Lactone Compounds Research Articles

A Behavioral Assay to Examine the Effects of Kavalactones on Caenorhabditis elegans Neuromuscular Excitability.

Kavalactones are a class of lactone compounds found in Kava, a traditional beverage from the South Pacific Islands that is derived from the root of Piper methysticum. When consumed, these compounds produce sedative and anxiolytic effects, suggesting their potent actions on the nervous system. Here, we provide a protocol to examine the effects of kavalactones on C. elegans neuromuscular excitability. Our methodology could provide insight into the neurophysiological actions of kavalactones.

Effect of Andrographolide on Gene Expression Profile and Intracellular Calcium in Primary Rat Myocardium Microvascular Endothelial Cells.

Andrographolide (ANDRO) is a diterpene lactone compound with extensive biological effects, such as antibacterial, antitumor and treatment of cardiovascular diseases. Until now, studies on the pharmacological functions of ANDRO are still in progress. However, little is known about the gene expression profile and calcium response of endothelial cells to ANDRO. In this study, we used a microarray technology to investigate the gene expression responses in primary rat myocardium microvascular endothelial cells treated with 10 μg/mL ANDRO. The expression of caveolin-1 and 1-phosphatidylinositol 4, 5-bisphosphate phosphodiesterase δ3 was verified by RT-PCR and western blot. In addition, we investigated the effect of ANDRO on intracellular calcium induced by exogenous adenosine triphosphate and on inflammatory response induced by lipopolysaccharide. Results showed that ANDRO treatment induced an abundance of differential expressed genes, exhibiting a multitarget regulatory effect. ANDRO significantly decreased caveolin-1 and phosphodiesterase δ3 expression, lipopolysaccharide-induced IL-6 and TNF-α levels and expression of several chemokine genes, which are associated with reducing inflammation response and decreasing calcium release without affecting normal endothelia cell function, suggesting that ANDRO may be a potential candidate to treat cardiovascular diseases with less toxicity.

Improvement in lactone production from biotransformation of ricinoleic acid based on the porous starch delivery system

AbstractBACKGROUNDThe natural gamma‐decalactone (GDL) produced by microbial fermentation is an essential lactone compound as a generally recognized as safe food additive. Effective control of the substrate ricinoleic acid (RA) concentration in the biotransformation medium is a bottleneck for the industrial manufacture of GDL. In this study, porous starch (P‐S) was utilized as a carrier of RA to control its distribution in the medium. The effect of P‐S on the biotransformation was evaluated and the mechanism was revealed.RESULTSScanning electron microscopy, Fourier‐transform infrared spectroscopy, and thermogravimetric analysis indicated that the RA layer was formed on the surface of P‐S, which increased the opportunity for interaction between microorganisms and the substrate. With P‐S‐embedded RA as a substrate, the yield of GDL increased to 3.36 g L‐1 which was 17.5% higher than in the control. In addition, the presence of P‐S in this system had no negative effect on the viability of the microorganism.CONCLUSIONThis study is a new attempt to apply P‐S as a delivery system in the biotransformation of GDL to increase its yield which indicates that the P‐S‐controlled release is a potential method of improving natural GDL production in industrial scale. © 2017 Society of Chemical Industry

Solid state fermentation for the production of γ-decalactones by Yarrowia lipolytica

Abstract The production of γ-decalactones as aroma compounds is highly dependent on the access of the biocatalyst to substrate and co-substrate (oxygen). In this work, the potential of solid state fermentation (SSF) is investigated for this production with Y. lipolytica W29. Luffa sponge was used as an inert support and the investigation focused on the impact of aeration on metabolites. In that goal, experiments were carried out in three different SSF reactor types, wide-mouth Erlenmeyer flask (static aeration), forced aeration mini-reactor, and small-headspace bottle (without aeration). Four lactones were detected by GC–MS during the degradation of ricinoleic acid from castor oil by Y. lipolytica W29: 3-hydroxy-γ-decalactone, which reached the high concentration of 5 g/L (in wide-mouth Erlenmeyer flask), γ-decalactone, dec-2-en-4-olide and dec-3-en-4-olide. In this study, some yeast cells changed their morphological properties from the yeast-like shape to pseudo-mycelium and mycelium. These cells may undergo a metabolic shift resulting in the high production of 3-hydroxy-γ-decalactone. The yield of lactone in the small-headspace bottle was very low suggesting insufficient oxygen availability. For their part, forced-aeration conditions in mini-reactors resulted in the stripping of lactone compounds. From the present work, an alternative process is proposed as a novel model for lactone production.

English

Inhibition of virulence genes expression of phytopathogenic bacteria can be done by degrading the acyl-homoserine lactone (AHL) compounds using AHL-lactonase. In this study, the AHL-lactonase genes were cloned and expressed from Bacillus cereus INT1c and Bacillus thuringiensis SGT3g in Escherichia coli, in order to understand the characteristics and biocontrol mechanisms of their AHL-lactonase. Amplification using aiiA primers succeeded to get 800 bp DNA fragments of AHL-latonase genes having a complete open reading frame (ORF) and encoding 250 amino acids. AHL-lactonase genes of B. cereus INT1c and B. thuringiensis SGT3g were expressed in E. coli BL21 (DE3) plasmid with T7 lysozyme coding sequence (pLysS). AHL-lactonase of the isolates is classified as metallo-β-lactamase superfamily domain and the AHL-lactonase inhibited violacein production of Chromobacterium violaceum. Key words: Acyl-homoserine lactone (AHL), lactonase, aiiA gene, cloning, Bacillus thuringiensis, Bacillus cereus.

Multi-Targeting Andrographolide, a Novel NF-κB Inhibitor, as a Potential Therapeutic Agent for Stroke.

A key focus in the field of drug discovery has been motivated by the neuroprotection of natural compounds. Cerebral ischemia is a multifaceted pathological process with a series of mechanisms, and a perspective for the development of neuroprotectants from traditional herbal medicine or natural products is a promising treatment for this disease. Natural compounds with the effects of anti-oxidation, anti-inflammation, anti-apoptosis, and neurofunctional regulation exhibit therapeutic effects on experimental ischemic brain injury. Conferring to the pharmacological mechanisms underlying neuroprotection, a study found that androgapholide, a diterpene lactone compound, exhibits varying degrees of neuroprotective activities in both in vitro and in vivo experimental models of stroke. The neuroprotective mechanisms of andrographolide are suggested as: (I) increasing nuclear factor E2-related factor 2-heme oxygenase (Nrf2-HO-1) expression through p38-mitogen activated protein kinase (MAPK) regulation, (II) inducing cerebral endothelial cells (CEC) apoptosis and caspase-3 activation, (III) down regulating Bax, inducible nitric oxide synthase (iNOS), and (IV) inhibiting hydroxyl radical (OH−) formation, and activating transcription factor NF-κB signaling pathways. Recently, several researchers have also been trying to unveil the principal mechanisms involved in the neuroprotective effects of andrographolide. Therefore, this review aims to summarize an overview on the neuroprotective effects of andrographolide and exemplifies the essential mechanisms involved. This paper can provide information that andrographolide drug discovery may be a promising strategy for the development of a novel class of neuroprotective drug.

Degradation and conversion of endosulfan by newly isolated Pseudomonas mendocina ZAM1 strain.

Endosulfan contamination is one of the major concerns of soil ecosystem, which causes detrimental effects not only to humans but also to animals and plants. Therefore, the aim of this study was to isolate and identify a novel bacterial strain capable of degrading endosulfan in agriculture contaminated soils. A novel bacterial strain was isolated from the sugarcane field contaminated with endosulfan, and was named as ZAM1 strain. The ZAM1 bacterial strain was further identified as Pseudomonas mendocina based on the biochemical and molecular analysis. 16sRNA sequence analysis of ZAM1 strain shows maximum similarity with known endosulfan-degrading bacteria (Pseudomonas putida), respectively. Enrichment was carried out using the endosulfan as sole sulfur source. The ZAM1 strain was able to use α and β endosulfan as a sole sulfur source. Our results showed that ZAM1 strain degrades endosulfan>64.5% (50mg/l) after 12days of incubation. The residues were analyzed by GC-MS analysis and confirmed the formation of metabolites of dieldrin, 2 heptanone, methyl propionate, and endosulfan lactone compounds. Hence, these results indicate that the ZAM1 strain is a promising bacterial source for detoxification of endosulfan residues in the environment.

A Behavioral Survey of the Effects of Kavalactones on Neuromuscular Transmission

Kava is a plant root extract that is widely consumed by Pacific Islanders. Kava contains a class of lactone compounds called kavalactones. The sedative and anxiolytic effects of kava are likely attributed to the efficacies of kavalactones on the nervous system. Although some studies have implicated the potencies of certain kavalactone species on γ-aminobutyric acid transmission, evidence supporting the action of kavalactones on the eukaryotic neuromuscular junction (NMJ) and acetylcholine (ACh) transmission is scant. Here, we used behavioral assays to demonstrate the effects of kavalactones at the Caenorhabditis elegans NMJ. Our results suggest that kavalactones disrupt the inhibitory-excitatory balance at the NMJ. Such perturbation of NMJ activity is likely due to excess or prolonged ACh transmission. In addition, we found that kavain, a major constituent of kava, induced worm paralysis but not convulsions. Hence, the modulatory action of kavain could be distinct from the other kavalactone species.

Structure-activity relationships of the antimalarial agent artemisinin and the research progress on the artemisinin analogues with novel pharmacological actions

Artemisinin is a sesquiterpene lactone compound containing a peroxy bridge structure, extracted from Compositae Artemisia annua L. in 1971. Discovered by Chinese researchers, artemisinin and its derivatives are currently the most effective drugs in the world for the treatment of chloroquine-resistant Plasmodium falciparumstrains and cerebral malaria. As first-line antimalarial medicines, artemisinin and its derivatives have saved millions of lives, and artemisinin has been reputed as “the best hope for malaria treatment” by World Health Organization. At Nobel Prize Award Ceremony in 2015, Tu Youyou, a natural product medicinal chemist at the China Academy of Chinese Medical Sciences who made significant contribution to the discovery of artemisinin as an antimalarial drug, delivered a speech entitled “Artemisinin—A gift from traditional Chinese medicine to the world”. Tu said: “From research experience gained from artemisinin discovery, we learnt strengths of both Chinese and Western medicines. There is great potential and future advances if these strengths can be fully integrated. We have a substantial amount of natural resource from which our fellow medical researchers can develop novel medicines”. Doubtless the discovery of artemisinin represents a banner in the history of Chinese pharmaceutical industry, which is of immense significance both to enlighten the currently much modernized drug discovery world and to encourage young generations of scientists working with the traditional Chinese medicines. In order to understand the antimalarial mechanism of artemisinin analogues, we firstly discussed on quantitative structure- activity relationship, structure-based physico-chemical properties, and molecular docking generated putative “bioactive” conformations of artemisinin analogues. In addition to the outstanding antimalarial activity, artemisinin and its derivatives also show significant immunosuppressive effects both in vitro and in vivo . We then summarized some typical artemisinin analogues that exhibit promising therapeutic effects on multiple autoimmune diseases, by suppressing the differentiation and expansion of pathologic T helper cells and accumulation of plasma cells, etc. The unusual endoperoxide and multiple cyclic structure of artemisinin has also been extensively explored to develop analogues with cytotoxic anticancer effects. Unfortunately, most of these artemisinin analogues failed to show tumor growth inhibition in vivo . To overcome this limitation, we finally reviewed some recent progresses to develop molecularly targeted anticancer therapies derived from artemisinin, by combining the typical skeleton of artemisinin or its fragmented intermediates with a molecularly targeted drug bullet. Among several tried approaches, the incorporation of a Smo antagonistic structural motif into the structure of artemisinin led to highly potent Smo-targeting antagonists. The recognition by the Nobel Prize does not mean that the study of artemisinin is over; instead, this great honor will inspire scientists around the world to move on to discover more therapeutic effects of artemisinin compounds, and to explore other potential gifts from Traditional Chinese Medicine.

Acyl-CoA oxidase 1 is involved in γ-decalactone release from peach (Prunus persica) fruit.

γ-Decalactone accumulation in peach mesocarp was highly correlated with ACX enzyme activity and natural PpACX1 content. Adding the purified recombinant PpACX1 induced γ-decalactone biosynthesis in cultured mesocarp discs in vitro. Previous gene expression studies have implied that acyl coenzyme A oxidase (ACX) is related to lactones synthesis, the characteristic aroma compounds of peach. Here, we analysed the correlation between γ-decalactone content and ACX enzyme activity in mesocarp of five different types of fully ripe peach varieties. Furthermore, 'Hu Jing Mi Lu' ('HJ') and 'Feng Hua Yu Lu' ('YL'), which have strong aroma among them, at four ripening stages were selected to study the role of ACX in lactone biosynthesis. The result showed that γ-decalactone was the most abundant lactone compound. γ-Decalactone accumulation was highly correlated with ACX enzyme activity. Mass spectrometry (MS) showed that PpACX1 was the most abundant PpACX protein in fully ripe mesocarp of cv. 'HJ'. To further elucidate the function of the PpACX1 protein, the PpACX1 gene was heterologously expressed in a bacterial system and characterized in vitro. MS identification gave the molecular weight of the recombinant PpACX1 as 94.44kDa and the coverage rate of the peptide segments was 47.3%. In cultured mesocarp discs in vitro, adding the purified recombinant PpACX1 and C16-CoA substrate induced the expected γ-decalactone biosynthesis. Using a sandwich ELISA based on mixed mono- and polyclonal antibodies against recombinant PpACX1, PpACX1 content in mesocarp was found to be highly correlated with γ-decalactone accumulation in mesocarp of five fully ripe varieties and four ripening stages of 'HJ' and 'YL'. This study revealed the vital function of PpACX1 in γ-decalactone biosynthesis in peach fruit.

Production of N-acyl homoserine lactones by the sponge-associated marine actinobacteria Salinispora arenicola and Salinispora pacifica.

The structures of acyl homoserine lactone (AHL) compounds and their quantification were accomplished using an integrated liquid chromatography-mass spectrometry approach. The precursor and product ions, along with retention times of peaks, were searched against an in-house database of AHLs and structures confirmed by accurate mass and by comparison with authentic AHL standards. The two compounds, N-(3-oxodecanoyl)-L-homoserine lactone and N-(3-oxododecanoyl)-L-homoserine lactone, were characterised and quantified in Salinispora sp. cultures.

A phytotoxic bicyclic lactone and other compounds from endophyte Xylaria curta

A new compound, (3aS,6aR)-4,5-dimethyl-3,3a,6,6a-tetrahydro-2H-cyclopenta [b]furan-2-one (2), along with two known metabolites, myrotheciumone A (1) and 4-oxo-4H-pyron-3-acetic acid (3) was isolated from the ethyl acetate extract of fermentation broth of Xylaria curta 92092022. The structures of these compounds were elucidated on the basis of spectroscopic methods (UV, IR, HRESITOFMS, 1D NMR, and 2D NMR). Compounds 1 and 2 showed moderate antibacterial and phytotoxic activities.

A Behavioral Survey of the Effects of Kavalactones on Caenorhabditis elegans Neuromuscular Transmission.

Kava is a plant root extract that is widely consumed by Pacific Islanders. Kava contains a class of lactone compounds called kavalactones. The sedative and anxiolytic effects of kava are likely attributed to the efficacies of kavalactones on the nervous system. Although some studies have implicated the potencies of certain kavalactone species on γ-aminobutyric acid transmission, evidence supporting the action of kavalactones on the eukaryotic neuromuscular junction (NMJ) and acetylcholine (ACh) transmission is scant. Here, we used behavioral assays to demonstrate the effects of kavalactones at the Caenorhabditis elegans NMJ. Our results suggest that kavalactones disrupt the inhibitory-excitatory balance at the NMJ. Such perturbation of NMJ activity is likely due to excess or prolonged ACh transmission. In addition, we found that kavain, a major constituent of kava, induced worm paralysis but not convulsions. Hence, the modulatory action of kavain could be distinct from the other kavalactone species.

Santamarine Inhibits NF-кB and STAT3 Activation and Induces Apoptosis in HepG2 Liver Cancer Cells via Oxidative Stress.

Sesquiterpene lactones have long been used in traditional Chinese medicines to treat inflammatory diseases. Recently, sesquiterpene lactone family compounds have been recognized as potential anticancer agents. Thus, it is necessary to explore new sesquiterpene lactones and their antitumor mechanism for cancer treatments. In the present study, we have explored the potential anti-cancer activity of a novel sesquiterpene lactone compound “santamarine” (STM) in HepG2 cells. It inhibited proliferation and induced apoptosis dose-dependently with IC50 ~ 70 μM. Induction of apoptosis was found to be linked with increased reactive oxygen species (ROS) generation, decreased activity of thioredoxin reductase (TrxR), glutathione (GSH) depletion, mitochondrial membrane potential (ΔΨm) dissipation, Bcl-2 family proteins modulation, cytochrome c release, caspases-9, -8 and -3 activation and PARP cleavage. Further mechanistic study demonstrated that STM inhibited the constitutive and TNF-α-induced translocation of NF-кB into nucleus by decreasing phosphorylation of IkB-α. Moreover, STM inhibited STAT3 activation by decreasing phosphorylation at tyrosine705. NAC pretreatment reversed the effect of STM-mediated cell death, NF-кB inhibition and blockage of STAT3 activity, indicating the involvement of oxidative stress in STM-mediated anticancer activity. Further studies are needed to explore the exact molecular mechanism of STM-induced apoptosis to develop it into a lead for treatment of liver cancer in future.

Enhanced candicidal compound production by a new soil isolate Penicillium verruculosum MKH7 under submerged fermentation.

BackgroundMicroorganisms are a rich source of structurally diverse secondary metabolites that exert a major impact on the control of infectious diseases and other medical conditions. The biosynthesis of these metabolites can be improved by manipulating the nutritional or environmental factors. This work evaluates the effects of fermentation parameters on the production of a lactone compound effective against Candida albicans by Penicillium verruculosum MKH7 under submerged fermentation. Design–Expert version8.0 software was used for construction of the experimental design and statistical analysis of the experimental data.ResultsThe important factors influencing antibiotic production selected in accordance with the Plackett–Burman design were found to be initial pH, temperature, peptone, MgSO4.7H2O. Orthogonal central composite design and response surface methodology were adopted to further investigate the mutual interaction between the variables and identify the optimum values that catalyse maximum metabolite production. The determination coefficient (R2) of the fitted second order model was 0.9852. The validation experiments using optimized conditions of initial pH 7.4, temperature 27 °C, peptone 9.2 g/l and MgSO4.7H2O 0.39 g/l resulted in a significant increase (almost 7 fold from 30 to 205.5 mg/l) in the metabolite production which was in agreement with the prediction (211.24 mg/l). Stability of the compound was also assessed on the basis of its response to physical and chemical stresses.ConclusionsSo far as our knowledge goes, till date there are no reports available on the production of antibiotics by Penicillium verruculosum through media optimization using RSM. Optimization not only led to a 7 fold increase in metabolite yield but the same was achieved at much lesser time (8–10 days compared to the earlier 12–15 days). The enhanced yield of the antibiotic strongly suggests that the fungus P. verruculosum MKH7 can be efficiently used for antibiotic production on a large scale.

The Tracing of VOC Composition of Acacia Honey During Ripening Stages by Comprehensive Two-Dimensional Gas Chromatography.

In this study, VOC profiles of acacia flowers and honey samples at different processing stages and related comb wax samples were studied using comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry. It was found that some monoterpene compounds like α-pinene, myrcene, cis-β-ocimene, and 4-terpineol were common for acacia flower and all acacia honey samples, and the presence of verbenone and ocimene was first established in acacia honey. The most enriched VOC profile was obtained for raw honey before cell capping, where the final composition of lactones was achieved. On the contrary, number of alcohols, esters, and variety of terpenes, as well as their concentration in the honey samples decrease through ripening processes. Strained honey was characterized by the absence of camphor, α-bisabolol, and 3-carene, while isophorone and hexanoic acid were identified only in this type of honey. The composition of final VOC profile of honey was also influenced by the age of comb wax. The additional aromatic and lactone compounds, e.g., phenol, 1-phenylethanol, δ-hexalactone, and γ-heptalactone were observed for honey maturated in old dark comb wax.

Atractylodes lactone compounds inhibit platelet activation

Platelets play a crucial role in the development and progression of atherosclerosis-thrombosis and, therefore, antiplatelet drugs are widely used in the treatment of coronary artery disease. Moreover, advances in understanding the biological functions of natural plant products can provide new pharmacological strategies aimed at promoting cardiovascular health. Atractylenolide I (ATL-1), ATL-2, and ATL-3 are the major bioactive components of a Qi tonifying medicinal herb Rhizoma Atractylodis Macrocephalae (Atractylodes macrocephala), which is commonly used in traditional Chinese medicine (TCM). These components possess well-documented anti-inflammatory and anticancer activities, but their effects on platelet activation are still unknown. In this study, the effects of ATL on platelet function in vitro and in vivo were investigated, and the underlying mechanism was explored. We found that ATL-2 and ATL-3 but not ATL-1 diminished agonist-induced platelet aggregation and diminished adenosine triphosphate (ATP) release from dense granules. The levels of phospho-Akt (Ser473) and phospho-p38 MAPK were downregulated in the presence of ATL-2 and ATL-3. We also found that ATL-2 and ATL-3 have a similar inhibitory effect on platelet activation as acetylsalicylic acid in response to agonists. Furthermore, ATL-2 and ATL-3 diminished the spreading of human platelets on immobilized fibrinogen (Fg), delayed clot retraction in platelet-depleted plasma containing human platelets, extended first occlusion time in a mouse model of ferric chloride (FeCl3)-induced carotid arterial thrombosis, and prolonged the bleeding time. These observations suggest that ATL-2 and ATL-3 are potential candidate therapeutic drugs for the prevention of thrombosis.

Preselection of A- and B- modified d-homo lactone and d-seco androstane derivatives as potent compounds with antiproliferative activity against breast and prostate cancer cells – QSAR approach and molecular docking analysis

The problem with trial-and-error approach in organic synthesis of targeted anticancer compounds can be successfully avoided by computational modeling of molecules, docking studies and chemometric tools. It has been proven that A- and B- modified d-homo lactone and d-seco androstane derivatives are compounds with significant antiproliferative activity against estrogen-independent breast adenocarcinoma (ER-, MDA-MB-231) and androgen-independent prostate cancer cells (AR-, PC-3). This paper presents the quantitative structure-activity relationship (QSAR) models based on artificial neural networks (ANNs) which are able to predict whether d-homo lactone and/or d-seco androstane-based compounds will express antiproliferative activity against breast cancer cells (MDA-MB-231) or not. Also, the present paper describes the molecular docking study of 3β-acetoxy-5α,6α-epoxy- (3) and 6α,7α-epoxy-1,4-dien-3-one (24) d-homo lactone androstane derivatives, as well as 4-en-3-one (15) d-seco androstane derivative, which are compounds with strong or moderate antiproliferative activity against prostate cancer cells (PC-3), and compares them with commercially available medicament for prostate cancer – abiraterone. The obtained promising results can be used as guidelines in further syntheses of novel d-homo lactone and d-seco androstane derivatives with antiproliferative activity against breast and prostate cancer cells.

Sideromimic Modification of Lactivicin Dramatically Increases Potency against Extensively Drug-Resistant Stenotrophomonas maltophilia Clinical Isolates.

Acetamido derivatives of the naturally antibacterial non-β-lactam lactivicin (LTV) have improved activity against their penicillin binding protein targets and reduced hydrolysis by β-lactamases, but penetration into Gram-negative bacteria is still relatively poor. Here we report that modification of the LTV lactone with a catechol-type siderophore increases potency 1,000-fold against Stenotrophomonas maltophilia, a species renowned for its insusceptibility to antimicrobials. The MIC90 of modified lactone compound 17 (LTV17) against a global collection of extensively drug-resistant clinical S. maltophilia isolates was 0.063 μg · ml(-1) Sideromimic modification does not reduce the ability of LTVs to induce production of the L1 and L2 β-lactamases in S. maltophilia and does not reduce the rate at which LTVs are hydrolyzed by L1 or L2. We conclude, therefore, that lactivicin modification with a siderophore known to be preferentially used by S. maltophilia substantially increases penetration via siderophore uptake. LTV17 has the potential to be developed as a novel antimicrobial for treatment of infections by S. maltophilia More generally, our work shows that sideromimic modification in a species-targeted manner might prove useful for the development of narrow-spectrum antimicrobials that have reduced collateral effects.

Effects of compounds isolated from a Litsea japonica fruit extract on the TNF-α signaling pathway and cell viability

Tumor necrosis factor-α (TNF-α) plays an important role in inflammatory responses. Deregulated activation of TNF-α signaling is associated with various inflammatory diseases. In view of the finding that the seventy percent ethanol extract of Litsea japonica (LJE) interferes with TNF-α-induced NF-κB activation, activity- guided fractionation was performed to identify the active components of the extract. The EtOAc, CH2Cl2 and n-Hexane fractions of LJE induced suppression of inhibitor of κB (IκB) kinase (IKK), p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK), and significant reduction of TNF-α- induced NF-κB activation. From the CH2Cl2 fraction, hamabiwalactone A, hamabiwalactone B, litsenolide B2 and litsenolide C2 were identified to inhibit TNF- α-induced NF-κB activation. The cytotoxic activities of these lactone compounds were additionally evaluated.