Vamshi Krishna Raola

Two rare antioxidative prenylated terpenoids from loop-root Asiatic mangrove Rhizophora mucronata (Family Rhizophoraceae) and their activity against pro-inflammatory cyclooxygenases and lipoxidase.

Abstract Two new biogenic prenylated terpenoids were isolated from the methanol extract of Rhizophora mucronata. The extended C20 sesquiterpenoid with prenylated guaiane framework was characterised as (4E, 8Z)-3, 3a, 6, 7-tetrahydro-3, 9-dimethyl-5-(6-methylheptan-2-yl) cycloocta[b]furan-2-(9aH)-one (1). (35E)-1,2,3,5,6,6-icosahydro-4,4,8b,10,14,17,20,20-octamethylpicen-3-yl-34,35-dimethyloct-31-enoate (2) represents the first example of naturally occurring C40 prenylated oleanane-type triterpenoid, whereas one 4,5-dimethyloct-5-enoate side chain remains attached at C-3 position of the oleanane framework formed by the E-ring closure of C30 saccharide moiety. The structures of the compounds were elucidated using NMR and mass spectrometric analysis. Compound 1 was found to have significantly greater antioxidant activities (IC50 ~ 0.75 mg/mL) compared to 2 (IC50 > 0.80 mg/mL). No significant differences in anti-cyclooxygenase-2 of these compounds were discernable (IC50 0.8 – 0.9 mg/mL), whilst compound 1 showed greater anti-5-lipoxidase activities (IC50 ~ 0.8 mg/mL) those that of 2 (IC50 0.96 mg/mL). Bioactivities of the prenylated terpenoids were inversely proportional to lipophilic and bulk descriptors.

O-heterocyclic derivatives with antibacterial properties from marine bacterium Bacillus subtilis associated with seaweed, Sargassum myriocystum

The brown seaweed, Sargassum myriocystum associated with heterotrophic bacterium, Bacillus subtilis MTCC 10407 (JF834075) exhibited broad-spectra of potent antibacterial activities against pathogenic bacteria Aeromonas hydrophila, Vibrio vulnificus, and Vibrio parahaemolyticus. B. subtilis MTCC 10407 was found to be positive for polyketide synthetase (pks) gene, and therefore, was considered to characterize secondary metabolites bearing polyketide backbone. Using bioassay-guided fractionation, two new antibacterial O-heterocyclic compounds belonging to pyranyl benzoate analogs of polyketide origin, with activity against pathogenic bacteria, have been isolated from the ethyl acetate extract of B. subtilis MTCC 10407. In the present study, the secondary metabolites of B. subtilis MTCC 10407 with potent antibacterial action against bacterial pathogens was recognized to represent the platform of pks-1 gene-encoded products. Two homologous compounds 3 (3-(methoxycarbonyl)-4-(5-(2-ethylbutyl)-5,6-dihydro-3-methyl-2H-pyran-2-yl)-butyl benzoate) and 4 [2-(8-butyl-3-ethyl-3,4,4a,5,6,8a-hexahydro-2H-chromen-6-yl)-ethyl benzoate] also have been isolated from the ethyl acetate extract of host seaweed S. myriocystum. The two compounds isolated from ethyl acetate extract of S. myriocystum with lesser antibacterial properties shared similar structures with the compounds purified from B. subtilis that suggested the ecological and metabolic relationship between these compounds in seaweed-bacterial relationship. Tetrahydropyran-2-one moiety of the tetrahydropyrano-[3,2b]-pyran-2(3H)-one system of 1 might be cleaved by the metabolic pool of seaweeds to afford methyl 3-(dihydro-3-methyl-2H-pyranyl)-propanoate moiety of 3, which was found to have no significant antibacterial activity. It is therefore imperative that the presence of dihydro-methyl-2H-pyran-2-yl propanoate system is essentially required to impart the greater activity. The direct involvement of polarisability (Pl) with the target bioactivity in 2 implied that inductive (field/polar) rather than the steric effect (parachor) appears to be the key factor influencing the induction of antibacterial activity. The present work may have a footprint on the use of novel O-heterocyclic polyketide products from seaweed-associated bacterium for biotechnological, food, and pharmaceutical applications mainly as novel antimicrobial secondary metabolites.

New sterols with anti-inflammatory potentials against cyclooxygenase-2 and 5-lipoxygenase from Paphia malabarica.

Abstract Marine bivalves occupy a leading share in the total edible molluscs at the coastline regions of south-eastern Asia, and are found to possess significant nutritional and biological potential. Various in vitro evaluation (antioxidant and anti-inflammatory) guided purification of ethyl acetate–methanol (EtOAc–MeOH) extract of bivalve clam, Paphia malabarica characterised two new sterol derivatives as 23-gem-dimethylcholesta-5-en-3β-ol (1) and (22E)-241,242-methyldihomocholest-5,22-dien-3β-ol (2) collected from the south-west coast of Arabian Sea. Their structures were unambiguously assigned on the basis of 1D, 2D NMR spectroscopy and mass spectrometry. The antioxidant and anti-inflammatory activities of 2 as determined by DPPH/ABTS+ radical scavenging and anti-cyclooxygenase-2/5-lipoxygenase assays were significantly greater (IC50 < 1 mg/mL) than 1 (IC50 > 1 mg/mL). Structure–activity relationship analysis revealed that the bioactivities of these compounds were directly proportional to the electronic and lipophilic parameters. This is the first report of the occurrence and characterisation of 23-gem-dimethyl-3β-hydroxy-Δ5-cholestane nucleus and C-30 dihomosterol from marine organisms.

Antibacterial polyketides from Bacillus amyloliquefaciens associated with edible red seaweed Laurenciae papillosa

Heterotrophic Bacillus amyloliquefaciens associated with edible red seaweed, Laurenciae papillosa was used to isolate antibacterial polyketide compounds. Antibacterial activity studies integrated with the outcome obtained by polyketide synthetase (pks) coding genes established that seaweed-affiliated bacterial flora had a wide-ranging antibacterial activities and potential natural product diversity, which proved that the bacterium is valuable reservoir of novel bioactive metabolites. Bioactivity-guided isolation of 3-(octahydro-9-isopropyl-2H-benzo[h]chromen-4-yl)-2-methylpropyl benzoate and methyl 8-(2-(benzoyloxy)-ethyl)-hexahydro-4-((E)-pent-2-enyl)-2H-chromene-6-carboxylate of polyketide origin, with activity against human opportunistic food pathogenic microbes, have been isolated from the ethyl acetate extract of B. amyloliquefaciens. Structure-activity relationship analysis revealed that hydrophobic descriptor of the polyketide compounds significantly contribute towards its antibacterial activity. Seaweed-associated microorganisms were shown to represent a potential source of antimicrobial compounds for food and health benefits. The antibacterial polyketide compounds described in the present study may find potential applications in the food industry to reduce food-borne pathogens.

Biogenic guaianolide-type sesquiterpene lactones with antioxidative and anti-inflammatory properties from natural mangrove hybrid Rhizophora annamalayana

Abstract Previously undescribed guaianolide-type sesquiterpene lactones were isolated from the chloroform fraction of the natural hybrid mangrove Rhizophora annamalayana, and were characterised as (Z)-3α,4,5,6-tetrahydro-5α-isobutyl-2β-(methoxymethyl)-7-methyl-3H-cyclohepta[b]carbolactone (1) and (7Z)-isopentyl 3α,4,5,6,7,8-hexahydro-2β-((E)-11-methylbut-10-enyl)-1-oxo-2H-cyclohepta[b]furan-6-carboxylate (2). Compound 2 displayed greater antioxidative activities {1, 1-diphenyl-2-picrylhydrazyl (DPPH) and 2, 2′-azino-bis-3 ethylbenzothiozoline-6-sulphonic acid diammonium salt (ABTS), IC50 0.65 and 0.62 mg/mL, respectively)} compared to 1 (IC50 0.83 and 1.14 mg/mL, respectively) (p < 0.05). Compound 2 recorded no significant difference in DPPH. scavenging activities (IC50 0.65 mg/mL) compared to α-tocopherol (IC50 0.63 mg/mL). Pro-inflammatory 5-lipoxygenase inhibitory activity of 2 was found to be comparable (IC50 0.98 mg/mL) to that displayed by synthetic anti-inflammatory drug ibuprofen (IC50 0.93 mg/mL). Compound 2 showed significantly greater selectivity index (anti-cyclooxygenase-1/anti-cyclooxygenase-2 = 2.15) than non-steroidal anti-inflammatory ibuprofen (<0.5) (p < 0.05), and therefore, might be used as selective cyclooxygenase-2 inhibitor. The hitherto undescribed guaianolide lactones might be used as potential anti-inflammatory and antioxidative pharmacophore leads.

Previously undescribed benzoxepins with bioactivities against inducible pro-inflammatory cyclooxygenase and lipoxygenase from Rhizophora annamalayana Kathir

Abstract Two unprecedented benzoxepins were obtained from the ethyl acetate fraction of the leaves of Rhizophora annamalayana Kathir, and characterized as 4-(11-(hydroxymethyl)-10-methylpentan-2-yl)-4, 5-dihydrobenzo[c]oxepin-1(3H)-one (1) and (E)-methyl-14-hydroxy-4-(11-(5-hydroxy-1-oxo-3,4,5-tetrahydrobenzo[c]oxepin-4-yl)ethyl)-10-methylhept-11-enoate (2). The benzoxepin 2 exhibited greater 1, 1-diphenyl-2-picrylhydrazyl and 2, 2′-azino-bis-3 ethylbenzothiozoline-6-sulfonic acid diammonium radical scavenging assays (IC50 0.68 and 0.84 mg/mL, respectively) than those recorded with 1 (IC50 0.70 and 0.89 mg/mL, respectively). The tetrahydrobenzo[c]oxepin analogue (2) exhibited significantly great cyclooxygenase-2 and 5-lipoxygenase inhibitory properties (IC50 0.87 and 0.94 mg/mL, respectively), while compared with its dihydrobenzo[c]oxepin-1(3H)-one isoform (1) (IC50 1.16 and 1.64 mg/mL, respectively). The dihydrobenzo[c]oxepin-1(3H)-one isoform (2) exhibited significantly greater selectivity index (~2) than synthetic ibuprofen (0.44) (p < 0.05), which attributed the higher anti-inflammatory selectivity of the former against inducible pro-inflammatory cyclooxygenase-2 than its constitutive isoform (cyclooxygenase-1). No significant difference in 5-lipoxygenase (5-LOX) inhibitory activities were apparent between compound 2 (IC50 0.94 mg/mL) and synthetic ibuprofen (IC50 0.93 mg/mL).

In vitro bioactive analysis and antioxidant activity of two species of seaweeds from the Gulf of Mannar

Abstract Evaluation of in vitro standard antioxidant assays, such as 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2′-azino-bis-3 ethylbenzothiozoline-6-sulphonic acid diammonium salt (ABTS+) radical scavenging, lipid peroxidation inhibitory (or thiobarbituric acid formation inhibitory activity) and ferrous ion (Fe+2) chelating activities of different solvent extracts of seaweeds, Jania rubens and Kappaphycus alvarezii collected from the Gulf of Mannar of the Peninsular India, were carried out. The methodology utilised bioactivity-guided extraction of seaweed with effective solvent comprised classical chromatographic and spectroscopic techniques. The ethyl acetate extraction of seaweeds displayed significantly greater antioxidant activity than dichloromethane and n-hexane extraction. Bioactivity-guided chromatographic separation of the ethyl acetate extract of seaweeds with potentially greater antioxidant activities, yielded 6α-methoxy-4bβ-methyl-7β-vinyl-1,2,3,4,4a,4b,5,6,7,8,8a,9-dodecahydro-2β-phenanthrenol (1) from J. rubens, whereas K. alvarezii yielded 2β-ethyl-9-oxo-5α-vinyl-1,2,5,5a,6,7,8,9-octahydroheptalene-10,1-carbolactone (2) and methyl-2-ethyl-9-oxo-5α-vinyl-1,2,5,5a,6,7,10,10a-octahydroheptalene-1α-carboxylate (3). Compound 1 displayed significantly greater DPPH scavenging activities (IC50 0.22 mg/mL) than α-tocopherol (IC50 0.63 mg/mL). The order of DPPH radical-scavenging activities were compounds 1 > 2 > 3.

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.

Anti-Inflammatory Concentrate Enriched with Substituted Oligofucans Derived from Brown Seaweed Turbinaria conoides (J. Agardh) Kützing and Its Safety Assessment on Wistar Rats

ABSTRACT Aqueous extract of the seaweed Turbinaria conoides was purified to obtain an oligofucan-enriched seaweed concentrate (OESC). Oligofucans isolated were characterized as two types with (→1)-fucose-(2,3-diSO3−)-(1→4)-fucose-(2-SO3−)-(1→3)-fucose-(2,3-diSO3−)-(1→4)-fucose-(2-SO3−, 3-OAc)-(4→) and (→1)-fucose-(3-SO3−)-(1→4)-fucose-(2-SO3−)-(1→4)-fucose-(3-SO3−)-(1→4)-fucose-(2-SO3−)-(4→) motifs. A 90-day accelerated shelf-life study (50°C) showed that OESC maintained its antioxidant properties (free radical scavenging, reducing, lipid peroxidation inhibition, and chelating activities) even after 30 days. In vitro COX-2 and 5-LOX inhibitory properties of OESC (67.2 and 95.2%, respectively) showed no significant variation even at the 30th day. OESC significantly mitigated the carrageenan-induced inflammation in rats at 0–2 h (59.7–70.3% inhibition), which were greater compared to the synthetic NSAID aspirin. The safety of OESC has been assessed by acute (14 days) and subchronic (90 days) oral toxicity studies, which showed no toxicity-related significant changes in renal or hepatic function, hematological indices, and serum biochemical parameters in the OESC-treated Wistar rats. No histopathological alterations were observed in the vital organs of rats treated with OESC. LD50 and sub-chronic no-observed-adverse-effect level (NOAEL) for this concentrate were found to be > 5,000 and 2,000 mg/kg BW, respectively. Hence, oligofucan-enriched seaweed concentrate is safe to consume without any adverse effects in the body.