect of WIN-34B, a new herbal formula for osteoarthritis composed of Lonicera japonica Thunb and Anemarrhena asphodeloides BUNGE in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Lonicera japonica Thunb and Anemarrhena asphodeloides BUNGE have been used for the treatment of a variety of inflammatory diseases, cold and infective diseases in many countries, including Korea and China. AIM OF THE STUDY: This study aimed to assess the anti-nociceptive and anti-inflammatory activities of n-butanol fraction (WIN-34B) prepared from dried flowers of Lonicera japonica and dried roots of Anemarrhena asphodeloides as potential novel treatment of osteoarthritis. MATERIALS AND METHODS: Anti-nociceptive activities of WIN-34B (100, 200 and 400 mg/kg, p.o.) were measured using acetic acid-induced writhing response, formalin-induced paw licking, hot plate, radiant heat tail-flick, carrageenan-induced paw pressure, and Hargreaves tests, respectively. Anti-inflammatory activities of WIN-34B (100, 200 and 400 mg/kg, p.o.) were assessed using acetic acid-induced vascular permeability, carrageenan-induced paw edema, and croton oil-induced ear edema. Anti-osteoarthritis effect of WIN-34B was analyzed using monosodium iodoacetate (MIA)-induced osteoarthritis animal model. RESULTS: WIN-34B exhibited better anti-inflammatory activity than that of celecoxib in carrageenan at the dose of 200 mg/kg and croton oil-induced paw edema and ear edema at the doses of 200 and 400 mg/kg. WIN-34B exhibited significant anti-inflammatory effects on vascular permeability. WIN-34B also exhibited significant anti-nociceptive activities in the late phase of formalin-induced paw licking and writhing response model in mice. In radiant heat tail-flick and carrageenan-induced paw pressure tests, WIN-34B at the dose of 400 mg/kg and at the doses of 200 and 400 mg/kg presented similar activities to indomethacin and celecoxib. Compared to indomethacin WIN-34B at 400mg/kg showed similar or better anti-nociceptive activities after 1 and 2h of theraphy in the hot plate test and better anti-nociceptive activity than that of celecoxib in Hargreves test. In the MIA-induced osteoarthritis animal models, WIN-34B at 400 mg/kg exhibited similar or better anti-nociceptive property than that of celecoxib throughout the pain measurement periods. CONCLUSION: When compared to celecoxib, WIN-34B exhibited similar or better anti-nociceptive and anti-inflammatory activities in osteoarthritic animal models, which may become a potential novel treatment for osteoarthritis.

Antiinflammatory effects of a combined herbal preparation (RAH13) of Phellodendron amurense and Coptis chinensis in animal models of inflammation.

In an attempt to develop an antiinflammatory herbal remedy that is as potent as current synthetic medicines, the cortex of Phellodendron amurense Rupr (Rutaceae) and the rhizomes of Coptis chinensis Franch (Ranunculaceae) were combined in a 2:1 ratio. This ratio was chosen based on in vitro experiments and traditional Asian medicine prescriptions. The combined ethanol extract, named RAH13, was evaluated for antiinflammatory properties using animal models of acute inflammation such as the croton oil-induced ear edema test and an acetic acid-induced capillary permeability test. Models of chronic inflammation were also tested using the cotton pellet test and a delayed-type hypersensitivity (DTH) test. Oral administration of RAH13 at a dose of 200 mg/kg showed in vivo antiinflammatory activity as potent as the effects associated with 100 mg/mL of celecoxib or 1 mg/kg of dexamethasone. These effects were seen in both acute and chronic inflammation models, suggesting that RAH13 may be effective in controlling some inflammation-related diseases.

Anti-inflammatory effects of an ethanolic extract from Clematis mandshurica Rupr.

Clematis mandshurica Rupr (Ranunculaceae) roots are used in traditional Korean medicine to treat inflammation-related diseases. Therefore, we undertook to investigate their inhibitory effect on inflammation under non-cytotoxic conditions. The ethanolic extract of Clematis mandshurica at 100 microg/ml was found to significantly block the production of the pro-inflammatory mediators, nitric oxide (NO) and prostaglandin E(2) (PGE(2)), in lipopolysaccharide (LPS)/interferon(IFN)-gamma-stimulated mouse peritoneal macrophages, by up to 77% and 59%, respectively. In addition, it significantly inhibited cell proliferation and cytokine production (interleukin (IL)-2 and IFN-gamma) in splenocytes stimulated with Con A (concanavalin A; 5 microg/ml). Furthermore, when splenocytes from extract fed mice (200 mg/kg for 2 weeks) were activated with Con A, cell proliferation and the production of IL-2 and IFN-gamma were significantly inhibited. In addition, the extract reduced in vivo inflammation in oxazolone-induced delayed type hypersensitivity (DTH) model mice. Taken together, these data suggest that Clematis mandshurica is able to ameliorate inflammatory disease by exerting an anti-inflammatory effect in cases of proinflammatory and cell-mediated inflammation.