In Silico Studies and In Vivo MAO_A Inhibitory Activity of Coumarins Isolated from Angelica archangelica Extract: An Approach toward Antidepressant Activity

Abstract

The current investigation was aimed at in vivo MAOA inhibitory activity of coumarins angelicin, bergapten, and scopoletin isolated from the roots of Angelica archangelica. The isolated compounds were screened for MAOA (pdb ID 2Z5y) binding through molecular docking studies. The molecular docking results displayed that bergapten has a maximum affinity for MAOA, followed by angelicin and scopoletin. In silico prediction of physicochemical parameters indicated that maximum blood–brain barrier (BBB) permeability was observed with angelicin (2.3), followed by bergapten (2.0) and least with scopoletin (0.644). In consonance to the results of molecular docking studies, appreciable in vivo antidepressant activity of angelicin and bergaptan was observed over the mouse model of reserpine-induced depression. The modulation of MAOA in the antidepressant effect of extract and its isolated fractions was also determined. Biochemical examination of the brain tissue indicated that bergapten has maximum MAOA inhibitory activity while scopoletin fails to inhibit brain MAOA.

Bergapten: A review of its pharmacology, pharmacokinetics, and toxicity

“…In reserpine‐induced depression of mice model, bergapten was proved to have the ability to inhibit MAOA activity. In consonance with the results of inhibiting MAOA activity in vivo, the molecular docking results displayed that bergapten has a maximum affinity for MAOA (Kaur et al, 2020). Therefore, the above studies indicated that bergapten could be used to treat some brain diseases, and the related mechanisms called for further research.…”

Unravelling high-affinity binding compounds towards transmembrane protease serine 2 enzyme in treating SARS-CoV-2 infection using molecular modelling and docking studies

“…Absorption, Distribution, Metabolism, Excretion/Toxicity (ADME/T) attributes of the selected compounds were evaluated using Swiss-ADME tool ( Kaur et al, 2020 ). These played an important role in analyzing drug filtration and predict other pharmacodynamic parameters of complex consequentially aiding towards determination of potent TMPRSS2 inhibitors.…”

Understanding the phytochemistry and molecular insights to the pharmacology of Angelica archangelica L. (garden angelica) and its bioactive components

“…The structures of various chemical constituents of essential oils of A. archangelica are given in Figure 1. The variability in the percentage content of different essential oil constituents has been observed with variations in growing altitudes, analysis techniques, genetic diversity, harvesting conditions, and geographic diversity (Kaur et al, 2020a). The biological activities attributed to essential oils include antioxidant activity, antiinflammatory activity, antimicrobial, antiviral, and immunotoxin (Sowndhararajan, Deepa, Kim, Park, & Kim, 2017; Voon, Bhat, & Rusul, 2012).…”

“…The composition of coumarins varies according to the type of raw material, method of extraction, geographic diversity, extraction conditions, and growing conditions (Forycka & Buchwald, 2019). Coumarins are documented for a variety of pharmacological activities in preclinical investigations, such as analgesic (Kaur et al, 2020a), antiinflammatory activity (Grover & Jachak, 2015), anti‐anxiety activity (Budzynska et al, 2012; Kumar et al, 2013), antioxidative activity (Cao, Zhang, Wang, & He, 2014; Kaur, Garg, et al, 2020a; Kaur, Singh, et al, 2020b), and antiseizure activity (Luszczki et al, 2007; Luszczki, Andres‐Mach, Gleńsk, & Skalicka‐Woźniak, 2010).…”