Sargassum Serratifolium Research Articles

Modulation of macrophage transcript and secretion profiles by Sargassum Serratifolium extract is associated with the suppression of muscle atrophy

Recent research has emphasized the role of macrophage-secreted factors on skeletal muscle metabolism. We studied Sargassum Serratifolium ethanol extract (ESS) in countering lipopolysaccharide (LPS)-induced changes in the macrophage transcriptome and their impact on skeletal muscle. Macrophage-conditioned medium (MCM) from LPS-treated macrophages (LPS-MCM) and ESS-treated macrophages (ESS-MCM) affected C2C12 myotube cells. LPS-MCM upregulated muscle atrophy genes and reduced glucose uptake, while ESS-MCM reversed these effects. RNA sequencing revealed changes in the immune system and cytokine transport pathways in ESS-treated macrophages. Protein analysis in ESS-MCM showed reduced levels of key muscle atrophy-related proteins, TNF-α, IL-6, IL-1, and GDF-15. These proteins play crucial roles in muscle function. These findings highlight the intricate relationship between the macrophage transcriptome and their secreted factors in either impairing or enhancing skeletal muscle function. ESS treatment has the potential to reduce macrophage-derived cytokines, preserving skeletal muscle function.

The beneficial effects of ethanolic extract of Sargassum serratifolium in DNCB-induced mouse model of atopic dermatitis

Atopic dermatitis is a chronic complex inflammatory skin disorder that requires sustainable treatment methods due to the limited efficacy of conventional therapies. Sargassum serratifolium, an algal species with diverse bioactive substances, is investigated in this study for its potential benefits as a therapeutic agent for atopic dermatitis. RNA sequencing of LPS-stimulated macrophages treated with ethanolic extract of Sargassum serratifolium (ESS) revealed its ability to inhibit a broad range of inflammation-related signaling, which was proven in RAW 264.7 and HaCaT cells. In DNCB-induced BALB/c or HR-1 mice, ESS treatment improved symptoms of atopic dermatitis within the skin, along with histological improvements such as reduced epidermal thickness and infiltration of mast cells. ESS showed a tendency to improve serum IgE levels and inflammation-related cytokine changes, while also improving the mRNA expression levels of Chi3l3, Ccr1, and Fcεr1a genes in the skin. Additionally, ESS compounds (sargachromanol (SCM), sargaquinoic acid (SQA), and sargahydroquinoic acid (SHQA)) mitigated inflammatory responses in LPS-treated RAW264.7 macrophages. In summary, ESS has an anti-inflammatory effect and improves atopic dermatitis, ESS may be applied as a therapeutics for atopic dermatitis.

1639-P: Meroterpenoid-Rich Fraction of the Ethanol Extract from Sargassum Serratifolium Suppressed Muscle Atrophy Induced by Dexamethasone in C2C12 Myotubes and C57BL/6 Mice

Decline in muscle mass and strength impairs the ability to perform normal daily functions and increases the risk of falls and fractures, significantly reducing the quality of life. In addition, as the muscle is considered a major regulator of systemic glucose homeostasis, maintaining muscle mass is important for glycemic control. Although dexamethasone (DEX), a synthetic glucocorticoid, is a well-known anti-inflammatory drug, high doses or long-term use induces side effects such as skeletal muscle atrophy. Sargassum serratifolium is a brown alga that contains high concentrations of meroterpenoids and exhibits antioxidant, anti-inflammatory, anti-obesity, anti-atherosclerosis, and hepatoprotective activities. However, its effects on DEX-induced muscle atrophy remain unknown. Here, we investigated the beneficial effects of the meroterpenoid-rich fraction of the ethanol extract from S. serratifolium (MES) on DEX-induced muscle atrophy in C2C12 myotubes and C57BL/6 mice. In the in vitro study using C2C12 myotubes, DEX (5 μM) treatment reduced cell viability, myotube diameter, and glucose uptake, whereas MES treatment reversed these effects. In addition, in DEX-stimulated C2C12 myotubes, MES treatment not only increased the phosphorylation of Akt and p706SK but also decreased the mRNA and protein expression of protein degradation factors such as MAFbx/Atrogin-1, MuRF1, and FoxO3a. In the in vivo study, MES suppressed DEX-induced decrease in body weight, ability to exercise, lean body mass, calf thickness, muscle weight, and cross-sectional area of the gastrocnemius muscle. Taken together, MES ameliorated DEX-induced muscle atrophy and maintained glucose homeostasis. Therefore, MES can be used as a potential therapeutic agent for the treatment of muscle atrophy. Disclosure M.Lee: None. H.Ryu: None. H.Jeong: None. B.Lee: None.

1640-P: Meroterpenoid-Rich Ethanolic Extract of Sargassum serratifolium (MES) Alters Macrophage Transcriptome and Secretion Profile toward Improving Muscle Atrophy and Glucose Intolerance

Skeletal muscle plays an essential role in glucose homeostasis. Of many cell types in the skeletal muscle, recent studies indicate that secretion factors derived from macrophages are important for glucose metabolism in the skeletal muscle. Here, RNA Sequencing analysis showed that Lipopolysaccharide (LPS) treatment broadly altered the transcriptome of macrophages, of which signaling related to secretion factors was markedly altered toward elevating unfavorable cytokines to maintain skeletal muscle metabolism. On the other hand, the treatment of the Meroterpenoid-Rich Extract of Sargassum Serratifolium (MES), a strong anti-inflammatory and antioxidant extract found in our previous studies, reversed the LPS-induced signaling pathways. We further tested whether the treatment of conditioned media (CM) derived from LPS-macrophage (LPS-CM) or CM derived from LPS-macrophage treated with MES (MES-CM) affects glucose homeostasis in differentiated C2C12 myotube cells. LPS-CM treatment notably increased mRNA levels of muscle atrophy-associated genes including MuRF1, MAFbx, and Myostatin, and decreased glucose uptake, and MES-CM treatment reversed these characteristics, indicating that secretion factors induced by LPS or MES either impair or improve muscle glucose homeostasis, respectively. We further analyzed secretion factors inside by proteome array and data showed that LPS-CM includes GDF-15, IL-1 α/β, RAGE, etc related to muscle atrophy and glucose intolerance, which were significantly reduced in MES-CM. These data indicate that LPS- or MES-induced changes in the transcriptome in macrophages are closely related to the alteration in secretion factors toward either impairing or improving glucose metabolism in the skeletal muscle respectively. Of many, the decrease in macrophage-derived cytokine mentioned above may be important for glucose homeostasis in the skeletal muscle. Disclosure H.Ryu: None. B.Lee: None.

Hypothalamic administration of sargahydroquinoic acid elevates peripheral thermogenic signaling and ameliorates high fat diet-induced obesity through the sympathetic nervous system

Sargassum serratifolium (C. Agardh) C.Agardh, a marine brown alga, has been consumed as a food and traditional medicine in Asia. A previous study showed that the meroterpenoid-rich fraction of an ethanolic extract of S. serratifolium (MES) induced adipose tissue browning and suppressed diet-induced obesity and metabolic syndrome when orally supplemented. Sargahydroquinoic acid (SHQA) is a major component of MES. However, it is unclear whether SHQA regulates energy homeostasis through the central nervous system. To examine this, SHQA was administrated through the third ventricle in the hypothalamus in high-fat diet-fed C57BL/6 mice and investigated its effects on energy homeostasis. Chronic administration of SHQA into the brain reduced body weight without a change in food intake and improved metabolic syndrome-related phenotypes. Cold experiments and biochemical analyses indicated that SHQA elevated thermogenic signaling pathways, as evidenced by an increase in body temperature and UCP1 signaling in white and brown adipose tissues. Peripheral denervation experiments using 6-OHDA indicated that the SHQA-induced anti-obesity effect is mediated by the activation of the sympathetic nervous system, possibly by regulating genes associated with sympathetic outflow and GABA signaling pathways. In conclusion, hypothalamic injection of SHQA elevates peripheral thermogenic signaling and ameliorates diet-induced obesity.

Protective effect of sargahydroquinoic acid against Aβ25–35-evoked damage via PI3K/Akt mediated Nrf2 antioxidant defense system

Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by memory loss and cognitive impairment. β-Amyloid (Aβ) is widely accepted as the main neurotoxin that triggers mitochondrial-associated oxidative stress, leading to neuronal death in AD. Following our preliminary research on the neuroprotective effects of the brown alga Sargassum serratifolium, its major compounds, including sargaquinoic acid, sargahydroquinoic acid (SHQA), and sargachromenol, were investigated to elucidate the antioxidant and anti-apoptotic properties of Aβ25–35-stimulated PC12 cells. SHQA exhibited the most potent effect on Aβ-induced mitochondrial-associated oxidative stress and apoptosis. In addition, the compound enhanced the expression and translocation of nuclear factor-E2-related factor 2 (Nrf2), while reducing the expression of cytoplasmic Kelch-like ECH-associated protein 1 (Keap1). Furthermore, the compound upregulated the expression of Nrf2-regulated antioxidant enzymes, including HO-1, NQO1, GCLc, GCLm, and TrxR1. Co-treatment with SHQA and LY294002, a specific PI3K inhibitor, inhibited nuclear Nrf2 expression and Akt phosphorylation, demonstrating that SHQA-mediated Nrf2 activation was directly associated with the PI3K/Akt signaling pathway. Mechanistic studies indicate that activation of the PI3K/Akt/Nrf2 pathway is the molecular basis for the neuroprotective effects of SHQA. In silico docking simulation revealed that SHQA established specific interactions with the key amino acid residues of PI3K, Akt, and Nrf2-Keap1 via hydrogen bonding and van der Waals interactions, which may affect the biological capacities of target markers. Overall, this is the first report of this novel mechanism of SHQA as a Nrf2 activator against Aβ-mediated oxidative damage, suggesting that the compound might be a potential agent for the prevention of AD.

Green Synthesis of Silver and Gold Nanoparticles via Sargassum serratifolium Extract for Catalytic Reduction of Organic Dyes

The green synthesis of inorganic nanoparticles (NPs) using bio-materials has attained enormous attention in recent years due to its simple, eco-friendly, low-cost and non-toxic nature. In this work, silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs) were synthesized by the marine algae extract, Sargassum serratifolium (SS). The characteristic studies of bio-synthesized SS-AgNPs and SS-AuNPs were carried out by using ultraviolet–visible (UV–Vis) absorption spectroscopy, dynamic light scattering (DLS), high-resolution transmission electron microscope (HR-TEM), selected area electron diffraction (SAED), energy-dispersive X-ray spectroscopy (EDX), X-ray powder diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR). Phytochemicals in the algae extract, such as meroterpenoids, acted as a capping agent for the NPs’ growth. The synthesized Ag and Au NPs were found to have important catalytic activity for the degradation of organic dyes, including methylene blue, rhodamine B and methyl orange. The reduction of dyes by SS-AgNPs and -AuNPs followed the pseudo-first order kinetics.

Meroterpenoid-Rich Fraction of the Ethanol Extract of Sargassum Serratifolium Suppresses Collagen-Induced Rheumatoid Arthritis in DBA/1J Mice Via Inhibition of Nuclear Factor κB Activation.

Rheumatoid arthritis (RA) is an autoimmune disorder related to the inflammation of cartilage due to the infiltration of inflammatory cells. Sargassum serratifolium, a brown alga, possesses strong anti-inflammatory activities. The effect of meroterpenoid-rich fraction from the ethanol extract of S. serratifolium (MES) on RA and its underlying mechanisms on the inhibition of RA using a collagen-induced arthritis (CIA) mouse model are examined. The results show that MES ameliorates paw swelling and reduces the arthritis score. MES considerably decreases the secretion of pro-inflammatory cytokines in the serum and joint tissue of mice. Histopathological analysis demonstrates that MES strongly inhibited bone damage and inflammatory cell intrusion in the joint tissue. The expression of inflammatory enzymes and adhesion molecules is significantly inhibited in the serum and joint tissue of MES-fed mice. In addition, MES downregulates the nuclear factor κB (NF-κB) signaling pathway by suppressing the phosphorylation of protein kinase B, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinases. MES supplementation remarkably reduces inflammatory response in CIA mouse model. These results indicate that MES can be used as a pharmaceutical agent against RA.

Preparation and characterization of nano-emulsions of Sargassum serratifolium extract

Preparation and characterization of nano-emulsions of Sargassum serratifolium extract

Effects of Sargaquinoic Acid in Sargassum Serratifolium on Inducing Brown Adipocyte-like Phenotype in Mouse Adipocytes In Vitro.

A previous study showed that the meroterpenoid-rich fraction of an ethanolic extract of Sargassum serratifolium (MES) stimulated adipose tissue browning and inhibited diet-induced obesity and metabolic syndrome. Sargaquinoic acid (SQA) is a major component in MES. We investigated the effects of SQA on the differentiation of preadipocytes to the beige adipocytes. SQA was treated in 3T3-L1 adipocytes differentiated under a special condition that has been reported to induce the browning of adipocytes. SQA at 10 µM reduced lipid accumulation by approximately 23%. SQA at 2.5 - 10 µM induced the differentiation of white adipocytes to beige adipocytes partially by increasing the mitochondrial density and the expression of beige/brown adipocyte markers. In addition, SQA activated lipid catabolic pathways, evidenced by the increased expression levels of perilipin, carnitine palmitoyltransferase 1, and acyl-CoA synthetase long-chain family member 1. As a partial mechanism, biochemical and in silico analyses indicate that SQA activated AMP-activated protein kinase signaling in adipocytes.

White Adipocyte Browning Effects of Sargaquinoic Acid in 3T3-L1 Preadipocytes (P06-109-19)

ObjectivesBrown and beige adipocytes are known to combat obesity and hyperlipidemia by increasing energy expenditure through non-shivering thermogenesis. Since sargassum serratifolium, a marine brown alga, exhibited anti-obesity effect through white adipose tissue browning in diet induced obese mice, the purpose of this study was to investigate the effects of sargaquinoic acid (SQA), a major component of S. serratifolium, on the induction of preadipocytes to beige adipocyte phenotype. Methods3T3-L1 preadipocytes were treated with SQA which was isolated from S. serratifolium. Triglyceride (TG) accumulation in 3T3-L1 cells was determined by lipid staining (Oil Red O) and colorimetric TG quantification assay. Change of free glycerol level in cell culture medium and gene expression related to fatty acid oxidation by SQA treatment in the 3T3-L1 cells were also measured. In addition, the expression of mitochondrial DNA was examined using real-time PCR to determine the mitochondrial biogenesis during adipocyte browning. Brown adipocyte related gene expressions were analyzed using real-time PCR. Western blot assay was utilized to examine the AMP-activated protein kinase (AMPK) activity during white adipocyte browning. ResultsSQA induced the differentiation of white adipocytes to beige adipocytes suggested by an increase in multilocular lipid droplets, mitochondrial density, and the brown adipocyte-specific gene expressions including uncoupling protein 1 and PR domain containing 16. Also, SQA increased the lipolysis and fatty oxidation related gene expressions. SQA increased AMPK activity to induce the expression of brown adipocyte-specific genes, since AMPK inhibitor (dorsomorphin) decreased the brown adipocyte-specific gene expressions. ConclusionsThese findings indicate that SQA induces white adipocyte browning by activating AMPK pathway, suggesting SQA has the potential to be used as a dietary supplement to treat obesity and related metabolic diseases. Funding SourcesThis study was a part of the projects, “Development of functional food products with natural materials derived from marine resources” funded by the Ministry of Oceans and Fisheries, Republic of Korea.

Sargahydroquinoic acid, a major compound in Sargassum serratifolium (C. Agardh) C. Agardh, widely activates lipid catabolic pathways, contributing to the formation of beige-like adipocytes

Abstract Sargassum serratifolium (C. Agardh) C. Agardh, a marine brown alga, has been consumed as food and traditional medicine in Asia. Previous study showed that the meroterpenoid-rich fraction of an ethanolic extract of Sargassum serratifolium (C. Agardh) C. Agardh (MES) stimulated adipose tissue browning and inhibited diet-induced obesity and metabolic syndrome. Sargahydroquinoic acid (SHQA) is a major component in MES. It is investigated whether SHQA is a contributor for the anti-obesity effect of MES and whether SHQA directly acts on adipocytes using 3T3-L1 differentiated under the classical and beige adipocyte-inducing conditions. Interestingly, SHQA notably reduced lipid accumulation despite the upregulation of adipogenic transcription factor PPARγ in adipocytes differentiated under both conditions. Western blotting and protein-ligand docking simulation further revealed that SHQA also activates PPARα and AMPKα, lipid-catabolic proteins. Thus, it is further focused on the signaling pathways mediated by these proteins. SHQA markedly elevated lipolysis and mitochondria number, but paradoxically reduced ATP production. When uncoupled metabolic signaling was examined, SHQA significantly increased UCP1-positive adipocytes as well as beige adipocyte markers. In conclusion, SHQA may activate PPARγ, PPARα, and AMPKα, contributing to the stimulation of lipid catabolic pathways and adipocyte browning. Therefore, SHQA may be used as a novel pharmaceutical agent to combat obesity and associated metabolic syndrome.

Hexane fraction from the ethanolic extract of Sargassum serratifolium suppresses cell adhesion molecules via regulation of NF-\u03baB and Nrf2 pathway in human umbilical vein endothelial cells

Sargassum serratifolium ethanolic extract has been known for strong antioxidant and anti-inflammatory properties. We prepared hexane fraction from the ethanolic extract of S. serratifolium (HSS) to improve biological activities. In this study, we investigated the effects of HSS on the inhibition of tumor necrosis factor (TNF)-α-induced monocyte adhesion to human umbilical vein endothelial cells (HUVECs). We found that HSS suppressed the production of cell adhesion molecules such as intracellular adhesion molecule-1 and vascular cell adhesion molecule-1 in TNF-α-induced HUVECs. Moreover, TNF-α-induced production of monocyte chemoattractant protein 1 and keratinocyte chemoattractant was inhibited by HSS treatment. HSS suppressed TNF-α-induced nuclear factor kappa B (NF-κB) activation via preventing proteolytic degradation of inhibitor κB-α. HSS induced the production of heme oxygenase 1 via translocation of Nrf2 into the nucleus in TNF-α-treated HUVECs. Overall, HSS alleviated vascular inflammation through the downregulation of NF-κB activation and the upregulation of Nrf2 activation in TNF-α-induced HUVECs. These results indicate that HSS may be used as therapeutic agents for vascular inflammatory disorders.

Effect of a Sargassum serratifolium Extract on Neuroinflammation Induced by Lipopolysaccharides in Mice

Effect of a Sargassum serratifolium Extract on Neuroinflammation Induced by Lipopolysaccharides in Mice

Evaluation of antioxidant activities of various solvent extract from Sargassum serratifolium and its major antioxidant components.

Sargassum serratifolium has been known to contain a high level of meroterpenoids as antioxidant components. We investigated antioxidant activities and active components in various solvent extracts from S. serratifolium. Ethyl acetate, ethanol, and methanol extracts showed relatively strong DPPH, ABTs, and superoxide radical scavenging activities. Hexane and ethyl acetate extract showed the strongest hydroxyl radical and reactive oxygen species (ROS), respectively, scavenging activities. Sargahydroquinoic acid (SHQA), sargachromanol (SCM) and sargaquinoic acid (SQA) were main antioxidant components in S. serratifolium. Ethanol extract showed the highest levels of SHQA, SCM, and SQA which comprised to be 227 ± 6.31 mg/g. SHQA and SCM exhibited stronger antioxidant capacities than SQA based on lower IC50 values in ROS, DPPH, ABTs, and superoxide radical scavenging assays. The result showed that ethanol is the most efficient extracting solvent for the active components from S. serratifolium and the plant has the potential as a natural antioxidant.

Sargassum serratifolium Extract Attenuates Interleukin-1β-Induced Oxidative Stress and Inflammatory Response in Chondrocytes by Suppressing the Activation of NF-κB, p38 MAPK, and PI3K/Akt.

Osteoarthritis (OA) is a degenerative joint disease that is characterized by irreversible articular cartilage destruction by inflammatory reaction. Among inflammatory stimuli, interleukin-1β (IL-1β) is known to play a crucial role in OA pathogenesis by stimulating several mediators that contribute to cartilage degradation. Recently, the marine brown alga Sargassum serratifolium has been reported to exhibit antioxidant and anti-inflammatory effects in microglial and human umbilical vein endothelial cell models using lipopolysaccharide and tumor necrosis factor-α, but its beneficial effects on OA have not been investigated. This study aimed to evaluate the anti-osteoarthritic effects of ethanol extract of S. serratifolium (EESS) in SW1353 human chondrocytes and, in parallel, primary rat articular chondrocytes. Our results showed that EESS effectively blocked the generation of reactive oxygen species in IL-1β-treated SW1353 and rat primary chondrocytes, indicating that EESS has a potent antioxidant activity. EESS also attenuated IL-1β-induced production of nitric oxide (NO) and prostaglandin E2, major inflammatory mediators in these cells, which was associated with the inhibition of inducible NO synthase and cyclooxygenase-2 expression. Moreover, EESS downregulated the level of gene expression of matrix metalloproteinase (MMP)-1, -3 and -13 in SW1353 chondrocytes treated with IL-1β, resulting in their extracellular secretion reduction. In addition, the IL-1β-induced activation of nuclear factor-kappa B (NF-κB) was restored by EESS. Furthermore, EESS reduced the activation of p38 mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathways upon IL-1β stimulation. These results indicate that EESS has the potential to exhibit antioxidant and anti-inflammatory effects through inactivation of the NF-κB, p38 MAPK, and PI3K/Akt signaling pathways. Collectively, these findings demonstrate that EESS may have the potential for chondroprotection, and extracts of S. serratifolium could potentially be used in the prevention and treatment of OA.

Sargassum serratifolium attenuates RANKL-induced osteoclast differentiation and oxidative stress through inhibition of NF-κB and activation of the Nrf2/HO-1 signaling pathway.

Sargassum serratifolium C. Agardh is a marine brown alga that has long been used as an ingredient for food and medicine by many people living along Asian coastlines. Recently, various beneficial effects of extracts or compounds isolated from S. serratifolium have been reported, but their efficacies against bone destruction are unclear. Therefore, in this study, we investigated the inhibitory property of an ethanol extract of S. serratifolium (EESS) on osteoclast differentiation by focusing on the receptor activator of nuclear factor-κB ligand (RANKL)-stimulated osteoclastogenesis model using RAW 264.7 macrophages. Our results demonstrated that EESS reduced RANKL-induced osteoclast differentiation in RAW 264.7 cells, by inhibiting tartrate-resistant acid phosphatase (TRAP) activity and destroying the F-actin ring formation. EESS also attenuated RANKL-induced expressions of key osteoclast-specific genes, such as nuclear factor of activated T cells cytoplasmic 1 (NFATC1), TRAP, cathepsin K and matrix metalloproteinase-9. These effects were mediated by impaired nuclear translocation of nuclear factor (NF)-κB and suppression of IκB-α degradation. In addition, EESS effectively inhibited the production of reactive oxygen species (ROS) by RANKL, which was associated with enhanced expression of nuclear translocation of nuclear factor-erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). Overall, our findings provide evidence that EESS suppresses RANKL-induced osteoclastogenesis and oxidative stress through suppression of NF-κB and activation of Nrf2/HO-1 signaling pathway, indicating that S. serratifolium has a potential application the prevention and treatment of osteoclastogenic bone disease.

Meroterpenoid-rich fraction of an ethanolic extract from Sargassum serratifolium alleviates obesity and non-alcoholic fatty liver disease in high fat-fed C57BL/6J mice

Sargassum serratifolium has diverse health-promoting effects because of high levels of meroterpenoids with strong antioxidant and anti-inflammatory activities. Here, we investigated the effects of a meroterpenoid-rich fraction of an ethanolic extract of S. serratifolium (MES) on obesity and obesity-related hepatic steatosis in high fat (HF)-fed C57BL/6J mice. MES supplementation markedly reduced HF diet-induced obesity and hepatic steatosis without changes in food intake. MES improved blood lipid profile and elevated circulating adiponectin. Furthermore, MES notably increased uncoupling protein 1 (UCP-1)-positive cells and decreased macrophage infiltration in adipose tissue. MES exerted the anti-obesity and lipid-lowering effects by activating AMPK-related fatty acid oxidation signaling and inhibiting SREBP1c-related lipogenesis signaling in liver and adipose tissues. Our study indicates that MES prevents diet-induced obesity and related metabolic disorders at least partially by activating energy expenditure signaling and inhibiting lipogenesis. MES may be used as a pharmaceutical agent against obesity and related metabolic syndrome.

Activation of the Nrf2/HO-1 Signaling Pathway Contributes to the Protective Effects of Sargassum serratifolium Extract against Oxidative Stress-Induced DNA Damage and Apoptosis in SW1353 Human Chondrocytes.

Oxidative stress in chondrocytes plays a critical role in the pathogenesis of osteoarthritis as an important cause of articular cartilage degradation. Sargassum serratifolium C. Agardh, a marine brown algae, is known to have potent antioxidant activity. Nevertheless, no study has been conducted yet on the protective efficacy against oxidative stress in chondrocytes. Therefore, the aim of the current study is to investigate the mechanism of the antioxidative effect of ethanol extract of S. serratifolium (EESS) on DNA damage and apoptosis induced by hydrogen peroxide (H2O2) in SW1353 human chondrocytes. For this purpose, SW1353 cells exposed to H2O2 in the presence or absence of EESS were applied to cell viability assay, comet assay, immunoblotting and flow cytometry analyses. Our results showed that EESS effectively attenuated H2O2-induced cytotoxicity and DNA damage associated with the inhibition of reactive oxygen species (ROS) accumulation. EESS also weakened the mitochondria membrane permeabilization by H2O2, and recovered H2O2-induced decreased expression of anti-apoptotic Bcl-2 and pro-caspase-3, and degradation of poly (ADP-ribose) polymerase. In addition, EESS increased not only expression, but also phosphorylation of nuclear factor-erythroid 2 related factor 2 (Nrf2), and promoted the expression of heme oxygenase-1 (HO-1), a critical target enzyme of Nrf2, but decreased the expression of kelch-like ECH-associated protein-1; however, the inhibition of HO-1 activity by zinc protoporphyrin abolished the antioxidant potential induced by EESS against H2O2-mediated oxidative stress. Therefore, the results of this study suggest that the antioxidant efficacy of EESS in chondrocytes is at least involved in the Nrf2/HO-1 signaling pathway-dependent mechanism.

Meroterpinoid-rich fraction of the ethanol extract from Sargassum serratifolium suppresses TNF-α-induced monocytes adhesion to vascular endothelium and vascular inflammation in high cholesterol-fed C57BL/6J mice

Sargassum serratifolium has been known to contain high concentration of meroterpinoids as anti-inflammatory compounds. We investigated the protective effects of the meroterpinoid-rich fraction of the ethanol extract from S. serratifolium (MES) on vascular inflammation using tumor necrosis factor (TNF)-α-induced human umbilical vein endothelial cells (HUVECs) and high cholesterol diet (HCD)-fed C57BL/6J mice. The in vitro results showed that MES inhibited the adhesion of monocytes to TNF-α-stimulated HUVECs by reduced levels of cell adhesion molecules, monocyte chemoattractant protein-1, and matrix metalloproteinase-9. Decreased levels of these proteins by MES were associated with down-regulated translocation of nuclear factor kappa B. Active compounds in MES were identified as sargahydroquinoic acid, sargacromenol and sargaquinoic acid based on the inhibition of adhesion molecules. In vivo study, MES supplementation remarkably decreased levels of vascular inflammatory proteins in serum and aorta tissue in HCD-fed mice. These results suggest that MES could be a potential supplement as an anti-atherogenic dietary agent for the prevention of atherosclerosis.