Exploring the efficacy and safety of herbal medicine on Korean obese women with or without metabolic syndrome risk factors: A study protocol for a double-blind, randomized, multi-center, placebo-controlled clinical trial.

BACKGROUND: The prevalence of obesity among women is increasing. Obesity is associated with various metabolic syndromes; conventional treatments are limited and may induce serious adverse events due to polytherapy regimens. Currently, demands for complementary and alternative medicine that has a proven safety profile for the treatment of obesity with or without metabolic risk factors are increasing.Our team of preclinical experts reported a significant anti-obesity effect of the Korean herbal medicine, Galgeun-tang (GGT). Thus, we designed this trial to explore the effects of GGT among obese women to accumulate optimal clinical evidence.Obesity is not only a component of metabolic syndrome and a factor associated with an increased risk of cardiovascular disease but is also related to insulin resistance. Previous research has confirmed that an increasing body mass index is highly related with increased risk of metabolic syndrome among overweight and obese individuals. The effectiveness of the Korean medicine herbal formula, GGT on obesity has been previously reported. The objective of this study is to assess the efficacy and safety of GGT for weight loss among obese Korean women with or without high risk for metabolic syndrome. METHODS/DESIGN: This study is a randomized, double-blinded, placebo-controlled, multi-center clinical trial. A total of 160 participants will be randomly distributed in 2 groups, the GGT group or the placebo group in a 1:1 ratio using a web-based randomization system. Each group will be administered GGT or placebo 3 times a day for 12 weeks. The primary endpoint is to assess the change in weight from baseline. The secondary endpoints are the following: the changes in body composition measurements, anthropomorphic measurements, obesity screening Laboratory tests, patient self-reported questionnaires, and economic evaluation outcomes. Adverse events will also be reported. DISCUSSION: The findings of this study will confirm methodologies regarding the efficacy and safety of GGT for weight loss among obese Korean women with or without metabolic risk factors.

Reduction of Escherichia Coli Using Metal Plates with the Influenced of Applied Low Current and Physical Barrier of Filter Layers.

Although metal contact is known to reduce bacterial growth, the effects of physical barriers and electricity need further investigation. This study examined the bacteria-reducing properties of copper and stainless-steel metal plates with an added electrical current and up to three filter layers on the growth of Escherichia coli (bacteria) and MS2 bacteriophages (virus). When used with a stainless-steel plate, electricity increased bacteria reduction by 39.5 ± 2.30% in comparison with no electricity added, whereas a three-layer physical barrier decreased its efficiency. Copper also reduced the growth of bacteria, by 58.2 ± 8.23%, and the addition of electricity reduced it further (79.5 ± 2.34%). Bacteriophages were also affected by the metal contact. Further experiments showed that MS2 was also reduced by copper, to 82.9 ± 4.5% after 24 h at 37 °C.

Emission Characteristics of Particulate Matter, Volatile Organic Compounds, and Trace Elements from the Combustion of Coals in Mongolia.

This study characterized emissions of particulate matter (PM), volatile organic compounds (VOCs), heavy metals, and anions from Mongolian bituminous coals in a controlled heating experiment. Three coal samples from Alag Tolgoi (coal 1), Baganuur (coal 2), and Nalaikh (coal 3) were combusted at a constant heat flux of 50 kW/m² using a dual-cone calorimeter. The coal samples were commonly used in ger district of Ulaanbaatar, Mongolia. PM10 emission factors were 1122.9 ± 526.2, 958.1 ± 584.0, and 472.0 ± 57.1 mg/kg for coal samples 1, 2, and 3, respectively. PM with a diameter of 0.35⁻0.45 µm was dominant and accounted for 41, 34, and 48% of the total PM for coal samples 1, 2, and 3, respectively. The emissions of PM and VOC from coals commonly used in Ulaanbaatar, Mongolia were significant enough to cause extremely high levels of indoor and outdoor air pollution.

Characteristics of Particulate Matter and Volatile Organic Compound Emissions from the Combustion of Waste Vinyl.

Vinyl samples were burned in a controlled environment to determine the characteristics of particulate matter (PM) and volatile organic compound (VOC) emissions during the combustion process. Open burning of plastic or vinyl products poses several environmental and health risks in developed and developing countries, due to the release of high concentrations of harmful pollutants. The production of fine and ultrafine particles was significant. At a heat flux of 25 kW/m², the production of PM of 0.35 µm in size was highest at 63.0 µg/m³. In comparison, at fluxes of 35 and 50 kW/m², the production of PM of 0.45 µm in size was highest with values of 67.8 and 87.7 µg/m³, respectively. Benzene, acetone, and other toxic compounds were also identified in the analyses.

Inactivation of filter bound aerosolized MS2 bacteriophages using a non-conductive ultrasound transducer.

The inactivation of viruses that retain their infectivity when transmitted through the air is challenging. To address this issue, this study used a non-contact ultrasound transducer (NCUT) to generate shock waves in the air at specific distances, input voltages, and exposure durations, targeting bacteriophage virus aerosols captured on to H14 HEPA filters. Initially, a frequency of 27.56 kHz (50V) at 25-mm distance was used, which yielded an inactivation efficiency of up to 32.69 ±â€¯12.10%. Other frequencies at shorter distances were investigated, where 29.10 kHz had the highest inactivation efficiency (up to 81.95 ±â€¯9.79% at 8.5-mm distance and 100 V). Longer exposure times also influenced virus inactivation, but the results were inconclusive because the NCUT overheated with time. Overall, NCUT appears to be a promising method for inactivating virus aerosols that may be safer than other forms of inactivation, which can cause genetic mutations or produce dangerous by-products.

Anti-inflammatory effect of tricin isolated from Alopecurus aequalis Sobol. on the LPS-induced inflammatory response in RAW 264.7 cells.

The aim of this study was to identify major anti-inflammatory compounds in Alopecurus aequalis Sobol. (A. aequalis). The ethanol extract and the hexane-, dichloromethane-, ethyl acetate- and n-butanol-soluble fractions derived from A. aequalis were evaluated in order to determine their inhibitory effects on nitric oxide (NO) production in RAW 264.7 cells stimulated with lipopolysaccharide (LPS). The ethanol extract decreased NO production in a dose-dependent manner without any evidence of cytotoxicity at a concentration range of 0-200 µg/ml. The ethyl acetate soluble fraction was the most potent among the four soluble fractions. A compound was isolated by reversed-phase high-performance liquid chromatography from the ethyl acetate soluble fraction and this was identified to be tricin. Tricin inhibited the LPS-induced NO production in a dose-dependent manner without any evidence of cytotoxity at a concentration range of 1-100 µg/ml. Tricin also inhibited the LPS-induced production of prostaglandin E2. Western blot analysis indicated that tricin decreased the LPS-induced increase in the protein levels of inducible NO synthase and cyclooxygenase. In addition, tricin suppressed the production of intracellular reactive oxygen species in the LPS-stimulated RAW 264.7 cells, as measured by flow cytometry. Taken together, our results clearly indicate that tricin is a major functional anti-inflammatory compound which can be isolated from A. aequalis extracts.

Acute toxicity and cytotoxicity evaluation of Dendrobium moniliforme aqueous extract in vivo and in vitro.

Dendrobium moniliforme (L.) Sw., an herb of the Orchidaceae family, has long been used in traditional medicine to strengthen bones, nourish the stomach, and promote the production of bodily fluid. Recently, polysaccharides isolated from Dendrobium have been used in functional foods and nutraceutical products. A traditional method to process Dendrobium is to soak fresh stems in an ethanol solution, which is the most important factor to ensure high yields of aqueous-extractable polysaccharides. The present study was carried out to investigate the potential acute toxicity of D. moniliforme aqueous extract (DMAE), by a single oral dose in Sprague-Dawley rats. The test article was orally administered once by gavage to male and female rats at doses of 0, 2,500, and 5,000 mg/kg body weight (n=5 male and female rats for each dose). Throughout the study period, no treatment-related deaths were observed and no adverse effects were noted in clinical signs, body weight, food consumption, serum biochemistry, organ weight, or gross findings at any dose tested. The results show that a single oral administration of DMAE did not induce any toxic effects at a dose below 5,000 mg/kg in rats, and the minimal lethal dose was considered to be over 5,000 mg/kg body weight for both sexes. With respect to cytotoxicity, the cell viability of human embryonic kidney (HEK293) cells was less than 50% when the cells were treated with 10 mg/mL aqueous extract for 24 h.

Identification of the sources of PM10 in a subway tunnel using positive matrix factorization.

The level of particulate matter of less than 10 µm diameter (PM10) at subway platforms can be significantly reduced by installing a platform screen-door system. However, both workers and passengers might be exposed to higher PM10 levels while the cars are within the tunnel because it is a more confined environment. This study determined the PM10 levels in a subway tunnel, and identified the sources of PM10 using elemental analysis and receptor modeling. Forty-four PM10 samples were collected in the tunnel between the Gireum and Mia stations on Line 4 in metropolitan Seoul and analyzed using inductively coupled plasma-atomic emission spectrometry and ion chromatography. The major PM10 sources were identified using positive matrix factorization (PMF). The average PM10 concentration in the tunnels was 200.8 ± 22.0 µg/m3. Elemental analysis indicated that the PM10 consisted of 40.4% inorganic species, 9.1% anions, 4.9% cations, and 45.6% other materials. Iron was the most abundant element, with an average concentration of 72.5 ± 10.4 µg/m3. The PM10 sources characterized by PMF included rail, wheel, and brake wear (59.6%), soil combustion (17.0%), secondary aerosols (10.0%), electric cable wear (8.1%), and soil and road dust (5.4%). Internal sources comprising rail, wheel, brake, and electric cable wear made the greatest contribution to the PM10 (67.7%) in tunnel air. Implications: With installation of a platform screen door, PM10 levels in subway tunnels were higher than those on platforms. Tunnel PM10 levels exceeded 150 µg/m3 of the Korean standard for subway platform. Elemental analysis of PM10 in a tunnel showed that Fe was the most abundant element. Five PM10 sources in tunnel were identified by positive matrix factorization. Railroad-related sources contributed 68% of PM10 in the subway tunnel.

The mixture of different parts of Nelumbo nucifera and two bioactive components inhibited tyrosinase activity and melanogenesis.

Melanin is the pigment responsible for the color of the eyes, hair, and skin in humans. Tyrosinase is well known to be the key enzyme in melanin biosynthesis. JKTM-12 is composed of the flowers, roots, seeds, and receptacles of Nelumbo nucifera (lotus). In this study, JKTM-12 was investigated for its inhibitory effects on tyrosinase activity and melanin biosynthesis in B16F10 melanoma cells. Moreover, two main bioactive compounds (hyperoside and astragalin) were found from the receptacles of N. nucifera, which are used as the main material of JKTM-12. JKTM-12 was shown to inhibit tyrosinase activity and melanin biosynthesis in alpha-melanocyte-stimulating hormone-stimulated B16F10 melanoma cells. Hyperoside and astragalin, which are the main bioactive compounds of JKTM-12, not only inhibited tyrosinase activity and melanogenesis but also tyrosinase-related protein 1 and tyrosinase-related protein 2 mRNA expression without cytotoxicity at various experiment doses (0.1, 1, and 10 µg/ml). These results suggest that JKTM-12 has the potential for skin whitening with hyperoside and astragalin as the main bioactive compounds.

Scolopendra subspinipes mutilans protected the cerulein-induced acute pancreatitis by inhibiting high-mobility group box protein-1.

AIM: To evaluate the inhibitory effects of Scolopendra subspinipes mutilans (SSM) on cerulein-induced acute pancreatitis (AP) in a mouse model. METHODS: SSM water extract (0.1, 0.5, or 1 g/kg) was administrated intraperitoneally 1 h prior to the first injection of cerulein. Once AP developed, the stable cholecystokinin analogue, cerulein was injected hourly, over a 6 h period. Blood samples were taken 6 h later to determine serum amylase, lipase, and cytokine levels. The pancreas and lungs were rapidly removed for morphological examination, myeloperoxidase assay, and real-time reverse transcription polymerase chain reaction. To specify the role of SSM in pancreatitis, the pancreatic acinar cells were isolated using collagenase method. Then the cells were pre-treated with SSM, then stimulated with cerulein. The cell viability, cytokine productions and high-mobility group box protein-1 (HMGB-1) were measured. Furthermore, the regulating mechanisms of SSM action were evaluated. RESULTS: The administration of SSM significantly attenuated the severity of pancreatitis and pancreatitis associated lung injury, as was shown by the reduction in pancreatic edema, neutrophil infiltration, vacuolization and necrosis. SSM treatment also reduced pancreatic weight/body weight ratio, serum amylase, lipase and cytokine levels, and mRNA expression of multiple inflammatory mediators such as tumor necrosis factor-α and interleukin-1ß. In addition, treatment with SSM inhibited HMGB-1 expression in the pancreas during AP. In accordance with in vivo data, SSM inhibited the cerulein-induced acinar cell death, cytokine, and HMGB-1 release. SSM also inhibited the activation of c-Jun NH2-terminal kinase, p38 and nuclear factor (NF)-κB. CONCLUSION: These results suggest that SSM plays a protective role during the development of AP and pancreatitis associated lung injury via deactivating c-Jun NH2-terminal kinase, p38 and NF-κB.

Piperine inhibits lipopolysaccharide-induced maturation of bone-marrow-derived dendritic cells through inhibition of ERK and JNK activation.

Piperine, one of the main components of Piper longum Linn. and P. nigrum Linn., is a plant alkaloid with a long history of medicinal use. Piperine has been shown to modulate the immune response, but the mechanism underlying this modulation remains unknown. Here, we examined the effects of piperine on lipopolysaccharide (LPS)-induced inflammatory responses in bone-marrow-derived dendritic cells (BMDCs). Piperine significantly inhibited the expression of major histocompatibility complex class II, CD40 and CD86 in BMDCs in a dose-dependent manner. Furthermore, piperine treatment led to an increase in fluorescein-isothiocyanate-dextran uptake in LPS-treated dendritic cells and inhibited the production of tumour necrosis factor alpha and interleukin (IL)-12, but not IL-6. The inhibitory effects of piperine were mediated via suppression of extracellular signal-regulated kinases and c-Jun N-terminal kinases activation, but not p38 or nuclear factor-κB activation. These findings provide insight into the immunopharmacological role of piperine.

Myrrh inhibits LPS-induced inflammatory response and protects from cecal ligation and puncture-induced sepsis.

Myrrh has been used as an antibacterial and anti-inflammatory agent. However, effect of myrrh on peritoneal macrophages and clinically relevant models of septic shock, such as cecal ligation and puncture (CLP), is not well understood. Here, we investigated the inhibitory effect and mechanism(s) of myrrh on inflammatory responses. Myrrh inhibited LPS-induced productions of inflammatory mediators such as nitric oxide, prostaglandin E(2), and tumor necrosis factor-α but not of interleukin (IL)-1ß and IL-6 in peritoneal macrophages. In addition, Myrrh inhibited LPS-induced activation of c-jun NH(2)-terminal kinase (JNK) but not of extracellular signal-regulated kinase (ERK), p38, and nuclear factor-κB. Administration of Myrrh reduced the CLP-induced mortality and bacterial counts and inhibited inflammatory mediators. Furthermore, administration of Myrrh attenuated CLP-induced liver damages, which were mainly evidenced by decreased infiltration of leukocytes and aspartate aminotransferase/alanine aminotransferase level. Taken together, these results provide the evidence for the anti-inflammatory and antibacterial potential of Myrrh in sepsis.

Dimethylsulfoxide (DMSO) induces downregulation of heme oxygenase-1 (HO-1) in HL-60 cells: involvement of HO-1 in HL-60 cell differentiation.

Heme oxygenase-1 (HO-1), an inducible enzyme with broad tissue expression, is wel1-regulated in response to hematopoietic stress and preserves vascular homeostasis. We investigated the involvement of HO-1 in HL-60 cell differentiation. Dimethyl sulfoxide (DMSO) completely decreased HO-1 expression in a time-dependent manner, but clearly induced HL-60 cell differentiation, as evidenced by a marked increase in CD11b expression. Interestingly, zinc protoporphyrin (ZnPP), a strong inhibitor of HO-1, induced HL-60 cell differentiation. In contrast, treatment with cobalt protoporphyrin (CoPP), an activator of HO-1, decreased CD11b expression. Additionally, ZnPP downregulated HO-1 protein expression in HL-60 cells, whereas CoPP induced upregulation. These results suggest that HO-1 might have a negative function in DMSO-induced HL-60 cell differentiation. This study provides the first evidence that HO-1 plays an important role in DMSO-induced HL-60 cell differentiation.

The roots of Nardostachys jatamansi inhibits lipopolysaccharide-induced endotoxin shock.

Nardostachys jatamansi (NJ) has been used in the treatment of inflammatory diseases. However, it is not clear how NJ produces anti-inflammatory effects. In the present study, using an experimental model of lipopolysaccharide (LPS)-induced endotoxin shock, the protective effects and mechanisms of action of NJ were investigated. The water extract of roots of NJ was administrated to mice orally (1, 5, and 10 mg/kg) 1 h after or before LPS challenge. The administration of NJ inhibited LPS-induced endotoxin shock and the production of inflammatory mediators, such as interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, and interferon (IFN)-α/ß. Murine peritoneal macrophages were used to determine the production of inflammatory mediators. In peritoneal macrophages, NJ also inhibited LPS-induced production of inflammatory mediators, such as IL-1ß, IL-6, TNF-α, and IFN-α/ß. In addition, NJ reduced the activation of mitogen-activated protein kinases (MAPKs) and the level of expression of interferon regulatory factor (IRF)-1 and IRF-7 mRNA. Furthermore, post-treatment with NJ reduced LPS-induced endotoxin shock and the production of inflammatory mediators. These results suggest that NJ inhibits endotoxin shock by inhibiting the production of IL-1ß, IL-6, TNF-α, and IFN-α/ß through the inhibition of MAPKs activation and IRF induction.

Inhibition of lipopolysaccharide-induced inflammatory responses by piperine.

Piperine, a main component of Piper longum Linn. and Piper nigrum Linn., is a plant alkaloid with a long history of medical use. Piperine exhibits anti-inflammatory activity; however, the underlying mechanism remains unknown. We examined the effects of piperine on lipopolysaccharide (LPS)-induced inflammatory responses. Administration of piperine inhibited LPS-induced endotoxin shock, leukocyte accumulation and the production of tumor necrosis factor-alpha (TNF-alpha), but not of interleukin (IL)-1beta and IL-6. In peritoneal macrophages, piperine inhibited LPS/poly (I:C)/CpG-ODN-induced TNF-alpha production. Piperine also inhibited LPS-induced endotoxin shock in TNF-alpha knockout (KO) mice. To clarify the inhibitory mechanism of LPS-induced endotoxin shock, type 1 interferon (IFN) mRNA expression was determined. Piperine inhibited LPS-induced expression of type 1 IFN mRNA. Piperine inhibited the levels of interferon regulatory factor (IRF)-1 and IRF-7 mRNA, and the phosphorylation and nuclear translocation of IRF-3. Piperine also reduced activation of signal transducer and activator of transcription (STAT)-1. In addition, activation of STAT-1 was inhibited in IFN-alpha/beta-treated cells by piperine. These results suggest that piperine inhibits LPS-induced endotoxin shock through inhibition of type 1 IFN production.

Selective GSK-3beta inhibitors attenuate the cisplatin-induced cytotoxicity of auditory cells.

Glycogen synthase kinase-3 (GSK-3) plays an important role in the regulation of apoptosis. However, the role of GSK-3 in the auditory system remains unknown. Here we examined whether the GSK-3-specific inhibitors, SB 216763 and LiCl, could protect against cisplatin-induced cytotoxicity of auditory cells. GSK-3 was activated by cisplatin treatment of HEI-OC1 cells. SB 216763 or LiCl treatments inhibited cisplatin-induced apoptosis in a dose-dependent manner and activated caspase-9, -8 and -3. In rat primary explants of the organ of Corti, SB 216763 or LiCl treatments completely abrogated the cisplatin-induced destruction of outer hair cell arrays. Administration of SB 216763 or LiCl inhibited cochlear destruction and the production of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and IL-6 in cisplatin-injected mice. Furthermore, administration of SB 216763 or LiCl reduced the thresholds of the auditory brainstem response (ABR) in cisplatin-injected mice. Collectively, these results suggest that cisplatin-induced ototoxicity might be associated with modulation of GSK-3 activation.

Gardenia jasminoides protects against cerulein-induced acute pancreatitis.

AIM: To investigate the effect of Gardenia jasminoides (GJ) on cerulein-induced acute pancreatitis (AP) in mice. METHODS: C57BL/6 mice weighing 18-20 g were divided into three groups. (1) Normal saline-treated group, (2) treatment with GJ at a dose of 0.1 g/kg, (3) treatment with GJ at a dose of 1 g/kg. GJ was administered orally (n = 6 per group) for 1 wk. Three hours later, the mice were given an intraperitoneal injection of cerulein (50 microg/kg), a stable cholecystokinin (CCK) analogue, every hour for a total of 6 h as described previously. The mice were sacrificed at 6 h after completion of cerulein injections. Blood samples were obtained to determine serum amylase, lipase and cytokine levels. The pancreas was rapidly removed for morphologic examination and scoring. A portion of pancreas was stored at -70 degree and prepared for the measurement of tissue myeloperoxidase (MPO) activity, an indicator of neutrophil sequestration, and for reverse-transcriptase PCR (RT-PCR) and real-time PCR measurements. RESULTS: Treatment with GJ decreased significantly the severity of pancreatitis and pancreatitis-associated lung injury. Treatment with GJ attenuated the severity of AP compared with saline-treated mice, as shown by reduction in pancreatic edema, neutrophil infiltration, serum amylase and lipase levels, serum cytokine levels, and mRNA expression of multiple inflammatory mediators. CONCLUSION: These results suggest that GJ attenuated the severity of AP as well as pancreatitis-associated lung injury.

Guggulsterone blocks IL-1beta-mediated inflammatory responses by suppressing NF-kappaB activation in fibroblast-like synoviocytes.

Guggulsterone is a plant sterol that is used to treat hyperlipidemia, arthritis, and obesity. Although its anti-inflammatory and anti-hyperlipidemic effects have been well documented, the effect of guggulsterone on fibroblast-like synoviocytes (FLS) has not yet been reported. Therefore, in this study, the effect of guggulsterone on interleukin (IL)-1beta-induced inflammatory responses in the FLS of rheumatic patients was investigated. Treatment of FLS with IL-1beta induced production of chemokines such as RANTES and ENA-78. In addition, Western blot analysis and gelatin zymography revealed that IL-1beta activated matrix metalloproteinase (MMP)-1 and -3 in FLS. However, pre-incubation with guggulsterone completely inhibited the ability of IL-1beta to induce the production of chemokines and to activate MMPs. Although the NF-kappaB binding activity and nuclear p50 and p65 subunit levels, as well as IkappaBalpha degradation in the cytoplasm was greater in cells stimulated with IL-1beta than in unstimulated cells, treatment with guggulsterone abolished all of these increases. Collectively, these results suggest that guggulsterone would be useful as an inhibitor of joint destruction in patients with rheumatoid arthritis.

Effects of bee venom on cholecystokinin octapeptide-induced acute pancreatitis in rats.

OBJECTIVES: Bee venom (BV) has frequently been used as a remedy for inflammatory diseases. The aim of this study was to investigate the effect of BV on cholecystokinin octapeptide (CCK-8)-induced acute pancreatitis (AP) in rats. METHODS: The BV pretreatment group: 0.25 mg/kg BV was administered subcutaneously, followed by 75 mug/kg CCK-8 subcutaneously 3 times after 1, 3, and 5 hours. This whole procedure was repeated for 5 days. CONTROL GROUP: CCK-8 subcutaneously 3 times after 1, 3, and 5 hours for 5 days. The BV posttreatment group: CCK-8 subcutaneously 3 times at an interval of 2 hours for 3 days, and then 0.25 mg/kg of BV was administered subcutaneously. CONTROL GROUP: CCK-8 subcutaneously 3 times at an interval of 2 hours for 3 days. RESULTS: The BV pretreatment and posttreatment ameliorated many of the examined laboratory parameters (the pancreatic weight [PW]/body weight [BW] ratio, the serum amylase and lipase activity) and reduced histological damages in pancreas. Furthermore, BV pretreatment reduced the production of tumor necrosis factor-alpha, interleukin 1, and interleukin 6 and also decreased pancreatic nuclearfactor-kappaB binding activity compared with saline-treated group in the AP model. The BV also increased heat shock protein 60 (HSP60) and heat shock protein 72 (HSP72) compared with the saline-treated group in the AP model. CONCLUSIONS: These findings suggest that the anti-inflammatory effect of BV in CCK-8-induced AP seems to be mediated by inhibiting nuclear factor-kappaB binding activity, and that BV may have a protective effect against AP.

Selective cyclooxygenase-2 inhibitor ameliorates cholecystokinin-octapeptide-induced acute pancreatitis in rats.

AIM: To investigate the effect of selective Cycloo-xygenase-2 (COX-2) inhibitor 4-[5-(4-Chloro-phenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl] benzenesulfonamide (SC-236), on the cholecystokinin (CCK)-octapeptide-induced acute pancreatitis (AP) in rats. METHODS: Wistar rat weighing 240 g to 260 g were divided into three groups. (1) Normal DMSO treated group, (2) SC-236 at 4 mg/kg treated group; SC-236 systemically administered via the intravenous (i.v.) catheter, followed by 75 microg/kg CCK octapeptide subcutaneously three times, after 1, 3 and 5 h. This whole procedure was repeated for 5 d. (3) Dimethyl sulfoxide (DMSO) treated group: an identical protocol was used in this group as in the SC-236 cohort (see 2. above). Repeated CCK octapeptide treatment resulted in a typical experimentally induced pancreatitis in the Wistar rats. RESULTS: SC-236 improved the severity of CCK-octapeptide-induced AP as measured by laboratory criteria [the pancreatic weight/body weight (p.w/b.w) ratio, the level of serum amylase and lipase]. The SC-236 treated group showed minimal histologic evidence of pancreatitis and a significant reduction in myeloperoxidase activity. SC-236 also increased heat shock protein (HSP)-60 and HSP72 compared with the DMSO-treated group in the CCK-octapeptide-induced AP and also reduced the pancreatic levels of COX-2. Furthermore, SC-236 reduced proinflammatory cytokine synthesis and inhibited NF-kappaB activation compared with the DMSO-treated group in the CCK-octapeptide-induced AP. CONCLUSION: Our results suggested that COX-2 plays pivotal role in the development of AP and COX-2 inhibitors may play a beneficial role in preventing AP.