Polygalacto-fucopyranose from marine alga as a prospective antihypertensive lead.

Consumption of marine alga-based polysaccharides as additional functional foods can endow with health benefits by diminishing the risk of chronic diseases. A polygalacto-fucopyranose characterized as [→1)-2, 4-SO3-α-Fucp-(3 → 1)-{2-SO3-α-Fucp-(3→}] with [(4 → 1)-6-OAc-ß-Galp-(4→] side chain isolated from marine alga Sargassum wightii exhibited potential antihypertensive activity. Upon treatment with studied polygalactofucan (50 mg/kg BW), serum hypertension biomarkers troponin-T (1.3 pg/mL), troponin-I (1.2 µg/dL) and angiotensin-II converting enzyme (0.18 pg/mL) were significantly recovered in hypertensive rats compared to disease control. Serum cardiovascular risk indices of diseased rats were significantly decreased (< 10%, p < 0.05) after administration of the studied galactofucan (50 mg/kg BW) related to hypertension group (> 17%), and were comparable with standard antihypertensive agent telmisartan (8.3-10.2% at 2 mg/kg BW). The studied compound was safe for consumption as obvious from the high LD50 value (>5 g/kg), and could be developed as a prospective functional food ingredient attenuating the pathophysiological attributes causing hypertension-related conditions.

Previously undescribed antioxidative O-heterocyclic angiotensin converting enzyme inhibitors from the intertidal seaweed Sargassum wightii as potential antihypertensives.

Four previously undescribed antioxidative O-heterocyclic analogues, characterized as 3″-isopropyl-3c-{3b-[(2-oxo-3,4-dihydro-2H-chromen-3-yl) methyl] butyl}-2″-butenyl-3'-hydroxy-2'-(2'b-methoxy-2'-oxoethyl)-3', 4'-dihydro-2H-pyran-4'-carboxylate (1), 2c-methylbutyl-6-[6c-(benzoyloxy)propyl]-6-methyl-tetrahydro-2H-pyran-2-carboxylate (2), 6-{6b-[3'-(5'a-methyl propyl)-3', 4'-dihydro-2H-pyran-6'-yl] ethyl}-tetrahydro-2H-pyran-2-one (3) and 7-(7c-methylpentyl)-hexahydro-2H-chromen-2-one (4) were isolated from the ethylacetate:methanol fraction of the brown seaweed Sargassum wightii. Nuclear magnetic resonance and mass spectroscopic experiments unambiguously attributed their structural identities. Antihypertensive activities of the studied compounds were determined in terms of their angiotensin converting enzyme (ACE) inhibitory potential. The 2H-pyranylcarboxylate derivative (1) displayed comparable activity (IC50 0.08 mg/mL) with standard antihypertensive agent captopril (IC50 0.07 mg/mL). The O-heterocyclic derivatives bearing 2H-pyran-4'-carboxylate (1) and 2H-pyran-2-carboxylate (2) frameworks showed significantly greater (p < 0.05) 1, 1-diphenyl-2-picryl-hydrazil radical quenching potential {IC50 (1) 0.34 and IC50 (2) 0.45 mg/mL} compared to the standard antioxidant α-tocopherol (IC50 0.63 mg/mL). Structure-activity relationship analyses demonstrated that the electronic and lipophilic descriptors might significantly contribute towards the target bioactivities of 2H-pyranylcarboxylates (1 and 2). Molecular docking simulations were carried out for ACE inhibition, and the binding energy obtained for the compounds (~7.04-8.48 kcal/mol) demonstrated their potential enzyme-ligand interactions. The potential of hitherto undescribed O-heterocyclic derivatives as natural antioxidant and antihypertensive functional food supplements and their utilization as therapeutic leads in the antihypertensive management were described in the present study.

Unprecedented antioxidative and anti-inflammatory aryl polyketides from the brown seaweed Sargassum wightii.

Previously undescribed aryl polyketide lactones, 4-(8-ethyl-tetrahydro-7-oxo-2H-pyran-5-yl)-propyl-4'-methylbenzoate (compound 1) and methyl-2-(12-oxo-7-phenyl-8-vinyl-1-oxa-4,9-cyclododecadien-3-yl)-acetate (compound 2) were purified from ethyl acetate-methanol fraction of the brown seaweed Sargassum wightii. The structures were proposed based on their NMR and mass spectrometric data. The antioxidative activities of the lactones were significantly greater (P<0.05) (IC50 1,1-diphenyl-2-picrylhydrazyl radical scavenging 0.24-0.32mg/mL) than α-tocopherol (IC50 0.63mg/mL). The title compounds displayed considerably greater 5-lipoxygenase inhibitory activity (IC50 0.56 and 0.29mg/mL, respectively) in conjunction with higher selectivity indices (anti-cycloxygense-1IC50/anti-cycloxygense-2IC50 >1) compared to non-steroidal anti-inflammatory drugs (SIaspirin 0.03, SIibuprofen 0.43). Putative biosynthetic pathway of title polyketide products through polyketide synthase enzyme cascade catalyzed reactions substantiated the structural attributions of the hitherto unreported aryl polyketides. This is the first report of the occurrence and characterization of two rare skeletal types, oxo-2H-pyranyl and oxa-cyclododecadienyl macrolactone featuring the aryl substituent from marine organisms with potential antioxidative and anti-inflammatory activities.

Previously undescribed fridooleanenes and oxygenated labdanes from the brown seaweed Sargassum wightii and their protein tyrosine phosphatase-1B inhibitory activity.

Previously undescribed fridooleanene triterpenoids 2α-hydroxy-(28,29)-frido-olean-12(13), 21(22)-dien-20-propyl-21-hex-4'(Z)-enoate, 2α-hydroxy-(28,29)-frido-olean-12(13), 21(22)-dien-20-prop-2(E)-en-21-butanoate and oxygenated labdane diterpenoids 2α-hydroxy-8(17), (12E), 14-labdatriene, 3ß, 6ß, 13α-tri hydroxy 8(17), 12E, 14-labdatriene were purified from the ethyl acetate-methanol and dichloromethane fractions of the air-dried thalli of Sargassum wightii (Sargassaceae), a brown seaweed collected from the Gulf-of-Mannar of Penninsular India. Inhibitory potential of Δ12 oleanenes towards protein tyrosine phosphatase-1B, the critical regulator of insulin-receptor activity were found to be significantly greater (IC50 0.1 × 10-2 and 0.09 × 10-2 mg/mL, respectively) than the standard sodium metavanadate (IC50 0.31 × 10-2 mg/mL). Fridooleanene triterpenoids displayed greater antioxidant activities (IC50DPPH 0.16-0.18 mg/mL) than the commercially available antioxidants, butylated hydroxytoluene and α-tocopherol (IC50DPPH 0.25 and 0.63 mg/mL, respectively). In general, the oxygenated labdane diterpenoids displayed significantly lesser antioxidant and tyrosine phosphatase-1B inhibitory properties than those exhibited by the fridooleanenes. Bioactivities of the titled compounds were primarily determined by the electronic and lipophilic parameters and not by the steric descriptors. Molecular docking simulations and kinetic studies were employed to describe the tyrosine phosphatase-1B inhibitory mechanism. The previously undescribed fridooleanene triterpenoids might be used as potential anti-hyperglycaemic pharmacophore leads to reduce the risk of elevated postprandial glucose levels.