Açaí (Euterpe Oleraceae Mart.) Seeds Regulate NF-κB and Nrf2/ARE Pathways Protecting Lung against Acute and Chronic Inflammation.

BACKGROUND/AIMS: Respiratory diseases are the world's biggest cause of mortality and disability. Specific nutrients have been proposed to positively affect disease progression as novel therapy alternatives to glucocorticosteroids. There has been a lot of attention in the possible health advantages of dietary assumption of Açai Seeds, popular native fruit found in the Amazon region which is rich in bioactive compounds. Until today nobody investigated the beneficial property of Açai Seeds administration in lung disease. METHODS: In our study we use two model of lung disease: for acute lung disease we use an intrapleural injection of Carrageenan; for chronic disease we used an intratracheal instillation of bleomycin. Açai Seeds was administered orally dissolved in saline. RESULTS: We found that Açai Seeds was able to reduce histological alteration, cells infiltration, pro inflammatory cytokine release, inflammation, and oxidative stress in both acute and chronic model of lung disease. CONCLUSION: Our data clearly demonstrate for the first time that Açai Seeds administration was useful against lung disease by the reduction of NF-κB nuclear translocation and by the stimulation of Nrf2/ARE pathways promoting the physiological antioxidant defense.

Enhanced anti-tumor effects of the PD-1 blockade combined with a highly absorptive form of curcumin targeting STAT3.

PD-1/PD-L1 immune checkpoint inhibitors are promising cancer immunotherapies however responses are still limited and the development of more effective combination immunotherapy is needed. We previously reported that STAT3 activation in cancer cells and immune cells was involved in immune-resistant mechanisms. In this study, we evaluated the effect of highly absorptive forms of curcumin extracts and synthetic curcumin on anti-tumor T cell responses. The curcumin po administration resulted in the significant augmentation of in vivo induction of tumor antigen-specific T cells through restoration of dendritic cells (DCs) by inhibiting directly STAT3 in DCs and indirectly via reduced IL-6 production from STAT3 activated cancer cells in 2 syngeneic MC38 and CT26 murine tumor models. Curcumin also showed direct DC enhancing activity and enhanced T cell induction for the immunized antigens in non-tumor-bearing mice and human hosts. Curcumin restored DC functions in xenogeneic nude mouse model implanted with high IL-6-producing human clear cell ovarian cancer cells. The combination of curcumin and PD-1/PD-L1 Abs demonstrated a synergistic anti-tumor activity in MC38 murine tumor models. These results indicated that curcumin augments the induction of tumor antigen-specific T cells by restoring the T cell stimulatory activity of DCs targeting activated STAT3 in both cancer cells and immune cells. Combination immunotherapy with curcumin and PD-1/PD-L1 Ab is an attractive strategy in the development of effective immunotherapy against various cancers.

Effects of 1,25-dihydroxyvitamin D3 on experimental periodontitis and AhR/NF-κB/NLRP3 inflammasome pathway in a mouse model.

Vitamin D has been known to have important regulatory functions in inflammation and immune response and shows inhibitory effects on experimental periodontitis in animal models. However, the potential mechanism has yet to be clarified. Recent studies have highlighted Aryl hydrocarbon receptor (AhR) and its downstream signaling as a crucial regulator of immune homeostasis and inflammatory regulation. OBJECTIVE: This study aimed to clarify the effect of 1,25-dihydroxyvitamin D3 (VD3) on experimental periodontitis and AhR/nuclear factor-κB (NF-κB)/NLR pyrin domain-containing 3 (NLRP3) inflammasome pathway in the gingival epithelium in a murine model. METHODOLOGY: We induced periodontitis in male C57BL/6 wild-type mice by oral inoculation of Porphyromonas gingivalis (P. gingivalis), and subsequently gave intraperitoneal VD3 injection to the mice every other day for 8 weeks. Afterwards, we examined the alveolar bone using scanning electron microscopy (SEM) and detected the gingival epithelial protein using western blot analysis and immunohistochemical staining. RESULTS: SEM images demonstrated that alveolar bone loss was reduced in the periodontitis mouse model after VD3 supplementation. Western blot analyses and immunohistochemical staining of the gingival epithelium showed that the expression of vitamin D receptor, AhR and its downstream cytochrome P450 1A1 were enhanced upon VD3 application. Additionally, VD3 decreased NF-κB p65 phosphorylation, and NLRP3, apoptosis-associated speck-like protein, caspase-1, interleukin-1ß (IL-1ß) and IL-6 protein expression. CONCLUSIONS: These results implicate the alleviation of periodontitis and the alteration of AhR/NF-κB/NLRP3 inflammasome pathway by VD3 in the mouse model. The attenuation of this periodontal disease may correlate with the regulation of AhR/NF-κB/NLRP3 inflammasome pathway by VD3.

Sambucus australis Modulates Inflammatory Response via Inhibition of Nuclear Factor Kappa B (NF-kB) in vitro.

Medicinal plants have long been used as an alternative to traditional drugs for the treatment of inflammatory conditions due to the classical side effects and restricted access of various commercially available drugs, such as steroids (GCs) and nonsteroidal anti-inflammatory drugs (NSAIDs). Sambucus australis is a Brazilian herb that is commonly used to treat inflammatory diseases; however, few studies have examined the use of this species in the treatment of inflammatory conditions. The present study aims to evaluate the potential anti-inflammatory activity of S. australis in vitro. We established spleen cell cultures stimulated with pokeweed mitogen (PWM) to evaluate the production of proinflammatory cytokines, such as IL-4, IL-5, IFN-y, and IL-10 (by ELISA), and the expression of the transcription factor NF-kB (by RT-PCR). In addition, we evaluated the levels of nitric oxide in macrophage cultures and the membrane-stabilizing activity of S. australis methanolic extract (EMSA). Treatment with EMSA at concentrations of 100, 50, 25 and 12.5 µg/ml significantly decreased IL-4 (p<0.001) and IL-5 (p<0.001) levels. Treatment with 100 µg/ml EMSA reduced IFN-у (p<0.001) levels. Moreover, at 100 mg/ml, EMSA also increased IL-10 production and reduced NF-kB expression (p<0.01). In macrophage cultures stimulated with LPS, EMSA decreased nitric oxide levels (p<0.001) at all concentrations tested (100, 50, 25 and 12.5 µg/ml). Additionally, EMSA had a protective effect in the erythrocyte membrane stabilization assay. Taken together, these results suggest that S. australis has anti-inflammatory potential in vitro, characterized by the reduction of both inflammatory cytokines and the expression of NF-kB along with the up-regulation of IL-10.

QingBai decoction regulates intestinal permeability of dextran sulphate sodium-induced colitis through the modulation of notch and NF-κB signalling.

OBJECTIVE: Chinese Herb QingBai decoction (QBD) has been approved affective in the treatment of IBD patients in clinic. However, the underlying mechanism remains unknown. We aim to investigate the effect of QBD on the mouse model of ulcerative colitis and its possible mechanism. METHODS: C57/bL mice were given 5% DSS to induce colitis and were divided as QBD and mesalazine group. Weight, faeces and mental status were recorded each day and the histopathological changes (goblet cells etc) of the colon were observed after sacrificed. Fluorescein isothiocyanate-dextran 4000 was measured to reflect the intestinal mucosal permeability. In addition, cell junction-related proteins and possible signal pathways were investigated. RESULTS: QingBai decoction could significantly alleviate the inflammation and the protection effect of colitis is comparable as those in mesalazine enema group. It was found that the permeability reduced significantly with QBD treatment vs the control group, while no significant difference between the mesalazine and QBD groups. QBD treatment could upregulate the expression of tight junction complex（ZO-1, claudin-1 and occludin）and muc-2 expression. It significantly reduced the production and secretion of serials proinflammatory cytokines (IL-1ß, IL-6, Kc and TNF-α) compared with the control group. Meanwhile, NF-κB and Notch pathways were regulated. CONCLUSION: QingBai decoction can effectively alleviate intestinal inflammation and mucosal barrier function in colitis mice, and the mechanism may be related to the inhibition of inflammatory cascade as well as enhanced mucus layer barrier and mechanical barrier function by NF-κB and Notch signalling.

Effects of 1, 25-dihydroxyvitamin D3 on experimental periodontitis and AhR/NF-κB/NLRP3 inflammasome pathway in a mouse model

Abstract Vitamin D has been known to have important regulatory functions in inflammation and immune response and shows inhibitory effects on experimental periodontitis in animal models. However, the potential mechanism has yet to be clarified. Recent studies have highlighted Aryl hydrocarbon receptor (AhR) and its downstream signaling as a crucial regulator of immune homeostasis and inflammatory regulation. Objective: This study aimed to clarify the effect of 1,25-dihydroxyvitamin D3 (VD3) on experimental periodontitis and AhR/nuclear factor-κB (NF-κB)/NLR pyrin domain-containing 3 (NLRP3) inflammasome pathway in the gingival epithelium in a murine model. Methodology: We induced periodontitis in male C57BL/6 wild-type mice by oral inoculation of Porphyromonas gingivalis (P. gingivalis), and subsequently gave intraperitoneal VD3 injection to the mice every other day for 8 weeks. Afterwards, we examined the alveolar bone using scanning electron microscopy (SEM) and detected the gingival epithelial protein using western blot analysis and immunohistochemical staining. Results: SEM images demonstrated that alveolar bone loss was reduced in the periodontitis mouse model after VD3 supplementation. Western blot analyses and immunohistochemical staining of the gingival epithelium showed that the expression of vitamin D receptor, AhR and its downstream cytochrome P450 1A1 were enhanced upon VD3 application. Additionally, VD3 decreased NF-κB p65 phosphorylation, and NLRP3, apoptosis-associated speck-like protein, caspase-1, interleukin-1β (IL-1β) and IL-6 protein expression. Conclusions: These results implicate the alleviation of periodontitis and the alteration of AhR/NF-κB/NLRP3 inflammasome pathway by VD3 in the mouse model. The attenuation of this periodontal disease may correlate with the regulation of AhR/NF-κB/NLRP3 inflammasome pathway by VD3.

Aromatic-turmerone ameliorates imiquimod-induced psoriasis-like inflammation of BALB/c mice.

Psoriasis is a usual immune-mediated inflammatory skin disease with undefined pathogenesis. Aromatic-turmerone (ATM) is a mainly constituent of essential oil from Curcuma longa L. It has been shown to exhibit strong anti-oxidant, anti-tumor activities and anti-inflammatory effects. In this study, we investigated the effects of ATM on imiquimod (IMQ)-induced psoriasis-like BALB/c mice and its molecular mechanisms for anti-inflammatory effect. ATM showed inhibition of the transfer of CD8+ T cells in epidermis, and reduced expression of NF-κB and COX-2 as well as phosphorylation of p38 MAPK. It also decreased the level of TNF-α and IL-6, and down-regulates IL-17 IL-22 and IL-23 mRNA synthesis. Notably, we demonstrated that topically applied ATM alleviated skin inflammation in IMQ-induced mice. These results indicate that ATM, a natural active compound exhibits anti-inflammatory activity and is a promising candidate molecule to treat inflammatory skin diseases, such as psoriasis.

Protective effects of hyperbaric oxygen preconditioning against LPS-induced acute lung injury in rats.

INTRODUCTION: Acute lung injury (ALI) is generally caused by oxidative damages and pulmonary overinflammations. Hyperbaric oxygen preconditioning (HBO2-PC) has been proven protective against oxidative-stress-related injuries. In this study, we investigated the effect of HBO2-PC on lipopolysaccharide (LPS)-induced ALI in rats. METHODS: Thirty-two Sprague-Dawley rats randomly assigned into Sham, HBO2-PC, ALI and HBO2-PC÷ALI groups (eight in each group) were sacrificed at 12 hours after the injection of LPS. The severity of ALI in rats was assessed in terms of histopathological changes in addition to wet/dry weight ratios. The levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1ß in serum and lung homogenates were measured by enzyme-linked immunosorbent and qRT-PCR assays. Activities by hydrogen peroxide (H2O2), malondialdehyde (MDA), myeloperoxidase (MPO) as well as superoxide dismutase (SOD) in rat lungs were tested for neutrophil infiltration. Meanwhile the oxidative stress molecular markers nuclear factor-kappa B(NF-κB) p65 and nuclear factor erythroid 2-related factor 2 (Nrf2), together with its downstream heme-oxygenase 1 (HO-1) and NAD(P)H: quinone oxidoreductase 1 (NQO1) were also quantified. RESULTS: HBO2-PC significantly alleviated LPS-induced ALI, lowered the lung injury scores, reduced lung water content, and reduced H2O2, MDA levels as well as MPO activity, while simultaneously improving the arterial partial oxygen pressure (PaO2) and SOD activity. Furthermore, HBO2-PC inhibited the nuclear translocation of NF-κB p65 while enhancing the nuclear translocation of Nrf2, thus upregulating HO-1 and NQO1. CONCLUSIONS: Our results suggest that HBO2-PC was potentially protective for LPS-induced ALI lungs in rats, with a presumed mechanism that suppressed NF-κB while activating Nrf2. We propose that HBO2-PC should be considered a potential therapeutic strategy against ALI in rats.

Molecular evaluation of anti-inflammatory activity of phenolic lipid extracted from cashew nut shell liquid (CNSL).

BACKGROUND: Anacardium occidentale L phenolic lipid (LDT11) is used in traditional medicine as anti-inflammatory, astringent, antidiarrheal, anti-asthmatic and depurative. Phenolic derivatives, such as anacardic acid, extracted from cashew nut shell liquid (CNSL) have demonstrated biological and pharmacological properties, and its profile makes it a candidate for the development of new anti-inflammatory agents. The objective of the present study was to evaluate the anti-inflammatory profile of a derivative, synthesized from LDT11, on an in vitro cellular model. METHODS: Organic synthesis of the phenolic derivative of CNSL that results in the hemi-synthetic compound LDT11. The cytotoxicity of the planned compound, LDT11, was analyzed in murine macrophages cell line, RAW264.7. The cells were previously treated with LDT11, and then, the inflammation was stimulated with lipopolysaccharide (LPS), in intervals of 6 h and 24 h. The analysis of the gene expression of inflammatory markers (TNFα, iNOS, COX-2, NF-κB, IL-1ß and IL-6), nitric oxide (NO) dosage, and cytokine IL-6 were realized. RESULTS: The results showed that the phenolic derivative, LDT11, influenced the modulatory gene expression. The relative gene transcripts quantification demonstrated that the LDT11 disclosed an immunoprotective effect against inflammation by decreasing genes expression when compared with cells stimulated with LPS in the control group. The NO and IL-6 dosages confirmed the results found in gene expression. DISCUSSION: The present study evaluated the immunoprotective effect of LDT11. In addition to a significant reduction in the expression of inflammatory genes, LDT11 also had a faster and superior anti-inflammatory action than the commercial products, and its response was already evident in the test carried out six hours after the treatment of the cells. CONCLUSION: This study demonstrated LDT11 is potentially valuable as a rapid immunoprotective anti-inflammatory agent. Treatment with LDT11 decreased the gene expression of inflammatory markers, and the NO, and IL-6 production. When compared to commercial drugs, LDT11 showed a superior anti-inflammatory action.

Anti-Inflammatory Activity of Chemical Constituents Isolated from the Willow Bracket Medicinal Mushroom Phellinus igniarius (Agaricomycetes).

Nuclear factor-κB (NF-κB) has an important role in immune response and inflammation. Phellinus igniarius (known as Sang huang in traditional Chinese medicine) has various pharmacologic effects. In this study, 19 chemical constituents (1-19) were isolated from the fruiting bodies of Ph. igniarius. Their structures were elucidated based on data from nuclear magnetic resonance spectroscopy and comparison with the literature. Overall, 3 compounds (2, 7, and 11) from this species were reported, to our knowledge for the first time. Two compounds (4 and 15) from the genus Phellinus and 9 compounds (1, 3, 5, 8-10, and 12-14) from the Hymenochaetaceae family were also reported for the first time. An NF-κB luciferase reporter assay of these compounds was carried out in tumor necrosis factor-α-induced HeLa cells-again, to our knowledge for the first time. Among them, compounds 5 and 7 showed moderate inhibition of NF-κB, with fold values of 0.48 ± 0.02 and 0.55 ± 0.09, respectively, in HeLa cells at 100 µmol/L. These results suggest that some of the ingredients from Ph. igniarius could be developed into antiinflammatory agents for use in clinical applications.

Determining the Effects of Geraniol on Liver Regeneration Via the Nuclear Factor kB Pathway After Partial Hepatectomy.

Context • Nuclear factor kB (NF-κB) is a dimeric transcription factor that is involved in the regulation of regenerative and apoptosic genes and plays a key role in liver regeneration after a partial hepatectomy (PH). Complementary medicine is used to treat various diseases and can be obtained from a large number of plants that are found in nature. One such plant is geraniol, and no studies have yet occurred assessing its in vivo effects on liver regeneration. Objective • The current study intended to assess the effects of geraniol on liver regeneration after a 70% PH in rats. Design • The research team studied geraniol in a rat model in vivo. Setting • The study took place in the medical and surgical experimental research center at Eskisehir Osmangazi University (Eskisehir, Turkey). Animals • The animals were Wistar albino male rats. Intervention • The rats were divided into 8 groups with 6 rats in each group. Two groups were the sham control groups. The other 6 groups received an injection of a single dose of saline, the negative control; silymarin, the negative control; or geraniol, the intervention. The injections were given intraperitoneally immediately after PH. A laparotomy was performed on the rats all of those groups at either 24 h or 48 h after the PH. Outcome Measures • Using the reverse transcription (RT)- polymerase chain reaction (PCR) method (RT-PCR) and Western blot analysis, the NF-κB, tumor necrosis factor α, and interleukin 6 gene expression and protein levels were measured. Moreover, the levels of the heat shock proteins (HSPs) HSP27 and HSP60 were examined by Western blot. Results • The data showed that geraniol had a significant role (P < .05) in increasing the process of liver regeneration when given intraperitoneally, and it protected the liver as assessed by histology and the HSP levels. In rats receiving 100 mg/kg geraniol intraperitoneally, the agent induced hepatic regeneration 24 h and 48 h after PH (70%).

The anti-inflammatory effect of Sonchus oleraceus aqueous extract on lipopolysaccharide stimulated RAW 264.7 cells and mice.

CONTEXT: Sonchus oleraceus L. (Asteraceae) (SO) is a dietary and traditional medicinal plant in China. However, its underlying mechanism of action as an anti-inflammatory agent is not known. OBJECTIVE: This study evaluates the anti-inflammatory activity of aqueous extract of SO. MATERIALS AND METHODS: The extract of SO was used to treat RAW 264.7 cells (in the working concentrations of 500, 250, 125, 62.5, 31.3 and 15.6 µg/mL) for 24 h. Pro-inflammatory cytokines and mediators produced in LPS-stimulated RAW 264.7 cells were assessed. Meanwhile, the expression level of TLR-4, COX-2, pSTATs and NF-κB was tested. Moreover, the anti-inflammatory activity of the extract in vivo was assessed using xylene-induced mouse ear oedema model and the anti-inflammatory compounds in the extracts were analyzed by HPLC-MS. RESULTS: SO extract significantly inhibited the production of pro-inflammatory cytokines and mediators at gene and protein levels with the concentration of 31.3 µg/mL, and suppressed the expression of TLR-4, COX-2, NF-κB and pSTAT in RAW 264.7 cells. The anti-inflammatory activity of SO in vivo has significant anti-inflammatory effects with the concentration of 250 and 125 mg/kg, and less side effect on the weights of the mice at the concentration of 250 mg/kg. Moreover, HPLC-MS analysis revealed that the anti-inflammatory compounds in the extract were identified as villosol, ferulaic acid, ß-sitosterol, ursolic acid and rutin. DISCUSSION AND CONCLUSION: This study indicated that SO extract has anti-inflammatory effects in vitro and in vivo, which will be further developed as novel pharmacological strategies in order to defeat inflammatory diseases.

Modulation of oxidative stress, inflammation, autophagy and expression of Nrf2 in hippocampus and frontal cortex of rats fed with açaí-enriched diets.

OBJECTIVE: Açaí (Euterpe spp.), an exotic palm fruit, has recently emerged as a promising source of natural antioxidants with wide pharmacological and nutritional value. In this study, two different species of açaí pulp extracts, naturally grown in two distinct regions of the Amazon, namely, Euterpe oleracea Mart. (habitat: Brazilian floodplains of the Amazon) and Euterpe precatoria Mart. (habitat: Bolivian Amazon), were studied for their effects on brain health and cognition. METHODS: Neurochemical analyses were performed in critical brain regions associated with memory and cognition of 19-month-old açaí-fed rats, in whom the cognitive benefits of açaí had been established. RESULTS: Results indicated significant reductions (P< 0.05) in prooxidant NADPH-oxidoreductase-2 (NOX2) and proinflammatory transcription factor NF-κB in açaí-fed rats. Measurement of Nrf2 expression, a transcription factor for antioxidant enzymes, and a possible link between oxidative stress, neuroinflammation and autophagy mechanisms, indicated significant overexpression (P<0.005) in the hippocampus and frontal cortex of the açaí-fed rats. Furthermore, significant activation of endogenous antioxidant enzymes GST and SOD were also observed in the açaí-fed animals when compared to control. Analysis of autophagy markers such as p62, phospho-mTOR, beclin1 and MAP1B-LC3 revealed differential expression in frontal cortex and hippocampus, mostly indicating an upregulation in the açaí-fed rats. DISCUSSION: In general, results were more profound for EP than EO in hippocampus as well as frontal cortex. Therefore, an açaí-enriched diet could possibly modulate Nrf2, which is known to modulate the intracellular redox status, thereby regulating the ubiquitin-proteosomal pathway, ultimately affecting cognitive function in the aging brain.

Comparison and evaluation of antimuscarinic and anti-inflammatory effects of five Bulbus fritillariae species based on UPLC-Q/TOF integrated dual-luciferase reporter assay, PCA and ANN analysis.

Many species of Bulbus fritillariae are used as traditional medicines for thousands of years; however, their application is not standardized. To clarify the differences and homologies, the antimuscarinic and anti-inflammatory effects of five BM species were firstly tested and compared at cellular level. With an integrated strategy combining UPLC-Q/TOF MS, PCA and ANN analysis, the active ingredients among 28 different chemical markers were predicted and identified. SB and QB extracts showed the best antimuscarinic effects and several steroidal alkaloids, such as solanidine, contributed to this effects. However, ZB was superior to reduce the inflammatory response. Another five components were responsible by decreasing the expression of NF-κB, including puqiedine, zhepeiresinol, 2-monopalmitin, N-demethylpuqietinone, and isoverticine. More novelty, a new cluster of five BM species based on active ingredients as potential quality markers was depicted to illustrate their functions. These results of the study could make a reference for the medicinal application of BM species in clinic; and the integrated strategy provided an effective method to obtain the quality markers from medical herbs, which was helpful for the quality control of traditional medicinal products.

Insights into the mechanism of natural terpenoids as NF-κB inhibitors: an overview on their anticancer potential.

The transcription factor, nuclear factor kappa B (NF-kB) is one of the principal inducible protein in mammals known to control the gene expression in many critical physiological responses such as oxidative stress, inflammation etc. and has been shown to play an important role in the pathogenesis of cancer. Terpenoids are major constituents present in nutritionally used fruits, vegetables and different spices which possess various pharmacological action including anticancer activity. Various terpenoids, viz. monoterpenoids, sesquiterpenoids, diterpenoids, sesterterpenoids, triterpenoids, tetraterpenoids and polyterpenoids inhibit NF-kB signa-ling pathway through IkB phosphorylation, DNA binding, p65 translocation etc. Keeping in mind these facts, the present review revealed the anti-cancer potential of naturally occurring terpenoids highlighting their mechanism of NF-kB inhibition. This review also focuses on some of the naturally occurring terpenoids belonging to various chemical categories with potential inhibitory effects on NF-kB and their role in the treatment of cancer.

Anti-inflammatory effects of Viola yedoensis and the application of cell extraction methods for investigating bioactive constituents in macrophages.

BACKGROUND: Viola yedoensis (VY, Violaceae) is a popular medicinal herb used in traditional eastern medicine for treating lots of diseases, including inflammation and its related symptoms. However, the anti-inflammatory properties of VY have not been demonstrated. In the present study, we investigated the anti-inflammatory effects of VY ethanol extract (VYE) on macrophages and attempted to identify the bioactive components of VYE. METHODS: We assessed the effects of VYE on secretion of nitric oxide (NO) and inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1ß. In addition, we explored the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, and changes in heme oxygenase (HO)-1, nuclear factor (NF)-kB, and mitogen-activated protein kinase (MAPK) signaling pathways in RAW 264.7 macrophages stimulated by lipopolysaccharide (LPS). In addition, a rapid and useful approach to identify potential bioactive components in VYE with anti-inflammatory effects was developed using murine macrophage cell extraction coupled with high-performance liquid chromatography tandem mass spectrometry (LC-MS). RESULTS: We found that VYE exerted anti-inflammatory activity by inhibiting the production of key inflammation mediators and related products, as well as suppression of HO-1, NF-kB, and MAPK signaling pathway activation in RAW 264.7 cells. In addition, we identified two compounds in VYE via the cell extraction method. CONCLUSIONS: Our results revealed that VYE exerts anti-inflammatory activities and its detailed inhibitory mechanism in macrophages. Furthermore, we identified bioactive components of VYE.

Curcumin improves LPS-induced preeclampsia-like phenotype in rat by inhibiting the TLR4 signaling pathway.

INTRODUCTION: Abnormal inflammation mediated by Toll-like receptor 4 (TLR4) signaling pathway contributes to preeclampsia (PE). Because curcumin can inhibit TLR4 signaling pathway, we investigated its effects on a PE rat model. METHODS: Twenty-one pregnant rats were randomly divided into three groups: 1) seven rats were injected 0.5 µg/kg lipopolysaccharide (LPS) on gestational day (GD) 5 to create a PE model (LPS-treated group), 2) seven rats were injected with a similar dosage of LPS and further treated with curcumin (0.36 mg/kg) (LPS-curcumin-treated group), 3) seven rats received saline (control group). Blood pressure and urinary protein level were observed. Immunostaining and periodic acid-Schiff staining of placenta were conducted. TLR4 and downstream Nuclear Factor-κB (NF-κB) expressions of placenta were analyzed by Western blot and immunohistochemistry. IL-6 and MCP-1 in rat serum and placenta were determined by ELISA and qRT-PCR. RESULTS: Compared to LPS-treated group, LPS-curcumin-treated group had decreased blood pressure and urinary protein level, similar to control group. Furthermore, deficient trophoblast invasion and spiral artery remodeling induced by LPS were improved by curcumin. Increased TLR4, NF-κB and IL-6, MCP-1 protein expressions in LPS-treated group were significantly decreased after curcumin administration. DISCUSSION: Curcumin improves the PE-like phenotype in rat model by reducing abnormal inflammation related to TLR4 signaling pathway.

Brown seaweeds protect against azoxymethane-induced hepatic repercussions through up-regulation of peroxisome proliferator-activated receptor gamma and attenuation of oxidative stress.

CONTEXT: Seaweeds of the genera Turbinaria and Padina have long been used as food and in traditional medicine for treating several diseases. OBJECTIVE: The current study determines the protective efficacy of the brown seaweeds Turbinaria ornata (Turner) J. Agardh (Sargassaceae) and Padina pavonia (Linnaeus) J.V. Lamouroux (Dictyotaceae) against liver injury induced by azoxymethane (AOM). MATERIALS AND METHODS: Male Swiss mice received 10 mg/kg AOM once a week for two consecutive weeks and then 100 mg/kg daily dose of either T. ornata or P. pavonia ethanolic extract. Thirteen weeks after the first AOM administration and 24 h after the last treatment, overnight fasted mice were sacrificed and samples collected. RESULTS: Compared with the AOM group, both T. ornata and P. pavonia significantly decreased the activity of aminotransferases and the concentration of bilirubin while increased albumin levels in the serum. The antioxidative effect of both extracts was observed from the increased activity of superoxide dismutase and glutathione peroxidase activities in the liver, both of which were decreased by AOM. Moreover, the levels of malondialdehyde and nitric oxide were reduced, and histological findings also confirmed the antihepatotoxic activity. In addition, treatment with T. ornata and P. pavonia significantly increased PPARγ and decreased NF-κB expression in the liver of AOM-administered mice. DISCUSSION AND CONCLUSION: Our findings indicate that the protective function of T. ornata and P. pavonia on AOM-induced liver injury may be possibly exerted by multiple pathways including abolishment of inflammation and oxidative damage, and activation of PPARγ.

Tetrandrine ameliorates sevoflurane­induced cognitive impairment via the suppression of inflammation and apoptosis in aged rats.

Tetrandrine is a bisbenzylisoquinoline alkaloid extracted from Stephania tetrandra, a traditional Chinese herbal medicine, which has been observed to exert anti­inflammatory effects. The aim of the current study was to investigate whether tetrandrine was able to ameliorate sevoflurane­induced cognitive impairment in aged rats. Male 20­month­old Sprague­Dawley rats underwent sevoflurane­induction in an environment containing 2% sevoflurane for 5 h. The Morris water maze test was used to measure the effect of tetrandrine on learning and memory in sevoflurane­treated aged rats. Western blot analysis of the protein expression levels of cyclooxygenase­2 (COX­2), inducible nitric oxide synthase (iNOS) and Bcl­2 was conducted. ELISAs were used to measure the levels of interleukin (IL)­1ß, tumor necrosis factor (TNF­α), nuclear factor­κB (NF­κB) and caspase­3. In the present study, tetrandrine improved the learning and memory deficits observed in sevoflurane­treated aged rats. Treatment with tetrandrine reduced the expression levels of COX­2, IL­1ß, TNF­α, NF­κB, iNOS and caspase­3, and increased the Bcl­2 protein expression in sevoflurane­treated aged rats. In conclusion, the current study indicated that tetrandrine ameliorates sevoflurane­induced cognitive impairment via the suppression of inflammation and apoptosis in aged rats. Thus, tetrandrine may be a potential novel candidate to protect against the effects of sevoflurane anesthesia on cognitive function.

Evaluation of protective effects of costunolide and dehydrocostuslactone on ethanol-induced gastric ulcer in mice based on multi-pathway regulation.

The aim of the present study was to evaluate the anti-ulcerogenic activity of costunolide (Co) and dehydrocostuslactone (De) on ethanol-induced gastric ulcer in mice and to elucidate the potential mechanisms of the action involved. Mice were pretreated orally with Co (5 or 20 mg/kg), De (5 or 20 mg/kg) and omeprazole (OME, 20 mg/kg) for 7 consecutive days, followed by ulcer induction using absolute ethanol (0.2 mL/20 g body weight). Treatment with Co had a remarkable gastroprotection compared to the ethanol-ulcerated mice that significantly reduced the ulcerative lesion index (ULI) and histopathological damage. Daily intragastric administration of Co exerted a powerful anti-inflammatory activity as evidenced by the suppression of nuclear factor (NF)-κB, tumor necrosis factor (TNF)-α, nitric oxide (NO), inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, as well as increased interleukin (IL)-10. Also, pretreatment with Co effectively inhibited ethanol-induced malondialdehyde (MDA) overproduction, increased the depleted superoxide dismutase (SOD) and promoted gastric mucosa epithelial cell proliferation by up-regulating proliferating cell nuclear antigen (PCNA) expression. Similarly, De had a protective effect on ethanol-induced ulcer, which was dependent on the inhibition of inflammatory cytokines and MDA generation, but independent of IL-10, SOD and PCNA improvement. Conclusively, the results have clearly demonstrated the anti-ulcerogenic potential of Co and De on ethanol-induced gastric ulcer; nevertheless, the gastroprotective activity of Co was superior to De due to more multi-pathway regulation than De. These findings suggested that Co or De could be a new useful natural gastroprotective tool against gastric ulcer, which provided a scientific basis for the gastroprotection of sesquiterpene lactones.