Arginase II inhibitory activity of flavonoid compounds from Scutellaria indica

Abstract

Arginase II has recently reported as a novel therapeutic target for the treatment of cardiovascular diseases such as atherosclerosis. In the course of screening plants used in natural medicines as arginase II inhibitory activity, a methanol extract of Scutellaria indica showed significant inhibitory effect. Further fractionation and repeated column chromatography led to the isolation of a new flavan-type (1), and seven known compounds (2–8). The chemical structures of isolated compounds were elucidated based on extensive 1D and 2D NMR spectroscopic data. The isolates 1–8 were investigated in vitro for their arginase II inhibitory activity using enzyme solution prepared from kidney of anesthetized C57BL/6 mice. Compounds 3 and 5 significantly inhibited arginase II activity with IC50 values of 25.1 and 11.6 μM, respectively, whereas the other compounds were apparently inactive.

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“…ARG isoforms are encoded by homologous genes that are mapped in distinct chromosomes (ARG 1 in chromosome 6q23 and ARG 2 in 14q24) [27,36,[53][54][55][56]. A genetic sequencing study that was performed with human kidney tissue detected that the ARG 2 sequence was 58 % homologous to that of ARG 1 [49], whereas human and mouse ARG 1 have 87 % of the sequence in common [27].…”

“…Of the secondary metabolites that have been isolated from plants, polyphenols have been extensively tested against ARG as a tool to control diseases attributed with the advancement of ED [11,25,27,29,36,38].…”

“…Furthermore, the hydroxyl in C5′ (catechol group) is essential to the inhibitory activity as well as the α bond between C2-C1′, which increases the activity (▶ Fig. 5) [34,36]. Based on the in vitro results obtained by Kim et al [36], who tested eight flavonoid-type substances isolated from a methanolic extract of Scutellavia indica L. in relation to ARG 2 from mouse kidney homogenate, another group of researchers sought to perform more in-depth in vivo research regarding the anti-ARG properties of the substance TDF, which had been previously isolated.…”

“…5) [34,36]. Based on the in vitro results obtained by Kim et al [36], who tested eight flavonoid-type substances isolated from a methanolic extract of Scutellavia indica L. in relation to ARG 2 from mouse kidney homogenate, another group of researchers sought to perform more in-depth in vivo research regarding the anti-ARG properties of the substance TDF, which had been previously isolated. In that study, the authors used a hyperlipidemia model to demonstrate that TDF inhibited both ARG 1 (IC 50 of 12.18 µM) and ARG 2 (IC 50 of 11.86 µM) in a noncompetitive manner, simultaneously increasing NO levels by the phosphorylation and dimerisation of eNOS, as well as indicating an improvement in vascular function in normal mice that received a standard diet, and also ApoE -/-mice fed on a high cholesterol diet [96].…”

“…With regard to the latter point, special attention has been paid to substances belonging to the class of polyphenols [26,29,[34][35][36][37][38]. Therefore, this article presents recent research regarding the search for new ARG inhibitors derived from medicinal plants with a potential therapeutic application in the fight against diseases related to the development of ED, as well as seeking to increase interest in the development of promising drugs in this field.…”