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

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Title Macrocyclic lactones from seafood Amphioctopus neglectus: Newly described natural leads to attenuate angiotensin-II induced cardiac hypertrophy
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Creator Joy,Minju
Krishnan,Soumya
Chakraborty,Kajal
 
Subject Amphioctopus neglectus
Macrocyclic lactone
Anti-hypertension
Angiotensin converting enzyme
Molecular docking simulations
Angiotensin-II induced cardiac hypertrophy
 
Description Not Available
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.
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Date 2021-09-18T04:42:37Z
2021-09-18T04:42:37Z
2019
 
Type Article
 
Identifier Not Available
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http://krishi.icar.gov.in/jspui/handle/123456789/64374
 
Language English
 
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Publisher Not Available