Anti-Diabetic Potential of Sargassum horneri and Ulva australis Extracts In Vitro and In Vivo.

Sargassum horneri (SH) and Ulva australis (UA) are marine waste resources that cause environmental and economic problems when entering or multiplying the coastal waters of Jeju Island. We analyzed their anti-diabetic efficacy to assess their reusability as functional additives. The alpha-glucosidase inhibitory activity of SH and UA extracts was confirmed, and the effect of UA extract was higher than that of SH. After the induction of insulin-resistant HepG2 cells, the effects of the two marine extracts on oxidative stress, intracellular glucose uptake, and glycogen content were compared to the positive control, metformin. Treatment of insulin-resistant HepG2 cells with SH and UA resulted in a concentration-dependent decrease in oxidative stress and increased intracellular glucose uptake and glycogen content. Moreover, SH and UA treatment upregulated the expression of IRS-1, AKT, and GLUT4, which are suppressed in insulin resistance, to a similar degree to metformin, and suppressed the expression of FoxO1, PEPCK involved in gluconeogenesis, and GSK-3ß involved in glycogen metabolism. The oral administration of these extracts to rats with streptozotocin-induced diabetes led to a higher weight gain than that in the diabetic group. Insulin resistance and oral glucose tolerance are alleviated by the regulation of blood glucose. Thus, the SH and UA extracts may be used in the development of therapeutic agents or supplements to improve insulin resistance.

Isolation and Characterization of Efficient Active Compounds Using High-Performance Centrifugal Partition Chromatography (CPC) from Anti-Inflammatory Activity Fraction of Ecklonia maxima in South Africa.

Ecklonia maxima is a brown seaweed, which is abundantly distributed in South Africa. This study investigated an efficient approach using high-performance centrifugal partition chromatography (HPCPC), which has been successfully developed for the isolation and purification of phlorotannins, eckmaxol, and dieckol from the ethyl acetate fraction of E. maxima (EEM). We evaluated EEM for its inhibitory effect against lipopolysaccharide (LPS)-induced inflammatory responses in zebrafish embryos. The separation of eckmaxol and dieckol from samples of EEM using HPCPC was found to be of high purity and yield under an optimal solvent system composed of n-hexane:ethyl acetate:methanol:water (2:7:3:7, v/v/v/v). To evaluate the anti-inflammatory efficacy of EEM containing active compounds, zebrafish embryos exposed to LPS were compared with and without EEM treatment for nitric oxide (NO) production, reactive oxygen species (ROS) generation, and cell death two days after fertilization. These evaluations indicate that EEM alleviated inflammation by inhibiting cell death, ROS, and NO generation induced by LPS treatment. According to these results, eckmaxol and dieckol isolated from brown seaweed E. maxima could be considered effective anti-inflammatory agents as pharmaceutical and functional food ingredients.

Profiles of Essential Oils and Correlations with Phenolic Acids and Primary Metabolites in Flower Buds of Magnolia heptapeta and Magnolia denudata var. purpurascens.

Magnolia flower buds are a source of herbal medicines with various active compounds. In this study, differences in the distribution and abundance of major essential oils, phenolic acids, and primary metabolites between white flower buds of Magnolia heptapeta and violet flower buds of Magnolia denudata var. purpurascens were characterised. A multivariate analysis revealed clear separation between the white and violet flower buds with respect to primary and secondary metabolites closely related to metabolic systems. White flower buds contained large amounts of monoterpene hydrocarbons (MH), phenolic acids, aromatic amino acids, and monosaccharides, related to the production of isoprenes, as MH precursors, and the activity of MH synthase. However, concentrations of ß-myrcene, a major MH compound, were higher in violet flower buds than in white flower buds, possibly due to higher threonine levels and low acidic conditions induced by comparatively low levels of some organic acids. Moreover, levels of stress-related metabolites, such as oxygenated monoterpenes, proline, and glutamic acid, were higher in violet flower buds than in white flower buds. Our results support the feasibility of metabolic profiling for the identification of phytochemical differences and improve our understanding of the correlated biological pathways for primary and secondary metabolites.

The mitochondrial genome of Stereolepis doederleini (Pempheriformes: Polyprionidae) and mitogenomic phylogeny of Pempheriformes.

The complete mitochondrial (mt) genome of Stereolepis doederleini was sequenced from a specimen collected in a commercial aquarium in Jeju Island. The sequence was 16,513 base pairs in length and, similar to other vertebrate mt genomes, included 37 mt genes and a noncoding control region; the gene order was identical to that of typical vertebrate mt genome. Mitochondrial genome sequences of 17 species from 12 families were used to reconstruct phylogenetic relationships within the order Pempheriformes. The phylogenetic trees were constructed with three methods (neighbor joining [NJ], maximum likelihood [ML], and Bayesian method) using 12 protein coding genes, but not ND6. In all phylogenetic trees, Pempheriformes were clustered into three strongly supported clades. Two Acropomatidae species (Synagrops japonicus in clade-Ⅰ and Doederleinia berycoides in clade-Ⅲ) were polyphyletic; S. japonicus was close to Lateolabracidae and was the sister of Glaucosomatidae + (Pempheridae/(Percophidae+Creediidae)), and D. berycoides was sister to Howellidae + Epigonidae. All phylogenetic trees supported a sister relationship between Creediidae and Percophidae in clade-Ⅰ. Glaucosomatidae formed a sister clade with Pempheridae. The relationships within clade-Ⅱ, which was composed of four families (Pentacerotidae, Polyprionidae, Banjosidae, and Bathyclupeidae), slightly differed between NJ/ML and BI tree topologies. In clade-Ⅲ, the relationships among Howellidae, Epigonidae, and Acropomatidae were strongly supported.

Anti-Arthritis Effect through the Anti-Inflammatory Effect of Sargassum muticum Extract in Collagen-Induced Arthritic (CIA) Mice.

(1) Background: Rheumatoid arthritis is a chronic autoimmune disease that causes progressive articular damage and functional loss. It is characterized by synovial inflammation that leads to progressive cartilage destruction. For this reason, research on functional foods that reduce the inflammatory response are under progress. (2) Methods: We focused on the anti-inflammatory effects of Sargassum muticum, and confirmed the effect of the extract on the collagen-induced arthritis (CIA) DBA/1J mice model. (3) Results: The extract was given at concentrations of 50, 100, and 200 mg/kg, and the arthritis score and edema volume of the experimental group were significantly different from the CIA group. The level of interleukin (IL)-6, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ were determined in serum and lymphocytes. The expression of these cytokines in the serum remarkably decreased from S. muticum extract (SME)100 mg/kg, and decreased from SME 200 mg/kg in lymphocytes. Also, immunohistochemical analysis of IL-6 and TNF-α in the joints revealed that the inflammatory response was noticeably lower when treated with S. muticum extract. (4) Conclusions: This study provides results of the experiment of S. muticum extract treatment in a mouse model. The treatment was found to contribute to the alleviation of edema and symptoms by reducing the expression of inflammatory cytokines. It was concluded that it may be a useful substance to help in the mitigation of arthritis symptoms.

Anti-Photoaging Effect of Jeju Putgyul (Unripe Citrus) Extracts on Human Dermal Fibroblasts and Ultraviolet B-induced Hairless Mouse Skin.

Ultraviolet (UV) radiation stimulates the expression of matrix metalloproteinases (MMPs) and inflammatory cytokines. These signaling pathways participate in the degradation of the extracellular matrix and induce inflammatory responses that lead to photoaging. This study evaluated the antioxidant activity and the effect on MMPs and procollagen of putgyul extract in vitro. The anti-photoaging activity of putgyul extracts was estimated in vivo using hairless mice (HR-1). The putgyul extracts reduced MMP-1 production and increased the content of procollagen type I carboxy-terminal peptide in human dermal fibroblasts. Ultravilot-B (UVB)-induced expression of inflammatory cytokines and MMPs was detected in mice, and putgyul extracts suppressed the expression. These results suggest that putgyul extract inhibits photoaging by inhibiting the expression of MMPs that degrade collagen and inhibiting cytokines that induce inflammatory responses. The mouse model also demonstrated that oral administration of putgyul extracts decreased wrinkle depth, epidermal thickness, collagen degradation, and trans-epidermal water loss, and increased ß-glucosidase activity on UVB exposed skin. Putgyul extract protects against UVB-induced damage of skin and could be valuable in the prevention of photoaging.

Metabolomics Reveals Rubiadin Accumulation and the Effects of Methyl Jasmonate Elicitation in Damnacanthus major Calli.

Callus suspension techniques have been considered attractive for improving bioactive metabolite productivity; methyl jasmonate (MeJA) is a widely used elicitor for stimulating synthetic pathways. In this study, a multivariate analysis-based metabolomics approach was employed to investigate the primary and specialized metabolites in the leaves, unelicited calli, and 100 or 200 µM MeJA elicited calli of Damnacanthus major. Rubiadin, a powerful anthraquinone with various therapeutic properties, was only identified in D. major calli, accumulating in a MeJA elicitation concentration-dependent manner. Callus cultures also contained high levels of amino acids, sugars, and phenolic compounds, indicating energy metabolism and metabolic adaptation responses for proliferation and stabilization. Regarding MeJA application, elicited calli contained higher amounts of quinic acid, kaempferol, and glucose with lower amounts of sucrose and raffinose than those in the unelicited control, which were closely related to protective mechanisms against MeJA. Moreover, excessive elicitation increased the asparagine, fructose, and raffinose levels and decreased the glucose and sucrose levels, which was ascribed to increased activation of the aminoacyl-tRNA biosynthesis pathway and wider utilization of glucose than of fructose after sucrose degradation. These results will be useful for optimizing plant cell culture techniques to achieve high production rates for valuable specialized metabolites.

Sargachromenol from Sargassum micracanthum inhibits the lipopolysaccharide-induced production of inflammatory mediators in RAW 264.7 macrophages.

During our ongoing screening program designed to determine the anti-inflammatory potential of natural compounds, we isolated sargachromenol from Sargassum micracanthum. In the present study, we investigated the anti-inflammatory effects of sargachromenol on lipopolysaccharide (LPS)-induced inflammation in murine RAW 264.7 macrophage cells and the underlying mechanisms. Sargachromenol significantly inhibited the LPS-induced production of nitric oxide (NO) and prostaglandin E2 (PGE2) in a dose-dependent manner. It also significantly inhibited the protein expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) in a dose-dependent manner in LPS-stimulated macrophage cells. Further analyses showed that sargachromenol decreased the cytoplasmic loss of inhibitor κBα (IκBα) protein. These results suggest that sargachromenol may exert its anti-inflammatory effects on LPS-stimulated macrophage cells by inhibiting the activation of the NF-κB signaling pathway. In conclusion, to our knowledge, this is the first study to show that sargachromenol isolated from S. micracanthum has an effective anti-inflammatory activity. Therefore, sargachromenol might be useful for cosmetic, food, or medical applications requiring anti-inflammatory properties.

Anti-inflammatory effects of apo-9'-fucoxanthinone from the brown alga, Sargassum muticum.

BACKGROUND: The marine environment is a unique source of bioactive natural products, of which Sargassum muticum (Yendo) Fensholt is an important brown algae distributed in Jeju Island, Korea. S. muticum is a traditional Korean food stuff and has pharmacological functions including anti-inflammatory effects. However, the active ingredients from S. muticum have not been characterized. METHODS: Bioguided fractionation of the ethanolic extract of S. muticum, collected from Jeju island, led to the isolation of a norisoprenoid. Its structure was determined by analysis of the spectroscopic data. In vitro anti-inflammatory activity and mechanisms of action of this compound were examined using lipopolysaccharide (LPS)-stimulated RAW 264.7 cells through ELISA assays and Western blot analysis. RESULTS: Apo-9'-fucoxanthinone, belonging to the norisoprenoid family were identified. Apo-9'-fucoxanthinone effectively suppressed LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production. This compound also exerted their anti-inflammatory actions by down-regulating of NF-κB activation via suppression of IκB-α in macrophages. CONCLUSIONS: This is the first report describing effective anti-inflammatory activity for apo-9'-fucoxanthinone'-fucoxanthnone isolated from S. muticum. Apo-9'-fucoxanthinone may be a good candidate for delaying the progression of human inflammatory diseases and warrants further studies.

Immature Persimmon (Diospyros kaki Thunb.) Ethanol Extract Ameliorates High-Fat Diet-Induced Obesity by Modulating Lipid Metabolism.

In this study, immature persimmon (Diospyros kaki Thunb.) ethanol extract was administered to an obese animal model fed a high-fat diet to measure weight change, adipose tissue weight, serum lipid level, and expression level of adipose-related genes to evaluate its efficacy. Administration of D. kaki ethanol extract (DKE) (100 and 500 mg/kg/d) decreased the body weight gain, adipose tissue weight, and serum triglyceride levels in mice fed a high-fat diet. Furthermore, it improved the leptin and adiponectin levels in the blood as well as gene expression in the liver. It also inhibited the expression of sterol regulatory element-binding protein-1c, inhibiting the production of triglyceride biosynthetic enzyme fatty acid synthesis and acetyl-CoA carboxylase, and decreased the expressions of peroxisome proliferator-activated receptor γ and CCAAT/enhancer-binding proteins that induce adipocyte differentiation. Therefore, these data suggest that DKE exerts beneficial effects on high-fat diet-induced obesity by modulating lipid metabolism in mice fed a high-fat diet.

Extracts of Citrus Juice Processing Wastes Induce Weight Gain and Decrease Serum Glucose in Sprague-Dawley Rats.

In this study, the safety and functionality of using citrus juice processing waste (CJPW) was confirmed. Large quantities of CJPW are generated on Jeju Island and cause environmental problems. CJPW extract (2,000 mg/kg) was administered intragastrically to male and female Sprague-Dawley (SD) rats for 14 days and the rats were analyzed. No general signs of toxicity were observed in SD rats administered CJPW extract. Feed intake did not differ between experimental and control animals. However, male and female rats administered CJPW extract had greater weight gain (102.9±5.53% and 114.15±6.89%, respectively) compared with the control animals. Higher weight gain was found in male and female experimental animals, but the difference was only significant in female animals. Serum analyses indicated that total protein and albumin, indicators of nutritional status, were significantly increased in animals administered CJPW. Further, serum glucose values were lower in male and female rats treated with CJPW (91.6±9.02% and 69.9±4.11%, respectively) compared with the controls; again, the difference was significant only for female animals. From the results of this study, CJPW can be considered as a safe material that does not induce toxicity in experimental animals. Therefore, CJPW is a potential raw material that can be used as a supplement in animal feed to help improve weight gain and achieve serum glucose con-trol.

Clinical Evidence of Effects of Green Mandarin (Putgyul) Extract on Skin Aging: A Randomized, Double Blind, Placebo-Controlled Study.

Green mandarins are widely consumed unripe as mandarin oranges (Citrus unshiu Marcov.), which exhibit anti-inflammatory and anti-wrinkle effects by inhibiting the production of inflammatory cytokines and matrix metalloproteinase. A randomized, double-blind, placebo-controlled clinical study was performed to verify the skin improvement efficacy and safety of green mandarin extract (PTE). For the standardization of PTE, narirutin was set as a marker compound, and PTE with a constant narirutin content was prepared for the study. After randomizing subjects with periorbital wrinkles, they were orally administered PTE (300 mg/day) or a placebo for 12 weeks. Periorbital wrinkles were measured using PRIMOSCR SF. Skin elasticity, moisture content, transepidermal water loss, and gloss were also measured. In the study results, the depth, volume, and skin roughness of the periorbital wrinkles were significantly improved compared to the control group (p = 0.011, 0.009, and 0.004, respectively). The survey confirmed that the skin condition improved after PTE consumption for 12 weeks. No adverse reactions associated with PTE were observed during the study period. Thus, the results demonstrate that PTE effectively improves UV-induced skin wrinkles. Therefore, it is considered that PTE has sufficient value as a functional food ingredient that can prevent skin aging.

Proliferation and Metabolic Profiling of Cynanchum wilfordii Adventitious Roots Using Explants from Different Cultivation Methods.

Cynanchum wilfordii root is used in traditional herbal medicine owing to its various pharmacological activities. However, C. wilfordii roots are misused owing to their morphological similarities with C. auriculatum. Adventitious root (AR) culture can prevent such misuse, and the selection of plant materials is an important procedure for producing high-quality ARs. This study aimed to compare the proliferation and metabolic profiles of C. wilfordii ARs in two types of explants from different cultivation methods (either cultivated in open field (ECF) or cultivated on a heap of C. wilfordii (ECH)). After 4 weeks of culture, the proliferation rate and number and length of secondary ARs were determined, and 3/4 Murashige and Skoog (MS) salt medium, 4.92 µM indole-3-butyric acid (IBA), and 5% sucrose were suggested as the best proliferation conditions for ARs originating from both ECF and ECH. Through metabolic profiling, ARs from ECH were found to show higher accumulation patterns for flavonoids, polysaccharides, hydroxyacetophenones, aromatic amino acids, and mono-unsaturated fatty acids, which were ascribed to the activation of flavonoid biosynthesis, the phenylpropanoid pathway, and fatty acid desaturase, stimulated by abiotic stresses. In contrast, ARs from ECF had higher levels of TCA cycle intermediates, amino acids in the aspartate-glutamate pathway, and saturated and polyunsaturated fatty acids, indicating energy metabolism and plant development. Overall, the current study provided information on the optimal conditions for inducing C. wilfordii ARs with higher amounts of bioactive compounds.

Effects of Sargassum horneri and Ulva australis Extracts on Body Weight and Serum Glucose Levels of Sprague-Dawley Rats.

This study investigated the safety and functionality of a functional additive for humans and animals from Sargassum horneri (SH) and Ulva australis (UA) waste for recycling marine refuse generated in large quantities in Jeju. Sprague-Dawley rats were orally administered functional additives at 2,000 mg/kg to assess 14-day repeated dose toxicity of the two extracts. For female rats, weight gain after administration of SH was 66.2±18.8% vs. controls. Male rats administered UA showed weight gain of 92.3±8.0% vs. controls. SH and UA significantly decreased serum glucose levels in male rats compared with controls (79.8±11.10% and 76.1±9.67%, respectively). Similarly, significant decrease in serum glucose levels were shown for female rats after administration of SH and UA (79.2±1.58% and 82.8±3.21%, respectively). Furthermore, rats showed significant differences vs. controls in several serological parameters after receiving extracts, however results remained within the normal range. Thus, the SH and UA extracts were considered safe substances that may be used as functional additives to help reduce body weight and serum glucose.

Lapathoside A Isolated from Fagopyrum esculentum Induces Apoptosis in Human Pancreatic Cancer Cells.

BACKGROUND/AIM: Lapathoside A, a phenylpropanoid ester, was isolated from the roots of buckwheat by searching for bioactive compounds against human pancreatic cancer cells. MATERIALS AND METHODS: Buckwheat root extracts, prepared by 70% ethanol, were separated into n-hexane, methylene chloride, ethyl acetate, n-butanol, and water fraction by solvent partitioning. Seven fractions were obtained from the ethyl acetate fraction by liquid chromatography, and fraction No. 6 contained lapathoside A. The effects of lapathoside A on Panc-1 and SNU-213 human pancreatic cancer cell lines were examined. RESULTS: The structure of lapathoside A was determined by liquid chromatography-mass spectrometry, liquid chromatography-tandem mass spectrometry, and nuclear magnetic resonance analysis. Next, we investigated whether lapathoside A has anticancer activity in human pancreatic cancer cell lines (PANC-1 and SNU-213). After treatment with 25 µM lapathoside A, viability of PANC-1 and SNU-213 cells decreased to about 40 and 27%, respectively. In addition, lapathoside A treatment also increased apoptosis while affecting the expression levels of apoptotic proteins. CONCLUSION: The effect of lapathoside A on apoptosis was confirmed in pancreatic cancer cell lines, supporting the application of lapathoside A in the treatment of pancreatic cancer.

Multioside, an active ingredient from adonis amurensis, displays anti-cancer activity through autophagosome formation.

BACKGROUND: Adonis amurensis Regel & Radde, commonly found in East Asia, has been traditionally used to treat cardiac insufficiency and edema. Although this plant extract has been shown to regulate cell growth and neovascularization, the anti-cancer mechanism of A. amurensis has not been fully investigated. PURPOSE: In this study, we aimed to examine the anti-cancer activity of A. amurensis and identify its underlying mechanism. METHODS: The growth of cancer cells was evaluated by MTT and hollow fiber assays. A cancer xenograft nude mouse model was used to assess the anti-cancer activities in vivo. Autophagic activity was measured by the detection of autophagosome formation and by performing a monodansylcadaverine (MDC) assay. RESULT: A. amurensis extract showed potent anti-cancer activity both in vitro and in vivo. Importantly, the treatment of cancer cells with A. amurensis extract dramatically increased the formation of autophagosomes and was involved in the activation of multiple signaling components including AKT, ERK, and MAPK. Furthermore, we isolated an active ingredient, Multioside, which exhibited strong anti-cancer activity through autophagy. CONCLUSION: A. amurensis displays anti-cancer activity that is mediated by the activation of autophagy, suggesting that A. amurensis could be a useful therapeutic anti-cancer agent.

Cynanchum wilfordii Etanolic Extract Controls Blood Cholesterol: A Double-blind, Randomized, Placebo-Controlled, Parallel Trial.

We evaluated the effects of Cynanchum wilfordii (CW) ethanolic extract on blood cholesterol levels in adults with high low-density lipoprotein cholesterol (LDL-C) levels. In a double-blind, randomized, placebo-controlled, parallel trial, 84 subjects were recruited. Participants were randomly divided into two groups with a low-dose (300 mg/d) or high-dose (600 mg/d) of CW. Levels of very low-density lipoprotein (p = 0.022) and triglycerides (p = 0.022) were significantly lower in the low-dose CW group than in the placebo group after 8 weeks. In a subgroup of participants with LDL-C≥ 150 mg/dL (n = 33), there was a significant decrease in total cholesterol (low-dose, p = 0.012; high-dose, p = 0.021), apolipoprotein B (low-dose, p = 0.022; high-dose, p = 0.016), and cholesteryl ester transfer protein (low-dose, p = 0.037; high-dose, p = 0.016) after 8 weeks of CW. The correlation between changes in total cholesterol and baseline LDL-C levels was significant in the groups that received both doses of CW (low-dose, p = 0.010; high-dose, p = 0.015). These results show that the CW ethanolic extract can regulate blood cholesterol in subjects with LDL-C≥ 150 mg/dL.

Effects of fermented Sorghum bicolor L. Moench extract on inflammation and thickness in a vascular cell and atherosclerotic mice model.

Atherosclerosis is a major cause of coronary heart disease. As a result of the development of atherosclerotic lesions, the walls of blood vessels become thicker and inhibit blood circulation. Atherosclerosis is caused by a high-fat diet and vascular injury. Chronic arterial inflammation plays an important role in the pathogenesis of atherosclerosis. In particular, secretion of the pro-atherogenic cytokine tumor necrosis factor-α induces expression of endothelial adhesion molecules including P-selectin, vascular cell adhesion molecule 1 (VCAM-1), and intercellular adhesion molecule 1 (ICAM-1), which mediate attachment of circulating monocytes and lymphocytes. In this study, we examined the anti-atherosclerotic effect of sorghum, which is known to have anti-oxidant and anti-inflammatory activity. A 50% ethanol extract of Sorghum bicolor L. Moench fermented with Aspergillus oryzae NK (fSBE) was used for experiments. In vitro expression of endothelial adhesion molecules VCAM-1 and ICAM-1 and pro-inflammatory factor cyclooxygenase-2 was significantly decreased and that of the anti-atherogenic factor heme oxygenase-1 significantly increased by fSBE (P < 0.05). At the in vivo level, we examined fat droplets of liver tissue, and aortic thickness via histological analysis, and determined the blood lipid profile through chemical analysis. fSBE at a dose of 200 mg/kg significantly improved blood and vascular health (P < 0.05). Taken together, these results demonstrate that fSBE has potential as a therapeutic anti-atherosclerotic agent.

Anti-inflammation effects of 8-oxo-9-octadecenoic acid isolated from Undaria peterseniana in lipopolysaccharide-stimulated macrophage cells.

The aim of this study was to investigate the anti-inflammatory activity of 8-oxo-9-octadecenoic acid (OOA) isolated from Undaria peterseniana by examining its ability to inhibit the lipopolysaccharide (LPS)-induced production of inflammatory mediators in RAW 264.7 macrophage cells. We found that OOA significantly suppressed the LPS-induced production of nitric oxide (NO) and inflammatory cytokines. OOA downregulated the LPS-induced expression of inducible nitric oxide synthase and cyclooxygenase-2 proteins. With respect to proinflammatory signaling pathways, OOA inhibited LPS-induced mitogen-activated protein kinase signaling by inhibiting the phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK). Moreover, OOA inhibited LPS-induced nuclear factor (NF)-κB signaling by reducing the phosphorylation of IκB-α and p50 proteins. These results indicate that OOA significantly reduces proinflammatory signaling, which results in reduced expression of cytokines and proinflammatory mediators. Taken together, these results suggest that OOA has potent anti-inflammatory effects and could be considered an effective anti-inflammatory agent.

Anti-inflammatory effect and mechanism of action of Lindera erythrocarpa essential oil in lipopolysaccharide-stimulated RAW264.7 cells.

The aim of this study was to investigate the chemical constituents of Lindera erythrocarpa essential oil (LEO) by gas chromatography-mass spectrometry and evaluate their inhibitory effect on the expression of pro-inflammatory mediators in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Fifteen compounds, accounting for 63.7 % of the composition of LEO, were identified. The main compounds were nerolidol (18.73 %), caryophyllene (14.41 %), α-humulene (7.73 %), germacrene-D (4.82 %), and α-pinene (4.47 %). LEO significantly inhibited the expression of inducible nitric oxide (NO) synthase and cyclooxygenase-2, and subsequent production of NO and prostaglandin E2. In addition, it reduced the release of pro-inflammatory cytokines in LPS-activated RAW264.7 cells. The molecular mechanism underlying the effect of LEO was associated with inhibition of the phosphorylation of mitogen-activated protein kinase (MAPK). Furthermore, LEO inhibited LPS-induced phosphorylation and degradation of inhibitor of kappa B-α, which is required for the activation of the p50 and p65 nuclear factor (NF)-κB subunits in RAW264.7 cells. Taken together, these data suggest that LEO exerted its anti-inflammatory effect by downregulating LPS-induced production of pro-inflammatory mediators through the inhibition of NF-κB and MAPK signaling in RAW264.7 cells.