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Adverse side effects reported for the use of statin drugs provided insights to develop potential anti-dyslipidemic derivatives from natural origin. The objective of the work was to develop the marine-derived polysaccharides attenuating 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), and as prospective natural anti-dyslipidemic leads. Physical and chromatographic purification methods were used to isolate the polygalactofucan from the marine macroalga Sargassum wightii and β-(2-deoxy)-amino-substituted glucopyrananan from a marine crustacean. Glycosidic linkage analysis by the process of methylation was used for structural elucidation of the polygalactofucan, and the methylated and partially methylated alditol acetates were characterized using extensive spectroscopic experiments. The polysaccharide composite constituting the titled polysaccharide motifs showed significant HMGCR inhibitory potential (IC90 0.12 mg mL−1) and an increase in HMG-CoA/mevalonate ratio (1.68 mg dL−1) compared with the high-fat diet (HFD)-treated animals (1.04 mg dL−1), which recognized its hypo-lipidemic efficacy. In vivo results demonstrated about 70% reduction in the triglyceride levels with the concomitant increase (~39%) of hepatic lipoprotein lipase (LPL) activity in the HFD-fed Wistar rats treated with 500 mg kg−1 body weight. The results illustrated the use of marine-derived polygalactofucan composite as potential anti-dyslipidemic agent. [ABSTRACT FROM AUTHOR]

A sulfated polygalactopyranosyl-fucopyranan characterized as ∙∙∙∙ → 1)-α-Fucp-(2SO3−)-(3 → 1)-α-Fucp-(2SO3−)-(4 → 1)-β-Galp-(4 → 1)-β-Galp-(4 → ∙∙∙∙ was isolated from the brown seaweed Sargassum wightii and evaluated for pharmacological properties with reference to antioxidant, anti-inflammatory, antidiabetic, and antihypertensive activities using different in vitro models. The sulfated polygalactopyranosyl-fucopyranan displayed potential di(phenyl)-(2,4,6-trinitrophenyl) iminoazanium (DPPH), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS+) radical scavenging, and Fe2+ ion chelating activities (IC90 ~ 1 mg mL−1). The studied polysaccharide displayed higher anti-inflammatory selectivity towards inducive pro-inflammatory enzyme cyclooxygenase-2 (COX-2, IC90 1.13 mg mL−1) than constitutive cyclooxygenase-1 (COX-1, IC90 > 1.20 mg mL−1) resulting in greater selectivity index (IC90 COX-2/COX-1, 0.93) than synthetic non-steroidal anti-inflammatory drug aspirin (0.88) and also showed potent lipoxygenase-5 inhibition (LOX-5, IC90 1.02 mg mL−1). The studied polysaccharide displayed significantly higher (P < 0.05) antidiabetic properties compared to the antidiabetic agents acarbose and diprotein-A in terms of α-amylase (IC90 0.93 mg mL−1), α-glucosidase (IC90 1.48 mg mL−1), and dipeptidyl peptidase-4 (IC90 0.11 mg mL−1) enzyme inhibition potentials. The sulfated polygalactopyranosyl-fucopyranan also displayed potential antihypertensive activity with reference to angiotensin-converting enzyme-I inhibitory activity (IC90 0.2 mg mL−1). Extensive spectroscopic experiments in conjugation with monosaccharide compositional analysis attributed (1 → 3)-linked α-fucopyranose units in the polygalactofucan chain with C-2 sulfation and C-4 substituents as O-acetyl/O-methyl/(1 → 4)-linked β-galactopyranose. The previously undescribed sulfated polygalactopyranosyl-fucopyranan could function as a potential pharmacophore lead against inflammation, type 2 diabetics, hypertension and utilization as natural antioxidant. [ABSTRACT FROM AUTHOR]