Lipopolysaccharide-stimulated RAW Research Articles

Three new chemical constituents of Senecio raphanifolius

Three new constituents, 4a-hydroxy-1-methyl-4,4a,8,8a-tetrahydro-1 H-isochromene-3,7-dione (1), 1-(2-(prop-1-en-2-yl)-3-((3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2 H-pyran-2-yl)oxy)-2,3-dihydrobenzofuran-5-yl)ethan-1-one (2), and 5-(hydroxymethyl)-2,3-dihydro-1 H-pyrrolizin-1-one (3), together with 3 known flavonoids (4-6), 6 organic acids (7-12), 1 glycoside (13), and 2 terpenoids (14-15) were isolated from the 50 % ethanol extract of the whole plant of Senecio raphanifolius Wall. ex DC. The structures of these novel compounds were determined using high-resolution electrospray ionization–mass spectrometry and NMR, mainly using 2D NMR. The anti-inflammatory activities of compounds 1-3 were evaluated based on their ability to inhibit nitric oxide (NO) production in lipopolysaccharide-stimulated RAW264.7 cells. Compound 1 could reduce NO levels and had an inhibition rate of 42.86 % at 100 µM.

Anti-Inflammatory Activity of the Combination of Nobiletin and Docosahexaenoic Acid in Lipopolysaccharide-Stimulated RAW 264.7 Cells: A Potential Synergistic Anti-Inflammatory Effect.

This study aimed to investigate a synergistic anti-inflammatory effect of a citrus flavonoid nobiletin and docosahexaenoic acid (DHA), one of n-3 long-chain polyunsaturated fatty acids, in combination. Simultaneous treatment with nobiletin and DHA synergistically inhibited nitric oxide production (combination index < 0.9) by mouse macrophage-like RAW 264.7 cells stimulated with lipopolysaccharide (LPS) without cytotoxicity. On the other hand, the inhibitory effect of nobiletin and DHA in combination on proinflammatory cytokine production was not synergistic. Neither nobiletin nor DHA affected the phagocytotic activity of RAW 264.7 cells stimulated with LPS. Immunoblot analysis revealed that the inhibition potency of DHA on the phosphorylation of ERK and p38 and nuclear translocation of NF-κB is markedly enhanced by simultaneously treating with nobiletin, which may lead to the synergistic anti-inflammatory effect. Overall, our findings show the potential of the synergistic anti-inflammatory effect of nobiletin and DHA in combination.

Alleviating Effect of a Flower Extract of Styphnolobium japonicum L. on Symptoms of Experimentally Induced Osteoarthritis in Rats

In the present study, we prepared an ethanol extract from the flowers of Styphnolobium japonicum L. (SJFE) and found that it contains rutin as a major constituent as well as quercetin kaempferol and isorhamnetin as minor components. In lipopolysaccharide-stimulated RAW 264.7 macrophages, we observed that SJFE significantly inhibited the production of nitric oxide and the expression of major inflammatory biomarkers such as inducible NO synthase, cyclooxygenase-2, interleukin (IL)-6, and IL-1β significantly. Based on these in vitro results, we investigated the anti-inflammatory properties of SJFE on osteoarthritis (OA) of the left hind knee joints induced by monosodium iodoacetate in rats. SJFE was orally administered to the rats with arthritis for 4 weeks, and the following results were obtained. The rats treated with SJFE exhibited a 24% improvement in the weight-bearing index of their affected legs, as well as reductions of 31.5% and 23.2% in serum levels of cartilage oligomeric matrix protein and C-terminal telopeptide 2, respectively. Additionally, Mankin’s score, an indicator used to assess the severity of joint cartilage damage, decreased by 2.75 points compared to the control with no treatment. These findings suggest that SJFE possesses anti-inflammatory properties and can alleviate symptoms of OA, indicating its potential to offer relief to individuals suffering from arthritis.

Genome Mining Leads to Diverse Sesquiterpenes with Anti-inflammatory Activity from an Arctic-Derived Fungus.

With the advancement of bioinformatics, the integration of genome mining with efficient separation technology enables the discovery of a greater number of novel bioactive compounds. The deletion of the key gene responsible for triterpene cyclase biosynthesis in the polar strain Eutypella sp. D-1 instigated metabolic shunting, resulting in the activation of dormant genes and the subsequent production of detectable, new compounds. Fifteen sesquiterpenes were isolated from the mutant strain, with eight being new compounds. The structural elucidation of these compounds was obtained through a combination of HRESIMS, NMR spectroscopy, and ECD calculations, revealing six distinct skeleton types. Compound 7 possessed a unique skeleton of 5/10 macrocyclic ether structure. Based on the gene functions and newly acquired secondary metabolites, the metabolic shunting pathway in the mutant strain was inferred. Compounds 6, 8, 11, 14, and 15 exhibited anti-inflammatory effects without cytotoxicity through the release of nitric oxide from lipopolysaccharide-stimulated RAW264.7 cells. Notably, acorane-type sesquiterpene 8 inhibited nitric oxide production and modulated the MAPK and NLRP3/caspase-1 signaling pathways. Compound 8 also alleviated the CuSO4-induced systemic neurological inflammation symptoms in a transgenic fluorescent zebrafish model.

Mesenchymal Stem Cells Alleviate Acute Liver Failure through Regulating Hepatocyte Apoptosis and Macrophage Polarization.

Acute liver failure (ALF) is a life-threatening clinical problem with limited treatment options. Administration of human umbilical cord mesenchymal stem cells (hUC-MSCs) may be a promising approach for ALF. This study aimed to explore the role of hUC-MSCs in the treatment of ALF and the underlying mechanisms. A mouse model of ALF was induced by lipopolysaccharide and d-galactosamine administration. The therapeutic effects of hUC-MSCs were evaluated by assessing serum enzyme activity, histological appearance, and cell apoptosis in liver tissues. The apoptosis rate was analyzed in AML12 cells. The levels of inflammatory cytokines and the phenotype of RAW264.7 cells co-cultured with hUC-MSCs were detected. The C-Jun N-terminal kinase/nuclear factor-kappa B signaling pathway was studied. The hUC-MSCs treatment decreased the levels of serum alanine aminotransferase and aspartate aminotransferase, reduced pathological damage, alleviated hepatocyte apoptosis, and reduced mortality in vivo. The hUC-MSCs co-culture reduced the apoptosis rate of AML12 cells in vitro. Moreover, lipopolysaccharide-stimulated RAW264.7 cells had higher levels of tumor necrosis factor-α, interleukin-6, and interleukin-1β and showed more CD86-positive cells, whereas the hUC-MSCs co-culture reduced the levels of the three inflammatory cytokines and increased the ratio of CD206-positive cells. The hUC-MSCs treatment inhibited the activation of phosphorylated (p)-C-Jun N-terminal kinase and p-nuclear factor-kappa B not only in liver tissues but also in AML12 and RAW264.7 cells co-cultured with hUC-MSCs. hUC-MSCs could alleviate ALF by regulating hepatocyte apoptosis and macrophage polarization, thus hUC-MSC-based cell therapy may be an alternative option for patients with ALF.

Enhancement of the water solubility of curcuminoids by micelle formulations with ginsenosides to improve antioxidant activity, suppress nitric oxide release, and reduce lipid accumulation

This study explores the formulation of self-micelle ginsenoside saponins from Panax ginseng with curcuminoids from turmeric. Although ginsenosides are hydrophilic and poorly membrane-permeable, they increase the solubility and absorption of insoluble compounds such as curcuminoids. The optimized ginsenoside-curcuminoid (GS-CUR) formulation achieved a water solubility of 2,450 µg/mL using Response Surface Methodology (RSM) at 42.9 % (v/v) water in ethanol, 389.7 mg/mL ginsenosides, and 9.06 mg/mL curcuminoids. Analytical techniques such as SEM, X-ray diffraction, and FTIR spectroscopy confirmed the presence of curcuminoids in GS-CUR. The GS-CUR complex exhibited enhanced antioxidant activities compared to free curcuminoids. Moreover, GS-CUR suppressed the release of nitric oxide in lipopolysaccharide-stimulated RAW264.7 cells by 3.77-fold and reduced lipid accumulation in 3 T3-L1 cells by 13.2-fold more than free curcuminoids. These findings suggest GS-CUR's potential as a functional material in the pharmaceutical, cosmetic, and food industries.

Anti-Inflammatory Effects of Hydroethanolic Extract from Ehretia asperula on Lipopolysaccharide-Stimulated RAW264.7 Macrophages.

Ehretia asperula is a medicinal plant of the Ehretiaceae family used to treat inflammatory disorders, but the underlying mechanisms are not fully elucidated. The anti-inflammatory potential was determined based on enzyme cyclooxygenase-2 (COX-2) inhibition, which showed that the 95% ethanol extract (95ECH) was most effective with a half-maximal inhibitory concentration (IC50) value of 34.09 μg/mL. The effects of 95ECH on phagocytosis, NO production, gene, and protein expression of the cyclooxygenase 2/prostaglandin E2 (COX-2/PGE2) and inducible nitric oxide synthase/ nitric oxide (iNOS/NO) pathways in lipopolysaccharide (LPS)-induced RAW264.7 cells were examined using the neutral red uptake and Griess assays, reverse-transcriptase polymerase chain reactions (RTPCR), and enzyme-linked immunosorbent assays (ELISA). The results showed that 95ECH suppressed phagocytosis and the NO production in activated macrophage cells (p < 0.01). Conversely, 95ECH regulated the expression levels of mRNAs for cytokines tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β) as well as the corresponding proteins. In addition, PGE2 production was inhibited in a dose-dependent manner by 95ECH, and the expression of iNOS and COX-2 mRNAs was decreased in activated macrophage cells, as expected. Therefore, 95ECH from E. asperula leaves contains potentially valuable compounds for use in inflammation management.

Anti-Inflammatory Efficacy of Resveratrol-Enriched Rice Callus Extract on Lipopolysaccharide-Stimulated RAW264.7 Macrophages

Resveratrol and its derivative piceid exhibit a wide spectrum of health-promoting bioactivities. A resveratrol-enriched variety of Dongjin rice (DJ526) has been developed by transfection of a resveratrol biosynthesis gene, and increased resveratrol content has been confirmed in seeds following germination. In the current study, these resveratrol-enriched seeds were induced to produce callus, and callus extracts were evaluated for in vitro anti-inflammatory activity. Callus cultures contained greater amounts of resveratrol and piceid than DJ526 seeds, and treatment with DJ526 callus extract significantly reduced the lipopolysaccharide (LPS)-induced production of proinflammatory mediators nitric oxide and prostaglandin E2 by RAW264.7 macrophages. The inflammation-related nuclear factor kappa B and mitogen-activated protein kinase pathways were also inhibited in DJ526 callus extract-treated RAW264.7 cells, resulting in downregulation of proinflammatory factor genes COX-2, iNOS, IL-1β, IL-6, and TNF-α. Expression of the LPS-binding toll-like receptor-4 was also markedly reduced in DJ526 callus extract-treated cells compared to DJ callus extract-treated cells. These findings demonstrate increased resveratrol and piceid content by callus culture of DJ526 rice seeds and the potent anti-inflammatory activity of resveratrol-enriched callus extract.

Exploring the anti-inflammatory effect of clove water extract in lipopolysaccharide-stimulated RAW264.7 cells and mouse peritoneal macrophages

Clove (Syzygium aromaticum L) is a precious spice that has been extensively used by many countries over the centuries to add flavor and for medicinal purposes. Because of its abundance of phytochemical compounds, clove has been shown to have positive benefits on human health. Hence, we investigated the anti-inflammatory activity of clove water extract (CWE) in LPS-stimulated RAW264.7 cells and mouse peritoneal. The results showed that CWE significantly inhibited the production of IL-6 and TNF-α in a dose-dependent manner, as well as the production of nitric oxide (NO), without any cytotoxic effects at less than 20 mg/mL, through down-regulating IL-6, TNF-α, and iNOS gene expression. Moreover, CWE impeded the MAPKs and inhibited the translocation of NF-kB from the cytosol to the nucleus. These results suggest that CWE possesses anti-inflammatory properties by inhibiting the MAPKs and NF-kB pathways.

Anti-inflammatory terpenoids from the seeds of Eucommia ulmoides

Eucommia ulmoides, a highly valuable economic crop, has been used in traditional Chinese medicine for over 2000 years. In this study, three new iridoids and one new alkaloid, along with 16 known compounds, were isolated from the seeds of E. ulmoides. Their structures incorporating absolute configurations were elucidated based on the comprehensive analyses of NMR data, HR-ESI-MS spectrometry, optical rotation, and ECD data. All compounds were tested for their anti-inflammatory effects in lipopolysaccharide-stimulated RAW 264.7 macrophages. Compounds 14, 17, and 18 significantly inhibited the production of NO with IC50 values of 10.37, 27.34, and 21.58 μM respectively. Further experiments demonstrated that compound 17 could intercept the nuclear translocation of NF-κB, and down-regulate the expression of iNOS, COX-2, IL-1β, and IL-6 in a dose-dependent manner.

Modulatory effect of Andean blackberry polyphenols on genes related to antioxidant and inflammatory responses, the NLRP3 inflammasome, and autophagy

BACKGROUND: The Andean blackberry (Rubus glaucus Benth) is one of Ecuador’s most iconic Andean berries for which a high anthocyanin content has been described. OBJECTIVE: The aim of the present study was to determine the chemical composition and anti-inflammatory potential of the Andean blackberry from Ecuador, with an emphasis on its effects on NLRP3 inflammasome activation and autophagy processes. RESULTS: Andean blackberry extracts were rich in hydroxycinnamates (coumaric acid and derivates), in addition to quercetin and kaempferol as principal flavonols. Cyanidin and its glycosides were identified as the main anthocyanins present. Andean blackberry extracts efficiently reduced oxidative stress markers in the lipopolysaccharide-stimulated RAW 264.7 cells. The extracts also caused a moderate decrease in the expression of the pro-inflammatory and antioxidant genes NFκB1, TNF, IL-1β, IL-6, and NOS2 expression, while they significantly increased the mRNA levels of both SOD1 and NFE2L2 genes. Andean blackberry extracts significantly decreased the activation of the NLRP3 inflammasome complex, as well as p62 levels, and the LC3I/LC3II ratio increased, suggesting a direct action of Andean blackberry compounds on the inflammatory response and restoration of the autophagy process. CONCLUSIONS: These results suggest that Andean blackberries potentially have an anti-inflammatory effect through their ability to regulate genes related to the inflammatory and antioxidant response, as well as modulate the activation of the NLRP3 inflammasome complex and autophagy processes.

Anti-inflammatory effect of gallic acid-conjugated chitooligosaccharides in lipopolysaccharide-stimulated RAW 264.7 macrophages

The aim of the present study is to investigate the anti-inflammatory effect of gallic acid grafted onto COS chains (GA-COS), focusing on the reduction of nitric oxide production, downregulation of inflammatory signals such as inducible nitric oxide synthase (iNOS), gene expression of cytokines such as TNF-α, IL-1β, IL-6, and nuclear factor kappa B (NF-κB) signalling, including the p50 and p65 subunits. The anti-inflammatory effect is mediated through the reduction of nitric oxide production and downregulation of inflammatory proteins such as inducible nitric oxide synthase (iNOS), gene expression of cytokines like TNF-α, IL-1β, IL-6, and nuclear factor kappa B (NF-κB) signalling, including the p50 and p65 subunits. Target proteins were identified by western blot analysis with specific monoclonal antibodies. The levels of gene expression were determined by the RT-PCR method. The results demonstrate that GA-COS effectively reduces nitric oxide generation and downregulates iNOS protein and cytokine expression and NF-κB signalling in lipopolysaccharide (LPS) -induced RAW 264.7 cells. GA-COS exhibits significantly enhanced anti-inflammatory activity compared to the free chitooligosaccharide chain. This study lays the groundwork for future research to demonstrate that GA-COS holds significant potential as a novel compound for the prevention of inflammatory diseases.

Spermacosides a and B, two new triterpenoid saponins from Spermacoce ocymoides burm.f.

Two new triterpenoid saponins, named spermacosides A–B (1 − 2), together with two known oleanane-type triterpenoid saponins, 3-O-β-D-xylopyranosyl-(1→3)-β-D-glucopyranosylbayogenin (3) and 3-O-β-D-glucopyranosylbayogenin (4), were isolated from the ethyl acetate extract of Spermacoce ocymoides Burm.f. in a phytochemical investigation. Their chemical structures were elucidated by spectroscopic data analysis (1D and 2D NMR, and HR-ESI-MS), as well as comparison with reported data. All these compounds were evaluated for inhibiting nitric oxide production in lipopolysaccharide-stimulated RAW 264.7 cells. Among them, 1 showed a slight effect with an IC50 value of 108.65 ± 7.91 µM, and compounds 2–4 were inactive.

Bioactive Fractions Isolated from Harungana madagascariensis Lam. and Psorospermum aurantiacum Engl. Regulate Collagen and Melanin Biosynthesis Gene Expression in UVB-Irradiated Cells with Additional Anti-Inflammatory Potential.

Harungana madagascariensis (HM) and Psorospermum aurantiacum (PA), used traditionally for skin care, have been reported to upregulate the expression of intracellular antioxidant genes, thereby preventing melanoma and protecting fibroblast cell lines from Ultraviolet B (UVB)-induced intracellular oxidative stress. This investigation aimed to identify major compounds in bioactive fractions using bioassay- guided fractionation. The anti-inflammatory effect of fractions was determined by measuring their inhibitory activity on 15-lipoxygenase and nitric oxide (NO) in lipopolysaccharide-stimulated RAW 264.7 macrophage cells. Additionally, the anti-aging efficacy of the fractions was determined by assessing the expression of markers for the aging process, i.e., expression of tyrosinase (TYR), tyrosinase-related protein-1 (TRP-1), procollagen type-1 (COL1A1), and matrix metalloproteinase- 1 (MMP-1) in UVB-induced photoaging in skin cell-lines. Furthermore, UHPLCMS- based identification of the bioactive compounds from the most prominent fraction was also carried out. Hexane fraction of HM significantly inhibited (p <0.05) the 15-lipoxygenase (IC50 = 46.80 μg/mL) and NO production (IC50 = 66.55 μg/mL), whereas hexane fraction of PA was effective (p <0.05) in inhibiting 15-lipoxygenase activity (IC50 = 27.55 μg/mL). Furthermore, the hexane fraction of HM and methanol fraction of PA were significantly effective (p <0.05) in reverting the UVB-mediated altered expressions of MMP-1, TYR, TRP-1, and COL1A1. Furthermore, hexane fraction of HM revealed the presence of harunganin and betulinic acid, whereas vismion D, vismin, kenganthranol B, and bianthrone 1a were identified from the methanol fraction of PA. Overall, the hexane fraction of HM and methanol fraction of PA displayed effective anti-aging activities, with additional anti-inflammatory effects.

Anti-Inflammatory Activity of Cyanobacteria Pigment Extracts: Physiological Free Radical Scavenging and Modulation of iNOS and LOX Activity.

Cyanobacteria are among the oldest organisms colonizing Earth. Their great biodiversity and ability to biosynthesize secondary metabolites through a variety of routes makes them attractive resources for biotechnological applications and drug discovery. In this pioneer study, four filamentous cyanobacteria (Cephalothrix lacustris LEGE 15493, Leptolyngbya boryana LEGE 15486, Nodosilinea nodulosa LEGE 06104 and Leptothoe sp. LEGE 11479) were explored for their anti-inflammatory potential in cell and cell-free in vitro bioassays, involving different inflammatory mediators and enzymes. Extracts of different polarities were sequentially prepared and chemically characterized for their content of phycobiliproteins (PBPs) and carotenoids. HPLC-PDA analysis of the acetone extracts revealed β-carotene to be the dominant carotenoid (18.4-44.3 mg/g) and zeaxanthin as the dominant xanthophyll (52.7-192.9 mg/g), with Leptothoe sp. LEGE 11479 and Nodosilinea nodulosa LEGE 06104, respectively, being the richest strains. The PBP profile was in accordance with the color presented by the aqueous extracts, with Leptolyngbya boryana LEGE 15486 being the richest in phycocyanin (204.5 μg/mg) and Leptothoe sp. LEGE 11479 the richest in phycoerythrin (78.5 μg/mg). Aqueous extracts were more effective in superoxide anion radical scavenging, while acetone ones were more effective in scavenging nitric oxide radical (●NO) and in inhibiting lipoxygenase. Acetone extracts also reduced ●NO production in lipopolysaccharide-stimulated RAW 264.7 macrophages, with the mechanistic study suggesting a downregulation of the inducible nitric oxide synthase expression. Nodosilinea nodulosa LEGE 06104 and Leptothoe sp. LEGE 11479 acetone extracts presented the lowest IC50 values for the mentioned assays, pointing them out as promising resources for the development of new multi-target anti-inflammatory therapies.

Six unprecedented 2-(2-phenethyl)chromone dimers from agarwood of Aquilaria filaria

Six new dimeric 2-(2-phenylethyl)chromones (1–6) were successfully isolated from the ethanol extract of agarwood of Aquilaria filaria from Philippines under HPLC-MS guidance. Compounds 1–6 are all dimers formed by linking 5,6,7,8-tetrahydro-2-(2-phenylethyl)chromone and flindersia 2-(2-phenylethyl)chromone via a single ether bond, and the linkage site (C5-O-C8′′) of compound 2 is extremely rare. A variety of spectroscopic methods were used to ascertain their structures, including extensive 1D and 2D NMR spectroscopic analysis, HRESIMS, and comparison with literature. The in vitro tyrosinase inhibitory and anti-inflammatory activities of each isolate were assessed. Among these compounds, compound 2 had a tyrosinase inhibition effect with an IC50 value of 27.71 ± 2.60 μM, and compound 4 exhibited moderate inhibition of nitric oxide production in lipopolysaccharide-stimulated RAW264.7 cells with an IC50 value of 35.40 ± 1.04 μM.

Caffeic acid-grafted chitooligosaccharides downregulate MAPK and NF-kB in RAW264.7 cells.

Chitooligosaccharide (COS) is a derivative of chitosan, which is a natural macromolecular compound. COS has been shown effects in an inflammatory response. Recent reports show that COS derivatives have enhanced anti-inflammatory activity by inhibiting intracellular signals. Evaluation of the anti-inflammatory effect of caffeic acid conjugated COS chain (CA-COS) was performed in this study. The effects of CA-COS on the inflammatory response were demonstrated in lipopolysaccharide-stimulated RAW264.7 macrophages. The results showed that CA-COS inhibited nitric oxide (NO) production and downregulated the gene expression of nitric oxide synthase (iNOS), and cytokines such as tumor necrosis factor-alpha (TNF-α), IL-1β, and IL-6 without cytotoxic effect. In addition, western blot analysis showed that CA-COS inhibits the protein expression of iNOS and nuclear factor kappa B (NF-kB), including p50 and p65, and mitogen-activated protein kinase (MAPK) signaling pathways. Collectively, these results provide clear evidence for the anti-inflammatory mechanism of CA-COS that show great potential as a novel agent for the prevention and therapy of inflammatory diseases.

Three rare anti-inflammatory sesquiterpene lactones from Magnolia grandiflora

Four new sesquiterpene lactones (SLs) (1–4), along with a biosynthetically related SL (5), have been isolated from the leaves of Magnolia grandiflora. Magrandate A (1) is notable as the first C18 homogemarane type SL, featuring a unique 1,7-dioxaspiro[4.4]nonan-6-one core. Compounds 2 and 3, representing the first instances of chlorine-substituted gemarane-type SL analogs in natural products, were also identified. The structures of these isolates were elucidated through a combination of spectroscopic data analysis, electronic circular dichroism calculations, and X-ray single-crystal diffraction analysis. All isolates demonstrated anti-inflammatory activity in lipopolysaccharide-stimulated RAW264.7 cells. Notably, 3–5 showed a significant inhibitory effect on nitric oxide production, with IC50 values ranging from 0.79 to 4.73 μmol·L−1. Additionally, 4 and 5 exhibited moderate cytotoxic activities against three cancer cell lines, with IC50 values between 3.09 and 11.23 μmol·L−1.

Seco-nortriterpenoids from Cirsium setosum and their anti-inflammatory activity

Five unusual seco-nortriterpenoids, 3β-hydroxy-20,21-seco-30-nortaraxastan-20,21-dioic acid (1), 3β-hydroxy-20,21-seco-30-nortaraxastan-20-oic-21-oate (2), 3β-hydroxy-20-oxo-21,22-seco-30-nortaraxastan-22-oic acid (3), 3β-hydroxy-19-oxo-20,21-seco-29,30-nortaraxastan-21-oic acid (4) and 3β-hydroxy-19-oxo-20,21-seco-19-norlupan-21-oic acid (5) were isolated and elucidated from the anti-inflammatory activity fraction of the ethanol extract of Cirsium setosum. The structures of these compounds were established through spectroscopic methods. Preliminary biological assays showed that compounds 1–5 had significant inhibitory effect on NO production on lipopolysaccharide-stimulated RAW 264.7 cells, and compound 1 showed the strongest anti-inflammatory activity. This type of ring-opening compound is the first seco-triterpenoid structure discovered from the genus of Cirsium.

The Role of Sargahydroquinoic Acid and Sargachromenol in the Anti-Inflammatory Effect of Sargassum yezoense.

The anti-inflammatory effect of the ethanol extract of Sargassum yezoense and its fractions were investigated in this study. The ethanol extract exhibited a strong anti-inflammatory effect on lipopolysaccharide-stimulated RAW 264.7 macrophages and effectively suppressed the M1 polarization of murine bone-marrow-derived macrophages stimulated by lipopolysaccharides and IFN-γ (interferon-gamma). Through a liquid-liquid extraction process, five fractions (n-hexane, chloroform, ethyl acetate, butanol, and aqueous) were acquired. Among these fractions, the chloroform fraction (SYCF) was found to contain the highest concentration of phenolic compounds, along with two primary meroterpenoids, sargahydroquinoic acid (SHQA) and sargachromenol (SCM), and exhibit significant antioxidant capacity. It also demonstrated a robust anti-inflammatory effect. A direct comparison was conducted to assess the relative contribution of SHQA and SCM to the anti-inflammatory properties of SYCF. The concentrations of SHQA and SCM tested were determined based on their relative abundance in SYCF. SHQA contributed to a significant portion of the anti-inflammatory property of SYCF, while SCM played a limited role. These findings not only highlight the potential of the chloroform-ethanol fractionation approach for concentrating meroterpenoids in S. yezoense but also demonstrate that SHQA and other bioactive compounds work additively or synergistically to produce the potent anti-inflammatory effect of SYCF.