Sulfated N-acetylglucosamino-glucuronopyranosyl-arabinopyranan from seafood Amphioctopus neglectus attenuates angiotensin-II prompted cardiac hypertrophy

• Published in: International journal of biological macromolecules 2020-11, Vol.163, p.1223-1232
• Main Authors: Chakraborty, Kajal, Krishnan, Soumya, Joy, Minju
• Format: Article
• Language: English
• Subjects: Acetylglucosamine - chemistry; Acetylglucosamine - isolation & purification; Acetylglucosamine - pharmacology; Amphioctopus neglectus; Angiotensin II - adverse effects; Angiotensin II - metabolism; Angiotensin-II induced cardiac hypertrophy; Animals; Antihypertensive Agents - chemistry; Antihypertensive Agents - isolation & purification; Antihypertensive Agents - pharmacology; Antioxidants - chemistry; Antioxidants - isolation & purification; Antioxidants - pharmacology; Cardiomegaly - drug therapy; Cardiomegaly - etiology; Cardiomegaly - metabolism; Cephalopoda - chemistry; Disease Susceptibility; Humans; Magnetic Resonance Spectroscopy; Molecular Docking Simulation; Molecular Dynamics Simulation; Monosaccharides - chemistry; Peptidyl-Dipeptidase A - metabolism; Polysaccharides - chemistry; Polysaccharides - isolation & purification; Seafood - analysis; Structure-Activity Relationship; Sulfated N-acetylglucosamino-glucuronopyranosyl-arabinopyranan; Sulfates - chemistry
• ISSN: 0141-8130; 1879-0003
• DOI: 10.1016/j.ijbiomac.2020.07.037

Angiotensin converting enzyme (ACE) is a multifunctional enzyme involved in translation of angiotensin-I (AngI) to vasoconstrictor angiotensin-II (AngII). A sulfated N-acetylglucosamino-glucuronopyranosyl-arabinopyranan characterized as poly-[(2-methoxy-β-arabinopyranosyl)-(1 → 3)-(β-glucurono)-(1 → 4)-(2-acetamido-2-deoxy-3,6-di-O-sulfonato-β-glucopyranose)] was purified and reported first time from the edible portion of Amphioctopus neglectus and evaluated for various pharmacological properties. The polysaccharide exhibited potential ACE attenuation property (IC50 0.11 mg mL−1), whereas molecular docking simulations displayed its efficient binding at the ACE active site with lesser inhibitory constant (Ki) of 17.36 nM and binding energy (−10.59 kcal mol−1). The in-vitro analysis showed that the studied polysacharide attenuated AngII prompted cardiac hypertrophy at 50 μg mL−1 in the cardiomyoblast cells, whereas 48% reduction in cellular surface area with extended viability could be correlated with anti-hypertrophic properties of the studied polysaccharide. The sulfated N-acetylglucosamino-glucuronopyranosyl-arabinopyranan purified from A. neglectus could function as a prospective functional lead against the pathophysiological conditions leading to hypertension. •Sulfated polyglucosamino arabinopyran was isolated from Amphioctopus neglectus.•The polysaccharide showed angiotensin converting enzyme inhibitory activity.•Purified polysaccharide attenuates angiotensin-2 induced cardiac hypertrophy.•Molecular docking simulation showed enzyme-ligand interaction in hypertension model.•The polysaccharide from A. neglectus could be used as potent antihypertensive agent.