In vitro arginase inhibitory effect of two Tunisian Artemisia species

Arginase is the responsible metalloenzyme for the conversion of L-arginine to L-ornithine and urea. Many studies performed these last years showed that excessive arginase activity in mammals is associated with an endothelial dysfunction leading to various diseases including hypertension. Moreover compelling evidence emerged that pharmacological arginase inhibitors hold great promise as new drugs for the treatment of these diseases [1] and at the same time, evidences suggest that natural substances from plants might constitute a promising source for new arginase inhibitors [2].

In traditional medicine, several Artemisia species are used for the treatment of hypertension and cardiovascular disorders [2].With the aim to find new arginase inhibitors from natural sources, we studied two native Tunisian species of Artemisia: A. campestris and A. herba alba. Six different crude extracts were prepared by maceration using petroleum ether, dichloromethane and methanol as extraction solvents. Then the extracts were evaluated in vitro for their capacity to inhibit liver bovine arginase I activity. All the chloromethylenic and methanolic extracts showed interesting activities with inhibition percentages reaching about 50% at 100 µg/mL. On the basis of the chromatographic profiles of these extracts, we performed phytochemical studies on the two chloromethylenic fractions. Several of the isolated compounds possess a flavonoid skeleton, which is not surprising in this genus. Moreover, considering that some flavonoids are known for their inhibitory properties on arginase [2], we hypothesized that these compounds could be responsible for the activity of the studied extracts. In conclusion, through this study it has been shown that chloromethylenic crude extracts from A. campestris and A. herba alba could constitute a source of potential arginase inhibitors. Further structural elucidation and arginase inhibitory evaluation on isolated compounds will aim to identify the active compounds.

Keywords: Arginase inhibitors, Artemisia, hypertension, cardiovascular diseases, natural sources.

References:

[1] Caldwell RB, Toque HA, Narayanan SP, Caldwell RW. Arginase: an old enzyme with new tricks. Trends Pharmacol Sci 2015; 36: 395 – 405

[2] Girard-Thernier C, Pham TN, Demougeot C. The promise of plant-derived substances as inhibitors of arginase. Mini Rev Med Chem 2015; 15: 798 – 808

[3] Ben-Nasr H; Ben Abderrahim MA; Salama M; Ksouda K; Zeghal KM. Potential phytotherapy use of Artemisia plants: insight for anti-hypertension. J Appl Pharm Sci 2013; 3:120 – 125