Pro-inflammatory 5-lipoxygenase Research Articles

Synthesis and Biological Activity Assessment of 2-Styrylbenzothiazoles as Potential Multifunctional Therapeutic Agents.

A current trend in healthcare research is to discover multifunctional compounds, able to interact with multiple biological targets, in order to simplify multi-drug therapies and improve patient compliance. The aim of this work was to outline the growing demand for innovative multifunctional compounds, achieved through the synthesis, characterisation and SAR evaluation of a series of 2-styrylbenzothiazole derivatives. The six synthesised compounds were studied for their potential as photoprotective, antioxidant, antiproliferative, and anti-inflammatory agents. In order to profile antioxidant activity against various radical species, in vitro DPPH, FRAP and ORAC assays were performed. UV-filtering activity was studied, first in solution and then in formulation (standard O/W sunscreen containing 3% synthesised molecules) before and after irradiation. Compound BZTst6 proved to be photostable, suitable for broad-spectrum criteria, and is an excellent UVA filter. In terms of antioxidant activity, only compound BZTst4 can be considered a promising candidate, due to the potential of the catechol moiety. Both also showed exceptional inhibitory action against the pro-inflammatory enzyme 5-lipoxygenase (LO), with IC50 values in the sub-micromolar range in both activated neutrophils and under cell-free conditions. The results showed that the compounds under investigation are suitable for multifunctional application purposes, underlining the importance of their chemical scaffolding in terms of different biological behaviours.

Anti-inflammatory and antiproliferative activity of Helichrysum odoratissimum Sweet. against lung cancer

Lung cancer remains the top killing cancer worldwide despite advances in treatment. Seven ethanolic plant extracts were selected and evaluated for their antiproliferative activity against the two main types of lung cancers: non-small cell (A549) and small cell lung cancer cells (SHP-77). An ethanolic extract of Helichrysum odoratissimum Sweet (HO) showed significant antiproliferative activity against lung cancer, with a fifty percent inhibitory concentration (IC50) of 83.43 ± 1.60 µg/mL (A549), 49.46 ± 0.48 µg/mL (SHP-77) and 50.71 ± 2.27 µg/mL, against normal lung epithelial cells (MRC-5), resulting in a selectivity index (SI) value of 0.61 on A549 cells and 1.03 on SHP-77 cells, which was compared to the positive drug control, actinomycin D where the SI values were found to be 2 and 0.25 against A549 and SHP-77 cells, respectively. Against murine macrophages (RAW 264.7) and hepatocytes (HepG2), the HO ethanolic extract showed IC50 values of 60.15 ± 1.98 µg/mL and 23.61 ± 1.06 µg/mL, respectively. Microscopy showed that the HO ethanolic extract induced apoptosis in the A549 and HepG2 cells at 50 µg/mL and 300 µg/mL, respectively. The HO ethanolic extract, furthermore, inhibited the pro-inflammatory enzymes, cyclooxygenase 2 (COX-2) and 5-lipoxygenase (5-LOX) with IC50 values of 7.94 ± 3.84 µg/mL and 2.08 ± 1.35 µg/mL, respectively, whereas the positive controls Ibuprofen (COX-2) and Zileuton (5-LOX) showed IC50 values of 0.85 ± 0.14 µg/mL and 0.06 ± 0.05 µg/mL, respectively. The activity of NAD(P)H quinone oxidoreductase-1 (NQO1), which is a direct target of nuclear factor erythroid-2-related factor-2 (NRF2), was significantly inhibited in the A549 cells by the HO ethanolic extract (at 125 µg/mL) when compared to the positive control, brusatol (at 500 nM). Using the ex ovo yolk sac membrane (YSM) assay, the HO ethanolic extract (at 18.5 µg/egg) showed a 31.65 ± 12.80% inhibition of blood vessel formation. This is the first report of the noteworthy antiproliferative activity of the HO ethanolic extract on lung cancer cells including its potential to target several enzymes associated with inflammation and therefore, should be considered for further analysis.

Molecular docking and ADMET prediction studies of Flavonoids as multi-target agents in COVID-19 therapy: anti-inflammatory and antiviral approaches

Recent studies showed that hyper-inflammatory reactions including cytokines storm leads to acute respiratory distress syndrome and responsible for death toll in COVID-19. Thus, the pathways involved in inflammation and SARS-Cov-2 replication represent a promising therapeutic target. By employing a computational model, we investigated the effect of plant flavonoids on pro-inflammatory proteins (glucocorticoid receptor (GR), cyclooxygenase-2 (COX-2) and 5-lipoxygenase (LOX) enzymes), and on proteins involved in virus replication (main protease (Mpro), and papain-like protease (PLpro)). This in silico study study aimed to identify promising flavonoids with anti-inflammatory and antiviral activities (multi-target) for combating COVID-19. Mpro (PDBID: 6LU7), PLpro (PDBID: 6WX4), COX-2 (PDBID: 6COX), LOX (PDBID: 6N2W), and GR (PDBID: 1P93) were selected as target proteins. The molecular docking experiment was done using PLANTS software. Parameters for Lipinski’s “Rule-of-Five'', and the prediction of pharmacokinetic and toxicity profiles were done using the online platform, pkCSM. We found that 2 flavonoids, diosmin and hesperidin demonstrated low binding score and stronger than that of the reference ligands for the target proteins of Mpro, PLpro, and LOX. These compounds interact with amino acid residues of the protein targets through hydrogen bonds and show similar binding pattern compared to the approved drugs and native ligands. The ADMET and drug-likeness profiles prediction indicated that they have low toxicity, and good pharmacokinetic properties with the exception of the absorption profile. Hesperidin and diosmin are the promising candidates to be further investigated as multi-target agent for the treatment of COVID-19 through simultaneous inhibition of inflammation and virus replication.

Cysteinyl–leukotriene and prostaglandin pathways in bronchial versus alveolar lavage in allergic asthmatics

Cysteinyl–leukotriene and prostaglandin pathways in bronchial versus alveolar lavage in allergic asthmatics

Brown and Red Marine Macroalgae as Novel Bioresources of Promising Medicinal Properties

ABSTRACT Bioactive compounds from marine macroalgae are gaining immense attention for their application as natural ingredients in various nutraceuticals and food supplements. The present study evaluated the medicinal properties of the organic extracts of four each of brown and red marine macroalgal species, using various in vitro assays. Organic extracts of brown algae of Fucophycidan subclass, such as Sargassum plagiophyllum, Turbinaria decurrens, and red alga Hydropuntia edulis, displayed potential inhibitory properties against antioxidants (IC50 0.2–0.8 mg/mL) and carbolytic enzymes (IC50 0.2–0.9 mg/mL) compared to those exhibited by other studied algae. Noticeably, organic extracts of red alga H. edulis and brown alga T. decurrens could effectively attenuate pro-inflammatory 5-lipoxygenase (IC50 0.4–0.6 mg/mL), thereby demonstrating their potential application to dissuade inflammatory pathogenesis. This study demonstrated the predominantly available brown and red macroalgae as potential marine bioresources to develop functional food candidates.

Metabolism of anti-inflammatory OXE (oxoeicosanoid) receptor antagonists by nonhuman primates

5-Oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE) is the only product of the proinflammatory 5-lipoxygenase pathway with potent chemoattractant effects for human eosinophils, suggesting an important role in eosinophilic diseases such as asthma. 5-Oxo-ETE, acting through its selective OXE receptor, induces dermal eosinophilia in both humans and monkeys. To block its effects, we designed selective indole-based OXE antagonists containing hexyl (S-230) or phenylhexyl (S-C025 and S-Y048) side chains, which inhibit allergen-induced dermal and pulmonary inflammation in monkeys, suggesting that they may be useful therapeutic agents in humans. In this study we identified two metabolic pathways for the phenylhexyl-containing antagonists in liver microsomes: benzylic and N-methyl hydroxylation, resulting in ω-hydroxy, ω-oxo, and NH-containing products with reduced potencies that were identified by mass spectrometry and comparison with synthetic standards. Products of both pathways were also identified in monkey plasma following oral administration of S-C025 and S-Y025, but were less abundant than the α-hydroxy metabolites that we previously identified. Interestingly, the α-hydroxy compounds were not detected in microsomal incubations, suggesting a different origin. The relative rates of metabolism of these antagonists were S-230 >> S-C025 > S-Y048, which may help to explain the differences in their plasma half-lives (S-230 < S-C025 < S-Y048). In conclusion, S-C025 and S-Y048 are metabolized by liver microsomes by benzylic and N-methyl hydroxylation but not by α-hydroxylation, whereas all three pathways exist in vivo. Addition of a phenyl group to the hexyl side chain of these antagonists dramatically reduced their rates of metabolism, which would explain their prolonged in vivo half-lives.

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 1.02mM) than the non-steroidal drug ibuprofen (IC50 4.61mM, p≤.05). Superior antioxidant properties of spiropharanone against free radicals (EC50 ~1.20mM) and other oxidants (hydroxyl [EC50 0.97mM] and superoxide [EC50 1.47mM] scavenging) also reinforced its promising anti-inflammatory activity. The studied spiropharanone also exhibited significant attenuation toward insulin secretion regulating enzyme dipeptidyl peptidase-4 (IC50 0.92mM) 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.

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 → 13)-abeo-euryfuranyls (1–2) from the spineless cuttlefish Sepiella inermis in lipopolysaccharide-stimulated macrophages. The euryfuranyl bearing (4 → 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.

Anti-inflammatory pregnane-type steroid derivatives clathroids A-B from the marine Microcionidae sponge Clathria (Thalysias) vulpina: Prospective duel inhibitors of pro-inflammatory cyclooxygenase-2 and 5-lipoxygenase

Two pregnane-type of steroid derivatives characterized as 5α-pregna-3β-methyl pent-3-enoate-12β, 16β diol-20-one (clathroid A) and 12β,15β- dihydroxypregna-4,6-diene-3,20-dione (clathroid B) were purified from the crude extract of the marine sponge, Clathria (Thalysias) vulpina (family Microcionidae) by extensive chromatographic fractionation. Spectroscopic methods including nuclear magnetic resonance spectroscopy were employed to characterize the purified clathroids A-B. The studied compounds exhibited duel inhibitory potentials against pro-inflammatory cyclooxygenase-2 and 5-lipoxygenase (median inhibitory concentration, IC50 < 1 mM), whereas the attenuation property of clathroid A against 5-lipoxygenase (IC50 0.85 mM) was greater than the standard anti-inflammatory ibuprofen (IC50 4.51 mM, p < 0.05). Greater selectivity index (anti cyclooxygense-2/anti cyclooxygense-1) of the studied clathroids (>1) than ibuprofen (0.43) attributed the greater selective attenuation properties towards pro-inflammatory inducible cyclooxygenase-2 than its constitutive isoenzyme cyclooxygenase-1. The antioxidant potentials of clathroid A against 2, 2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (IC50 0.80 mM) and diphenyl-1-picrylhydrazyl (IC50 0.83 mM) free radicals were greater than those of clathroid B (IC50 0.86–0.96 mM). Structure–activity analyses showed that the bioactivities of the clathroids were directly related to their electronic parameters coupled with permissible hydrophobic properties. Clathroid A exhibited grater electronic parameter (topological polar surface area tPSA, 83.83) than clathroid B (74.60) and ibuprofen (37.30), which were found to be in agreement with the prospective anti-inflammatory profile of clathroid A. Clathroid A exhibited higher number of hydrogen bonding interactions with 5-lipoxygenase active site and lesser docking values, such as docking score (DS −12.90 kcal mol−1) and inhibition constant (Ki 1.11 nM) than those recorded by clathroid B (DS −10.49 kcal mol−1; Ki 13.88 nM). The molecular binding properties of clathroid A with 5-lipoxidase inferred that its docking score/ binding energy were positively correlated with their in vitro bioactivie potentilas. A putative biosynthetic pathway of the studied clathroids was proposed from a pregnenolone precursor. The present study recognized the potential of clathroid A isolated from C. (Thalysias) vulpina as prospective anti-inflammatory lead that could find its use in medicinal applications.

Anti-inflammatory β-sitosterols from the Asiatic loop-root mangrove Rhizophora mucronata attenuate 5-lipoxygenase and cyclooxygenase-2 enzymes

Four biogenic β-sitosterol analogues were identified from methanolic extract of the leaves of loop-root mangrove Rhizophora mucronata. These were characterized as 4, 14, 23-trimethyl-3β-sitosterol (1), 7-ethyl-3β-sitosterol (2), sitosteryl-3β-(33E)-pent-33-enoate (3) and 12α-hydroxy-3β-sitosterol (4) based on comprehensive spectroscopic techniques. Anti-inflammatory activities of β-sitosterol 4 against pro-inflammatory enzymes 5-lipoxygenase and cyclooxygenase-2 were found to be significantly higher (IC50 1.85 and 1.92 mM, respectively) compared to those demonstrated by compounds of 1–3 (p < 0.05). These β-sitosterol analogues disclosed superior selectivity indices (1.43–2.07) with regard to inducible cyclooxygenase-2 than its constitutive isoform cyclooxygenase-1, when compared to the standard, ibuprofen (0.44). Antioxidant properties of 12α-hydroxy-β-sitosterol (4) were found to be significantly greater (IC50 1.43–1.67 mM) than those of other sitosterol analogues. Structure-activity correlation analyses put forward that the bioactive potencies of the titled β-sitosterols were positively correlated to their electronic parameters. Molecular docking simulations were carried out in the active sites of 5-lipoxygenase/cyclooxygenase-2, and the docking scores and binding energies of the studied β-sitosterol analogues were positively correlated with their attenuation properties against 5-lipoxygenase and cyclooxygenase-2.

Pharmacological properties of some mangrove sediment-associated bacillus isolates.

Mangrove sediment-associated bacteria are of significantly important in the field of medicine and pharmaceuticals as new promising sources of biologically active pharmacophores due to the extreme conditions, such as high salt concentration and soil anoxia. The sediment bacteria associated with Acanthus ilicifolius and Avicennia officinalis collected from the Mangalavanam mangrove ecosystem of the Kerala State of India were evaluated using various in vitro models for the assessment of their pharmacological properties. The bacteria exhibiting significant antioxidant and antimicrobial activities were isolated, identified, and characterized by the integrated microbiological, biochemical, and 16S rRNA sequencing. Among the varied bacteria isolated from mangrove sediments, Bacillus amyloliquefaciens MBMS5 (GenBank accession number MK765025) exhibited significant antimicrobial activities against various pathogenic bacteria, such as Aeromonas caviae, Vibrio parahemolyticus, and methicillin-resistant Staphylococcus aureus. The extracellular extracts of B. amyloliquefaciens MBMS5 exhibited potential antioxidant activity against free radical species coupled with anti-inflammatory property as displayed by the attenuation activity against pro-inflammatory 5-lipoxygenase.

An anti-inflammatory salmachroman from the sea urchin Salmacis bicolor: a prospective duel inhibitor of cyclooxygenase-2 and 5-lipoxygenase

An isochroman derived polyketide, salmachroman characterized as methyl 153(11-(10-hydroxy-12-oxo-6-pent-63-en-61-yl)isochroman-10-yl)-13-oxotetrahydrofuran-15-yl was isolated from the organic extract of the Echinodermata sea urchin Salmacis bicolor (family Temnopleuridae) through chromatographic fractionation. The structure of the compound was identified by detailed spectroscopic techniques. Salmachroman demonstrated significant duel inhibition potential against pro-inflammatory enzymes, cyclooxygense-2 (IC50 1.29 mM) and 5-lipoxygenase (IC50 1.39 mM). The compound exhibited significantly greater anti-inflammatory selectivity index (1.03) than that displayed by the anti-inflammatory agent ibuprofen (0.43). The isochroman analogue exhibited greater antioxidant activities against 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (IC50 1.19 mM) and 2,2-diphenyl-1-picrylhydrazyl (IC50 1.24 mM) than the standard antioxidative agent α-tocopherol (IC50 > 1.50 mM). The binding properties of the compound with the active site of cyclooxygense-2 and 5-lipoxygenase enzymes, combined with its higher electronic parameters as attributed by the structure-activity relationship accounted for its significant anti-inflammatory properties.

Antioxidative 2H-chromenyls attenuate pro-inflammatory 5-lipoxygenase and carbolytic enzymes: Prospective bioactive agents from Babylonidae gastropod mollusk Babylonia spirata.

Oxygenated heterocycles are emerging as valuable pharmacophores involved in the prophylaxis and treatment of several diseases elicited by the reactive oxygen species. Bioassay-led chromatographic fractionation of the organic extract of the gastropod mollusk Babylonia spirata (family Babylonidae) yielded two unprecedented 2H-chromenyl derivatives characterized as 2-(butyryloxy)-5-hydroxy-hexahydro-2H-chromene-3-methyl carboxylate (1) and (3-hydroxy-hexahydro-2H-chromen-2-yl)methyl pentanoate (2). The chromenyl derivative (1) registered significantly greater attenuation potential against pro-inflammatory 5-lipoxygenase (IC50 ~2.02mM) than those exhibited by the compound (2) (IC50 2.76mM) and the non-steroidal anti-inflammatory drug ibuprofen (IC50 4.36mM, p<.05). The compound (1) exhibited comparable antioxidant activity (IC50 1.47-1.72mM) with standard antioxidative agent α-tocopherol (IC50 1.4-1.7mM). Inhibitory potential of chromenyl derivative (1) toward α-glucosidase (IC50 1.18mM) and α-amylase (IC50 0.92mM) was greater than those displayed by 2 (IC50 1.16-1.56mM). Structure-activity relationships revealed that bioactivities of the compounds were determined by the electronic factors and hydrophilic-lipophilic balance. PRACTICAL APPLICATIONS: The marine gastropod Babylonia spirata is one of the prominent edible gastropod species harvested from the coastlines along the southwestern region of the Indian peninsula. Two 2H-chromenyl derivatives were isolated to homogeneity from the organic extract of the marine buccinid gastropod B. spirata by the bioactivity-guided chromatographic fractionation and were found to possess potential antioxidant and attenuation properties against pro-inflammatory 5-lipoxygenase and carbolytic enzymes. The attenuation properties of the 2H-chromenyls against pro-inflammatory 5-lipoxygenase showed that 2H-chromenyl analogs possessed significantly greater anti-inflammatory potential than the non-steroidal anti-inflammatory drug ibuprofen. In particular, the chromenyl derivative bearing 2H-chromene-3-methyl carboxylate framework might constitute a prospective biogenic constituent in functional food and pharmaceutical applications for use against oxidative agents, including inflammation and hyperglycemic pathologies.

Anti-inflammatory polyether triterpenoids from the marine macroalga Gracilaria salicornia: Newly described natural leads attenuate pro-inflammatory 5-lipoxygenase and cyclooxygenase-2

5-Lipoxygenase (5-LOX)/cyclooxygenase-2 (COX-2) were found to be the two major inducible pro-inflammatory enzymes catalysing the rate-limiting stage in the development of pro-inflammatory prostaglandins/thromboxanes by COX-2 pathway and leukotrienes by 5-LOX pathway. Instantaneous quenching of COX-2/5-LOX-associated cascade is an important therapeutic objective in the attenuation of inflammatory pathologies. Two polyether triterpenoids, characterised as 15-(octahydro-7-(4,5-dihydro-3-methoxy-2,6-dimethyl-2H-pyran-6-yl)-10-methylpyrano[3,2-b]pyran-14-yl)-18-(19-methyl-23-methyleneoxepan-19-yl)pent-15-en-18-ol (1) and tetrahydro-6-(hexahydro-13-((tetrahydro-18-(23-hydroxy-23-methylheptan-19-yl)-15-methylfuran-15-yl)methyl)-10-methyl-2H-furo[3,2-b]pyran-7-yl)-2,2,6-trimethyl-2H-pyran-3-yl butyrate (2) were isolated from the organic extract of the marine macroalga, Gracilaria salicornia harvested from southeast-coastal zones of the Indian peninsular. Polyether analogue bearing trimethyl-2H-pyran-3-yl butyrate moiety (2) disclosed potent attenuation properties against 5-LOX (IC50 1.89 mM) and COX-2 (IC50 1.87 mM) enzymes. In-silico molecular docking methods designated the anti-inflammatory mechanisms of isolated compounds and their comparison of docking factors assigned that the polyether 2 displayed the smallest binding energy of −10.29 and −10.96 kcal mol−1 in COX-2 and 5-LOX active sites, respectively and designated competent hydrogen-bonding associations with the enzymatic catalytic regions. Greater electronic factors along with lesser steric bulk of the polyether 2 bearing furanyl-furo[3,2-b]pyran-2H-pyran moiety was found to have noteworthy functional roles to attenuate the inflammatory enzymes. Proposed bio-synthetic origin leading to the polyether analogues comprising the cyclization of squalene epoxides through the sequences of enzyme-catalysed cascade corroborated their structural attributions. These reports designated that polyether triterpenoid enclosing furanyl-furo[3,2-b]pyran-2H-pyran skeleton might be considered as a prospective anti-inflammatory therapeutic source to alleviate COX-2 and 5-LOX-mediated inflammatory pathologies.

Stomopnolides A-B from echinoidea sea urchin Stomopneustes variolaris: prospective natural anti-inflammatory leads attenuate pro-inflammatory 5-lipoxygenase

Two fourteen-membered macrocyclic pyrone derivatives named as stomopnolides were identified from the organic extract of echinoidea sea urchin Stomopneustes variolaris by extensive chromatographic purification, and were characterised as methyl 10-butyl-4a-methyl-2-oxo-octahydro-2H-cyclodeca[b]pyran-8-carboxylate (stomopnolide A) and methyl 82-(4a-methyl-10-(102-methylbutyl)-2-oxo-octahydro-2H-cyclodeca[b]pyran-8-yl)acetate (stomopnolide B) by spectroscopic methods. The macrocyclic pyrone derivative bearing pyran-8-carboxylate moiety (stomopnolide A) exhibited significantly greater antioxidant properties against 2,2-diphenyl-1-picrylhydrazyl (IC50DPPH 1.43 mM) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (IC50ABTS+ 1.63 mM) free radicals than stomopnolide B (IC50 > 1.85 mM) and the commercial standard α-tocopherol (IC50 1.51 mM). Stomopnolide A exhibited potential attenuation property against pro-inflammatory 5-lipoxygenase (IC50 2.78 mM) than those exhibited by stomopnolide B (IC50 3.09 mM) and non-steroidal anti-inflammatory drug, ibuprofen (IC50 4.50 mM, p < 0.05), which signified the prospective anti-inflammatory activity of the former. The greater electronic parameters of stomopnolide A, along with greater number of hydrogen bonds and docking score obtained from the molecular docking studies attributed its potential anti-inflammatory activity.

Pharmacological Properties of Seaweeds against Progressive Lifestyle Diseases

ABSTRACT Seaweeds are consumed as staple food items in the cuisines of many Asian countries and are considered as essential components of a healthy diet. The pharmacological potential of ethyl acetate-methanol (EtOAc-MeOH) extract of 10 species of seaweeds belonging to the subclasses Dictyotophycidae, Rhodymeniophycidae, and Corallinophycidae against progressive lifestyle diseases was determined by various in vitro models. Among the studied species, the organic extracts of Gracilaria salicornia and Padina tetrastromatica exhibited potential dipeptidyl-peptidase-4 inhibiting activity (IC50 ~ 0.03 mg mL−1) and angiotensin converting enzyme-I inhibitory property (ACE-I) (IC50 0.12 mg mL−1) compared to those displayed by other studied species. The organic extracts of G. salicornia and P. tetrastromatica also displayed significantly greater attenuation properties against pro-inflammatory cyclooxygenase-2 and 5-lipoxygenase (IC50 0.98–1.34 mg mL−1, P < .05) compared to those derived from other species (IC50 1.99–5.02 mg mL−1). The nuclear magnetic resonance-guided dereplication of organic extracts of the studied seaweed species recognized the co-linearity between the bioactive potential and downfield electronegative functionalities. These results recognized the significance of the organic extracts of G. salicornia and P. tetrastromatica to isolate compounds for functional food applications against oxidative stress and induced diseases, such as diabetes, hypertension, and inflammation.

First report of a glycosaminoglycan-xylopyranan from the buccinid gastropod mollusk Babylonia spirata attenuating proinflammatory 5-lipoxygenase.

A previously undescribed xylated glycosaminoglycan characterized as β-D-Xylop(1→3)-(⋯→4)-GlcpA(1→3)-GlcpNAc(1→⋯) was purified from the buccinid gastropod Babylonia spirata and was evaluated for pharmacological properties using different in vitro models. The glycosaminoglycan-xylopyranan displayed prospective free radical quenching activities (IC50 <0.7mg/ml), whereas it exhibited potentially greater attenuation against the inductive proinflammatory enzyme 5-lipoxygenase (5-LOX, IC50 0.36mg/ml) than the synthetic nonsteroidal anti-inflammatory drug aspirin (0.42). Gel permeation chromatography analysis specified the average molecular mass of the purified polysaccharide to be 231.88kDa. The linkage sites, anomeric configuration, and the sequence of sugar residues of the purified xylated glycosaminoglycan were attributed by the inter-residue correlation obtained via two-dimensional nuclear resonance spectroscopic techniques. The results specified that the studied compound was composed of GlcpA(1→3)-GlcpNAc (1→⋯) disaccharide repeating unit in the glycosaminoglycanbackbone, with the xylose residues branching as C-3 substituents of the GlcpA. . PRACTICAL APPLICATIONS: The edible marine buccinid mollusk Babylonia spirata is a gastropod species of economic significance in the coastal regions of peninsular India. A previously unreported xylated glycosaminoglycan with a β-D-Xylop(1→3)-(⋯→4)-GlcpA(1→3)-GlcpNAc(1→⋯) framework was isolated to homogenity and was found to possess potential antioxidant and 5-lipoxygenase attenuation activities. The isolated metabolite mightbe anticipated as potential naturally-derived bioactive constituent in functional food and pharmaceutical applications.

First report of antioxidant 1H-benzochromenone from muricid gastropod Chicoreus ramosus as dual inhibitors of pro-inflammatory 5-lipoxygenase and carbolytic enzymes

Chromene derivatives with manifold structural framework and pharmacological properties were ubiquitous in the mollusks of marine origin. A previously undescribed 1H-benzochromenone was isolated through bioassay-guided chromatographic purification of the organic extract of the marine gastropod mollusk Chicoreus ramosus. The compound was characterised as 6-(2′,2′-dimethyl)-3′-en-1′-yl-1′-oxy)-3-hydroxy-1H-benzo[c]chromene-2(10aH)-one based on integrated spectroscopic analysis. The antioxidant studies by employing the stable free radicals reported that the antioxidant activity (IC50 1.4–1.6 mM) was comparable to α-tocopherol (IC50 1.4–1.7 mM). The attenuating potential of the studied compound against pro-inflammatory 5-lipoxygenase (IC50 2.12 mM) was significantly greater than that exhibited by anti-inflammatory drug ibuprofen (IC50 4.4 mM), whereas its inhibitory properties against carbolytic α-amylase (IC50 ∼0.72 mM) was comparable with that displayed by acarbose (IC50 0.43 mM). The present study recognised the potential of 1H-benzochromenone derivative isolated from C. ramosus as important pharmaceutical lead with anti-diabetic and anti-inflammatory potentials to reduce the risk of hyperglycaemia and inflammatory pathologies.

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 1.42mM and 1.72mM, respectively} and was proportionate with those (IC50 1.39 and 1.69mM, respectively) exhibited by α-tocopherol. The studied sesquiterpenoid exhibited potential attenuation property countering the pro-inflammatory 5-lipoxygenase (IC50 ~4mM), and its activity was analogous with that exhibited by the anti-inflammatory ibuprofen (IC50 4.36mM), whereas its carbolytic α-amylase activity (IC50 0.96mM) was commensurate with that displayed by acarbose (IC50 0.43mM). 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.

Functional Properties of Ethyl Acetate-methanol Extract of Commonly Edible Molluscs

ABSTRACTMarine molluscs are consumed as culinary delicacies and represent a relatively untapped source of natural functional food ingredients. The bioactive potential of ethyl acetate-methanol (C2H5OAc/CH3OH) extract of molluscs Uroteuthis duvaucelii, Amphioctopus marginatus, Crassostrea madrasensis, and Sepiella inermis were demonstrated using different in vitro systems. The C2H5OAc/CH3OH extract of A. marginatus displayed greater 2, 2-diphenyl-1-picryl-hydrazil (IC90 1.76 mg mL−1) radical quenching capacity along with potential hydroxymethylglutaryl coenzyme-A reductase (HMGCR)-inhibiting activity (IC90 1.21 mg mL−1) and angiotensin converting enzyme-I inhibitory property (ACE-I) (IC90 0.87 mg mL−1) compared to those displayed by other molluscs. The organic extract of S. inermis set forth significantly higher pro-inflammatory 5-lipoxygenase inhibitory property (IC90 1.96 mg mL−1) along with potential antidiabetic activity as determined by dipeptidyl peptidase-4 (DPP-4) antagonistic activities (IC90 2.62 mg mL−1, P < .05). Significant correlations were observed between bioactive properties and electronegative groups of organic extracts of a mollusc. The free radical quenching property of the extracts exhibited a positive correlation towards other bioactivities, implicating the role of antioxidant property of the compounds in the extract to inhibit lifestyle ailments. The present study indicated that S. inermis and A. marginatus could be utilized as functional food ingredients to combat hypertension, hyperlipidemia, and inflammation-related risks.