Immunomodulatory effect of sulfated galactofucan from marine macroalga Turbinaria conoides.

Sulfated polysaccharides are effective immunostimulating agents by activating several intracellular signaling pathways. A sulfated (1 â†’ 3)/(1 â†’ 4)-linked galactofucan TCP-3 with promising immunomodulatory effects was purified from a marine macroalga Turbinaria conoides. The immune-enhancing potential of TCP-3 (100-400 mg/kg BW) was evaluated on cyclophosphamide-induced immunosuppressed animals by increasing bone marrow cellularity (10-13 cells/femur/mL x 106), α-esterase activity (1200-1700 number of positive cells/4000 BMC), interferon-γ (1.31-1.49 pg/mL), interleukin-2 (3.49-3.99 pg/mL) secretion, and WBC count (> 3000 cells/cu mm). The proliferation of lymphocytes for in vitro and in vivo conditions was enhanced by administering TCP-3 besides regulating the secretion of pro-inflammatory cytokines (interleukin-6/1ß/12, tumor necrosis factor-α, transforming growth factor-ß), and an inducible isoform of nitric oxide synthase. A promising reduction of viral copy formation was observed by administering TCP-3 (< 2 × 107 number) on SARS CoV-2 (delta variant) induced Vero cells in comparison with the infected group (> 5 × 107 number).

Sulfated polygalactofucan from triangular sea bell Turbinaria decurrens attenuates inflammatory cytokines on THP-1 human monocytic macrophages.

Inflammation is one of the most significant causes of several chronic diseases, which includes the expression of cytokines activating immune cells to up-regulate the inflammatory cascade. Polysaccharides from marine macroalgae are promising anti-inflammatory agents because of their potential to attenuate inflammatory cytokines. The triangular sea bell Turbinaria decurrens (Sargassaceae) among marine macroalgae is ubiquitous in oceanic waters, and a sulfated polygalactofucan SPTd-2 [→3-(α-L-fucp-(2-OSO3-)-(1 â†’ 4)-α-L-fucp-(3-OAc)-(1 â†’ 4)-ß-D-galp-(1→] was purified from the species. The studied polygalactofucan SPTd-2 exhibited anti-inflammatory activities against cyclooxygenase-2 (IC50 10.56 µM) and 5-lipoxygenase (IC50 3.36 µM) with a greater selectivity index (2.35) than ibuprofen (0.44), besides attenuating pro-inflammatory cytokine production, including tumor necrosis factor-α, transforming growth factor-ß, interleukin-2, 1ß, and interferon-γ. Quantitative real-time polymerase chain reaction displayed that SPTd-2 blocked the mRNA of interferon-γ and interleukin-2, in the human monocytic cell line THP-1. The results showed the potential of SPTd-2 to attenuate inflammation-associated disorders.

Seaweed-associated heterotrophic Bacillus altitudinis MTCC13046: a promising marine bacterium for use against human hepatocellular adenocarcinoma.

Since the report of the antibiotic with anticancer properties, scientists have been focusing to isolate and characterize novel anti-microbial natural products possessing anticancer activities. The current study describes the production of seaweed-associated heterotrophic Bacillus altitudinis MTCC13046 with potential anticancer properties. The bacterium was screened for its capacity to diminish the cell proliferation of the human hepatocellular adenocarcinoma (HepG2) cell line, without upsetting the normal cells. The bacterial extract showed anticancer properties in a dose-reactive form against HepG2 (IC50, half maximal inhibitory concentration ~ 29.5 µg/ml) on tetrazolium bromide analysis with less significant cytotoxicity on common fibroblast (HDF) cells (IC50 ~ 77 µg/ml). The potential antioxidant ability of the organic extract of B. altitudinis MTCC13046 (IC90 133 µg/ml) could corroborate its capacity to attenuate the pathophysiology leading to carcinogenesis. The results of the apoptosis assay showed that the crude extracts of B. altitudinis maintained 68% viability in normal cells compared to 11% in the cancer cells (IC50 76.9 µg/ml). According to the findings, B. altitudinis MTCC13046 could be used to develop prospective anticancer agents.

Apoptotic effect of sulfated galactofucan from marine macroalga Turbinaria ornata on hepatocellular and ductal carcinoma cells.

Tumor protein or cellular tumor antigen p53, is considered a critical transcriptional regulation factor, which can suppress the growth of tumor cells by activating other functional genes. The current study appraised the p53 activation pathways, which could be used as an alternative therapeutic strategy for the treatment of hepatocellular and ductal carcinoma. Algal polysaccharides have been used as emerging sources of bioactive natural pharmacophores. A sulfated galactofucan characterized as [→1)-O-4-sulfonato-α-fucopyranose-(3 â†’ 1)-α-fucopyranose-(3→] as the main branch with [→1)-6-O-acetyl-ß-galactopyranose-(4→] as side chain isolated from marine macroalga Turbinaria ornata exhibited prospective apoptosis on HepG2 (hepatocellular carcinoma) and MCF7 (ductal carcinoma) cells. Annexin V-fluorescein isothiocyanate-propidium iodide study displayed higher early apoptosis in MCF7 and HepG2 cell lines (56 and 24.2%, respectively) treated with TOP-3 (at IC50 concentration) than those administered with standard camptothecin. Upregulation of the p53 gene expression was perceived in TOP-3 treated HepG2 and MCF7 cells.

Newly described antioxidant disecolactonic ergosteroids from marine cuttlefish Sepia pharaonis: Pharaonoids A-B as prospective carbohydrate digestive enzyme inhibitors.

Biochemical investigation of crude solvent extract of pharaoh cuttlefish Sepia pharaonis (family Sepiidae) led to the isolation of two undescribed disecolactonic ergosteroids, pharaonoids A-B. The compounds were characterized as 11ß-acteoxy-7α-hydroxy-19-Nor-1,10:9,10-disecoergosta-3-ene-61-oxa-1-one (pharaonoid A) and 11ß-hydroxy-19-Nor-1,10:9,10-disecoergosta-3-ene-61-oxa-1-one (pharaonoid B) in conjunction with spectroscopic analysis encompassing one and two-dimensional nuclear magnetic resonance and mass spectrometric analyses. Pharaonoid A, bearing an acetoxy and hydroxyl groups, respectively at C-11 and C-7 positions exhibited considerably greater inhibition potential against carbohydrate hydrolysing enzymes α-amylase (IC50 1.14 mM) and α-glucosidase (IC50 1.23 mM) than those displayed by pharaonoid B (IC50 1.49/1.38 mM), and was proportionate with those exhibited by standard drug acarbose (IC50 0.60 and 0.40 mM, respectively), thereby recognizing the anti-hyperglycemic potential of pharaonoid A. Promising anti-oxidant property for pharaonoid A (IC50 âˆ¼ 1 mM) could conceivably corroborate its attenuation potential against carbohydrate digestive enzymes. Greater electronic parameters along with optimum lipophilic-hydrophobic balance of pharaonoid A were directly corroborated to the anti-carbolytic properties occurring via transcellular mechanism. Greater binding energies (-9.50 kcal mol-1) and inhibition constant (Ki 48.21 nM) at the active site of α-amylase enzyme were displayed by pharaonoid A than those exhibited by its B analogue. Promising bioactive properties of the disecolactonic steroids isolated from the marine pharaoh cuttlefish are anticipated to be utilized as functional food components and potential nutraceuticals against oxidative stress and hyperglycemic disorders.

Antioxidant spiropharanone, an undescribed variant of trans-decalin spiro-γ-lactone, from pharaoh cuttlefish Sepia pharaonis: Twin inhibitors of inflammatory 5-lipoxygenase and serine protease dipeptidyl peptidase-4.

Marine pharaoh cuttlefish Sepia pharaonis (family Sepiidae) is regarded as an economically important class of cephalopod in the coastal Mediterranean and Asian regions. Bioassay-guided chromatographic purification of solvent extract of S. pharaonis led to the identification of a trans-decalin based spirolactone, spiropharanone, which was characterized as 1-hydroxy-7-(4'-methoxy-3-methylbut-2-enyl)-3,9,15-trimethyl-8-oxo-octahydro-5H-spiro[furan-8,9-naphtho]-8-yl-acetate by spectroscopic techniques. Spiropharanone exhibited significantly greater anti-inflammatory activity by attenuating pro-inflammatory 5-lipoxygenase (IC50 1.02 mM) than the non-steroidal drug ibuprofen (IC50 4.61 mM, p ≤ .05). Superior antioxidant properties of spiropharanone against free radicals (EC50 ~1.20 mM) and other oxidants (hydroxyl [EC50 0.97 mM] and superoxide [EC50 1.47 mM] scavenging) also reinforced its promising anti-inflammatory activity. The studied spiropharanone also exhibited significant attenuation toward insulin secretion regulating enzyme dipeptidyl peptidase-4 (IC50 0.92 mM) recognizing its anti-hyperglycemic potential. Significantly higher electronic properties (topological polar surface area ~100) combined with balanced hydrophilic-lipophilic properties (partition coefficient of logarithmic octanol-water ~3) and lesser docking parameters of spiropharanone demonstrated that the compound could be utilized as an important bioactive lead against oxidative stress, inflammation, and hyperglycemic-related ailments. PRACTICAL APPLICATIONS: Nutritionally rich edible marine pharaoh cuttlefish Sepia pharaonis occupies a prominent place among seafood fisheries owing to the presence of bioactive nutrients and functional food ingredients. These marine cuttlefish are widely distributed along the Asian and Mediterranean coasts, and consumed as culinary delicacy for decades. An undescribed trans-decalin spirolactone, spiropharanone was isolated from the organic extract of S. pharaonis based on bioactivity-assisted sequential chromatographic fractionation. Spiropharanone displayed promising antioxidant potential along with attenuation properties against inducible pro-inflammatory 5-lipoxygenase and insulin secretion regulating enzyme dipeptidyl peptidase-4. This study established the ameliorating potential of a naturally derived marine food constituent against inflammatory and diabetic ailments, and thus anticipated as functional food lead in pharmaceutical formulations towards inflammation and maintaining glucose homeostasis.

Polygalacto-fucopyranose biopolymer structured nanoparticle conjugate attenuates glucocorticoid-induced osteoporosis: An in vivo study.

Naturally occurring polysaccharide-structured nanoparticles have developed as promising materials for treatment of bone health disorders. Silver nanoparticle (ST-AgNP) structured from sulfated polygalacto-fucopyranose comprising of recurring structural entities of 2-SO3-α-(1 â†’ 3)-fucopyranose and 6-O-acetyl-ß-(1 â†’ 4)-galactopyranose isolated from marine macroalga Sargassum tenerrimum demonstrated potential activities associated with osteogenesis. Subsequent treatment with ST-AgNP, activity of alkaline phosphatase (63 mU/mg) was raised in osteoblast stem cells (human mesenchymal, hMSC) than that in control (30 mU/mg). Intense growth of mineralized nodule on the surface of hMSC was apparent following treatment with ST-AgNP. Increased population of bone morphogenic protein-2 (23%) and osteocalcin+ cells (50%) on M2 macrophages were apparent following treatment with ST-AgNP (0.25 mg/mL). Glucocorticoid-induced in vivo animal model studies of ST-AgNP exhibited significant recovery of serum biochemical parameters along with serum estradiol and parathyroid hormone compared to disease control. Disease-induced groups treated with ST-AgNP showed the disappearance of osteoporotic cavities in the trabecular bone. Following treatment with ST-AgNP, serum calcium and phosphorus contents were significantly recovered.

Apoptotic effect of chromanone derivative, hyrtiosone A from marine demosponge Hyrtios erectus in hepatocellular carcinoma HepG2 cells.

The tumor suppressor proteins p53 and p27 exhibited a significant role in the survival of cells and regulation of cellular division and growth. In majority of the human tumors, particularly in hepatocellular carcinoma, these proteins are inactivated by mutation or deletion, and are considered to predict the pathophysiology related to liver cancer. The present study evaluated the activation of the p53 and p27 pathways as a useful therapeutic tool to attenuate hepatocellular carcinoma. Three undescribed homologous chromanone derivatives, hyrtiosones A-C were isolated from the organic extract of marine demosponge Hyrtios erectus (family Thorectidae). Preliminary bioactivity assessments found that hyrtiosone A exhibited prospective anti-inflammatory (IC50 1.02-1.86 mM) and antioxidant (IC50 0.74-0.83 mM) properties. Molecular docking analysis of the hyrtiosones using p53-murine double minute complex revealed lesser docking parameters for hyrtiosone A (binding energy -11.12 kcal mol-1, docking score -12.18 kcal mol-1) thereby attributing its greater bioactivity. Hyrtiosone A was furthermore analyzed for in vitro anticancer activity in hepatocellular carcinoma HepG2 cells. Morphological assessment of hyrtiosone A treated HepG2 cell line by acridine orange/ethidium bromide fluorescence staining revealed greater number of apoptotic cells, and was found to be comparable with the cells treated with the standard doxorubicin. Further the Annexin V-fluorescein isothiocyanate assay of hyrtiosone A treated HepG2 cell line by flow cytometry displayed greater number of early apoptotic cells (51.24%) than that exhibited by the standard (21.45%). Cell cycle distribution analysis showed that hyrtiosone A arrested the S and G2/M phase of cell cycle and upregulate the gene expression of p53 and p27 in hepatocellular carcinoma HepG2 cells.

Euryfuranyl compounds from edible species of cuttlefish as potential anti-inflammatory leads attenuating NF-κB signaling cascade in lipopolysaccharide-activated macrophages.

Nuclear factor-kappa B is an inducible transcription element, which was considered as an important regulator of immune functions, and plays a critical role to induce inflammatory reactions. In this study, we have demonstrated the anti-inflammatory potentials of previously undescribed (4 â†’ 13)-abeo-euryfuranyls (1-2) from the spineless cuttlefish Sepiella inermis in lipopolysaccharide-stimulated macrophages. The euryfuranyl bearing (4 â†’ 13)-abeo-euryfuranyl-2-ene-6-hydroxymethyl-propanoate framework (compound 1) displayed prominent inhibitory effects against pro-inflammatory cyclooxygenase-2 (IC50 0.36 mM) and 5-lipoxygenase (IC50 0.70 mM). Additionally, it suppressed the generation of inducible nitric oxide synthase along with cyclooxygenase-2 and 5-lipoxygenase in lipopolysaccharide-stimulated macrophages. The euryfuranyl analogue (1) down-regulated the mRNA expression of cyclooxygenase-2 and nuclear factor-κB signaling pathway in lipopolysaccharide-activated macrophage cells by hindering the degradation of inhibitor-κB proteins, and transfer of the subunit NF-κB p65 to the nucleus from the cytosol. These results demonstrated that the euryfuranyl analogue could be explored as a promising anti-inflammatory therapeutic lead attenuating nuclear factor-κB signaling cascade.

Marine Macroalgal Polygalactan-Built Nanoparticle Construct for Osteogenesis.

Naturally derived polysaccharide biopolymer-based nanoparticles with their size and drug release potentials have appeared as promising biomaterials for osteogenic differentiation. A metallic nanoparticle (GS-AgNP) prepared from a sulfated polygalactan characterized as →3)-2-O-methyl-O-6-sulfonato-ß-d-galactopyranosyl-(1 → 4)-2-O-methyl-3,6-anhydro-α-d-galactopyranose-(1→ isolated from the marine macroalga Gracilaria salicornia exhibited a prospective osteogenic effect. Upon treatment with the studied GS-AgNP, alkaline phosphatase activity (88.9 mU/mg) was significantly elevated in human mesenchymal osteoblast stem cells (hMSCs) compared to that in the normal control (33.7 mU/mg). A mineralization study of GS-AgNPs demonstrated an intense mineralized nodule formation on the hMSC surface. A fluorescence-activated cell sorting study of osteocalcin and bone morphogenic protein-2 (BMP-2) expression resulted in an increased population of osteocalcin (78.64%) and BMP-2-positive cells (46.10%) after treatment with GS-AgNPs (250 µg/mL) on M2 macrophages. A time-dependent cell viability study of GS-AgNPs exhibited its non-cytotoxic nature. The studied polygalactan-built nanoparticle could be developed as a promising bioactive pharmacophore against metabolic bone disorder and the treatment for osteogenesis therapy.

Marine macroalga-associated heterotroph Bacillus velezensis as prospective therapeutic agent.

Marine macroalgae and their accompanying microbial flora were proved to be the reservoir of potential bioactive compounds with promising pharmacological applications. Heterotrophic bacteria concomitant with the marine algae were isolated and screened for their antibacterial potential against clinically recognized pathogens. The bacterial isolate with greater bioactive properties was identified as Bacillus velezensis MBTDLP1 (phylum Firmicutes), which was isolated from the marine macroalga Laurencia papillosa, by integrated morphological, biochemical and molecular characterization. B. velezensis showed promising antibacterial property against methicillin-resistant Staphylococcus aureus and Vibrio parahemolyticus with inhibition zone of 32-36 mm. Organic ethyl acetate extract of the isolate also displayed prospective antibacterial activity against the test pathogens (minimum inhibitory concentration 7.5-15 µg/mL), coupled with promising antioxidant (IC50 0.1-0.9 mg/mL against oxidants), anti-inflammatory (IC50 0.01 mg/mL against 5-lipoxygenase), and carbolytic enzyme attenuation properties (IC50 0.1-0.4 mg/mL in response to α-amylase and α-glucosidase). Significant anticancer potential against breast carcinoma (MCF-7) cells (IC50 0.03 mg/mL) coupled with lesser cytotoxicity to the normal fibroblast (3T3L) cells (IC50 0.14 mg/mL) were also recognized. The apoptosis assay could give reasonable outcome as the organic extract of B. velezensis induced apoptosis to 81% of the cancer cells while maintaining almost 60% viability in normal cells. The results put forward that B. velezensis MBTDLP1 could be used to isolate bioactive compounds with therapeutic potential and biomedical applications.

Callypyrones from marine Callyspongiidae sponge Callyspongia diffusa: antihypertensive bis-γ-pyrone polypropionates attenuate angiotensin-converting enzyme.

Angiotensin I-converting enzyme (ACE) catalyses the biosynthesis of angiotensin II, a potent blood vessel constrictor, from angiotensin I, and ACE inhibitors were recognised as medications for hypertension. Undescribed bis-γ-pyrone polypropionate compounds, callypyrones A and B were purified from the organic extract of Callyspongiidae sponge species Callyspongia diffusa by repeated chromatographic purification. Callypyrone A exhibited significantly greater attenuation potential against ACE (IC50 0.48 mM) than that displayed by callypyrone B (IC50 0.57 mM) and showed comparable activity with standard ACE inhibitor captopril (IC50 0.36 mM). Higher electronic parameters of callypyrone A (topological surface area of 108.36) combined with balanced hydrophilic-lipophilic parameter (octanol-water coefficient, log Pow 1.9), as deduced from the structure-activity relationship analyses, could further indicate the improved ligand-receptor interactions resulting in its prospective ACE inhibitory activity. In silico docking analyses of the callypyrones with ACE recorded lowest binding energy (-12.58 kcal mol-1) for callypyrone A, which further supported the antihypertensive potential of the compound.

Seaweed-associated heterotrophic bacteria: new paradigm of prospective anti-infective and anticancer agents.

Ever since the development of the first antibiotic compound with anticancer potential, researchers focused on isolation and characterization of prospective microbial natural products with potential anti-infective and anticancer activities. The present work describes the production of bioactive metabolites by heterotrophic bacteria associated with intertidal seaweeds with potential anti-infective and anticancer activities. The bacteria were isolated in a culture-dependent method and were identified as Shewanella algae MTCC 12715 (KX272635) and Bacillus amyloliquefaciens MTCC 12716 (KX272634) based on combined phenotypic and genotypic methods. Further, the bacteria were screened for their ability to inhibit drug-resistant infectious pathogens and prevent cell proliferation of human liver carcinoma (HepG2) and breast cancer (MCF7) cell lines, without affecting the normal cells. Significant anti-infective activity was observed with bacterial cells and their organic extracts against broad-spectrum multidrug-resistant pathogens, such as vancomycin-resistant Enterococcus faecalis, methicillin-resistant Staphylococcus aureus, Klebsiella pneumonia and Pseudomonas aeruginosa with minimum inhibitory concentration ≤ 3.0 µg mL-1 as compared to the antibiotic agents' chloramphenicol and ampicillin, which were active at ≥ 6.25 mg mL-1. The extracts also exhibited anticancer activity in a dose-responsive pattern against HepG2 (with IC50, half maximal inhibitory concentration ~ 78-83 µg mL-1) and MCF7 (IC50 ~ 45-48 µg mL-1) on tetrazolium bromide screening assay with lesser cytotoxic effects on normal fibroblast (L929) cell lines (IC50 > 100 µg mL-1). The results revealed that seaweed-associated heterotrophic bacteria could occupy a predominant role for a paradigm shift towards the development of prospective anti-infective and anticancer agents.

High-value compounds from the molluscs of marine and estuarine ecosystems as prospective functional food ingredients: An overview.

Extensive biodiversity and availability of marine and estuarine molluscs, along with their their wide-range of utilities as food and nutraceutical resources developed keen attention of the food technologists and dieticians, particularly during the recent years. The current review comprehensively summarized the nutritional qualities, functional food attributes, and bioactive properties of these organisms. Among the phylum mollusca, Cephalopoda, Bivalvia, and Gastropoda were mostly reported for their nutraceutical applications and bioactive properties. The online search tools, like Scifinder/Science Direct/PubMed/Google Scholar/MarinLit database and marine natural product reports (1984-2019) were used to comprehend the information about the molluscs. More than 1334 secondary metabolites were reported from marine molluscs between the periods from 1984 to 2019. Among various classes of specialized metabolites, terpenes were occupied by 55% in gastropods, whereas sterols occupied 41% in bivalves. The marketed nutraceuticals, such as CadalminTM green mussel extract (Perna viridis) and Lyprinol® (Perna canaliculus) were endowed with potential anti-inflammatory activities, and were used against arthritis. Molluscan-derived therapeutics, for example, ziconotide was used as an analgesic, and elisidepsin was used in the treatment of cancer. Greater numbers of granted patents (30%) during 2016-2019 recognized the increasing importance of bioactive compounds from molluscs. Consumption of molluscs as daily diets could be helpful in the enhancement of immunity, and reduce the risk of several ailments. The present review comprehended the high value compounds and functional food ingredients from marine and estuarine molluscs.

Polygalactan from bivalve Crassostrea madrasensis attenuates nuclear factor-κB activation and cytokine production in lipopolysaccharide-activated macrophage.

A polygalactosamino-glucopyranosyl fucopyranose →4)-ß-GlcAp{(3→1)-α-Fucp}-ß-GalNAcp-(4,6-SO3-)-(1→ isolated from the bivalve Crassostrea madrasensis exhibited prospective anti-inflammatory activity against cyclooxygenase-2 and 5-lipoxygenase (IC50 < 50 µg mL-1) on lipopolysaccharide-induced macrophages. The polygalactan attenuated inducible nitric oxide synthase (IC50 65.7 µg mL-1) in lipopolysaccharide-prompted inflammation leading to the reduction of pro-inflammatory cytokine nitric oxide (236.2 µg mL-1 lysate), nuclear factor-κB, tumor necrosis factor-α, and interleukins (0.19-0.22 units mg-1 protein at 100 µg mL-1) by inhibiting cyclooxygenase-2. The polygalacatan suppressed the mRNA of nuclear factor-κB and cyclooxygenase-2 in lipopolysaccharide-induced macrophages. Western blot experiment revealed that the polygalactan attenuated the migration of nuclear factor-κB-p65 to the nucleus from cytoplasm, and suppressed the phosphorylation of α-subunit of κB inhibitor. Greater selectivity index of sulfated polygalactan (3.93) towards inducible cyclooxygenase-2 as compared with the anti-inflammatory agent ibuprofen (1.11), and the potential to inhibit nuclear factor-κB cascade to generate chemokine production manifested its utilization in the development of functional food attenuating inflammation-related disorders.

Stomopneulactone D from long-spined sea urchin Stomopneustes variolaris: Anti-inflammatory macrocylic lactone attenuates cyclooxygenase-2 expression in lipopolysaccharide-activated macrophages.

Cyclooxygenase-2 is one of the prominent enzymes to cause an increased production of prostaglandins during inflammation and immune responses. Cyclooxygenase-2 expression is up-regulated in inflammatory conditions owing to the induction by different inflammatory stimuli including cytokines, and therefore, the expression studies of cyclooxygenase-2 in lipopolysaccharide-induced macrophage cells (RAW 264.7 cell line) could be used for screening of the compounds with anti-inflammatory potential. The present study evaluated the anti-inflammatory properties of four homologous stomopneulactones A-D, classified under the class of macrocyclic lactones isolated from the solvent extract of the long-spined sea urchin Stomopneustes variolaris (familyStomopneustidae) in the lipopolysaccharide-induced macrophages. The structures of these isolated compounds were assigned using detailed spectroscopic techniques. Stomopneulactone D bearing 5-butyl-4-hydroxy-12-oxo-1-oxa-5,9-cyclododecadienyl moiety exhibited relatively greater anti-inflammatory potentials against cyclooxygenase-2 (IC50 ~ 2 mM) and 5-lipoxygenase (IC50 2.6 mM) than those displayed by other macrocyclic lactones. The studied compounds displayed higher selectivity index values (anti-cyclooxygenase-1IC50/anti-cyclooxygenase-2IC50 > 1), which designated the selective anti-inflammatory potentials of the macrocyclic lactones against inducible inflammatory mediators than those exhibited by the anti-inflammatory agent ibuprofen (0.43). The in silico molecular modelling analyses of the stomopneulactones with cyclooxygenase-2/5-lipoxygenase enzymes recorded lowest binding energy (-7.71 and -9.60 kcal mol-1, respectively) and docking score (-8.82 and -11.12 kcal mol-1, respectively) for stomopneulactone D along with its higher electronic parameter (topological polar surface area of 72.83), which further confirmed its greater anti-inflammatory potential than other compounds in the series. Stomopneulactone D also inhibited the generation of inducible nitric oxide synthase, intracellular reactive oxygen species, along with 5-lipoxygenase and cyclooxygenase-2 in the lipopolysaccharide-stimulated macrophage cells. Additionally, the studied macrocyclic lactone decreased the mRNA expression of cyclooxygenase-2 in the inflammatory cells in dose-dependent manner, which demonstrated the therapeutic potential of stomopneulactone D in down-regulating the inflammatory pathogenesis.

Antioxidant drimane-type sesquiterpenoid from muricid gastropod Chicoreus ramosus attenuates pro-inflammatory 5-lipoxygenase and carbolytic enzymes.

The muricid gastropod, Chicoreus ramosus, is a nutrient-enriched food source available along the coastal peninsular of the Indian subcontinent. This study was aimed at bioactivity-directed chromatographic fractionation of the organic extract of C. ramosus to isolate an unprecedented drimane-type sesquiterpenoid Ramosane, characterized as 3-hydroxy-7,9b-dimethyl-5-methylene-8-pentyl-octahydro-1H-cyclopenta[a]naphthalen-9(2H)-one. The compound possessed potential antioxidant activities {2, 2'-diphenyl-1-picryl hydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging activities of IC50 1.42 mM and 1.72 mM, respectively} and was proportionate with those (IC50 1.39 and 1.69 mM, respectively) exhibited by α-tocopherol. The studied sesquiterpenoid exhibited potential attenuation property countering the pro-inflammatory 5-lipoxygenase (IC50  ~ 4 mM), and its activity was analogous with that exhibited by the anti-inflammatory ibuprofen (IC50 4.36 mM), whereas its carbolytic α-amylase activity (IC50 0.96 mM) was commensurate with that displayed by acarbose (IC50 0.43 mM). The isolated metabolite might anticipate as potential naturally derived bioactive constituent in functional food and pharmaceutical applications. PRACTICAL APPLICATIONS: The edible marine muricid gastropod C. ramosus is a prominently available gastropod species of commercial significance in the coastal regions of Indian Peninsula. An unprecedented drimane-type sesquiterpenoid Ramosane was isolated through the bioactivity-directed chromatographic fractionation of the organic extract of muricidae C. ramosus displaying potential anti-inflammatory and anti-diabetic properties. The present study apprehended the prospective of drimane-type sesquiterpenoid derivative Ramosane purified from C. ramosus as a naturally derived pharmacophore with anti-diabetic and anti-inflammatory potential for utilization in functional food and pharmaceutical formulations to minimize the likelihood of inflammation and hyperglycemic pathologies.

First report of chromenyl derivatives from spineless marine cuttlefish Sepiella inermis: Prospective antihyperglycemic agents attenuate serine protease dipeptidyl peptidase-IV.

Spineless marine cuttlefish Sepiella inermis has been considered as a popular dietary cephalopod species in Asian and Mediterranean coasts. Bioassay-directed purification of organic extract of S. inermis ensued in the characterization of two chromenyl derivatives. The studied compounds exhibited significantly greater antioxidant potencies (IC50  ≤ 0.5 mg/ml) when compared with α-tocopherol. The substituted 1H-isochromenyloxy-11-hydroxyethyl pentanoate isoform (compound 1) efficiently inhibited the carbolytic enzymes along with key regulator of insulin secretion dipeptidyl peptidase-IV (IC50 0.16 mg/ml). The molecular docking simulations displayed optimum binding affinity of the compound 1 (-10.01 kcal/mol) with dipeptidyl peptidase-IV and lesser inhibition constant (Ki 46.41 nM), which along with its permissible hydrophobic-hydrophilic balance (log Pow  ~ 2) appeared to play significant roles in its greater antihyperglycemic activity compared to other studied chromenyl isoform. The greater antioxidant and antidiabetic properties of compound 1 could be utilized as an important natural lead against hyperglycemic-related disorders. PRACTICAL APPLICATIONS: The edible spineless marine cuttlefish Sepiella inermis are ubiquitously available in Asian and Mediterranean coasts. The sequential chromatographic purification of the organic extract of S. inermis led to the identification of two pure chromenyl chemotypes. The metabolites with substituted 1H-isochromenyloxy-11-hydroxyethyl pentanoate isoform (compound 1) displayed potential antioxidative and antihyperglycemic activities compared to the chemotype (2) bearing 3H-isochromen-5-yl moiety. The attenuating potential of chromenyl chemotype 1 against carbohydrate hydrolyzing enzymes and insulin secretion regulator attributed towards its efficiency as an important natural lead against postprandial hyperglycemia and incretin hormone regulation to maintain glucose homeostasis in the biological system. The chromenyl metabolites isolated from S. inermis could be utilized as a functional food ingredient in the nutraceutical formulations against hyperglycemic-related disorders.

Antioxidant and antiinflammatory secondary metabolites from the Asian green mussel Perna viridis.

The Asian green mussel, Perna viridis is a nutritious health food in the estuarine and coastal sea beds of the Arabian Sea along the west coast of India. In the present study, bioactivity-guided purification of the chloroform fraction of the methanolic extract of P. viridis was carried out. The isolated secondary metabolites were characterized by spectroscopic experiments, and their antioxidative/antiinflammatory properties were evaluated. The titled compounds were characterized as 3-hydroxy-13-vinyl-dodecahydro-11-phenanthrenone (1), 4,4,9-trimethyl-13-vinyl-dodecahydro-2-phenanthrenone (2), 11,20-dihydroxy-6,6-dimethyl-decahydro-5H-benzo[h]naphtho[1,2-c]chromene-16-carbaldehyde (3), 16-acetyl-20-hydroxy-6,6-dimethyl-dodecahydro-5H-benzo[h]naphtho[1,2-c]chromen-12-one (4), cholest-5-en-3ß-3-yl-(30-hydroxy-3-methyl-36-methyleneundeca-30E,34E-dienoate) (5), and cholest-5-en-3ß-3-yl-((E)-33-oxooct-31-enoate) (6). No significant differences in the antioxidant activities of the compounds with chromene-16-carbaldehyde (3) and chromen-12-one (4) functionalities (IC50 0.52-0.68 mg/ml) vis-à-vis the positive control, α-tocopherol (IC50 0.65-0.76 mg/ml) were registered. The studied compounds, 1-4, displayed potential antiinflammatory activities against pro-inflammatory 5-lipoxygenase (5-LOX) (IC50  < 1 mg/ml). The balanced hydrophilic-lipophilic properties and lower steric values of the studied compounds, 1-4, were correlated with their bioactive potentials. PRACTICAL APPLICATIONS: The edible bivalve green mussels, P. viridis, are broadly available in the estuarine and coastal regions of the Indian Peninsula. The sequential chromatographic purification of the chloroform fraction of the methanolic extract of P. viridis led to the identification of six pure secondary metabolites. The metabolites with substituted chromene-16-carbaldehyde and chromen-12-one functionalities displayed potential antioxidative and antiinflammatory activities compared to other studied compounds. These bioactive metabolites could be used in functional food formulations and as antioxidant leads in medicinal food applications.

Effect of antioxidant compounds from seaweeds on storage stability of C20-22 polyunsaturated fatty acid concentrate prepared from dogfish liver oil.

Ethyl acetate extracts of seaweeds were chromatographically fractionated to yield 14-methyl pentyl tetrahydro-8-hydroxy-10-methylnaphthalene-8-carboxylate (1) and tetrahydro-4-isopropyl-9-(9, 14-dimethyldec-9-enyl)-pyran-1-one (2) from Sargassum ilicifolium, whereas Padina gymnospora afforded dihydro-2-(10-(hydroxymethyl)-7,15-dimethyl-9-oxoundec-11-enyl)-2-methyl-2H-pyran-1(4H)-one (3) and 1-(decahydro-1-hydroxy-7-methyl-8-vinylnaphthalen-2-yl)ethanone (4) as major constituents. Compound 1 displayed significantly higher antioxidant activity (IC50 < 1 mg/mL, p < 0.05) comparable to other analogues (IC50 > 1 mg/mL). The C20-22 polyunsaturated fatty acid (C20-22 PUFA) concentrate (CFA) prepared from the deep-sea dogfish liver oil was added with the studied compounds and physiochemical properties and fatty acid composition during an accelerated storage were evaluated. No significant reduction in C20-22 PUFAs (∼6%) in the CFA treated with 1 as compared to that with the control (∼35%) was recorded. A greater induction time was observed for the CFA supplemented with 1 (6.8 h) than other compounds (≤6 h) and control (∼1.6 h), maintaining the oxidation indices of the CFA within desirable limits.