{"id":61281,"date":"2024-09-30T10:52:28","date_gmt":"2024-09-30T10:52:28","guid":{"rendered":"https:\/\/biomedpharmajournal.org\/?p=61281"},"modified":"2024-10-09T18:29:55","modified_gmt":"2024-10-09T18:29:55","slug":"in-silico-molecular-docking-of-two-bioactive-constituents-quercetin-3-glucuronide-and-quercitrin-from-polygonum-minus-leaves-into-monoamine-oxidase-a-crystal-structure","status":"publish","type":"post","link":"https:\/\/biomedpharmajournal.org\/staging\/vol17no3\/in-silico-molecular-docking-of-two-bioactive-constituents-quercetin-3-glucuronide-and-quercitrin-from-polygonum-minus-leaves-into-monoamine-oxidase-a-crystal-structure\/","title":{"rendered":"In-silico Molecular Docking of Two Bioactive Constituents (Quercetin 3-Glucuronide and Quercitrin) from Polygonum minus Leaves into Monoamine Oxidase-A Crystal Structure"},"content":{"rendered":"\n

Introduction<\/strong><\/p>\n\n\n\n

Molecular docking is a type of computer modelling that predicts the\noptimal binding orientation of two molecules one as a ligand and another as a\nreceptor, when they interact to create a complex which is stable 1<\/sup>.\nThe study of bioactive peptides or chemical medicinal compounds that bind to\nparticular receptors is known as in-silico molecular docking. That demonstrates\nthe binding\u2019s shape, pattern and affinity 2<\/sup>. In-silico approaches\ncan locate prospective binding sites and discover and build novel molecules\nthat can bind to a known site. To find novel drugs, blind docking and virtual\nscreening are frequently used 3<\/sup>. Within the molecular docking\ncommunity, two techniques are particularly prominent. One method employs a\nmatching strategy in which the protein and ligand are described as\ncomplementary surfaces 4<\/sup>. The second technique simulates the docking\nprocess by computing the pairwise interaction energies between the ligand and\nthe protein. Both systems have several advantages 5<\/sup>. There are some\nhydrogen bond donors and also the acceptors in the ligand, which are charged,\ngroups. They interact with oppositely charged side chains in the receptor or\nmight be falling into hydrophobic pockets. It can also be checked that\nhydrophobic groups in the ligand are buried in the receptor’s hydrophobic\npockets 6<\/sup>. In docking, root-mean-square deviation, RMSD value is\nused to compare the docked conformation with the reference confirmation,\nsuccess is typically regarded if its value is less than 2 \u00c5 7,8<\/sup> Docking mostly\ndepends on the hydrophobic contacts and hydrogen bonds which could be formed\nbetween the proteins and ligand. Its main part is interaction sites, which are located\nat discrete positions in space suitable for forming the hydrogen bonds or for\nfilling a hydrophobic pocket. Conventional and non-conventional hydrogen bonds,\npi-pi bonds and other rotatable bonds are also an important part of the results\n9,10<\/sup>. The most likely corresponding intermolecular interactions and binding\nconformations are identified. The protein backbone is represented as a cartoon.\nThe active site residues\nand ligand are shown in the stick representation. The water molecule is\nshown as a white sphere, and hydrogen bonds are shown as dashed lines 11<\/sup>.\nAnother vital part of molecular docking is to determine the amino acid\nresidues, which residues are under the interaction of ligand 12<\/sup>.\nMonoamine oxidases are important in enzymes in brain that break down the\nmonoamines\u2019 through oxidation by changing their amine group with oxygen. Most\ncell types in the body have them linked to the outer membrane of mitochondria.\nBoth monoamine oxidase A and B have long been targeted as a vital therapeutic destination for the\ntreatment of the depression and various neurodegenerative diseases.\nBecause of its participation in the modulation of serotonin, MAO-A is found associated\nwith the depression treatment many times 13<\/sup>. These enzymes belong to\na flavin-containing amine oxidoreductase protein family14<\/sup>. They play\nan important role for the inactivation of monoamine neurotransmitters and the\nbreakdown of monoamines present in food. They have been linked with various\nmental and neurological diseases, which can be treated with the monoamine oxidase inhibitors\n(MAOIs), which prevent MAOs to perform their functions efficiently 15<\/sup>.\nMOE software is a molecular modelling program, it is specifically designed to\nstudy large biological molecules. This software is also designed to use\nsemi-empirical and ab initio quantum mechanics calculations and different force\nfields as well 16<\/sup>.<\/p>\n\n\n\n

Polygonum minus<\/em> Huds is a member of the Polygonaceae\nfamily and commonly referred to as Kesum or laksa leaf as local name in\nMalaysia. It is used as a preventive healthcare agent. Most of these herbs are\nbelieved to be associated with the anti-oxidant activities and have many beneficial effects 17,18<\/sup>.\nThe leaf part of this herb has been reported to have two major flavonoids like\nquercetin-3- glucuronide ((Miquelianin) and quercitrin\n(quercetin-3-rhamnoside) 19<\/sup>.<\/p>\n\n\n\n

The current research aimed to dock the two abundant bioactive\nconstituents of Polygonum minus<\/em> leave extract which are Quercitrin and Quercetin\n3-Glucuronide. This molecular docking study was efficiently performed to\nobserve the binding energy of selected ligands and their interactions with\namino acid residue along with bond types in Monoamine Oxidase (MAO-A)\nstructure.<\/p>\n\n\n\n

Materials and Methods<\/strong><\/p>\n\n\n\n

The docking experiments based on computer aided assistance were carried out by using the crystal structure of MAO-A (PDB ID:2BXR). Docking simulation study of the Bioactive flavonoids of P. minus<\/em>, Tricyclic antidepressant and MAO-A inhibitors were docked with MAO-A structure. Ligand\u2019s formula structures were derived from the PubChem database. Quercitrin also known as Quercetin-3-rhamnoside (Compound CID 5280459), Quercetin-3-glucuronide (Com-pound CID: 5274585), Clorgyline (Compound CID: 4380) (crystal ligand and MAO-A inhibitor), Moclobemide (Compound CID: 4235) (standard MAO-A inhibitor), Amitriptyline (Compound CID: 2160) (Positive control of current study). Ligands were further prepared and docking simulation was finally done by using MOE dock 2015 software, the following published protocol 20<\/sup>.<\/p>\n\n\n\n

Enzyme structures were examined for the missing atoms, bonds and associations.<\/p>\n\n\n\n

Then, hydrogen atoms were added to the structure of MAO-A enzyme. Already bound ligands and water molecules were manually deleted.<\/p>\n\n\n\n

The structures of ligand molecules were taken from the PubChem database and prepared further for docking through MOE software. <\/p>\n\n\n\n

MOE-Alpha Site Finder used to generate the active site.<\/p>\n\n\n\n

Dummy atoms were made up from the obtained alpha spheres.<\/p>\n\n\n\n

All Ligands were docked within the active site of MAO-A enzyme using the MOE Dock with simulated annealing used as the search protocol.<\/p>\n\n\n\n

The least energy conformation was picked and subjected to the\nminimization of energy.<\/p>\n\n\n\n

Finally, the investigation of the 2D and 3D hydrogen-bond linkages was\ncompleted using the Biovia Discovery Studio 4.5 program. This program was used\nto visualise the docking results as an image. This molecular visualization\ngenerates graphical images that help in studying the nature of the hydrogen and\nhydrophobic bonds. This graphical image shows the bond length between\ninteracting atoms of ligands and protein.<\/p>\n\n\n\n

Results and Discussion<\/strong><\/p>\n\n\n\n

Molecular docking was performed by using the Molecular Operating Environment (MOE) software. Clorgyline, Moclobemide, Amitriptyline, Quercetin 3-glucuronide (Miquelianin) and Quercitrin (Quercetin-3-rhamnoside) were docked individually into MAO-A prepared structure. Table 1. shows the results of their docking interactions. The lowest binding energy was selected for an individual binding score which determines the high affinity of a ligand with the MAO-A attachment site. RMSD (bond length) was determined by angstrom (\u00c5). All selected values have less than 2 \u00c5 RMSD values which are under the range of good docking angle values. This table also explains the residues of amino acid which were interacted with different ligands. Further, each docking interaction has been explained individually.<\/strong><\/p>\n\n\n\n

Table 1: Molecular Docking interactions of Ligands into MAO-A <\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n
\n

Name of ligand<\/strong><\/p>\n<\/td>\n

\n

Description<\/strong><\/p>\n<\/td>\n

\n

Binding<\/strong><\/p>\n

Energy<\/strong><\/p>\n<\/td>\n

\n

Rmsd<\/strong><\/p>\n

value<\/strong><\/p>\n<\/td>\n

\n

H-bonding<\/strong><\/p>\n<\/td>\n

\n

Hydrophobic Interactions<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

Conventional<\/strong><\/p>\n<\/td>\n

\n

Carbon-hydrogen<\/strong><\/p>\n<\/td>\n

\n

Alkyl and Pi-alkyl<\/strong><\/p>\n<\/td>\n

\n

Others<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

Amitriptyline<\/p>\n<\/td>\n

\n

Positive control Antidepressant<\/p>\n<\/td>\n

\n

-7.8829<\/p>\n<\/td>\n

\n

1.52<\/p>\n<\/td>\n

\n

–<\/p>\n<\/td>\n

\n

GLY A:443<\/p>\n

TYR A:407<\/p>\n<\/td>\n

\n

LYS A:305, MET A:445, VAL A:303<\/p>\n<\/td>\n

\n

CYS A:406 (\u03c0-sulfur), GLY A:67 (Vander walls), GLY A:66 (\u03c0- \u03c0 stacked), TRP A:397 (amide- \u03c0 stacked)<\/p>\n<\/td>\n<\/tr>\n

\n

Clorgyline<\/p>\n<\/td>\n

\n

Co crystal ligand -re-dock<\/p>\n

MAO-A inhibitor<\/p>\n<\/td>\n

\n

-7.2970<\/p>\n<\/td>\n

\n

1.47<\/p>\n<\/td>\n

\n

–<\/p>\n<\/td>\n

\n

GLN A:215, GLY A:66<\/p>\n<\/td>\n

\n

CYS A:323, ILE A:180,<\/p>\n

ILE A:335, LEU A:337, LYS A:305, PHE A:352, TYR A:407, TYR A:69<\/p>\n<\/td>\n

\n

–<\/p>\n<\/td>\n<\/tr>\n

\n

Moclobemide<\/p>\n<\/td>\n

\n

Standard MAO-A inhibitor<\/p>\n<\/td>\n

\n

-7.0720<\/p>\n<\/td>\n

\n

1.31<\/p>\n<\/td>\n

\n

–<\/p>\n<\/td>\n

\n

GLY A:443, TYR A:69<\/p>\n<\/td>\n

\n

ILE A:180, ILE A:335, MET A:445, TYR A:444<\/p>\n<\/td>\n

\n

–<\/p>\n<\/td>\n<\/tr>\n

\n

Quercitrin <\/p>\n

(Quercetin-3-rhamnoside)<\/p>\n<\/td>\n

\n

Bioactive constituent of P. minus<\/em><\/p>\n<\/td>\n

\n

-8.5182<\/p>\n<\/td>\n

\n

1.15<\/p>\n<\/td>\n

\n

GLN A:215, CYS A:406, GLY A:67, ARG A:51 MET A:445<\/p>\n<\/td>\n

\n

PHE A:352, TYR A:444 GLY A:443<\/p>\n<\/td>\n

\n

TYR A:69<\/p>\n<\/td>\n

\n

TRP A:397 (\u03c0-\u03c0 T-shape)<\/p>\n<\/td>\n<\/tr>\n

\n

Quercetin-3-glucuronide<\/strong><\/p>\n<\/td>\n

\n

Bioactive constituent of P. minus<\/em><\/p>\n<\/td>\n

\n

-8.3633<\/p>\n<\/td>\n

\n

1.29<\/p>\n<\/td>\n

\n

GLY A:443, TYR A:197, MET A:445, ALA A:68, TYR A: 69<\/p>\n<\/td>\n

\n

GLY A: 67, TYR A:444<\/p>\n<\/td>\n

\n

ILE A:335, ILE A:480,<\/p>\n<\/td>\n

\n

TYR A:407 (\u03c0- \u03c0 stacked)<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n\n\n

Docking of Amitriptyline into MAO-A <\/strong><\/p>\n\n\n\n

Amitriptyline showed the binding energy of -7.8828 kcal\/mol which exhibits the good inhibitory potential of a compound. Detailed molecular interaction pattern of amitriptyline docked pose demonstrated that one of the phenyl ring A and aliphatic nitrogen is involved in the formation of carbon-hydrogen bonding with TYR A: 407 and GLY A:443 amino acid residues. Substituted methyl group and phenyl ring B establish alkyl and \u03c0-alkyl interaction with LYS A:305, MET A:445, VAL A:303 and respectively. The hydrophobic cleft formed by GLY A:67 (Vander walls), GLY A:66 (\u03c0- \u03c0 stacked), and TRP A:397 (amide- \u03c0 stacked) provides additional stability to a ligand. Apart from this CYS A:406 (\u03c0-sulphur linkages) contributes to the high binding affinity of a ligand with MAO-A (Figure 1).<\/p>\n\n\n\n\n\n
\"\"<\/td>\n\n

Figure 1<\/strong>: Docking Interactions of Amitriptyline into MAO-A<\/strong><\/p>\n

<\/p>\n

Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n

Docking of Clorgyline into\nMAO-A <\/strong><\/p>\n\n\n\n

Clorgyline having the binding energy -7.2970 kcal\/mol was found to be positioned into the binding pocket assembled by CYS A:323, ILE A:180, ILE A:335, LEU A:337, LYS A:305, PHE A:352, TYR A:407, TYR A:69 amino acid residues. Moreover, the docked complex between Clorgyline and MAO-A was stabilized by hydrogen bond interactions between the aliphatic hydrogen of the ligand and the chains of GLN A:215 and GLY A:66 amino acids (Figure 2).<\/p>\n\n\n\n\n\n
\"\"<\/td>\n\n

Figure 2<\/strong>: Docking Interactions of Clorgyline into MAO-A<\/strong><\/p>\n

<\/p>\n

Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n

Docking of Moclobemide into MAO-A <\/strong><\/p>\n\n\n\n

Moclobemide showed binding energy of -7.0719 kcal\/mol and exhibits the good inhibitory potential of the compounds. Detailed molecular interaction pattern of Moclobemide docked pose demonstrated that aliphatic hydrogen was involved in the formation of hydrogen bonding with GLY A:443 and TYR A:69 amino acid residues. Substituted chloride group and morpholine ring established an alkyl and \u03c0-alkyl interaction with MET A:445, TYR A:444, and ILE A:180, ILE A:335 residues respectively (Figure 3).<\/p>\n\n\n\n\n\n
\"\"<\/td>\n\n

Figure 3<\/strong>: Docking Interactions of Moclobemide into MAO-A<\/strong><\/p>\n

<\/p>\n

Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n

Docking of Quercitrin (Quercetin-3-rhamnoside) into MAO-A <\/strong><\/p>\n\n\n\n

Quercitrin (Quercetin-3-rhamnoside) showed binding\nenergy of -8.5182 kcal\/mol that exhibits the good inhibitory potential of the\ncompounds. Detailed molecular interaction pattern of LIGAND docked pose\ndemonstrated that GLN A:215, CYS A:406, GLY A:67, ARG A:51 and MET A:445 amino\nacid residues are involved in the formation of Conventional hydrogen bonds.\nWhereas, PHE A:352, TYR A:444 and GLY A:443 are forming a Carbon hydrogen bond.\nSubstituted phenyl ring forms \u03c0-\u03c0 T-shape interaction with TRP A:397 and\naliphatic methyl forms \u03c0-alkyl interaction with TYR A:69 amino acid residues\nrespectively (Figure 4).<\/p>\n\n\n\n\n\n
\"\"<\/td>\n\n

Figure 4<\/strong>: Docking Interactions of Quercitrin (Quercetin-3-rhamnoside) into MAO-A<\/strong><\/p>\n

<\/p>\n

Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n

Docking of Quercetin 3-glucuronide into MAO-A <\/strong><\/p>\n\n\n\n

Quercetin-3-glucuronide showed -8.3633 kcal\/mol binding energy which indicates a higher inhibitory effect as compared to all other docked ligands in this study. Querce-tin-3-glucuronide formed 7 hydrogen bonds with GLY A:443, TYR A:197, MET A:445, ALA A:68, TYR A: 69 (conventional), and GLY A: 67, TYR A:444 (Carbon-hydrogen) respectively. It also forms hydrophobic alkyl and \u03c0-alkyl interactions with ILE A:335, and ILE A:480 respectively. Moreover, docked complex between Quercetin-3-glucuronide and protein was stabilized by \u03c0-\u03c0 stacked interactions between the phenyl ring of the ligand and the side chain of TYR A:407 amino acid (Figure 5).<\/p>\n\n\n\n\n\n
\"\"<\/td>\n\n

Figure 5<\/strong>: Docking Interactions of Quercetin 3-glucuronide into MAO-A<\/strong><\/p>\n

<\/p>\n

Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n

Amongst all docked ligands, Quercitrin\n(Quercetin-3-rhamnoside) and Quercetin-3-glucuronide showed the higher binding\nenergy-8.5182 kcal\/mol and -8.3633 kcal\/mol respectively as compared to other\nMAO-A inhibitors (standard drugs). and both were well oriented into the binding\npocket of MAO-A as well. As shown in Table 1 Q3G and quercitrin had some common\namino acid residue interactions with moclobemide and clorgyline. They possessed\nsome similarities to standard MAOIs but with higher binding affinity. Table 2\nexpresses the common amino acid residue interactions between different ligands.<\/p>\n\n\n\n

Table 2: Common amino acid residue interactions between different pairs of ligands.<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
\n

Ligand Pairs<\/strong><\/p>\n<\/td>\n

\n

Common Interactions<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

Moclobemide and Clorgyline<\/p>\n<\/td>\n

\n

TYR A:69, ILE A:335, ILE A:180,<\/p>\n<\/td>\n<\/tr>\n

\n

Moclobemide and Quercetin-3-glucuronide<\/p>\n<\/td>\n

\n

TYR A:69, GLY A:443, ILE A:335, Tyr A:444, ILE A:335<\/p>\n

MET A:445<\/p>\n<\/td>\n<\/tr>\n

\n

Moclobemide and Quercitrin<\/p>\n

(Quercetin-3-rhamnoside)<\/p>\n

 <\/p>\n<\/td>\n

\n

TYR A:69, GLY A:443, MET A:445, TYR A:444<\/p>\n<\/td>\n<\/tr>\n

\n

Clorgyline and Quercetin-3-glucuronide<\/p>\n<\/td>\n

\n

TYR A:69, ILE A:335, TYR A:407<\/p>\n<\/td>\n<\/tr>\n

\n

Clorgyline and Quercitrin (Quercetin-3-rhamnoside)<\/p>\n<\/td>\n

\n

TYR A:69, GLN A:215,<\/p>\n

PHE A:352<\/p>\n<\/td>\n<\/tr>\n

\n

Moclobemide, Clorgyline<\/p>\n

Quercetin-3-glucuronide and Quercitrin,<\/p>\n<\/td>\n

\n

TYR A:69<\/p>\n<\/td>\n<\/tr>\n

\n

Moclobemide, Clorgyline<\/p>\n

Quercetin-3-glucuronide<\/p>\n<\/td>\n

\n

TYR A:69, GLY A:443<\/p>\n<\/td>\n<\/tr>\n

\n

Moclobemide, Clorgyline and Quercitrin (Quercetin-3-rhamnoside)<\/p>\n<\/td>\n

\n

TYR A:69, ILE A:335<\/p>\n<\/td>\n<\/tr>\n

\n

Quercetin-3-glucuronide<\/p>\n

and Quercitrin (Quercetin-3-rhamnoside)<\/p>\n<\/td>\n

\n

TYR A: 69, GLY A:443, MET A:445, GLY A: 67, TYR A:444<\/p>\n<\/td>\n<\/tr>\n

\n

Moclobemide and Amitriptyline<\/p>\n<\/td>\n

\n

GLY A:443, MET A:445<\/p>\n<\/td>\n<\/tr>\n

\n

Clorgyline and Amitriptyline<\/p>\n<\/td>\n

\n

GLY A:66, TYR A:407<\/p>\n<\/td>\n<\/tr>\n

\n

Moclobemide, Clorgyline and Amitriptyline<\/p>\n<\/td>\n

\n

———–<\/p>\n<\/td>\n<\/tr>\n

\n

Amitriptyline and Quercetin-3-glucuronide<\/p>\n<\/td>\n

\n

GLY A:443, TYR A:407,<\/p>\n

MET A:445, GLY A:67<\/p>\n<\/td>\n<\/tr>\n

\n

Amitriptyline and Quercitrin<\/p>\n

(Quercetin-3-rhamnoside)<\/p>\n<\/td>\n

\n

GLY A:443, MET A:445<\/p>\n

GLY A:67, TRP A:397<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n\n\n

The current study is providing the results\nregarding molecular docking of Quercitrin (Quercetin-3-rhamnoside) and\nQuercetin-3-glucuronide with MAO-A structure first time in literature, it\nshowed that these constituents have many similar amino acid residues with\nstandard MAO-A inhibitors but there are no any previous studies on docking of\nthese constituents for their comparison.<\/p>\n\n\n\n

Moclobemide is selective reversible inhibitor of\nMAO-A, it increases the monoamines level inside the brain. Moclobemide was used\nas a standard MAO-A inhibitor in this docking study. It showed similar interactions\nby using MOE software in the present study in comparison to the latest\nperformed research on Moclobemide and MAO-A docking examination carried out by\nusing Auto Dock 4 software. In which amino acid residues like GLY A:443, TYR\nA:69, ILE A:180, ILE A:335, MET A:445 and TYR A:444 were similar 21<\/sup>.<\/p>\n\n\n\n

Clorgyline was used as a co-crystal ligand in this\nstudy. The mechanism of interaction of reversible monoamine oxidase\n(MAO)\u2010A inhibitor with monoamine oxidase Its interactions with CYS A:323, ILE\nA:180, ILE A:335, LEU A:337, LYS A:305, PHE A:352, TYR A:407 and TYR A:69 were\nquite similar to previously done research work regarding MAO-A inhibition\nthrough molecular docking, but in that study, researchers used Auto dock 3.0\nsoftware instead of MOE software 22<\/sup>.<\/p>\n\n\n\n

Amitriptyline also showed some interactions with\nTYR A:407, GLY A:443, LYS A:305, MET A:445, VAL A:303, CYS A:406 (\u03c0-sulphur),\nGLY A:67 (Vander walls), GLY A:66 (\u03c0- \u03c0 stacked), TRP A:397 (amide- \u03c0 stacked)\nlike other MAO-A inhibitors, which confirms that it also has some MAO-A\ninhibition activity, before this previous research has al-ready demonstrate\nthat although it is a tricyclic antidepressant it has also inhibitory effect on\nMAO-A 23<\/sup>.<\/p>\n\n\n\n

The current molecular study suggested that\nQuercitrin (Quercetin-3-rhamnoside) and Quercetin-3-glucuronide, both ligands\nmay have the capability to act like moclobemide and clorgyline with more\nbinding affinity with MAO-A structure as compare to these standard ligands.\nThis work also recommended that P. minus <\/em>aqueous leaf extract may have\nan MAO-A inhibitory effect due to the presence of these two bioactive\nconstituents.<\/p>\n\n\n\n

Conclusion<\/strong><\/p>\n\n\n\n

Quercetin 3-glucuronide (Miquelianin) and Quercitrin\n(Quercetin-3-rhamnoside) have more binding affinity with MAO-A structure as\ncompared to standard MAO inhibitors like Clorgyline, Moclobemide and\nAmitriptyline (Tricyclic antidepressants). Based on a Molecular docking study,\nQuercetin 3-glucuronide (Miquelianin) and Quercitrin\n(Quercetin-3-rhamnoside) may responsible for MAO-A inhibition activity of P.\nminus<\/em> leaf because they have several same bonding interactions with amino\nacid residues of MAO-A enzyme, like other standard MAO-A inhibitors. Quercetin\n3-glucuronide (Miquelianin) and Quercitrin\n(Quercetin-3-rhamnoside) can be proved to be a potent MAO-A inhibitor substance\nin future.<\/p>\n\n\n\n

Acknowledgement <\/strong><\/p>\n\n\n\n

The author acknowledge the Biovia software company to provide the free software.<\/p>\n\n\n\n

Conflict of Interest<\/strong><\/p>\n\n\n\n

The author(s) do not have any conflict of interest <\/p>\n\n\n\n

Funding Source<\/strong><\/p>\n\n\n\n

The author(s) received no financial support for the research.<\/p>\n\n\n\n

Data Availability Statement<\/strong> <\/p>\n\n\n\n

The\nmanuscript incorporates all datasets produced or examined throughout this\nresearch study and can be\naccessed easily on request<\/p>\n\n\n\n

Ethic Statement<\/strong><\/p>\n\n\n\n

This research did not\ninvolve human participants, animal subjects, or any material that requires\nethical approval<\/p>\n\n\n\n

Informed Consent Statement<\/strong><\/p>\n\n\n\n

This study did not involve\nhuman participants, and therefore, informed consent was not required.<\/p>\n\n\n\n

Authors\u2019 Contributions<\/strong><\/p>\n\n\n\n

Muhammad Irfan Bashir: Performed the molecular\ndocking and conceptualized as well as designed the experiment.  <\/p>\n\n\n\n

Nur Hidayah Kaz Abdul Aziz and Dzul Azri Mohamed\nNoor: conceptualized and design the experiments. <\/p>\n\n\n\n

Muhammad Irfan Bashir and Nur Hidayah Kaz Abdul\nAziz: wrote the article. <\/p>\n\n\n\n

Umar Idris Ibrahim: visualization <\/p>\n\n\n\n

Zalina Zahri: review and editing.<\/p>\n\n\n\n

References<\/strong><\/p>\n\n\n\n

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