Sulphated glycosaminoglycan isolated from the edible slipper oyster Magallana bilineata (Röding, 1798) attenuates inflammatory cytokines on lipopolysaccharide-prompted macrophages.

The slipper oyster Magallana bilineata (Ostreidae) is considered as culinary delicacy among marine bivalves, and a sulphated glycosaminoglycan, 4,6-O-SO3-ß-(1→3)-GalNAcp (unit A) and ß-(1→4)-GlcAp (unit B) as principle structural motif containing laterally branched 4-O-SO3-ß-glucopyranose (unit C) (MBP-3) was isolated from this species. Nuclear magnetic resonance (NMR), Fourier transform infra-red (FTIR), and mass spectroscopy techniques were used to characterise MBP-3. MBP-3 exhibited anti-inflammatory activities against inflammatory 5-lipoxygenase (IC50 0.11 mg mL-1) and cyclooxygenase-2 (IC50 0.12 mg mL-1) enzymes. MBP-3 (at 100 µg mL-1) showed effective downregulation against pro-inflammatory cytokines generation, namely interleukins-6, 1ß, (IL-6, 1ß) (1-1.7 pg mL-1) and tumour necrosis factor-α (TNF-α) (4 pg mL-1) along with substantial downregulation of ROS production in lipopolysaccharide (LPS)-inflamed cells. MBP-3 blocked the mRNA of NF-κB, cyclooxygenase-2 (COX-2), and other cytokines, in lipopolysaccharide-induced macrophages. The potential to constrain inflammatory cytokine production revealed its application to develop functional food to attenuate inflammation-associated disorders.

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.

Non-sulfated steroidal glycosides cistoindosides from marine 'old woman octopus' Cistopus indicus attenuate pro-inflammatory lipoxygenase.

Two non-sulfated steroidal glycosides, cistoindosides A-B were isolated from organic extract of the marine 'old woman octopus' Cistopus indicus (family Octopodidae). Their structures were characterized as 3ß-acteoxy-23ß-hydroxy-cholesta-9-ene-ß-D-xylopyranoside (cistoindoside A) and 22,23-epoxy-3ß-hydroxy-cholesta-5-ene-ß-D-4'-O-acetoxy-xylopyranoside (cistoindoside B). Cistoindoside B, glycosylated with ß-D-4'-O-acetoxy-xylopyranoside in conjunction with epoxy moieties displayed superior anti-inflammatory properties as acknowledged by its promising 5-lipoxygenase attenuation potential (IC50 2.11 µM) than the 5-lipoxygenase inhibitor drug zileuton (IC50 3.76 µM). The anti-inflammatory properties were corroborated by the promising antioxidant activities (IC50 ∼ 1.0-1.5 mM) of these steroid glycosides. Sizeably greater electronic properties, balanced hydrophobic-lipophilic properties (log POW ∼ 4.0) and comparatively lower steric factors were directly proportional to their bioactivities. Molecular simulation studies in the active sites of 5-lipoxygenase displaying lesser binding energies and inhibition constant (Ki) of cistoindoside B could be correlated with anti-inflammatory properties. Cistoindosides could be projected for their utilization as potential bioactive leads in functional food and pharmaceutical applications.

Anti-inflammatory decurrencyclics A-B, two undescribed nor-dammarane triterpenes from triangular sea bell Turbinaria decurrens.

Intertidal triangular sea bell Turbinaria decurrens (Bory de Saint-Vincent) (family Sargassaceae) belongs to one of the largely abundant genus of marine brown alga. Bioactivity-directed chromatographic purification of the organic extract of T. decurrens afforded two new nor-dammarane triterpenoids named as decurrencyclic A-B. Decurrencyclic B showed superior attenuation properties against cyclooxygenase-2 (IC50 13.98 µM) and 5-lipoxygenase (IC50 3.02 µM) in contrast with decurrencyclic A. Decurrencyclic B showed higher inhibition potential against COX-2 than that revealed by the anti-inflammatory agent, ibuprofen (IC50 70.44 µM). The higher selectivity index of decurrencyclics (1.39-1.57) acknowledged their selective attenuation property against inducible cyclooxygenase-2. In-silico molecular modeling analysis of decurrencyclic B with the inflammatory enzymes showed least binding energy of -14.55 kcal mol-1. These reports have proven that decurrencyclic B could be a potential therapeutic lead for use against inflammatory pathogenesis.

A novel anti-hyperglycemic sulfated pyruvylated polysaccharide from marine macroalga Hydropuntia edulis.

Dipeptidyl peptidase is a crucial enzyme that regulates glucose metabolism by degrading incretins, such as glucagon-like-peptide-1, thereby reducing insulin secretion from the pancreatic ß-cells. Consequently, dipeptidyl peptidase-IV inhibitors are an important remedial approach to moderate the hyperglycemic pathophysiology. A pyruvylated polysaccharide characterized as [→3)-4,6-O-(1-carboxyethylidene)-ß-D-galp-(2SO3-)-(1→4)-3,6-α-L-AnGalp-(2OMe)-(1→], isolated from the marine macroalga Hydropuntia edulis, showed attenuation potential against dipeptidyl peptidase-IV (IC50 4.44 µM). The structure was elucidated using mass and one/two-dimensional nuclear magnetic resonance spectroscopic analyses of hydrolyzed polysaccharide besides glycosidic linkages obtained from partially methylated alditol acetate derivative. The isolated polysaccharide also revealed potential anti-carbolytic properties against α-amylase/α-glucosidase (IC50 45-47 µM). The results proved the candidacy of pyruvylated polysaccharide isolated from H. edulis as a potential therapeutic lead against hyperglycemia.

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.

Pharmacological potential of seaweed-associated heterotrophic bacterium Bacillus atrophaeus.

Extremities in marine environmental conditions led the marine macroalga-associated bacteria to adapt and biosynthesize potential bioactive agents. The myriad of marine macroalgae and the bacterial flora they are associated with constitute a potential source of bioactive components with significant biotechnological and pharmacological applications. Heterotrophic bacteria associated with the intertidal macroalgae were isolated and assessed for their pharmacological properties. Subsequently, Firmicutes dominated more than half of the 152 cultivable isolates from macroalgae-associated bacteria collected from the Gulf of Mannar (9°17'0'' N, 79°7'0'' E), on Peninsular India's southern coast. A total of 43 of those demonstrated steady antibacterial activities against a wide range of nosocomial pathogens. Among the bacteria isolated from marine macroalgae, Bacillus atrophaeus SHB2097 (MW821482) exhibited significant antimicrobial activities against clinically important pathogens. Organic extract of B. atrophaeus SHB2097 showed potential antimicrobial activities against test pathogens (minimum inhibitory concentration 6.25 µg/mL). Organic extract of B. atrophaeus SHB2097 revealed promising inhibition potential against cyclooxygenase-2 (IC90 53.26 µg/mL) and 5-lipoxygenase (IC90 9.74 µg/mL). The carbolytic enzyme α-glucosidase inhibition potential of the organic extract of the studied heterotrophic bacterium was significantly greater than (IC90 118 µg/mL) than that displayed by acarbose (IC90 645 µg/mL, p < 0.05). The significance of nuclear magnetic resonance-centered analyses of distinguishing signals in the organic extract and correlating those with bioactive potential was accentuated. The utilities of nuclear magnetic resonance-based fingerprinting emphasized the assessment of the distinctive signals in the solvent extracts and their correlation with the pharmacological properties. Thus, the heterotrophic B. atrophaeus SHB2097 could be used to develop potential therapeutic and biomedical agents.

Antibacterial and wound healing potential of topical formulation of marine symbiotic Bacillus.

The inevitability to develop novel antimicrobial agents has considerably increased because of mounting alarms concerning multidrug-resistant microbial strains. The present study evaluated an antibacterial and wound healing topical formulation prepared with the ethyl acetate extract of marine symbiotic Bacillus amyloliquefaciens MTCC 12716 as the basic ingredient and the grafted macroalgal polysaccharide as the gel base with an appropriate proportion of natural stabilizing agents. The formulation exhibited potent antibacterial activities against clinical isolates of Staphylococcus aureus (18 mm inhibition zone) and Pseudomonas aeruginosa (19 mm) causing infection when compared with commercially available antimicrobial cream clindamycin. The in-vitro results indicated that the organic extract of B. amyloliquefaciens MTCC 12716 at its MIC and the formulation sealed the wound by 78 and 94%, respectively, at 48 h in the scratch-induced L929 cells, compared to 84% exhibited by clindamycin. The topical formulation of marine symbiotic Bacillus induced greater than 80% viability of the normal fibroblasts compared to 78% exhibited by clindamycin, when administered at a dose of 25 µg mL-1. The studied antibacterial formulation could accelerate the wound healing by prompting the migration of fibroblasts towards the artificially created wound resulting in rapid wound closure, and at an even higher concentration of formulation, it displayed no cytotoxicity on L929 cells. The stability studies showed that the formulation maintained its physicochemical characteristics and minimal growth (<10 cfu g-1) of bacteria on the plates throughout the time period of 18 months at 30 °C and 65% relative humidity. This study has established the antibacterial and wound healing potential of a topical formulation of marine symbiotic B. amyloliquefaciens.

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.

Anti-hyperglycemic Δ5 steroids, marginoids A-C from marine veined octopus Amphioctopus marginatus (Octopodidae): Prospective natural leads inhibit serineexopeptidase dipeptidyl peptidase-4.

Three Δ5 steroid analogues, marginoids A-C were purified from the organic extract of marine veined octopus Amphioctopus marginatus (Taki, 1964) (family Octopodidae) distributed on the Asian and Mediterranean coasts. Their structures were elucidated as (5Z)-3ß-acetoxy-cholesta-5-en-25-ethylene-22ß-hydroxy-23,26-lactone (marginoid A), (5Z, 25Z)-3ß-yl-(1'-(E)-3'-hydroxy-4'-methyl-hex-5'-enoate)-22-oxo-26-furanyl-cholesta-5,25-diene (marginoid B), and (5Z)-3ß-yl-(7'-methoxypropan-8'-yl)-tetrahydro-2H-pyran-2-one-cholesta-5,24-dien (marginoid C) based on extensive spectroscopic experiments. Marginoid B with hydroxyl-methyl-hexanoate at the C-3 position in conjunction with the heterocyclic furanyl ring displayed superior anti-hyperglycemic properties as acknowledged by its promising serine protease dipeptidyl peptidase-4 attenuation potential (IC50 3.49 µM) displaying comparable activity with the standard DPP-4 inhibitor (DPP-4i) diprotin A (IC50 4.53 µM). The anti-hyperglycemic properties were corroborated by the promising antioxidant activities (IC50 âˆ¼ 0.8-1.0 mM) of these Δ5 steroids, marginoids A-C. Sizeably greater electronic properties, balanced hydrophobic-lipophilic properties (log POW 6.4-8.3), and comparatively lower steric factors were directly proportional to their bioactive properties. Molecular simulation studies in the binding sites of DPP-4 and lesser binding energy (-12.17 kcal/mol) and inhibition constant (Ki 1.20 nM) of marginoid B could be correlated with anti-hyperglycemic properties. Promising bioactivities of marginoid B isolated from A. marginatus are anticipated for nutraceutical applications against hyperglycemia.

Oxaspiro Indiculides from Old Woman Octopus Cistopus indicus as Dual Inhibitors of Inducible Cyclooxygenase and Lipoxygenase.

The organic extract of the old woman octopus Cistopus indicus (Octopodidae), ubiquitous in the Central and South Indo-Pacific to the tropical Indian Ocean, was chromatographically fractionated over a reverse-phase adsorbent to yield two oxygenated spiro heterocyclic compounds, named indiculides A and B. Their structures were elucidated by using comprehensive spectroscopic methods. The radical scavenging potential displayed by indiculide A (IC50 ∼1.2 mM) besides attenuating the cyclooxygenase isoforms (COX-1/COX-2; IC50 3.36/3.02 µM) showed considerably superior activities when equated to those showed by indiculide B (IC50 3.45/3.22 µM). The inhibition property of indiculide A against 5-LOX (IC50 2.57 µM) was significantly greater than that of the standard 5-LOX inhibitor zileuton (IC50 3.70 µM, p<0.05). A greater selectivity index (anti-COX-1/anti-COX-2, 1.11) was perceived for indiculide A than that demonstrated by indiculide B (1.07) and anti-inflammatory drug diclofenac (0.96). Structure bio-activity relation study of indiculide A disclosed proportionality to the electronic properties besides permissible hydrophobicity-lipophilicity equilibrium, which could result in its efficient interface with the active site of inflammatory enzyme causing promising anti-inflammatory potential. Larger hydrogen bond networks of indiculide A on account of the more electronic-rich centers in conjunction with reduced docking factors reinforced its noteworthy attenuation potential against 5-LOX. The in vitro bioactivity assessment and in silico docking results were further validated by the superior drug-like characteristics of indiculide A (drug-likeness score, 0.21) than B analog, and therefore, the former metabolite could be a potential anti-inflammatory lead.

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.

Seaweed-associated heterotrophic bacteria: are they future novel sources of antimicrobial agents against drug-resistant pathogens?

Emergence of multidrug-resistant microorganisms and requirements for novel antimicrobial compounds necessitate exploring newer habitats to develop potential bioactive leads. Culture-contingent analysis of heterotrophic bacterial flora from the seaweeds led to the isolation of bioactive strains possessing potential antibacterial properties against wide-ranging clinical pathogens viz., methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecalis (VREfs). Seven of the most active strains belonging to the phylum Firmicutes isolated from a brown seaweed (Phaeophyceae) Sargassum wightii exhibited spot-over-lawn assay guided inhibition zone of larger than 30 mm. Integrated phenotypic and genotypic studies have led to the characterization of the seaweed-associated bacteria particularly belonging to the phylum Firmicutes. The organic extracts of the studied bacteria exhibited promising antibacterial properties against MRSA and VREfs with minimum inhibitory concentration ranging between 6.25 and 12.50 µg/mL. Time-kill kinetic profiles of those bacteria displayed rapid bactericidal activity against both E. coli and MRSA, showing a ≥ 3log10 reduction in viable cell count than the initial. Among the studied bioactive Bacillus spp, B. tequilensis MTCC13043 and B. altiitudinis MTCC13046 were found to possess functional polyketide synthase (pks) gene (MW027664 and MW027660) that could be amplified. The outcome of amplified genes encrypting for polyketide synthase in conjunction with antibacterial activities unveiled the broad-spectrum antimicrobial activities of the marine heterotrophic Firmicutes, which could be further used against the emergent problem of antibiotic-resistant bacterial pathogens.

Antibiotic-active heterotrophic Firmicutes sheltered in seaweeds: can they add new dimensions to future antimicrobial agents?

Appearance of drug-resistant microorganisms prompted researchers to unravel new environments for development of novel antimicrobial agents. Culture-supported analysis of heterotrophic bacteria associated with seaweeds yielded 152 strains, in that larger share of the isolates was embodied by Bacillus atrophaeus SHB2097 (54%), B. velezensis SHB2098 (24%), B. subtilis SHB2099 (12%), and B. amyloliquefaciens SHB20910 (10%). One of the most active strains characterized as B. atrophaeus SHB2097 (MW821482) with an inhibition zone more than 30 mm on spot-over-lawn experiment, was isolated from a seaweed Sargassum wightii, was selected for bioprospecting studies. Significant antibacterial potential was displayed by bacterial organic extract against vancomycin-resistant Enterococcus faecalis, Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus, and Klebsiella pneumonia with minimum inhibitory concentration 6.25 µg/mL and comparable to the antibiotics ampicillin and chloramphenicol. The genes of type 1 pks (MZ222383, 700 bp) and hybrid nrps/pks (MZ222389, 1000-1400 bp) of B. atrophaeus MW821482 could be amplified. The bacterium displayed susceptibility to the commercially available antibiotic agents, and was negative for the pore-forming non-hemolytic hemolysin BL (hbl) and enterotoxin (nhe) genes, and therefore, was not pathogenic. The bacterium was found to possess genes (1000-1400 bp) involved in the biosynthesis of siderophore-class of compounds (MZ222387 and MZ222388) that showed 99% of similarity in BLAST search, and showed production of siderophore. Noteworthy antibacterial activities against clinically important pathogenic bacteria in conjunction with occurrence of genes coding for antimicrobial metabolites inferred that the marine heterotrophic bacterium B. atrophaeus SHB2097 could be used for the development of antibacterial agents against the emerging antibiotic resistance.

Marine cuttlefish derived 2H-benzochromenone: Pharachromenone as a dual inhibitor of pro-inflammatory 5-lipoxygenase and cyclooxygenase-2.

Cephalopod cuttlefish, Sepia pharaonis, has been considered as a commercially important resource, which is widely regarded as nutritious food in the southwest of Indian and Mediterranean coasts. Chemical analysis of the crude extract of S. pharaonis resulted in the isolation of an undescribed 2H-benzochromenone, pharachromenone, which was characterized as methyl-2″-(7-hydroxy-4-(5'-methylpent-5'-en-1'-yl-oxy-methyl)-2-oxo-2H-benzo[h]chromen-5-yl-methyl)-butanoate by mass and nuclear magnetic resonance spectral experiments. Pharachromenone revealed effective biopotency against 5-lipoxygenase (IC50 1.85 mM) and cyclooxygenase-2 (IC50 0.52 mM) than that displayed by nonsteroidal anti-inflammatory drug ibuprofen (IC50 4.36 mM, p < .05). Promising antioxidant property for pharachromenone (IC50 1.42-1.61 mM) compared with those exhibited by antioxidative agents butylated hydroxyl anisole (BHA) and α-tocopherol (IC50 1.40-1.90 mM) could conceivably validate its dual inhibition potential against 5-lipoxygenase and cyclooxygenase-2. Greater electronic parameters, lesser steric bulkiness, along with acceptable lipophilic-hydrophobic balance significantly contributed toward its promising anti-inflammatory activities. Molecular docking studies showing significantly greater inhibition constant (Ki) 8.24 nM and binding energy (-11.03 kcal/mol) of pharachromenone than the standard ibuprofen (Ki 4.65 µM, binding energy -7.27 kcal/mol) at the binding site of 5-lipoxygenase recognized its noncompetitive binding, which could describe the promising anti-inflammatory potential. Pharachromenone could be developed as a functional food component against oxidative stress-related inflammatory disorders. PRACTICAL APPLICATIONS: The cuttlefish Sepia pharaonis (family Sepiidae) comprises a major share in the global fishery sector due to its culinary delicacy and nutritionally valued high-quality meat. Furthermore, cephalopod mollusks are gaining pharmaceutical acceptance as resources to derive bioactive compounds with therapeutic significance. Bioassay-guided chromatographic fractionation of crude extract of S. pharaonis could result in the isolation of a 2H-benzochromenone derivative, pharachromenone exhibiting potent antioxidant and anti-inflammatory properties. This study recognized the therapeutic potential of a marine cuttlefish-originated food constituent against inflammatory conditions, and could be anticipated as a high-value functional food lead to minimize oxidative stress-related inflammatory disorders.

Sulfated galactofucan from seaweed Padina tetrastromatica attenuates proteolytic enzyme dipeptidyl-peptidase-4: a potential anti-hyperglycemic lead.

Dipeptidyl-peptidase-4 is a multifunctional ectoenzyme, which is implicated with hyperglycemic pathophysiology. Therefore, dipeptidyl-peptidase-4 inhibitors could be used as an attractive therapeutic strategy in blood-glucose homeostasis to attenuate the pathophysiologies of diabetes. A sulfated galactofucan characterized as [→1)-O-4-sulfonato-α-fucopyranosyl-(2→1)-O-2-sulfonato-α-fucopyranose-(3→] along with a branch of [→1)-6-O-methyl-ß-galactopyranosyl-(4→] unit at the C-4 position of O-2-sulfonato-α-fucopyranose, isolated from the seaweed Padina tetrastromatica, exhibited prospective attenuation property against dipeptidyl-peptidase-4 (IC50 0.25 mg mL-1). The studied sulfated galactofucan exhibited potential inhibitory properties against carbolytic enzymes α-amylase (IC50 0.98 mg mL-1) and α-glucosidase (IC50 0.87 mg mL-1) in comparison with the standard antidiabetic agent acarbose, along with radical scavenging activities. The seaweed-originated galactofucan could be developed as a promising natural therapeutic lead against hyperglycemic disorder.

Undescribed Anti-Inflammatory Thalysiaketides from Marine Sponge Clathria (Thalysias) vulpina (Lamarck, 1814).

Two undescribed polyketide-type compounds, thalysiaketide A and thalysiaketide B were isolated from a sponge of marine origin Clathria (Thalysias) vulpina (Lamarck, 1814). Thalysiaketide A exhibited significantly greater inhibitory potential against inflammatory 5-lipoxygenase (IC50 0.87 mM) and cyclooxygense-2 (IC50 0.93 mM) compared to those displayed by its thalysiaketide B analog (IC50 ≥1.05 mM). The 5-lipoxygenase inhibitory activity of thalysiaketide A was considerably superior to ibuprofen (standard, IC50 >4 mM). Higher degree of polar belongings (topological polar surface area 93.06) in conjunction with relatively lower docking parameters of thalysiaketide A with the aminoacyl residues of cyclooxygense-2 and 5-lipoxygenase (docking score -12.99 and -12.27 kcal/mol, respectively) recognized its prospective anti-inflammatory potential.

Clathriolide from marine demosponge Clathria (Thalysias) vulpina (Lamarck, 1814): previously undescribed macrocylic lactone with attenuating potential against angiotensin converting enzyme.

Angiotensin-I converting enzyme catalyses the rate-determined step of the conversion of angiotensin-I to angiotensin-II that narrows the blood vessels, and angiotensin-I converting enzyme inhibitors were recognised as important medications for hypertension-related diseases. Chemical investigation of angiotensin-I converting enzyme inhibitors from marine demospongiae Clathria (Thalysias) vulpina (family Microcionidae), resulted in a previously undescribed 22-membered macrocyclic lactone derivative, named as clathriolide. The studied compound showed potential angiotensin converting enzyme attenuation property (IC50 0.41 mM), which was comparable with the standard captopril (IC50 0.36 mM). Clathriolide revealed significantly greater antioxidant potentials against free radical species (IC50 < 1 mM) in comparison with the standard α-tocopherol (IC50 > 1.5 mM). Superior electronic characteristics (topological polar surface area > 100) coupled with relatively smaller binding energy and docking score of clathriolide with the aminoacyl residues of angiotensin-I converting enzyme (-11.5 and -12.2 kcal/mol, respectively) described its potential inhibitory property against angiotensin-I converting enzyme.