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. 2024 Feb 14;29(4):849.
doi: 10.3390/molecules29040849.

Chemical Composition Antioxidant and Anti-Inflammatory Activities of Myrtus communis L. Leaf Extract: Forecasting ADMET Profiling and Anti-Inflammatory Targets Using Molecular Docking Tools

Samia Belahcene  1 , Widad Kebsa  2 , Tomilola Victor Akingbade  3 , Haruna Isiyaku Umar  3 , Damilola Alex Omoboyowa  4 , Abdulaziz A Alshihri  5 , Adel Abo Mansour  6 , Abdulaziz Hassan Alhasaniah  7 , Mohammed A Oraig  8 , Youssef Bakkour  5 , Essaid Leghouchi  1
Affiliations

Chemical Composition Antioxidant and Anti-Inflammatory Activities of Myrtus communis L. Leaf Extract: Forecasting ADMET Profiling and Anti-Inflammatory Targets Using Molecular Docking Tools

Samia Belahcene et al. Molecules. .

Abstract

Compounds derived from natural sources continue to serve as chemical scaffolds for designing prophylactic/therapeutic options for human healthcare. In this study, we aimed to systematically unravel the chemical profile and antioxidant and anti-inflammatory activities of myrtle methanolic extract (MMEx) using in vitro, in vivo, and in silico approaches. High levels of TPC (415.85 ± 15.52 mg GAE/g) and TFC (285.80 ± 1.64 mg QE/g) were observed. Mass spectrophotometry (GC-MS) analysis revealed the presence of 1,8-cineole (33.80%), α-pinene (10.06%), linalool (4.83%), p-dimethylaminobenzophenone (4.21%), thunbergol (4%), terpineol (3.60%), cis-geranyl acetate (3.25%), and totarol (3.30%) as major compounds. MMEx induced pronounced dose-dependent inhibition in all assays, and the best antioxidant activity was found with H2O2, with an IC50 of 17.81 ± 3.67 µg.mL-1. MMEx showed a good anti-inflammatory effect in vivo by limiting the development of carrageenan-induced paw edema. The pharmacokinetic profiles of the active molecules were determined using the SwissADME website, followed by virtual screening against anti-inflammatory targets including phospholipase A2 (PLA-2), cyclooxygenase-2 (COX-2), tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), and NF-κB. A pharmacokinetic study revealed that the molecules have good absorption, distribution, and metabolism profiles, with negative organ toxicity. Among the compounds identified by GC-MS analysis, pinostrobin chalcone, cinnamyl cinnamate, hedycaryol, totarol, and p-dimethylaminobenzophenone were observed to have good binding scores, thus appreciable anti-inflammatory potential. Our study reveals that MMEx from Algerian Myrtus communis L. can be considered to be a promising candidate for alleviating many health complaints associated with oxidative stress and inflammation.

Keywords: ADMET; Myrtus communis L.; anti-inflammatory; antioxidant; bioactive molecules; methanolic extract; molecular docking.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Representative GC-MS chromatogram of Myrtus communis L. methanolic extract. Peak numbers correspond to compound numbers in Table 2.
Figure 2
Figure 2
Antioxidant properties of MMEx and ascorbic acid (reference) by (A) DPPH and (B) H2O2, and their IC50 values (b, d, f, h, and j, respectively). Data are expressed as mean ± SEM (n = 3). Ns, no significant difference. * p < 0.05, ** p < 0.01, *** p < 0.001. (t test) using GraphPad Prism 8 for Microsoft Office 10.
Figure 3
Figure 3
Antioxidant properties of MMEx and ascorbic acid (reference) by (A) hydroxyl radical, (B) ABTS, and (C) FRAP and their IC50 values. Data are expressed as mean ± SEM (n = 3). ns, no significant difference. * p < 0.05, ** p < 0.01, *** p < 0.001 (t-test) using GraphPad Prism 8 for Microsoft Office.
Figure 4
Figure 4
Inhibition of heat-induced BSA denaturation. Data are expressed as mean ± SEM (n = 3). DCF was used as positive control. Mean values of samples showing significant differences compared to control (untreated 5% BSA water solution). *** p < 0.001 (t-test) using GraphPad Prism 8 for Microsoft Office. IC50 analysis performed using GraphPad Prism 8.
Figure 5
Figure 5
(A) Influence of MMEx (25 and 50 mg/kg) on Car-induced paw edema. Data represent percentage of increased paw edema (mean ± SEM) in different groups. (B) Inhibition of paw edema in rats treated with myrtle methanolic extract. Ns, no significant difference. * p < 0.05, ** p < 0.01, *** p < 0.001 (t test) using GraphPad Prism 8 for Microsoft Office. IC50 analysis performed using GraphPad Prism 8.
Figure 6
Figure 6
Chemical structure of five compounds from myrtle methanolic extract that presented good binding affinity against key anti-inflammatory proteins (Cox-2, IL-1β, NF-κB, PLA2, and TNF-α). (A) pinostrobin chalcone; (B) cinnamyl cinnamate; (C) hedycaryol; (D) totarol; (E) p-dimethylaminobenzophenone.
Figure 7
Figure 7
Binding interaction of COX-2 with (A) diclofenac, (B) cinnamyl cinnamate, and (C) pinostrobin chalcone. Purple indicates pi-sigma, violet indicates pi-pi stacked, and light pink indicates alkyl/pi-alkyl.
Figure 7
Figure 7
Binding interaction of COX-2 with (A) diclofenac, (B) cinnamyl cinnamate, and (C) pinostrobin chalcone. Purple indicates pi-sigma, violet indicates pi-pi stacked, and light pink indicates alkyl/pi-alkyl.
Figure 8
Figure 8
Binding interaction of IL-1β with (A) diclofenac, (B) hedycaryol, and (C) totarol.
Figure 8
Figure 8
Binding interaction of IL-1β with (A) diclofenac, (B) hedycaryol, and (C) totarol.
Figure 9
Figure 9
Binding interaction of NF-κB with (A) diclofenac, (B) cinnamyl cinnamate, and (C) totarol.
Figure 9
Figure 9
Binding interaction of NF-κB with (A) diclofenac, (B) cinnamyl cinnamate, and (C) totarol.
Figure 10
Figure 10
Binding interaction of phospholipase A2 with (A) diclofenac, (B) p-dimethylaminobenzophenone, and (C) totarol.
Figure 11
Figure 11
Binding interaction of TNF-α with (A) diclofenac, (B) p-dimethylaminobenzophenone, and (C) totarol.
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