Intermittent Fasting Modulates Immune Response by Generating Tregs via TGF-ß Dependent Mechanisms in Obese Mice with Allergic Contact Dermatitis.

People with obesity maintain low levels of inflammation; therefore, their exposure to foreign antigens can trigger an excessive immune response. In people with obesity or allergic contact dermatitis (ACD), symptoms are exacerbated by a reduction in the number of regulatory T cells (Tregs) and IL-10/TGF-ß-modified macrophages (M2 macrophages) at the inflammatory site. Benefits of intermittent fasting (IF) have been demonstrated for many diseases; however, the immune responses regulated by macrophages and CD4+T cells in obese ACD animal models are poorly understood. Therefore, we investigated whether IF suppresses inflammatory responses and upregulates the generation of Tregs and M2 macrophages in experimental ACD animal models of obese mice. The IF regimen relieved various ACD symptoms in inflamed and adipose tissues. We showed that the IF regimen upregulates Treg generation in a TGF-ß-dependent manner and induces CD4+T cell hypo-responsiveness. IF-M2 macrophages, which strongly express TGF-ß and inhibit CD4+T cell proliferation, directly regulated Treg differentiation from CD4+T cells. These results indicate that the IF regimen enhances the TGF-ß-producing ability of M2 macrophages and that the development of Tregs keeps mice healthy against ACD exacerbated by obesity. Therefore, the IF regimen may ameliorate inflammatory immune disorders caused by obesity.

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.

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.

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.

Osmunda japonica Extract Suppresses Pro-Inflammatory Cytokines by Downregulating NF-κB Activation in Periodontal Ligament Fibroblasts Infected with Oral Pathogenic Bacteria.

Periodontal diseases are caused by bacterial infection and may progress to chronic dental disease; severe inflammation may result in bone loss. Therefore, it is necessary to prevent bacterial infection or control inflammation. Periodontal ligament fibroblasts (PDLFs) are responsible for the maintenance of tissue integrity and immune and inflammatory events in periodontal diseases. The formation of bacterial complexes by Fusobacterium nucleatum and Porphyromonas gingivalis is crucial in the pathogenesis of periodontal disease. F. nucleatum is a facultative anaerobic species, considered to be a key mediator of dental plaque maturation and aggregation of other oral bacteria. P. gingivalis is an obligate anaerobic species that induces gingival inflammation by secreting virulence factors. In this study, we investigated whether Osmunda japonica extract exerted anti-inflammatory effects in primary PDLFs stimulated by oral pathogens. PDLFs were stimulated with F. nucleatum or P. gingivalis. We showed that pro-inflammatory cytokine (IL-6 and IL-8) expression was induced by LPS or bacterial infection but decreased by treatment with O. japonica extract following bacterial infection. We found that the activation of NF-κB, a transcription factor for pro-inflammatory cytokines, was modulated by O. japonica extract. Thus, O. japonica extract has immunomodulatory activity that can be harnessed to control inflammation.

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.

Inhibition of lipid accumulation by the ethyl acetate fraction of Distylium racemosum in vitro and in vivo.

This study confirms the anti-obesity effect of the ethyl acetate fraction of Distylium racemosum (DRE), a member of Hamamelidaceae, that naturally grows on Jeju Island, on adipocyte differentiation in 3T3-L1 cells. This study further demonstrated that DRE exhibits anti-obesity effects in C57BL/6 obese mice. The degree of adipocyte differentiation was determined using Oil red O stain; results indicated a decrease in fat globules, which was dependent on DRE concentration, when pre-adipocytes were treated with differentiation-inducing agents. In addition, this significantly reduced the expression of the adipogenic transcription factor and related genes. C57BL/6 obese mice treated with DRE showed a lower rate of body weight gain than the high-fat diet (HFD) group mice. Further, the level of serum triglyceride in the DRE treatment group was lower than that in the HFD group. The findings show that DRE are capable of suppressing adipocyte accumulation; therefore, DRE may represent a promising source of functional materials for the anti-obesity.

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.

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.

Litsea japonica Leaf Extract Suppresses Proinflammatory Cytokine Production in Periodontal Ligament Fibroblasts Stimulated with Oral Pathogenic Bacteria or Interleukin-1ß.

Periodontal disease, a chronic disease caused by bacterial infection, eventually progresses to severe inflammation and bone loss. Regulating excessive inflammation of inflamed periodontal tissues is critical in treating periodontal diseases. The periodontal ligament (PDL) is primarily a connective tissue attachment between the root and alveolar bone. PDL fibroblasts (PDLFs) produce pro-inflammatory cytokines in response to bacterial infection, which could further adversely affect the tissue and cause bone loss. In this study, we determined the ability of Litsea japonica leaf extract (LJLE) to inhibit pro-inflammatory cytokine production in PDLFs in response to various stimulants. First, we found that LJLE treatment reduced lipopolysaccharide (LPS)-induced pro-inflammatory cytokine (interleukin-6 and interleukin-8) mRNA and protein expression in PDLFs without cytotoxicity. Next, we observed the anti-inflammatory effect of LJLE in PDLFs after infection with various oral bacteria, including Fusobacterium nucleatum, Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia. These anti-inflammatory effects of LJLE were dose-dependent, and the extract was effective following both pretreatment and posttreatment. Moreover, we found that LJLE suppressed the effect of interleukin-1 beta-induced pro-inflammatory cytokine production in PDLFs. Taken together, these results indicate that LJLE has anti-inflammatory activity that could be exploited to prevent and treat human periodontitis by controlling inflammation.

Erratum to "Anti-Inflammatory Effect of 3-Bromo-4,5-Dihydroxybenzaldehyde, a Component of Polysiphonia morrowii, In Vivo and In Vitro" [Toxicol. Res. 33 (2017) 325-332].

[This corrects the article on p. 325 in vol. 33, PMID: 29071017.].

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.

Anti-Inflammatory Effect of 3-Bromo-4,5-Dihydroxybenzaldehyde, a Component of Polysiphonia morrowii, In Vivo and In Vitro.

3-Bromo-4,5-dihydroxybenzaldehyde (BDB) is a natural bromophenol compound that is most commonly isolated from red algae. The present study was designed to investigate the anti-inflammatory properties of BDB on atopic dermatitis (AD) in mice induced by 2,4-dinitrochlorobenzene (DNCB) and on lipopolysaccharide (LPS)-stimulated murine macrophages. BDB treatment (100 mg/kg) resulted in suppression of the development of AD symptoms compared with the control treatment (induction-only), as demonstrated by reduced immunoglobulin E levels in serum, smaller lymph nodes with reduced thickness and length, a decrease in ear edema, and reduced levels of inflammatory cell infiltration in the ears. In RAW 264.7 murine macrophages, BDB (12.5, 25, 50, and 100 µM) suppressed the production of interleukin-6, a proinflammatory cytokine, in a dose-dependent manner. BDB also had an inhibitory effect on the phosphorylation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and signal transducer and activator of transcription 1 (STAT1; Tyr 701), two major signaling molecules involved in cellular inflammation. Taken together, the results show that BDB treatment alleviates inflammatory responses in an atopic dermatitis mouse model and RAW 264.7 macrophages. These results suggest that BDB may be a useful therapeutic strategy for treating conditions involving allergic inflammation such as atopic dermatitis.

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.

Anti-inflammatory effect of supercritical extract and its constituents from Ishige okamurae.

The anti-inflammatory properties of the supercritical fluid extract of Ishige okamurae (SFEIO) on lipopolysaccharide (LPS)-stimulated murine RAW 264.7 macrophages. The lipid profile of the SFEIO, reviled the presence of palmitic acid (220.2 mg/g), linoleic acid (168.0 mg/g), and oleic acid (123.0 mg/g). SFEIO was found to exert it's anti-inflammatory effects through inhibiting nitric oxide (NO), prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6 production in LPS-stimulated RAW 264.7 cells, without inducing cytotoxicity. SFEIO did not effect on the LPS-induced p38 kinase phosphorylation, whereas it attenuated the extracellular-related signaling kinase (ERK) and c-Jun N-terminal kinase (JNK) phosphorylation. Furthermore, SFEIO inhibited the LPS-induced IκB-α degradation and p50 NF-κB activation. These results suggest that SFEIO exerts its anti-inflammatory effects in LPS-activated RAW 264.7 cells by down-regulating the activation of ERK, JNK, and NF-κB.

Anti-wrinkle effects of Sargassum muticum ethyl acetate fraction on ultraviolet B-irradiated hairless mouse skin and mechanistic evaluation in the human HaCaT keratinocyte cell line.

The present study investigated the photoprotective properties of the ethyl acetate fraction of Sargassum muticum (SME) against ultraviolet B (UVB)­induced skin damage and photoaging in a mouse model. HR­1 strain hairless male mice were divided into three groups: An untreated control group, a UVB­irradiated vehicle group and a UVB­irradiated SME group. The UVB­irradiated mice in the SME group were orally administered with SME (100 mg/kg body weight in 0.1 ml water per day) and then exposed to radiation at a dose of 60­120 mJ/cm2. Wrinkle formation and skin damage were evaluated by analysis of skin replicas, epidermal thickness and collagen fiber integrity in the dermal connective tissue. The mechanism underlying the action of SME was also investigated in the human HaCaT keratinocyte cell line following exposure of the cells to UVB at a dose of 30 mJ/cm2. The protein expression levels and activity of matrix metalloproteinase­1 (MMP­1), and the binding of activator protein­1 (AP­1) to the MMP­1 promoter were assessed in the HaCaT cells using western blot analysis, an MMP­1 fluorescent assay and a chromatin immune­precipitation assay, respectively. The results showed that the mean length and depth of the wrinkles in the UVB­exposed hairless mice were significantly improved by oral administration of SME, which also prevented the increase in epidermal thickness triggered by UVB irradiation. Furthermore, a marked increase in collagen bundle formation was observed in the UVB­treated mice with SME administration. SME pretreatment also significantly inhibited the UVB­induced upregulation in the expression and activity of MMP­1 in the cultured HaCaT keratinocytes, and the UVB­enhanced association of AP­1 with the MMP­1 promoter. These results suggested that SME may be useful as an anti-photoaging resource for the skin.

Anti-obesity effect of Crinum asiaticum var. japonicum Baker extract in high-fat diet-induced and monogenic obese mice.

This study determined the anti-obesity effect of Crinum asiaticum var. japonicum Baker extract (CAE) on adipocytes and obese mice. The inhibitory effects of CAE on adipocyte differentiation and adipogenesis were determined using differentiation induction medium in 3T3-L1 cells. To get an insight into underlying molecular actions of CAE, we investigated the changes in the expression levels of genes involved in lipogenesis by CAE treatment using qRT-PCR. CAE strongly suppressed adipocyte differentiation through downregulation of PPARγ, C/EBPα, C/EBP ß, and aP2. CAE treatment could also suppress the expression levels of ACC, FAS, LPL and HMGCR gene in 3T3-L1 cells. Male C57BL/6 strain and C57BL/6J-ob/ob strain mice were fed with HFD containing 60% fat and normal diet in the presence or absence of 25, 50, and 100mg/kg CAE for 7 weeks. CAE supplementation could highly suppress the body weight gain and epididymal fat accumulation without changes in food uptake in both obese models. Increases in total cholesterol, LDL-cholesterol and triglyceride were highly suppressed in the presence of CAE. In summary, CAE has an anti-obesity effect and this anti-obesity potential might be associated with downregulation of genes involved in adipocyte differentiation and lipogenesis.

External Application of Apo-9'-fucoxanthinone, Isolated from Sargassum muticum, Suppresses Inflammatory Responses in a Mouse Model of Atopic Dermatitis.

Allergic skin inflammation such as atopic dermatitis is characterized by skin barrier dysfunction, edema, and infiltration with various inflammatory cells. The anti-inflammatory effects of Apo-9'-fucoxanthinone, isolated from Sargassum muticum, have been described in many diseases, but the mechanism by which it modulates the immune system is poorly understood. In this study, the ability of Apo-9'-fucoxanthinone to suppress allergic reactions was investigated using a mouse model of atopic dermatitis. The Apo-9'-fucoxanthinone-treated group showed significantly decreased immunoglobulin E in serum. Also, Apo-9'-fucoxanthinone treatment resulted in a smaller lymph node size with reduced the thickness and length compared to the induction group. In addition, Apo-9'-fucoxanthinone inhibited the expression of interleukin-4, interferon-gamma and tumor necrosis factor-alpha by phorbol 12-myristate 13-acetate and ionomycin-stimulated lymphocytes. These results suggest that Apo-9'-fucoxanthinone may be a useful therapeutic strategy for treating chronic inflammatory diseases.

Anti-inflammatory effects of isoketocharbroic acid from brown alga, Sargassum micracanthum.

During our on-going screening program designed to isolate natural compounds from marine environments, we isolated isoketochabrolic acid (IKCA) from Sargassum micracanthum, an important brown algae distributed in Jeju Island, Korea. Furthermore, we evaluated the inhibitory effects of IKCA on nitric oxide (NO) production in lipopolysaccharide (LPS)-triggered macrophages. IKCA strongly inhibited NO production, with an IC50 value of 58.31 µM. Subsequent studies demonstrated that IKCA potently and concentration-dependently reduced prostaglandin E2 (PGE2), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1ß, and IL-6 cytokine production. In conclusion, to the best of our knowledge, this is the first study to show that IKCA isolated from S. micracanthum has a potent anti-inflammatory activity. Therefore, IKCA might be useful as an anti-inflammatory health supplement or functional cosmetics.