Macrocyclic lactones from seafood Amphioctopus neglectus: Newly described natural leads to attenuate angiotensin-II induced cardiac hypertrophy

Chakraborty, Kajal and Krishnan, Soumya and Joy, Minju (2019) Macrocyclic lactones from seafood Amphioctopus neglectus: Newly described natural leads to attenuate angiotensin-II induced cardiac hypertrophy. Biomedicine and Pharmacotherapy, 110. pp. 155-167.

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Abstract

Amphioctopus neglectus (Family: Octopodidae) is recognised as culinary delicacy in many cultures and a common sea food item on the Mediterranean and Asian coasts. Bioassay-directed fractionation of ethyl acetate/methanol extract of A. neglectus ensued in the characterisation of four previously undescribed macrocyclic lactones (1-4). These compounds exhibited potential radical-scavenging capacities (IC50 0.95–1.73 mM) along with anti-hypertensive activities (IC50 1.12–2.34 mM) against angiotensin converting enzyme (ACE). The optimum binding affinity of compound 2 (−9.84 kcal mol−1) bearing furo[1,4,8]trioxacyclohexadecine-12,19-dione moiety with ACE, along with its permissible hydrophobic-hydrophilic balance, manifested towards its greater anti-hypertensive activity compared to other analogues. The compound 2, with lesser values of the inhibitory constant (Ki = 1.0 mM) towards ACE, was found to bind more effectively to the enzyme in a non-competitive manner, and could describe the greater inhibitory ramifications than those displayed by other compounds (Ki >1.1 mM). The ex-vivo studies revealed that compound 2 imparted protective effects against angiotensin-II induced cardiac hypertrophy at 25 μg mL−1 on H9C2 cell lines, wherein about 34 percent decrease in cell area with increase in viability could be attributed to anti-hypertrophic effects of the compound administrated. These results confirmed that the protective effect of the isolated macrocyclic lactones is mediated by enhancement of anti-oxidant defense systems, which subsequently attenuates the hypertensive related disorders.

Item Type:	Article
Uncontrolled Keywords:	Amphioctopus neglectus; Macrocyclic lactone; Anti-hypertension; Angiotensin converting enzyme; Molecular docking simulations; Angiotensin-II induced cardiac hypertrophy
Subjects:	Biochemistry > Bioactive compounds Biochemistry
Divisions:	CMFRI-Kochi > Marine Biotechnology, Fish Nutrition and Health Division Subject Area > CMFRI > CMFRI-Kochi > Marine Biotechnology, Fish Nutrition and Health Division CMFRI-Kochi > Marine Biotechnology, Fish Nutrition and Health Division Subject Area > CMFRI-Kochi > Marine Biotechnology, Fish Nutrition and Health Division
Depositing User:	Arun Surendran
Date Deposited:	21 Nov 2018 04:50
Last Modified:	15 Mar 2023 11:07
URI:	http://eprints.cmfri.org.in/id/eprint/13241

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