First report of chromenyl derivatives from spineless marine cuttlefish Sepiella inermis : Prospective antihyperglycemic agents attenuate serine protease dipeptidyl peptidase‐IV

Abstract

Spineless marine cuttlefish Sepiella inermis has been considered as a popular dietary cephalopod species in Asian and Mediterranean coasts. Bioassay‐directed purification of organic extract of S. inermis ensued in the characterization of two chromenyl derivatives. The studied compounds exhibited significantly greater antioxidant potencies (IC50 ≤ 0.5 mg/ml) when compared with α‐tocopherol. The substituted 1H‐isochromenyloxy‐11‐hydroxyethyl pentanoate isoform (compound 1) efficiently inhibited the carbolytic enzymes along with key regulator of insulin secretion dipeptidyl peptidase‐IV (IC50 0.16 mg/ml). The molecular docking simulations displayed optimum binding affinity of the compound 1 (−10.01 kcal/mol) with dipeptidyl peptidase‐IV and lesser inhibition constant (Ki 46.41 nM), which along with its permissible hydrophobic‐hydrophilic balance (log Pow ~ 2) appeared to play significant roles in its greater antihyperglycemic activity compared to other studied chromenyl isoform. The greater antioxidant and antidiabetic properties of compound 1 could be utilized as an important natural lead against hyperglycemic‐related disorders. Practical applications The edible spineless marine cuttlefish Sepiella inermis are ubiquitously available in Asian and Mediterranean coasts. The sequential chromatographic purification of the organic extract of S. inermis led to the identification of two pure chromenyl chemotypes. The metabolites with substituted 1H‐isochromenyloxy‐11‐hydroxyethyl pentanoate isoform (compound 1) displayed potential antioxidative and antihyperglycemic activities compared to the chemotype (2) bearing 3H‐isochromen‐5‐yl moiety. The attenuating potential of chromenyl chemotype 1 against carbohydrate hydrolyzing enzymes and insulin secretion regulator attributed towards its efficiency as an important natural lead against postprandial hyperglycemia and incretin hormone regulation to maintain glucose homeostasis in the biological system. The chromenyl metabolites isolated from S. inermis could be utilized as a functional food ingredient in the nutraceutical formulations against hyperglycemic‐related disorders.

High-value compounds from the molluscs of marine and estuarine ecosystems as prospective functional food ingredients: An overview

“…Spineless cuttlefish, S. inermis was found to possess four chromenyl derivatives, named as methyl 7-ethyl-hexahydro-8a-methyl-2 H -chromene-4-carboxylate 10 and methyl 1-acetoxy-hexahydro-3-methyl-3-propyl-1 H -isochromene-4-carboxylate 11 with selective in vitro antioxidative/anti-inflammatory potentials ( Krishnan, Chakraborty, & Joy, 2020 ). The same species was reported for 11-(hexahydro-8-methoxy-4-methyl-1 H -isochromen-4-yloxy)-11-hydroxyethyl pentanoate 12 and methyl 9-(tetrahydro-3-oxo-3 H -isochromen-5-yl)hexanoate 13 with antioxidative and antihyperglycemic potentials ( Krishnan, Chakraborty, & Joy, 2019 ). A cephalopod mollusc, A. marginatus was reported with antioxidant and anti-inflammatory compounds, such as sterol derivative 14 and octahydroazulenopyrandione 15 ( Chakraborty & Joy, 2018 ).…”

“…*mg/100 g; # mg/g; $ g/100 g; § mg/kg; μg/100 g. a Joy and Chakraborty, 2017a . b Krishnan, Chakraborty, & Joy, 2019 . c Chakraborty, Chakkalakal, & Joseph, 2016 .…”

“…The polyol, durinskiol A from Chelidonura fulvipunctata , mycosporine-like amino acids, aplysiapalythine A-C from A. californica , cytotoxic isonitrile-containing lipid, actisonitrile from A. papillatus , phorboxazole related metabolites from the Indian nudibranch, Aldisa andersoni were also classified as miscellaneous ( Blunt et al, 2006 ; 2007; 2008; 2009; 2010; 2013; 2014; 2015; 2016; 2017; 2018). Chromenoids/isochromenoids from S. inermis ( Krishnan et al, 2019 ), isochromenone/furano-chromene derivatives from P. malabarica ( Joy & Chakraborty, 2017 ) and pyranoids/isochromenoids/spirocyclic ethers from V. cyprinoides ( Joy and Chakraborty, 2018c , Joy and Chakraborty, 2018b ) with anti-inflammatory, antioxidative, and antihyperglycemic potentials were previously described.…”

“…Methanol extract of Cerithidea obtuse (snail) was composed of alkaloids, terpenoids, and flavonoids with potential antidiabetic property (IC 50 value of 36.40 mg/mL) ( Cahyani, Purwaningsih, & Azrifitria, 2015 ). An isochromenyl derivative isolated from S. inermis exhibited efficient inhibition of carbolytic (IC 50 0.19–0.28 mg/mL) and dipeptidyl peptidase-IV enzymes (IC 50 0.16–0.23 mg/mL) ( Krishnan, Chakraborty, & Joy, 2019 ). An antioxidant 1 H -benzochromenone reported from C. ramosus displayed greater inhibitory activity against the carbolytic enzymes (IC 50 ~ 0.72 mM) when compared to the standard acarbose (IC 50 0.43 mM) ( Chakraborty & Salas, 2019 , Chakraborty & Salas, 2019b ).…”

Assessment of the DPP‐IV inhibitory activity of a novel octapeptide derived from rapeseed using Caco‐2 cell monolayers and molecular docking analysis

“…There are many purified oligopeptides isolated from the enzymatic hydrolysates of food protein, such as casein (Zheng et al., 2019), whey protein (Lacroix & Li‐Chan, 2014), cuttlefish (Krishnan, Chakraborty, & Joy, 2019), marine algae (Harnedy, O’Keeffe, & FitzGerald, 2015), soybean (Lammi et al., 2018), rapeseed (Xu et al., 2019), etc., that have DPP‐IV inhibitory activities. Current in vitro enzymatic assays based on the reaction substrate (Gly‐Pro‐p‐nitroanilide) are insufficient and have limitations (Caron, Domenger, Dhulster, Ravallec, & Cudennec, 2017).…”