Fasina Makkar

Unprecedented antioxidative cyclic ether from the red seaweed Kappaphycus alvarezii with anti-cyclooxygenase and lipoxidase activities.

Abstract An unprecedented non-isoprenoid oxocine carboxylate cyclic ether characterised as (3S, 4R, 5S, 6Z)-3-((R)-hexan-2′-yl)-3,4,5,8-tetrahydro-4-methyl-2H-oxocin-5-yl acetate was isolated from the ethyl acetate–methanol extract of the red seaweed Kappaphycus alvarezii. The structure, as well as its relative stereochemistry, was proposed on the basis of extensive spectral data. The antioxidative activity of the isolated metabolite was found to have significantly greater as determined by 1, 1-diphenyl-2-picrylhydrazyl and 2,2′-azino-bis-3-ethylbenzothiozoline-6-sulfonic acid radical scavenging activities (IC50 ~ 0.3 mg/mL) compared to α-tocopherol (IC50 > 0.6 mg/mL) and was comparable to the synthetic antioxidants butylated hydroxytoluene and butylated hydroxyanisole (IC50 ~ 0.35–0.34 mg/mL). The compound exhibited greater activity against COX-2 (cyclooxygenase-2) than COX-1 (cyclooxygenase-1) isoform, and therefore, the selectivity index remained significantly lesser (anti-COX-1IC50: anti-COX-2IC50 0.87) than synthetic anti-inflammatory drugs (0.02–0.44). No significant difference of in vivo 5-lipoxidase activity (IC50 0.95 mg/mL) than ibuprofen (IC50 0.93 mg/mL) indicated the potential anti-inflammatory properties of the title compound.

Previously undescribed antioxidative azocinyl morpholinone alkaloid from red seaweed Gracilaria opuntia with anti-cyclooxygenase and lipoxygenase properties

Abstract In vitro antioxidative and anti-inflammatory bioassay-guided fractionation of the methanol: ethyl acetate crude extract of the thalli of red seaweed Gracilaria opuntia collected from the Gulf of Mannar led to the isolation of a new morpholine alkaloid 3-(2-ethyl-6-((3Z,7Z)-1,2,5,6-tetrahydroazocin-5-yl)hexyl) morpholin-6-one. The substituted azocinyl morpholinone recorded significant 1,1-diphenyl-2-picryl-hydrazil free radical scavenging activities (IC50 ~ 0.086 mg/mL) compared to the commercially available antioxidants, butylated hydroxyanisole, butylated hydroxytoluene, and α-tocopherol (IC50 > 0.20 mg/mL). The title compound showed greater cyclooxygenase-2 (COX-2) inhibitory activity (IC50 0.84 mg/mL) in conjunction with in vitro 5-lipoxidase inhibitory activity (IC50 0.85 mg/mL) than non-steroidal anti-inflammatory drugs (NSAIDs). The test compound had better selectivity index (COX-1/COX-2 ratio) (1.17 mg/mL) compared to aspirin (0.02 mg/mL), Na salicylate (0.73 mg/mL) and ibuprofen (0.44 mg/mL). The animals challenged with the substituted azocinyl morpholinone significantly mitigated the carrageenan-induced paw edema in time-dependent manner till the end of 6 h.

Antidiabetic and anti-inflammatory potential of sulphated polygalactans from red seaweeds Kappaphycus alvarezii and Gracilaria opuntia

ABSTRACT Antidiabetic and anti-inflammatory potential of sulphated polygalactans isolated from the red seaweeds Kappaphycus alvarezii and Gracilaria opuntia were acquired by employing different in vitro systems. The sulphated galactopyran motif derived from G. opuntia possessed significant antidiabetic properties as identified by α-amylase (IC50 0.04 mg/mL), α-glucosidase (IC50 0.09 mg/mL) and dipeptidyl peptidase-4 (DPP-4, IC50 0.09 mg/mL) inhibitory activities. Based on the detailed nuclear magnetic resonance spectroscopy experiments the sulphated galactopyran motif of G. opuntia was designated as →3)-4-O-sulfonato-(6-O-acetyl)-β-D-galactopyranosyl-(1→4)-3,6-anhydro-(2-O-sulfonato)-α-D-galactopyranosyl-(1→3)-4-O-sulfonato-(6-O-acetyl)-β-D-xylosyl-(1→3)-4-O-sulfonato-(6-O-acetyl)-β-D-galactopyranosyl-(1→4)-3,6-anhydro-(2-O-sulfonato)-α-D-galactopyranan, while the one from K. alvarezii was demonstrated to be →4)-4-O-sulfonato-(2-O-methyl)-β-D-galactopyranosyl-(1→4)-3,6-anhydro-(2-O-methyl)-α-D-galactopyranan. The sulphated galactans from G. opuntia showed greater anti-inflammatory inhibitory activities as determined by cyclooxygenase-1 (COX-1, IC50 0.01 mg/mL), cyclooxygenase-2 (COX-2, IC50 0.03 mg/mL), and 5-lipoxygenase inhibitory activities (5-LOX, IC50 0.24 mg/mL). This study revealed that the sulfated polygalactan enriched concentrate from G. opuntia can be used as potential therapeutic candidate to suppress the hyperglycemic response in diabetic conditions and inflammatory activity. They can be used to develop functional food ingredient in nutraceutical products.

Pharmacological activities of brown seaweed Sargassum wightii (Family Sargassaceae) using different in vitro models

ABSTRACT Recently a great deal of interest has been developed towards natural bioactive components from seaweeds as functional food ingredients. Antioxidant, anti-inflammatory, antidiabetic, and antihypertensive activities of ethyl acetate:methanol and chloroform solvent fractions of the brown seaweed Sargassum wightii were evaluated using different in vitro systems. The ethyl acetate:methanol fraction registered greater Fe2+ ion chelating ability (IC50 0.52 mg/ml), and were effective in stabilizing the 2,2-azino-bis-3-ethylbenzothiozoline-6-sulfonic acid (IC50 0.82 mg/mL), and 1,1-diphenyl-2-picryl hydrazil radicals (IC50 0.32 mg/mL) than those derived from chloroform solvent fractions. The chloroform solvent fraction showed greater angiotensin converting enzyme-I inhibitory activity (IC50 0.084 mg/mL), while the ethyl acetate:methanol fraction exhibited greater anti-COX-1, 2, and 5-LOX (IC50 0.03-0.05 mg/mL) and DPP-4 inhibitory (IC50 ~ 0.013 mg/mL) properties. A significant co-linearity was recorded between target bioactive properties and the electronegative groups appeared in the downfield space of the nuclear magnetic resonance spectra of the ethyl acetate:methanol and chloroform solvent fractions from S. wightii.

Antioxidative sulphated polygalactans from marine macroalgae as angiotensin-I converting enzyme inhibitors

Abstract Antioxidant and antihypertensive potential of the sulphated polygalactans isolated from the marine macroalgae Kappaphycus alvarezii and Gracilaria opuntia were assessed by utilising different in vitro systems. The galactans isolated from K. alvarezii possessed significantly greater antioxidative properties as determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH IC90 0.97 mg/mL) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS.+ IC90 0.72 mg/mL) scavenging activities than those isolated from G. opuntia (DPPH IC90 1.2 mg/mL and ABTS 0.86 mg/mL). The sulphated polygalactan →4)-4-O-sulphonato-(2-O-methyl)-β-D-galactopyranosyl-(1→4)-3,6-anhydro-(2-O-methyl)-α-D-galactopyranan from K. alvarezii showed greater angiotensin-I-converting enzyme (ACE) inhibitory activity (IC50 0.02 μg/mL) than →3)-4-O-sulphonato-(6-O-acetyl)-β-D-galactopyranosyl-(1→4)-3,6-anhydro-(2-O-sulphonato)-α-D-galactopyranosyl-(1→3)-4-O-sulphonato-(6-O-acetyl)-β-D-xylosyl-(1→3)-4-O-sulphonato-(6-O-acetyl)-β-D-galactopyranosyl-(1→4)-3,6-anhydro-(2-O-sulphonato)-α-D-galactopyranan motif extracted from G. opuntia (IC50 0.70 μg/mL). Structure activity correlation studies displayed that the ACE inhibitory properties of titled polygalactans were directly proportional to their electronic properties and inversely with the steric and hydrophobic characteristics. Putative ACE inhibitory mechanism of action of sulphated galactans from marine macroalgae corroborated the structure bioactivity correlation analysis.

Highly oxygenated antioxidative 2H-chromen derivative from the red seaweed Gracilaria opuntia with pro-inflammatory cyclooxygenase and lipoxygenase inhibitory properties

Abstract Phytochemical investigation of the thalli of ethyl acetate-methanol extract of the red seaweed Gracilaria opuntia led to isolation of a substituted 2H-chromen derivative of unusual structure possessing highly oxygenated carbon skeleton, characterised as 2-acetoxy-2-(5-acetoxy-4-methyl-2-oxotetrahydro-2H-pyran-4-yl)ethyl 4-(3-methoxy-2-(methoxymethyl)-7-methyl-3,4,4a,7,8,8a-hexahydro-2H-chromen-4-yloxy)-5-methylheptanoate, which have not been reported in nature. The chemical structure was resolved by detailed spectroscopic analysis. The anti-inflammatory activity of the newly reported metabolite was determined by pro-inflammatory cyclooxygenase and 5-lipoxygenase inhibitory assays. The anti-inflammatory selectivity index of the title compound recorded greater value (SI: anti-cycloxygense-/anti-cycloxygense- ~ 1.26) than synthetic NSAIDs (aspirin and ibuprofen, SI: 0.02 and 0.44, respectively), and consequently, appeared to be safer. The antioxidative activity of the title compound was significantly greater as determined by 2, 2-diphenyl-1-picrylhydrazyl and 2, 2′-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) radical scavenging activities (IC50 0.26–0.32 mg/mL) compared to α-tocopherol (IC50 > 0.6 mg/mL), and was comparable to the synthetic antioxidants butylated hydroxytoluene and butylated hydroxyanisole (IC50 ~ 0.25–0.34 mg/mL).

Novel furanyl derivatives from the red seaweed Gracilaria opuntia with pharmacological activities using different in vitro models

Two previously undescribed furanyl compounds, characterized as 5-(7-(5-ethyl-3,4-dimethoxycyclooctyl) benzofuran-6-yl)-7-methyl-3,4,7,8-tetrahydro-2H-oxocin-2-one (compound 1) and 2-(3-ethyl-9-(2-methoxyethoxy)-1-oxo-2,3,4,9-tetrahydro-1H-xanthen-2-yl) ethyl-5-hydroxy-9-methoxy-7,8-dimethyl-8-(5-methylfuran-2-yl) nona-3,6-dienoate (compound 2) were derived from the ethyl acetate–methanol (EtOAc:MeOH) crude extract of red seaweed Gracilaria opuntia. The isolated compounds are the first furanyl natural products featuring methoxycyclooctyl benzofuran with tetrahydro-2H-oxocin framework and tetrahydro-1H-xanthenyl methoxy methylfuran skeletons. These compounds were assessed for anti-inflammatory activities against pro-inflammatory cyclooxygenase-2/5-lipoxygenase (COX-1, 2, and 5-LOX) and antioxidative effects in various in vitro models. The methylfuran derivative exhibited comparable inhibitory activities towards 5 LOX (IC50 0.209 × 10−2 M) with synthetic non-steroidal anti-inflammatory drugs (NSAID) ibuprofen (IC50 0.451 × 10−2 M, P < 0.05), which indicated its potential anti-inflammatory properties. The antioxidative properties of the furanyl derivatives as resolved by 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2ʹ-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid (ABTS) free radical scavenging activities were found to be significantly greater (IC50 ~0.051–0.055 × 10−2 M) than those exhibited by α-tocopherol (IC50 > 0.146 × 10−2 M), and were similar to those displayed by the synthetic antioxidants (butylated hydroxytoluene (BHT)/ butylated hydroxyanisole (BHA) (IC50 ~0.144–0.189 × 10−2 M, P < 0.05). The anti-inflammatory selectivity indices of the isolated compounds recorded significantly greater values (SI: anti-COX-1IC50/anti-COX-2IC50 ~1.08–1.09) than NSAIDs (aspirin, and ibuprofen, SI: 0.02 and 0.44, respectively, P < 0.05), and consequently, appeared to be safer. The isolated compounds showed significant anti-diabetic properties as determined by α-amylase/α-glucosidase (IC50 < 0.052 × 10−2 M) and dipeptidyl peptidase-4 (DPP-4, IC50 < 0.002 × 10−2 M) inhibitory activities. The angiotensin converting enzyme-I (ACE-I) inhibitory activity of the compounds (IC50 0.023–0.024 × 10−2 M) was found to be comparable with that recorded by commercial ACE inhibitor, captopril (IC50 0.037 × 10−2 M).

Antioxidant Activity of Brown Seaweeds

ABSTRACT Antioxidant potential of three brown seaweeds, Anthophycus longifolius, Sargassum plagiophyllum, and Sargassum myriocystum, obtained from the Gulf of Mannar region of India were evaluated utilizing different in vitro systems. Ethyl acetate (EtOAc) fraction of Anthophycus longifolius registered significantly greater hydroxyl radical scavenging ability (IC50 0.19 mg/mL) and was effective in stabilizing the 2,2′-azino-bis-3-ethylbenzothiozoline-6-sulfonic acid (IC50 1.23 mg/mL) and 1,1-diphenyl-2-picryl-hydrazil (DPPH) radicals (IC50 0.48 mg/mL) (p < 0.05). No significant differences in hydrogen peroxide (H2O2) scavenging and ferrous ion chelating properties of the EtOAc extracts of the seaweeds were apparent. The utilities of the reverse-phase high-performance liquid chromatography (RP-HPLC) method hyphenated to diode-array detection for analyzing the fingerprints of phenolic constituents in the solvent extracts and fractions of the seaweeds were denoted. High-performance liquid chromatographic analysis indicated the presence of phenolic acids in the solvent extracts of seaweeds. This study demonstrated the potential use of A. longifolius as candidate species to be used as a nutritional food supplement/functional foods to increase the shelf life of food items for human consumption.

Antioxidant and anti-inflammatory oxygenated meroterpenoids from the thalli of red seaweed Kappaphycus alvarezii

Three antioxidant and anti-inflammatory oxygenated meroterpenoids, 1-(3-methoxypropyl)-2-propylcyclohexane (C13) (1), 3-(methoxymethyl)heptyl 3-(cyclohex-3-enyl) propanoate (C18) (2), and 2-ethyl-6-(4-methoxy-2-((2-oxotetrahydro-2H-pyran-4-yl)methyl)butoxy)-6-oxohexyl 5-ethyloct-4-enoate (C29) (3) were purified from the methanol:ethyl acetate fraction of red seaweed Kappaphycus alvarezii (family Solieriaceae) collected from the Gulf-of-Mannar on the southeast coast of peninsular India. The highly oxygenated C29 meroterpenoid 3 displayed potential antioxidative activities (IC50 < 0.35 mg/mL) as evaluated by 2, 2’-azino-bis (3-ethylbenzothiazoline)-6-sulphonic acid and 1, 1-diphenyl-2-picryl-hydrazil free radical scavenging assays. The compound 3 displayed potential in vitro inhibitory activities towards pro-inflammatory 5-lipoxidase (IC50 1.04 mg/mL), which indicated its potential anti-inflammatory properties against inducible inflammatory mediators causing an inflammatory response. Structure-activity relationship analyses displayed the functional roles of lipophilic-hydrophobic characteristics and electronic parameter to determine its potential anti-inflammatory activity in terms of inhibiting inducible inflammatory cyclooxygenase and lipoxidase.

Nutritional attributes in the fillet of skipjack tuna ( Katsuwonus pelamis ) from the Arabian Sea near the south-west coast of India

Inter-annual and seasonal variability in the nutritional parameters of the edible portion of skipjack tuna (Katsuwonus pelamis) collected from the Arabian Sea were determined for a period of 4 years. Greater levels of long chain n-3 fatty acids (35% during pre-monsoon), critical in the human diet for their anti-inflammatory properties with greater n-3:n-6 fatty acid ratio (8:12) demonstrated that this species may serve as an alternative to balance the greater amount of n-6 fatty acids. The present study demonstrated skipjack tuna as a significant source of protein, amino acids, minerals and vitamins. A balanced essential to non-essential amino acid ratio (1.2:1.4) in the fillets indicated that this species could provide well-balanced protein depositions. Vitamins A and K1 demonstrated post-monsoon maxima, whilst vitamins D3 and E showed pre-monsoon maxima. Greater calcium (172 mg 100 g21 ) and phosphorus contents (923 mg 100 g21 ) were recorded in the fillets of skipjack tuna during the pre-monsoon season. The chlorophyll-a concentration and sea surface temperature of its habitat were considered to understand their effect on the nutritional composition of skipjack tuna all through the study period. Significant correlation between long chain n-3 polyunsaturated fatty acids such as eicosapentaenoic acid and docosahexaenoic acid (r 2 0.99) of skipjack tuna alongside chlorophyll-a concentration was observed, particularly during the monsoon. The lesser atherogenic/thrombogenicity indices (,1), greater hypocholesterolaemic/hypercholesterolaemic ratio (.1.0), and lesser cholesterol contents (,50 mg 100 g21 ) of the fillets in skipjack tuna contributed towards its parameters to be qualified as a high value, balanced nutritional source.