Rumphellaoic Acid A,a Novel Sesquiterpenoid from the Formosan Gorgonian Coral Rumphella antipathies

A novel sesquiterpenoid, rumphellaoic acid A (1), was isolated from the gorgonian coral Rumphella antipathies, and was found to possess a carbon skeleton that was obtained for the first time from a natural sources. The structure of 1 was elucidated by spectroscopic methods and this compound and was found to exert a moderate inhibitory effect on the release of elastase by human neutrophils.     

Carijoside A,a Bioactive Sterol Glycoside from an Octocoral Carijoa sp. (Clavulariidae)

A new bioactive sterol glycoside, 3β-O-(3′,4′-di-O-acetyl-β-d-arabinopyranosyl) -25ξ-cholestane-3β,5α,6β,26-tetrol-26-acetate) (carijoside A, 1), was isolated from an octocoral identified as Carijoa sp. The structure of glycoside 1 was established by spectroscopic methods and by comparison with spectral data for the other known glycosides. Carijoside A (1) displayed significant inhibitory effects on superoxide anion generation and elastase release by human neutrophils and this compound exhibited moderate cytotoxicity toward DLD-1, P388D1, HL-60, and CCRF-CEM tumor cells.     

Bioactive compounds from a gorgonian coral Echinomuricea sp. (Plexauridae)

A new labdane-type diterpenoid, echinolabdane A (1), and a new sterol, 6-epi-yonarasterol B (2), were isolated from a gorgonian coral identified as Echinomuricea sp. The structures of metabolites 1 and 2 were elucidated by spectroscopic methods. Echinolabdane A (1) possesses a novel tetracyclic skeleton with an oxepane ring jointed to an α,β-unsaturated-γ-lactone ring by a hemiketal moiety, and this compound is the first labdane-type diterpenoid to be obtained from marine organisms belonging to the phylum Cnidaria. 6-epi-Yonarasterol B (2) is the first steroid derivative to be isolated from gorgonian coral belonging to the genus Echinomuricea, and this compound displayed significant inhibitory effects on the generation of superoxide anions and the release of elastase by human neutrophils.     

Cladielloides A and B: new eunicellin-type diterpenoids from an Indonesian octocoral Cladiella sp

Two new eunicellin-type diterpenoids, cladielloides A (1) and B (2), which were found to possess a 2-hydroxybutyroxy group in their structures, were isolated from an Indonesian octocoral identified as Cladiella sp. The structures of eunicellins 1 and 2 were elucidated by spectroscopic methods. Cladielloide B (2) exhibited moderate cytotoxicity toward CCRF-CEM tumor cells and this compound displayed significant inhibitory effects on superoxide anion generation and elastase release by human neutrophils.     

Discovery of new eunicellins from an Indonesian octocoral Cladiella sp

Two new 11-hydroxyeunicellin diterpenoids, cladieunicellin F (1) and (-)-solenopodin C (2), were isolated from an Indonesian octocoral Cladiella sp. The structures of eunicellins 1 and 2 were established by spectroscopic methods, and eunicellin 2 was found to be an enantiomer of the known eunicellin solenopodin C (3). Eunicellin 2 displayed inhibitory effects on the generation of superoxide anion and the release of elastase by human neutrophils. The previously reported structures of two eunicellin-based compounds, cladielloides A and B, are corrected in this study.     

Discovery of Novel Diterpenoids from Sinularia arborea

Two novel diterpenoids, sinularbols A (1) and B (2), which were found to possess a new carbon skeleton were isolated from the soft coral Sinularia arborea. The structures of compounds 1 and 2 were elucidated by spectroscopic methods and 2 displayed a moderately inhibitory effect on the generation of superoxide anion by human neutrophils.     

Lobocrassins A-E: new cembrane-type diterpenoids from the soft coral Lobophytum crassum

Five new cembrane-type diterpenoids, lobocrassins A-E (1-5), were isolated from the soft coral Lobophytum crassum. The structures of cembranes 1-5 were established by spectroscopic and chemical methods and by comparison of the spectral data with those of known cembrane analogues. Lobocrassin A (1) is the first cembranoid possessing an α-chloromethyl-α-hydroxy-γ-lactone functionality and is the first chlorinated cembranoid from soft corals belonging to the genus Lobophytum. Lobocrassins B (2) and C (3) were found to be the stereoisomers of the known cembranes, 14-deoxycrassin (6) and pseudoplexaurol (7), respectively. Lobocrassin B (2) exhibited modest cytotoxicity toward K562, CCRF-CEM, Molt4, and HepG2 tumor cells and displayed significant inhibitory effects on the generation of superoxide anion and the release of elastase by human neutrophils.     

Metabolites with Anti-Inflammatory Activity from the Mangrove Endophytic Fungus Diaporthe sp. QYM12

One new diterpenoid, diaporpenoid A (1), two new sesquiterpenoids, diaporpenoids B–C (2,3) and three new α-pyrone derivatives, diaporpyrones A–C (4–6) were isolated from an MeOH extract obtained from cultures of the mangrove endophytic fungus Diaporthe sp. QYM12. Their structures were elucidated by extensive analysis of spectroscopic data. The absolute configurations were determined by electronic circular dichroism (ECD) calculations and a comparison of the specific rotation. Compound 1 had an unusual 5/10/5-fused tricyclic ring system. Compounds 1 and 4 showed potent anti-inflammatory activities by inhibiting the production of nitric oxide (NO) in lipopolysaccharide (LPS)-induced RAW264.7 cells with IC₅₀ values of 21.5 and 12.5 μM, respectively.     

Diterpenoids from the Brown Alga Rugulopteryx okamurae and Their Anti-Inflammatory Activity

Brown algae of the Family Dictyotaceae produce an array of structurally diverse terpenoids, whose biomedical potential in the anti-inflammatory area has been scarcely explored. Herein, the chemical study of the alga Rugulopteryx okamurae has led to the isolation of ten new diterpenoids: rugukadiol A (1), rugukamurals A–C (2–4), and ruguloptones A–F (6–10). The structures of the new compounds were established by spectroscopic means. Compound 1 exhibits an unprecedented diterpenoid skeleton featuring a bridged tricyclic undecane system. Compounds 2–10 belong to the secospatane class of diterpenoids and differ by the oxygenated functions that they contain. In anti-inflammatory assays, the new diterpenoid 1 and the secospatanes 5 and 10 significantly inhibited the production of the inflammatory mediator NO in LPS-stimulated microglial cells Bv.2 and macrophage cells RAW 264.7. Moreover, compounds 1 and 5 were found to strongly inhibit the expression of Nos2 and the pro-inflammatory cytokine Il1b in both immune cell lines.     

Structural Characterization and In Vivo Anti-Inflammatory Activity of Fucoidan from Cystoseira crinita (Desf.) Borry

The aim of this study was to evaluate the effects of fucoidan isolated from C. crinita on histamine-induced paw inflammation in rats, and on the serum levels of TNF-α, IL-1β, IL-6, and IL-10 in rats during systemic inflammation response. The levels of TNF-α in a model of acute peritonitis in rats were also investigated. The isolated crude fucoidan was identified as a sulfated xylogalactofucan with high, medium, and low molecular weight fractions and a content of fucose of 39.74%, xylose of 20.75%, and galactose of 15.51%. Fucoidan from C. crinita showed better anti-inflammatory effects in the rat paw edema model, and this effect was present during all stages of the experiment. When compared to controls, a commercial fucoidan from F. vesiculosus, the results also displayed anti-inflammatory activity on the 60th, 90th, and 120th minute of the experiment. A significant decrease in serum levels of IL-1β in rats treated with both doses of C. crinita fucoidan was observed in comparison to controls, whereas TNF-α concentrations were reduced only in the group treated with fucoidan from C. crinita at the dose of 25 mg/kg bw. In the model of carrageenan-induced peritonitis, we observed a tendency of decrease in the levels of the pro-inflammatory cytokine TNF-α in peritoneal fluid after a single dose of C. crinita fucoidan, but this did not reach the statistical significance margin. Single doses of C. crinita fucoidan did not alter serum levels of the anti-inflammatory cytokine IL-10 in animals with lipopolysaccharide-induced systemic inflammation.     

Echinohalimane A, a Bioactive Halimane-Type Diterpenoid from a Formosan Gorgonian Echinomuricea sp. (Plexauridae)

A new halimane-type diterpenoid, echinohalimane A (1), was isolated from a gorgonian, identified as Echinomuricea sp. The structure of 1 was determined by spectroscopic methods and this compound was found to exhibit cytotoxicity toward various tumor cells and display an inhibitory effect on the release of elastase by human neutrophils. Echinohalimane A (1) is the first halimane analogue from the marine organisms belonging to phylum Cnidaria.     

Molecular Mechanism of Anti-Inflammatory Activities of a Novel Sulfated Galactofucan from Saccharina japonica

Seaweed of Saccharina japonica is the most abundantly cultured brown seaweed in the world, and has been consumed in the food industry due to its nutrition and the unique properties of its polysaccharides. In this study, fucoidan (LJNF3), purified from S. japonica, was found to be a novel sulfated galactofucan, with the monosaccharide of only fucose and galactose in a ratio of 79.22:20.78, and with an 11.36% content of sulfate groups. NMR spectroscopy showed that LJNF3 consists of (1→3)-α-l-fucopyranosyl-4-SO₃ residues and (1→6)-β-d-galactopyranose units. The molecular mechanism of the anti-inflammatory effect in RAW264.7 demonstrated that LJNF3 reduced the production of nitric oxide (NO), and down-regulated the expression of MAPK (including p38, ENK and JNK) and NF-κB (including p65 and IKKα/IKKβ) signaling pathways. In a zebrafish experiment assay, LJNF3 showed a significantly protective effect, by reducing the cell death rate, inhibiting NO to 59.43%, and decreasing about 40% of reactive oxygen species. This study indicated that LJNF3, which only consisted of fucose and galactose, had the potential to be developed in the biomedical, food and cosmetic industries.     

Lochmolins A-G, New Sesquiterpenoids from the Soft Coral Sinularia lochmodes

Seven new sesquiterpenoids, lochmolins A-G (1-7), were isolated from a Taiwanese soft coral Sinularia lochmodes. The structures of these metabolites were elucidated by extensive spectroscopic study. Compounds 1-4 were found to inhibit the accumulation of the LPS-induced pro-inflammatory COX-2 protein in RAW264.7 macrophage cells.     

Characterization of Molecular Species and Anti-Inflammatory Activity of Purified Phospholipids from Antarctic Krill Oil

The phospholipids (PLs) from Antarctic krill oil were purified (>97.2%) using adsorption column chromatography. Forty-nine PL molecular species were characterized by ultrahigh-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF-MS). Most of molecular species contained eicosapentaenoic acid (EPA, 20:5), docosahexaenoic acid (DHA, 22:6), docosapentaenoic acid (DPA, 22:5), and arachidonic acid (AA, 20:4). Notably, a special species PC (20:5/22:6) (1298.17 nmol/g) and many ether PLs were detected. The Antarctic krill PL liposome (IC₅₀ = 0.108 mg/mL) showed better anti-inflammatory activity than crude Antarctic krill oil (IC₅₀ = 0.446 mg/mL). It could block NF-κB signaling pathway via suppression of IκB-α degradation and p65 activation and dose-dependently reduce the cellular content of inflammatory mediators including nitric oxide (NO), reactive oxygen species (ROS), and inflammatory cytokines in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. In addition, it can suppress carrageenan-induced mouse paw swelling. Results from the present study could provide a reference for better evaluation of nutritional and medicinal values of Antarctic krill oil.     

Homo/Hetero-Dimers of Aromatic Bisabolane Sesquiterpenoids with Neuroprotective Activity from the Fungus Aspergillus versicolor A18 from South China Sea

Chromatographic fractionation of the EtOH extracts of the marine-derived fungus Aspergillus versicolor A18 has led to the isolation of 11 homo/hetero-dimers of aromatic bisabolane sesquiterpenoids including eight diphenyl ether-coupled aromatic bisabolanes (1a/1b and 5–10) and three homodimers (2–4), together with their monomers including three aromatic bisabolanes (11–13) and two diphenyl ethers (14 and 15). Their structures and absolute configurations were elucidated by extensive spectroscopic analysis including HRESIMS, 1D/2D NMR, calculated ECD, and the optical rotatory data. Among the four new compounds, (+/−)-asperbisabol A (1a/1b), asperbisabol B (2), and asperbisabol C (3), the enantiomers 1a and 1b represent an unprecedented skeleton of diphenyl ether-coupled aromatic bisabolane sesquiterpenoids with a spiroketal core moiety. The neuroprotective effects of selected compounds against sodium nitroprusside (SNP)-induced injury were evaluated in PC12 cells by the MTT assay. Five compounds (1a, 6, and 8–10) showed remarkable neuroprotective activities at 10 μM, being more active than the positive control edaravone.     

Terpenoids from the octocorals Menella sp. (Plexauridae) and Lobophytum crassum (Alcyonacea)

A new germacrane-type sesquiterpenoid, menelloide E (1), and a new cembrane-type diterpenoid, lobocrassin F (2), were isolated from the octocorals Menella sp. and Lobophytum crassum, respectively. The structures of terpenoids 1 and 2 were determined by spectroscopic and chemical methods and compound 2 was found to display a significant inhibitory effect on the release of elastase by human neutrophils.     

Streptoglycerides E–H,Unsaturated Polyketides from the Marine-Derived Bacterium Streptomyces specialis and Their Anti-Inflammatory Activity

Four new streptoglycerides E–H (1–4), with a rare 6/5/5/-membered ring system, were isolated from a marine-derived actinomycete Streptomyces specialis. The structures of 1–4 were elucidated by detailed analysis of HRESIMS, 1D and 2D NMR data and ECD spectra as well as comparison of their spectroscopic data with those reported in literature. Compounds 1–4 showed significant anti-inflammatory activity by inhibiting lipopolysaccharide (LPS)-induced nitric oxide (NO) production in Raw 264.7 cells with IC₅₀ values ranging from 3.5 to 10.9 µM. Especially, 2 suppressed mRNA expression levels of iNOS and IL-6 without cytotoxicity.     

Preparation and Antitumor Activity of CS5931, A Novel Polypeptide from Sea Squirt Ciona Savignyi

CS5931 is a novel anticancer agent isolated from the sea squirt Ciona savignyi. However, its content in the species is very low, and developing a novel approach for production of the polypeptide is promising. In the present study, we expressed and purified the polypeptide from E. coli, and the fermentation conditions were studied using response surface methodology. The yield of CS5931 was increased from 2.0 to 7.5 mg/L. The denaturing and renaturation conditions were also studied. Using the optimized renaturation condition, the anticancer activity of refolding CS5931 was increased significantly; the value of IC₅₀ was decreased from 23.2 to 11.6 μM. In vivo study using xenograft nude mice bearing HCT116 cancer cells revealed that CS5931 was able to inhibit the growth of tumor significantly. The study provides a useful approach for obtaining enough amount of CS5931 for further study. This study is also important for developing the polypeptide as a novel anticancer agent.     

A Novel Angiotensin-I-Converting Enzyme (ACE) Inhibitory Peptide from Takifugu flavidus

Alcalase, neutral protease, and pepsin were used to hydrolyze the skin of Takifugu flavidus. The T. flavidus hydrolysates (TFHs) with the maximum degree of hydrolysis (DH) and angiotensin-I-converting enzyme (ACE)-inhibitory activity were selected and then ultra-filtered to obtain fractions with components of different molecular weights (MWs) (<1, 1–3, 3–10, 10–50, and >50 kDa). The components with MWs < 1 kDa showed the strongest ACE-inhibitory activity with a half-maximal inhibitory concentration (IC₅₀) of 0.58 mg/mL. Purification and identification using semi-preparative liquid chromatography, Sephadex G-15 gel chromatography, RP-HPLC, and LC–MS/MS yielded one new potential ACE-inhibitory peptide, PPLLFAAL (non-competitive suppression mode; IC₅₀ of 28 μmmol·L⁻¹). Molecular docking and molecular dynamics simulations indicated that the peptides should bind well to ACE and interact with amino acid residues and the zinc ion at the ACE active site. Furthermore, a short-term assay of antihypertensive activity in spontaneously hypertensive rats (SHRs) revealed that PPLLFAAL could significantly decrease the systolic blood pressure (SBP) and diastolic blood pressure (DBP) of SHRs after intravenous administration. These results suggested that PPLLFAAL may have potential applications in functional foods or pharmaceuticals as an antihypertensive agent.     

Antioxidative and Antigenotoxic Activity of Extracts from Cosmos (Cosmos bipinnatus) Flowers

The Cosmos bipinnatus has been used in a traditional herbal remedy for various diseases such as jaundice, intermittent fever, and splenomegaly. The present study describes the preliminary evaluation of antioxidant activities and antigenotoxic effect of Cosmos bipinnatus flowers according to four different colors (white, pink, orange, and violet). The antioxidants properties were evaluated by determining TPC, DPPH RSA, ABTS RSA, and RP. The highest TPC of methanolic CFE (at concentration of 1 mg/ml) showed in violet colored CF (1,013 μM), and IC₅₀ of DPPH RSA, ABTS RSA, and RP were also the lowest in violet colored CFE with values of 0.61, 1.48, and 0.82 mg/ml, respectively. The antigenotoxic effect of the CFE on DNA damage induced by H₂O₂ in human leukocytes was evaluated by Comet assay. Pretreatments with CFE produced significant reductions in oxidative DNA damage at the concentration of 500 μg/ml, except for violet colored CFE. The ED₅₀ value of white colored CFE has shown the highest inhibition (0.40 mg/ml) on H₂O₂ induced DNA damage, followed by orange > pink > violet color. These results suggested that Cosmos bipinnatus has significant antioxidant activity and protective effect against oxidative DNA damage.