Arginase inhibitory properties of flavonoid compounds from the leaves of Mulberry (Morus alba, Moraceae)

Abstract

Objectives We aimed to isolate and identify bioactive molecules from Morus alba (Moraceae) leaves having arginase inhibitory activity towards the combat of clinical outcomes related to endothelial dysfunction. Method Extraction and isolation were carried out by successive macerations, prepurification by using a Solid Phase Extraction (SPE) and separation using preparative PLC. The structures of the isolated components were established and confirmed by spectroscopic analyses, including the ESI-HRMS and NMR spectroscopic investigations. Biological evaluation was performed by using an in vitro assay with liver bovine purified arginase and by an ex vivo aortic ring study. Key findings We demonstrated that a phenolic extract from the leaves of M. alba possesses mammalian arginase inhibitory capacities. Investigation of the chemical constituents of its leaves results in the isolation and identification of ten compounds investigated in vitro for their arginase inhibitory capacities. Four compounds showed significant inhibition of arginase, with percentage inhibition ranging from 54% to 83% at 100 µm. In isolated rat aortic rings incubated with NO synthase inhibitor, Luteolin-7-diglucoside compound (2) was able to increase acetylcholine-induced relaxation. Conclusions These results demonstrated the attractive ability of M. alba to be a potential source for the discovery of new active products on vascular system.

Arginase as a Potential Biomarker of Disease Progression: A Molecular Imaging Perspective

“…The treatment of atherosclerosis-susceptible mice models with this flavonoid [ 145 ] was shown to increase the production of NO • and to improve vascular function. More recently, several flavonoids have also been extracted from the leaves of Mulberry ( Morus alba ) and showed arginase IC50 values ranging from 64.1 µm to 177.2 µm [ 209 ]…”

“…The treatment of atherosclerosis-susceptible mice models with this flavonoid [145] was shown to increase the production of NO • and to improve vascular function. More recently, several flavonoids have also been extracted from the leaves of Mulberry (Morus alba) and showed arginase IC50 values ranging from 64.1 µm to 177.2 µm [209] Beyond the moderate IC 50 values for arginase inhibition and the lack of isoform selectivity, all the above-mentioned plant-derived compounds have potent antioxidant activity due to the presence of a dihydroxyphenyl group in their structures, providing potential scaffolds and structural diversity for the design of new therapeutic agents targeting arginase. Furthermore, the intrinsic fluorescence emission properties in some of these natural compounds may be explored, together with optical imaging techniques, to evaluate the arginase function or expression in cell culture or tissue samples [210,211].…”

Fisetin, a major component derived from mulberry (Morus australis Poir.) leaves, prevents vascular abnormal contraction

“…In contrast, luteolin is a known constituent of mulberry leaves that can improve vascular function by inhibiting arginase, thereby improving vascular endothelial function. 32 However, to the best of our knowledge, there are no reports on the preventive effect of either compound on vascular abnormal contraction. Therefore, we investigated the effect of fisetin in preventing abnormal contractions.…”

“…Fisetin regulates vascular contraction by inhibiting the activity of Rho kinase in a vascular endothelial cell‐independent manner, 31 although no study has isolated fisetin from mulberry leaves. In contrast, luteolin is a known constituent of mulberry leaves that can improve vascular function by inhibiting arginase, thereby improving vascular endothelial function 32 . However, to the best of our knowledge, there are no reports on the preventive effect of either compound on vascular abnormal contraction.…”

Kuwanons, Promising inhibitors against the ACE-2, main protease of SARS-CoV-2 and falcipan-2 using molecular docking

“…Various parts of the mulberry plant have paramount signi cance for humans due to the presence of natural compounds such as avonoids, polyphenols, alkaloids, terpenoids, steroids, and anthocyanins resveratrol, quercetin rutin, deoxynojirimycin (DNJ). (Nomura and Fukai 1981;Nomura, Hano et al 2009;Akande, Falade et al 2020;Arraki, Totoson et al 2020;Gao, Zhang et al 2020;Liu, Yan et al 2020) In addition to the aforementioned bioactive phytochemicals, mulberry is also a rich source of Kuwanons. (Ramappa, Srivastava et al 2020) Kuwanons are the natural isoprenylated avonoids considered to be formed via an enzymatic Diels-Alder type reaction between an isoprenyl portion of an isoprenylphenol as the diene and and a, b-double bond of chalcone as the dienophile.…”