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.

Marine Macroalgal Polygalactan-Built Nanoparticle Construct for Osteogenesis.

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

Antioxidative dolabellanes and dolastanes from brown seaweed Padina tetrastromatica as dual inhibitors of starch digestive enzymes.

New dolabellanes {6-methoxy-dolabella-8(17),12-diene-10ß,18-diol (1), 3-methoxy-dolabella-12(18)-ene-4ß-ol (2), 3-methoxy-dolabella-10,18(19)-diene-5α,8ß-diol (3)} and dolastanes {2,7-dimethoxy-14α-hydroxy-dolasta-1(15),9-diene (4) and 4,7-dimethoxy-9ß,14α-dihydroxy-dolasta-1-ene (5)} were identified from brown seaweed Padina tetrastromatica (family Dictyotaceae), collected from the southeast coast of India. Compounds 1-3 were found to possess dolabellane skeleton with [9.3.0] cyclotetradecane framework whereas, 4-5 were composed of tricyclic diterpenes with linear arrangement of six-seven-five fused alicyclic rings. Compounds 3 and 5 registered greater antioxidative activities (IC50 ≤0.63 mg/mL) than other analogues (IC50 ≥0.65 mg/mL), whereas their attenuating potentials against carbolytics α-amylase and α-glucosidase (IC50 ∼0.12-0.14 mg/mL) were comparable with those displayed by acarbose (IC50 0.14-0.12 mg/mL). Bioactive potentials of titled compounds were assessed by electronic and lipophilic parameters. The lesser binding energies of 3 (-9.71 kcal/mol) and 5 (-8.59 kcal/mol) through molecular docking demonstrated their effective hydrogen bonding interactions with α-amylase. Thus, dolabellanes and dolastanes might be used as anti-diabetic and antioxidant leads to reduce the risk of hyperglycaemia.

First report of spiro-compounds from marine macroalga Gracilaria salicornia: prospective natural anti-inflammatory agents attenuate 5-lipoxygenase and cyclooxygenase-2.

The inflammation pathology is an orchestrated biological process and the dual inhibition of pro-inflammatory enzymes 5-lipoxygenase and cyclooxygenase-2 has been found to be an effective approach against inflammation. This study involves the characterisation of two previously undescribed spiro[5.5]undecanes, 3-(hydroxymethyl)-7-(methoxymethyl)-3,11-dimethyl-9-oxospiro[5.5]undec-4-en-10-methylbutanoate (1) and 4-ethoxy-11,11-dimethyl-7-methylene-8-(propionyloxy)spiro[5.5]undec-2-en-104,106-dihydroxytetrahydro-2H-pyran-10-carboxylate (2) with potential anti-inflammatory properties, from seaweed Gracilaria salicornia by extensive-spectroscopic-experiments. These metabolites recorded prospective bioactivities against 5-lipoxygenase (IC50 < 2.80 mM), whereas their selectivity indices were significantly greater (∼1) than ibuprofen (0.89) (p < 0.05), which attributed selective anti-inflammatory potencies of the studied spiro[5.5]undecane derivatives against inducible cyclooxygenase-2 than constitutive cyclooxygenase-1. Radical scavenging potential of spiro[5.5]undec-2-en-104,106-dihydroxytetrahydro-2H-pyran-10-carboxylate analogue (2) against oxidants, 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azino-bis-3 ethylbenzothiozoline-6-sulfonic acid were found to be greater (IC50 < 1.25 mM) than commercial standard, α-tocopherol (IC50 1.42-1.79 mM). The greater hydrogen-bonding interactions and binding affinity of 2 (-10.13 kcal/mol) with 5-LOX appropriately corroborated its prospective anti-inflammatory activity.

Salicornolides A-C from Gracilaria salicornia attenuate pro-inflammatory 5-lipoxygense: Prospective natural anti-inflammatory leads.

Three macrolides bearing the carbon framework of oxabicyclo[21.3.1]heptacosa-ene-diones (A and B) and oxabicyclo[19.3.1]pentacosa-ene-dione (C) were isolated and characterised from the organic extract of the intertidal red seaweed Gracilaria salicornia (family Gracilariaceae), which were named as salicornolides A-C. These natural macrolides were conformationally pre-organised ring structure providing diverse functionalities, and their potential bioactive properties led to the development of pharmacophores with anti-inflammatory properties. The 21-membered pyran-enclosed salicornolide B displayed greater cyclooxygenase-2 (IC50 COX-2 1.13 mM) inhibitory activity than those exhibited by the 21-membered aryl salicornolide A and 19-membered salicornolide C (IC50 COX-2-1.2 mM). The attenuating potential of the studied compounds against pro-inflammatory enzyme, 5-lipoxygenase (IC50 LOX < 1.5 mM) was significantly greater than that displayed by the non-steroidal anti-inflammatory ibuprofen (IC50 4.5 mM), whereas the selectivity indices exhibited by salicornolides against cyclooxygenase-2 was significantly higher (1.18-1.41, P < 0.05) when compared to that of ibuprofen (SI 0.43) attributing the greater selectivity profile of the former towards inducible pro-inflammatory mediators than the latter. The minimal binding energy of salicornolide B (-9.64 kcal mol-1), a greater number of hydrogen-bonds and lesser inhibitory constant (Ki 85.15 nM) might be responsible for effective binding towards 5-lipoxygenase, and that could attribute its greater anti-inflammation potential than those displayed by other compounds. The putative biosynthetic cascade initiated by malonate-acyl carrier protein unambiguously confirmed the structural attributions of the titled macrocyclic lactones. The undescribed salicornolides A-C from seaweed Gracilaria salicornia attenuating pro-inflammatory 5-lipoxygense might be considered as prospective natural anti-inflammatory leads for pharmaceutical applications.

First report of antioxidant abeo-labdane type diterpenoid from intertidal red seaweed Gracilaria salicornia with 5-lipoxygenase inhibitory potential.

Phytochemical investigation on the biologically active compounds of seaweed Gracilaria salicornia {(C. Agardh) E.Y. Dawson} (family Gracilariaceae) guided to the separation of a previously unreported abeo-labdane class of diterpenoid. The compound was characterized as methyl-16(13→14)-abeo-7-labdene-(12-oxo) carboxylate by extensive spectroscopic experiments, and comparison with the related compounds. The studied compound registered significantly greater activities against pro-inflammatory 5-lipoxygenase (IC50 0.86 mg/mL) than that exhibited by non-steroidal anti-inflammatory agent ibuprofen (IC50 0.92 mg/mL, P < 0.05). Likewise, this compound exhibited comparable radical quenching (1, 1-diphenyl-2-picryl-hydrazil) activity (IC50 0.66 mg/mL) as standard antioxidant agent α-tocopherol (IC50 0.62 mg/mL).

First report of antioxidative 2H-chromenyl derivatives from the intertidal red seaweed Gracilaria salicornia as potential anti-inflammatory agents.

Phytochemical investigation on biologically active compounds of an intertidal red seaweed Gracilaria salicornia (family Gracilariaceae) guided to the separation of two previously undisclosed 2H-chromenyl derivatives. The compounds were characterised as 4'-[10'-[7-hydroxy-2,8-dimethyl-6-(pentyloxy)-2H-chromen-2-yl]ethyl]-3',4'-dimethyl-cyclohexanone (1) and 3'-[10'-(8-hydroxy-5-methoxy-2,6,7-trimethyl-2H-chromen-2-yl)ethyl]-3'-methyl-2'-methylene cyclohexyl butyrate (2) by extensive spectroscopic experiments. The studied metabolites recorded prospective bioactivities against 5-lipoxygenase (IC50 < 2.50 mM), whereas their selectivity indices were significantly greater (∼1) than ibuprofen (0.89) (p < 0.05), which attributed higher anti-inflammatory selectivity of 2H-chromenyl compounds against inducible cyclooxygenase-2 than its constitutive pro-inflammatory isoform of cyclooxygenase-1. The radical scavenging potential of 2 against oxidants, 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azino-bis-3 ethylbenzothiozoline-6-sulfonic acid were higher (IC50 < 1.35 mM) than standard antioxidant, α-tocopherol (IC50 1.42-1.79 mM). The greater hydrogen bond interactions and binding affinity of 2 (-7.35 kcal mol-1) bearing 2H-chromenyl ethyl-3'-methyl-4'-methylenecyclohexyl butyrate moiety with 5-lipoxygenase, along with higher electronic properties and permissible hydrophobic-hydrophilic balance, manifested towards its greater anti-inflammatory activity than 1.