In Vitro Mammalian Arginase Inhibitory and Antioxidant Effects of Amide Derivatives Isolated from the Hempseed Cakes (Cannabis sativa)

Abstract

In an effort to identify novel inhibitors of arginase, a phytochemical study was performed on hempseed cakes (Cannabis sativa L.). It led to the isolation of a new lignanamide, cannabisin I (

1), together with seven known lignanamides, cannabisins A, B, C, F, M, 3,3′-demethylgrossamide, grossamide, and two phenylpropanoid amides, N-trans-caffeoyltyramine and N-trans-caffeoyloctopamine, among which was later identified for the first time from C. sativa. Their structures were elucidated by comprehensive analysis of NMR spectroscopy and mass spectrometry data. These compounds were evaluated on mammal arginase (purified liver bovine arginase), showing that N-trans-caffeoyltyramine exhibited the higher activity with an IC₅₀ value of 20.9 µM, which remains, however, less active than the reference compound S-(2-boronoethyl)-l-cysteine (IC₅₀ = 4.3 µM). Radical scavenging capacity of these compounds was determined by the ORAC-FL method. All tested cannabisins displayed antioxidant activity close to or better than the reference compounds. N-trans-Caffeoyltyramine has both arginase inhibitory property and antioxidant capacity.

Key words

Cannabis sativa - Cannabaceae - hempseed - cannabisins - lignanamides - caffeoyl derivatives - arginase - antioxidant

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