Antrodin A from Antrodia camphorata modulates the gut microbiome and liver metabolome in mice exposed to acute alcohol intake.

This study aimed to investigate the protective effect of Antrodin A (AdA) from Antrodia camphorata (A. camphorata) mycelium on alcohol-induced gut microbiota and liver metabolomic disorders. In acute alcoholic liver injury mice, AdA ameliorated alcoholic exposure-induced hepatic lipid deposition (TC and TG), oxidative stress (MDA), inflammation (TNF-α, IL-1ß, IL-6, IL-17 and IFN-γ), and liver damage via modulating microbiome and metabolomic responses. AdA restored the composition of intestinal flora with an increase in the relative abundance of Lactobacillus and Dubosiella and a decrease in Clostridium_sensu_stricto_1, Lachnospiraceae_NK4A136_group, Prevotellaceae_NK3B31_group, and Prevotellaceae_UCG-001. Besides, AdA favorably regulated alcohol-induced metabolic disorders, including glutathione metabolism (S-(2-hydroxyethyl)glutathione and glutathione oxidized), ascorbate and aldarate metabolism (l-ascorbic acid), and taurine and hypotaurine metabolism (taurine). In conclusion, AdA in A. camphorata is a beneficial active ingredient to treat the microbiomic and metabolic disturbance induced by alcohol intake.

Epoxy Coatings Based on Modified Vegetable Oils for Wood Surface Protection against Fungal Degradation.

The study describes the curing and thermal behavior of a new castor oil maleic anhydride adduct/epoxy oils/5-Bromosalicylic acid coatings and their composites with wood. The epoxidized oils were flax and hemp. The kinetic parameters of the curing and thermal degradation processes were calculated. The resistance of the coated wood surfaces against Cladosporium cladosporioides, Aspergillus brasiliensis, and Penicillium chrysogenum was tested. Color changes, FT-IR and SEM were conducted before and after fungal attack. The decay resistance and color change of raw wood and wood treated samples against fungi was tested. Based on the color changes and according to ASTM D 2017, the decay resistance rating for covered samples was considered as "highly resistant". Chemical resistance and coating performance tests were also undertaken. The obtained results recommend the described materials for applications in wood protective coatings.

Antrodin A from mycelium of Antrodia camphorata alleviates acute alcoholic liver injury and modulates intestinal flora dysbiosis in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Antrodia camphorata (A. camphorata) is a rare functional fungus in Taiwan and contains a variety of biologically active ingredients. Antrodin A (AdA) is one of the main active ingredients in the solid-state fermented A. camphorata mycelium. It protects the liver from alcohol damage by improving the antioxidant and anti-inflammatory capacity of the liver and maintaining the stability of the intestinal flora. AIM OF THE STUDY: The aim of this study was to evaluate the hepatoprotective activities of ethyl acetate layer extract (EALE), AdA, and Antroquinonol (Aq) from mycelium of A. camphorata on alcoholic liver injury. MATERIALS AND METHODS: Mice were given with intragastrically vehicle (NC, 2% CMC-Na), alcohol (AL, 12 mL/kg bw), or different A. camphorata samples (EALE, AdA, Aq) at low (100 mg/kg bw) or high (200 mg/kg bw) dosages. The positive control (PC) group was given with silymarin (200 mg/kg bw). Except the NC group, each group of mice was fasted for 4 h after the last treatment and was intragastrically administrated with 50% alcohol (12 mL/kg bw). At the end of experiment, mouse serum was collected and the liver was excised. A portion of the liver was fixed in formalin and used for histopathological analysis, whereas the rest was used for biochemical analysis and real-time PCR analysis. The intestinal flora structure of feces was analyzed by determining the v3-v4 region sequence in 16S rDNA. RESULTS: The high-dose groups of the three samples (EALEH, AdAH, and AqH) significantly alleviated the alcohol-induced increases in liver index, serum ALT, AST, and AKP activities. Serum TG level was significantly reduced in all treatment groups. The increase of HDL-C content indicated that active ingredients of A. camphorata could reduce the lipid content in serum. Furthermore, MDA contents of the AdAH and AqH groups in liver were significantly reduced, accompanying with the levels of SOD, CAT, and GSH elevated to various extents. Antioxidant and anti-inflammatory capabilities in the liver were increased in the AdAH group, as evidenced by the mRNA expression levels of Nrf-2 and HO-1 were significantly increased; while those of CYP2e1, TNF-α, and TLR-4 were significantly decreased. Analysis of intestinal flora of feces showed that alcohol treatment significantly changed the composition of intestinal flora. Supplementation with AdA could mitigate dysbiosis of intestinal flora induced by alcohol. Flora of Faecalibaculum, Lactobacillus, and Coriobacteriaceae_UCG-002 showed significantly negative correlations with ALT, AST, AKP, and MDA levels. CONCLUSION: Antrodin A could improve the antioxidant and anti-inflammatory capacities of the liver and maintain the stability of intestinal flora. It is potentially a good candidate compound against acute alcoholic liver injury.

A review on various maleic anhydride antimicrobial polymers.

The basic requirement of human beings is better health but the serious health effects and numerous infections caused by rapid growth of harmful pathogens resulting in a large number of deaths and is a significant challenge to modern science. Microbes infecting humans can be stopped in two ways: disinfectants and antimicrobial agents. There is considerable interest from both academics and industry in antimicrobial polymers due to their favorable properties. Maleic anhydride incredibly bears diverse commercial applications due to its versatile chemical structure. Maleic anhydride is an electron-acceptor monomer where the property comes from reactive double bonds and also reactive anhydride groups. This review presents the development of antimicrobial polymers involving maleic anhydride in the macromolecular structure. This article also addresses the applications of antimicrobial polymers with maleic anhydride in numerous sectors.

Induction of a non-apoptotic mode of cell death associated with autophagic characteristics with steroidal maleic anhydrides and 7ß-hydroxycholesterol on glioma cells.

Steroidal maleic anhydrides were prepared in one step: lithocholic, chenodeoxicholic, deoxicholic, ursocholic, and hyodeoxicholic acid derivatives. Their capability to induce cell death was studied on C6 rat glioma cells, and 7ß-hydroxycholesterol was used as positive cytotoxic control. The highest cytotoxicity was observed with lithocholic and chenodeoxicholic acid derivatives (23-(4-methylfuran-2,5-dione)-3α-hydroxy-24-nor-5ß-cholane (compound 1a), and 23-(4-methylfuran-2,5-dione)-3α,7α-dihydroxy-24-nor-5ß-cholane (compound 1b), respectively), which induce a non-apoptotic mode of cell death associated with mitochondrial membrane potential loss and reactive oxygen species overproduction. No cells with condensed and/or fragmented nuclei, no PARP degradation and no cleaved-caspase-3, which are apoptotic criteria, were observed. Similar effects were found with 7ß-hydroxycholesterol. The cell clonogenic survival assay showed that compound 1b was more cytotoxic than compound 1a and 7ß-hydroxycholesterol. Compound 1b and 7ß-hydroxycholesterol also induce cell cycle modifications. In addition, compounds 1a and 1b, and 7ß-hydroxycholesterol favour the formation of large acidic vacuoles revealed by staining with acridine orange and monodansylcadaverine evocating autophagic vacuoles; they also induce an increased ratio of [LC3-II / LC3-I], and modify the expression of mTOR, Beclin-1, Atg12, and Atg5-Atg12 which is are autophagic criteria. The ratio [LC3-II / LC3-I] is also strongly modified by bafilomycin acting on the autophagic flux. Rapamycin, an autophagic inducer, and 3-methyladenine, an autophagic inhibitor, reduce and increase 7ß-hydroxycholesterol-induced cell death, respectively, supporting that 7ß-hydroxycholesterol induces survival autophagy. Alpha-tocopherol also strongly attenuates 7ß-hydroxycholesterol-induced cell death. However, rapamycin, 3-methyladenine, and α-tocopherol have no effect on compounds 1a and 1b-induced cell death. It is concluded that these compounds trigger a non apoptotic mode of cell death, involving the mitochondria and associated with several characteristics of autophagy.

Impact of styrene maleic anhydride (SMA) based hydrogel on rat fallopian tube as contraceptive implant with selective antimicrobial property.

Development of non-hormonal female contraception is a need to combat against increasing population growth. The presently available short term or long term female contraceptives and sterilization methods have their own restrictions and side effects. With this objective, herein, we describe an innovative insight about the use of hydrogel formulation consisting of Styrene Maleic Anhydride (SMA) dissolved in Dimethyl Sulfoxide (DMSO) as non-hormonal fallopian tube contraceptive implant. Firstly, in vitro behavior of SMA hydrogel was evaluated by in vitro swelling and rheological properties to comprehend the polymeric hydrogel property post implantation inside the fallopian tube. Simulated Uterine Fluid (SUF) was used to simulate female reproductive tract environment in this study. Mechanical strength of the hydrogel when subjected to dynamic environment post implantation in the fallopian tube was estimated by the G' values demonstrated. SMA hydrogel expressed selective antimicrobial activity against opportunistic pathogens (Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus) while having limited consequence over the growth of Lactobacillus spp. After confirmation of cytocompatibility against primary rat endometrial cell lines, the polymeric hydrogel was implanted inside the uterine horns of Sprague-Dawley rats. In vivo biocompatibility of the hydrogel was confirmed by histological and immunohistochemical evaluation of uterine tissue sections. Hematology, blood biochemistry and organ toxicity (kidney, liver, spleen, lungs and heart) also revealed biocompatibility of SMA hydrogel. The results of the current study indicated that the SMA copolymer dissolved in DMSO to form hydrogel has excellent biocompatibility for application as female contraceptive gel which can be implanted in the fallopian tube.

Encapsulation of tDodSNO generates a photoactivated nitric oxide releasing nanoparticle for localized control of vasodilation and vascular hyperpermeability.

We report the synthesis and characterization of a photoactive nitric oxide (NO) releasing nanoparticle (NP) by encapsulation of the NO donor tert-dodecane S-nitrosothiol (tDodSNO) into a co-polymer of styrene and maleic anhydride (SMA) to afford SMA-tDodSNO. Encapsulation did not affect tDodSNO's stability or NO release profile, but imparted water solubility and protection from degradation reactions with glutathione. Under photoactivation the NP acted as a potent NO donor, with photoactivation acting as a switch to induce localized vasodilation in aortic rings (EC50* 660 nM at 2700 W/m2) and cause vascular hyperpermeability in mesenteric beds (8-fold increase in dye uptake at 1 µM SMA-tDodSNO with 460 W/m2 photoactivation). The NP was markedly superior as a photoactive NO donor in comparison to the S-nitrosothiols GSNO and SNAP, which are commonly used in experimental studies, as well as sodium nitroprusside, a clinically used vasodilator. Future development of this NP may find wide ranging therapeutic applications for treating cardiovascular disease and other disorders related to NO signaling, as well as enhancing macromolecular drug delivery to target organs through selective hyperpermeability. Supporting information describing the biophysical characterization of SMA-tDodSNO is supplied in an accompanying Data in Brief article (Alimoradi et al., doi: 10.1016/j.dib.2018.10.149).

Charge reversible and biodegradable nanocarriers showing dual pH-/reduction-sensitive disintegration for rapid site-specific drug delivery.

Dual pH-/reduction-sensitive biodegradable poly(methacrylic acid-co-N,N-bis(acryloyl)cystamine)/chitosan/dimethylmaleic anhydride-modified chitosan (PMAABACy/CS/CS-DMMA) nanoparticles with PMAABACy cores as carriers and dimethylmaleic anhydride-modified chitosan as charge reversible shells were rationally designed. PMAABACy cores using N,N-Bis(acryloyl)cystamine (BACy) as a crosslinker and methacrylic acid (MAA) as a monomer were fabricated via a mild and facile one-pot distillation-precipitation polymerization. After that, CS and CS-DMMA were alternately adsorbed on the surface of PMAABACy cores through a mild self-assembly. The results from TEM and DLS reveal that the PMAABACy/CS/CS-DMMA nanoparticles with desired size and hydrodynamic diameter. And then the nanoparticles exhibit the excellent drug-loading capacity and encapsulation efficiency toward anti-cancer agent doxorubicin (DOX), whereas be rapidly triggered to realize the GSH-sensitive site-specific release via the destruction of sulfide cross-linked structure in response to the intracellular environment of tumor cells. Furthermore, their surface charges could transfer from negative in neutral or basic medium to positive in acidic medium to enhance cellular uptake. Most importantly, the excellent anticancer activity has been also revealed using confocal laser scanning microscope (CLSM) analysis, namely successfully delivering DOX molecules to the cell nucleus. These experimental results indicate that such the novel dual pH-/reduction-sensitive biodegradable PMAABACy/CS/CS-DMMA with surface charge reversal have great potential as a desired anticancer drug carrier for cancer therapy.

Maleic anhydride and chromone derivatives from the endophytic fungus BCC 54265 (Botryosphaeriaceae).

A maleic anhydride derivative, botryoanhydride (1), and a chromone derivative, botryochromone (2), together with three known chromones, eugenitin (3), 6-hydroxymethyleugenin (4) and 6-methoxymethyleugenin (5), were isolated from cultures of the endophytic fungus BCC 54265 of the family Botryosphaeriaceae. The structures were elucidated on the basis of NMR, HRMS and CD data. Compound 2 showed weak cytotoxic activity to cancer cell-lines.

Cytotoxicity, Oxidative Stress, Cell Cycle Arrest, and Mitochondrial Apoptosis after Combined Treatment of Hepatocarcinoma Cells with Maleic Anhydride Derivatives and Quercetin.

The inflammatory condition of malignant tumors continually exposes cancer cells to reactive oxygen species, an oxidizing condition that leads to the activation of the antioxidant defense system. A similar activation occurs with glutathione production. This oxidant condition enables tumor cells to maintain the energy required for growth, proliferation, and evasion of cell death. The objective of the present study was to determine the effect on hepatocellular carcinoma cells of a combination treatment with maleic anhydride derivatives (prooxidants) and quercetin (an antioxidant). The results show that the combination of a prooxidant/antioxidant had a cytotoxic effect on HuH7 and HepG2 liver cancer cells, but not on either of two normal human epithelial cell lines or on primary hepatocytes. The combination treatment triggered apoptosis in hepatocellular carcinoma cells by activating the intrinsic pathway and causing S phase arrest during cell cycle progression. There is also clear evidence of a modification in cytoskeletal actin and nucleus morphology at 24 and 48 h posttreatment. Thus, the current data suggest that the combination of two anticarcinogenic drugs, a prooxidant followed by an antioxidant, can be further explored for antitumor potential as a new treatment strategy.

Biochemical efficacy, molecular docking and inhibitory effect of 2, 3-dimethylmaleic anhydride on insect acetylcholinesterase.

Evolution of resistance among insects to action of pesticides has led to the discovery of several insecticides (neonicotinoids and organophosphates) with new targets in insect nervous system. Present study evaluates the mode of inhibition of acetylchlonesterase (AChE), biochemical efficacy, and molecular docking of 2,3-dimethylmaleic anhydride, against Periplaneta americana and Sitophilus oryzae. The knockdown activity of 2,3-dimethylmaleic anhydride was associated with in vivo inhibition of AChE. At KD99 dosage, the 2,3-dimethylmaleic anhydride showed more than 90% inhibition of AChE activity in test insects. A significant impairment in antioxidant system was observed, characterized by alteration in superoxide dismutase and catalase activities along with increase in reduced glutathione levels. Computational docking programs provided insights in to the possible interaction between 2,3-dimethylmaleic anhydride and AChE of P. americana. Our study reveals that 2,3-dimethylmaeic anhydride elicits toxicity in S. oryzae and P. americana primarily by AChE inhibition along with oxidative stress.

Protecting group-free radical decarboxylation of bile acids: Synthesis of novel steroidal substituted maleic anhydrides and maleimides and evaluation of their cytotoxicity on C6 rat glioma cells.

We report the first Barton radical decarboxylation of unprotected bile acids via in situ irradiation of their thiohydroxamic esters in the presence of citraconic anhydride and citracoimide, leading to the synthesis a series of steroidal maleic anhydrides and maleimides as novel hybrid bile acids. The cytotoxic activities were evaluated on C6 rat glioma cells.

Tumor Acidity-Induced Sheddable Polyethylenimine-Poly(trimethylene carbonate)/DNA/Polyethylene Glycol-2,3-Dimethylmaleicanhydride Ternary Complex for Efficient and Safe Gene Delivery.

Amphiphilic PEI derivatives/DNA complexes are widely used for DNA delivery, but they are unstable in vivo and have cytotoxicity due to the excess cationic charge. PEGylation of cationic complexes can improve sterical stability and biocompatibility. However, PEGylation significantly inhibits cellular uptake and endosomal escape. In this work, sheddable ternary complexes were developed by coating a tumor acidity-sensitive ß-carboxylic amide functionalized PEG layer on the binary complexes of amphiphilic cationic polyethylenimine-poly(trimethylene carbonate) nanoparticles/DNA (PEI-PTMC/DNA). Such sheddable ternary complexes markedly reduced their nonspecific interactions with serum protein in the bloodstream and obtained minimal cytotoxicity due to the protection of the PEG shell. At the tumor site, the PEG layer was deshielded by responding to the tumor acidic microenvironment and the positively charged complexes re-exposed that had higher affinity with negatively charged cell membranes. Meanwhile the positively charged complexes facilitated endosomal escape. Accordingly, this delivery system improved the biocompatibility of gene-loaded complexes and enhanced the gene transfection efficiency. Such PEGylated complexes with the ability to deshield the PEG layer at the target tissues hold great promise for efficient and safe gene delivery in vivo.

Anti-herpes simplex virus activities of bioactive extracts from Antrodia camphorata mycelia.

BACKGROUND: Antrodia camphorata, a traditional Chinese medicine, is widely used in the treatment of liver diseases and cancers. Anti-inflammatory properties have also been described. HSV infection represents one of the most serious public health concerns globally because of its devastating impact. Searching for new antiviral agents, especially those with different mechanisms of action, is a crucial goal and there is an unmet need for alternative and complementary therapy against HSV infection. In this study, anti-herpes screening was performed with extracts from A. camphorata mycelia. METHODS: MTT assay, fractional inhibitory concentration index and median-effect principle were used to evaluate antiviral activity and to calculate drug combination effect. RESULTS: Crude ethanol extracts and isolated constituents showed inhibition of HSV replication at a very low concentration. Fraction A and antrodin A showed viral inhibitory effect with reduction of viral cell-to-cell spread. In addition, neither fraction A nor antrodin A showed interaction in combination with acyclovir. CONCLUSIONS: A. camphorata mycelia and antrodin A might have potential use as anti-HSV agents and are promising candidates for future antiviral drug design.

Bioactive Maleic Anhydrides and Related Diacids from the Aquatic Hyphomycete Tricladium castaneicola.

Four maleic anhydride derivatives, tricladolides A-D (1-4), and three alkylidene succinic acid derivatives, tricladic acids A-C (5-7), were isolated from the aquatic hyphomycete Tricladium castaneicola. The structures of these compounds were determined by spectroscopic analysis, and all were found to be novel. The compounds exhibited inhibitory activity against fungi, particularly Phytophthora sp., a plant pathogen of oomycetes. The inhibitory activity of these metabolites revealed the importance of the cyclic anhydride structure and the lipophilicity of the alkyl side chain. On the other hand, the cytotoxicity of the compounds against B16 melanoma cells indicated that the cyclic anhydride structure was not essential.

Anti-HIV activities of precisely defined, semirigid, carboxylated alternating copolymers.

Di-tert-butyl (E)-4,4'-stilbenedicarboxylate and tert-butyl 4-vinylbenzoate were copolymerized with maleic anhydride and tert-butyl 4-maleimidobenzoate, individually and respectively. After conversion into polyanions, these four copolymers exhibited activity against four HIV-1 strains: IIIb, BaL, JR-CSF, and 92UG037. For both the IIIb and BaL HIV-1 strains, the lowest IC50 (0.095 and 0.23 µg/mL, respectively) values were obtained with poly(4,4'-stilbenedicarboxylate-alt-maleic acid) (DCSti-alt-MA). For JR-CSF and 92UG037, both tier 2 clinical isolates but different clades, DCSti-alt-MA exhibited the lowest IC50 (0.76 and 0.75 µg/mL, respectively). Although DCSti-alt-MA had the lowest IC50 in µg/mL for each strain, the other copolymers had IC50s less than 2-fold higher. Further, these copolymers achieved high selectivity indices (>100) for these clinical isolates. Polymer rigidity, as measured by the statistical segment length, emerged as a key property when comparing anti-HIV activities with those of other polyanions. A speculative illustration was proposed for possible modes of inhibition.

Wharton-fragmentation-based approach to the carbocyclic core of the phomoidrides.

The carbocyclic core of the phomoidrides has been synthesized efficiently and in high yield. Key steps include a phenolic oxidation/intramolecular Diels-Alder sequence, tandem radical cyclization, and a late-stage Wharton fragmentation of a densely functionalized isotwistane skeleton.

Bioengineering functional copolymers. XXI. Synthesis of a novel end carboxyl-trithiocarbonate functionalized poly(maleic anhydride) and its interaction with cancer cells.

A novel carboxyl-trithiocarbonate functionalized polymer with a highly selective antitumor activity was synthesized by a reversible addition-fragmentation chain transfer (RAFT) polymerization of maleic anhydride (MA) with benzoyl peroxide as an initiator and S-1-dodecyl-S-(α,α'-dimethyl-α"-acetic acid)trithiocarbonate as a RAFT agent with the aim to design and synthesize an effective anticancer agent with minimum side effects. The structure, molecular weights and composition of synthesized polymers were investigated by (1)H ((13)C) NMR, MALDI-TOF-MS and GPC analyzes. It was demonstrated that RAFT polymerization of MA was accompanied by a partially controlled decarboxylation of anhydride units and the formation of conjugated double bond fragments in backbone macromolecular chains. The mechanism of interaction of pristine RAFT agent and PMA-RAFT polymer with cancer (HeLa human cervix carcinoma) and normal (L929 Fibroblast) cells was investigated by using a combination of chemical, biochemical, statistical, spectroscopic (SEM and fluorescence inverted microscope) and real-time analysis (RTCA) methods. PMA-RAFT exhibited higher and selective cytotoxicity, apoptotic and necrotic effects toward HeLa cells at relatively low concentrations (around 7.5-75 µg mL(-1), IC(50) = 11.183 µg mL(-1)) and toward Fibroblast cells at high concentrations (IC(50) > 100 µg mL(-1)). The observed highly selective antitumor activity render PMA-RAFT polymers as promising candidates for the utilization in cancer chemotherapy.

Methanol extract of Antrodia cinnamomea mycelia induces phenotypic and functional differentiation of HL60 into monocyte-like cells via an ERK/CEBP-ß signaling pathway.

Antrodia cinnamomea (named as Niu-chang-chih), a well-known Taiwanese folk medicinal mushroom, has a spectrum of biological activities, especially with anti-tumor property. This study was carried out for the first time to examine the potential role and the underlying mechanisms of A. cinnamomea in the differentiation of human leukemia HL60 cells. We found that the methanol extract of liquid cultured mycelia of A. cinnamomea (MEMAC) inhibited proliferation and induced G1-phase cell cycle arrest in HL60 cells. MEMAC could induce differentiation of HL60 cells into the monocytic lineage, as evaluated by the morphological change, nitroblue tetrazolium reduction assay, non-specific esterase assay, and expression of CD14 and CD11b surface antigens. In addition, MEMAC activated the extracellular signal-regulated kinase (ERK) pathway and increased CCAAT/enhancer-binding protein ß (C/EBPß) expression. Reverse transcriptase polymerase chain reaction analysis showed that MEMAC upregulated the expression of C/EBPß and CD14 mRNA in HL60 cells. DNA affinity precipitation assay and chromatin immunoprecipitation analyses indicated that MEMAC enhanced the direct binding of C/EBPß to its response element located at upstream of the CD14 promoter. Furthermore, inhibiting ERK pathway activation with PD98059 markedly blocked MEMAC-induced HL60 monocytic differentiation. Consistently, the MEMAC-mediated upregulation of C/EBPß and CD14 was also suppressed by PD98059. These findings demonstrate that MEMAC-induced HL60 cell monocytic differentiation is via the activating ERK signaling pathway, and downstream upregulating the transcription factor C/EBPß and differentiation marker CD14 gene, suggesting that MEMAC might be a potential differentiation-inducing agent for treatment of leukemia.

Potent anti-inflammatory effect of a novel furan-2,5-dione derivative, BPD, mediated by dual suppression of COX-2 activity and LPS-induced inflammatory gene expression via NF-κB inactivation.

BACKGROUND AND PURPOSE: We previously reported that 3-(benzo[d]-1,3-dioxol-5-yl)-4-phenylfuran-2,5-dione (BPD) showed strong inhibitory effects on PGE(2) production. However, the exact mechanism for the anti-inflammatory effect of BPD is not completely understood. In this study, we investigated the molecular mechanism involved in the effects of BPD on inflammatory mediators in LPS-stimulated macrophages and animal models of inflammation. EXPERIMENTAL APPROACH: The expressions of COX-2, inducible NOS (iNOS), TNF-α, IL-6 and IL-1ß, in LPS-stimulated RAW 264.7 cells and murine peritoneal macrophages, were determined by Western blot and/or qRT-PCR, respectively. NF-κB activation was investigated by EMSA, reporter gene assay and Western blotting. Anti-inflammatory effects of BPD were evaluated in vivo in carrageenan-induced paw oedema in rats and LPS-induced septic shock in mice. KEY RESULTS: BPD not only inhibited COX-2 activity but also reduced the expression of COX-2. In addition, BPD inhibited the expression of iNOS, TNF-α, IL-6 and IL-1ß at the transcriptional level. BPD attenuated LPS-induced DNA-binding activity and the transcription activity of NF-κB; this was associated with a decrease in the phosphorylation level of inhibitory κB-α (IκB-α) and reduced nuclear translocation of NF-κB. Furthermore, BPD suppressed the formation of TGF-ß-activated kinase-1 (TAK1)/TAK-binding protein1 (TAB1), which was accompanied by a parallel reduction of phosphorylation of TAK1 and IκB kinase (IKK). Pretreatment with BPD inhibited carrageenan-induced paw oedema and LPS-induced septic death. CONCLUSION AND IMPLICATIONS: Taken together, our data indicate that BPD is involved in the dual inhibition of COX-2 activity and TAK1-NF-κB pathway, providing a molecular basis for the anti-inflammatory properties of BPD.