In vitro leishmanicidal potential and silico study of flavonoids isolated from Pistacia integerrima Stew ex Brandis

Objective: Medicinal plants are the mainstay of various chemical constituents responsible for curing or mitigating different pathological and non-pathological health issues. In this regard, the current research work was subjected to finding the best effective, new and safe leishmanicidal molecules. Pistacia integerrima is an important medicinal plant growing in Asia with various ethnopharmacological uses such as skin, respiratory and hepatic disorders. The folklore of this plant in skin problems encouraged us to evaluate the isolated compounds for leishmanicidal activity.Methods: In the current study, whole ethyl acetate extract was subjected to chromatographic analysis affording two flavonoid constituents, namely naringenin (1) and 3,5,4'-trihydroxy-7-methoxy-flavanone (2). The extract and isolated constituents were tested for leishmanicidal activity. Both compounds were docked into the target binding site (PDB ID: 5HJ9) using MOE 2016. Arginase was taken as the targeted enzyme which is an important enzyme for leishmania species' survival. Arginase up-regulates amastin that impacts amastigote replication and survival. This approach aimed to explore the binding modes of the two isolated flavonoids and to predict their inhibitory activity against arginase.Results: The two flavonoid compounds isolated from P. integerrima were evaluated for their antileishmanial activity. Compounds 1 and 2 were tested at a concentration of 5 lg/mL against the selected Leishmanial species. The percent inhibition was 70.43 and 74.76 regarding compounds 1 and 2, respectively with IC50 of 29.43 and 16.43 lM. The reference standard drug used, amphotericin-B, displayed the highest leishmanicidal effect (IC50 of 0.22 lM) with 84.09 % inhibition at half concentration compared to compounds 1 and 2. The molecular docking studies of these two compounds and the standard drug were performed in MOE software. According to the findings, compound 1, naringenin, docked well in the binding site, with a docking score of -9.28 followed by compound 2, 3,5,4'-trihydroxy-7-methoxy-flavanone with a docking score of -8.37.Conclusion: Both of the tested samples demonstrated excellent leishmanicidal effects. This pharmacological inhibitory profile provides a strong scientific profile to the folklore of Pistacia integerrima in the treatment of skin disorders especially leishmanial. A further mechanistic study is recommended to find the extract target responsible for the said activity. (c) 2023 The Author(s). Published by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).