Computational Study of Phytoconstituents in Myxopyrum Smilacifolium Blume against Inflammatory Mediator TNF-α

Received: 30-Nov-2022, Manuscript No. JDAR-23-88492; Editor assigned: 02-Dec-2022, Pre QC No. JDAR-23-88492 (PQ); Reviewed: 16-Dec-2022, QC No. JDAR-23-88492; Revised: 21-Dec-2022, Manuscript No. JDAR-23-88492 (R); Published: 28-Dec-2022, DOI: 10.4303/JDAR/236215

Introduction

Harmful stimuli like pathogens, damaged cells, toxic substances etc., activate the immune system’s response leads to Inflammation. Thereby the immune system removes injurious stimuli and initiates the process of healing [1,2]. In other words Inflammation is said as a defence mechanism [3]. Inflammatory pathways shows its impact on pathogenesis of chronic diseases, involves the inflammatory mediators and signalling pathways. An inflammatory stimulus activates intracellular signalling pathways leads to the active production of inflammatory mediators. The primary inflammatory stimuli includes cytokines such as interleukin-1β, interleukin-6, and tumour necrosis factor-α (TNF-α), IL-1 and IL-6 receptor and the TNF receptor (TNFR) [3-5].

Since ancient times, herbs played an important role in human health care as they produce several substances which exert biological activities. These substances are resultant of biogenetic pathway of secondary metabolism. These secondary metabolites exert numerous therapeutic actions [6,7]. Due to importance of the secondary metabolites, plants became the prime source for the development of new drugs [8-11]. Myxopyrum smilacifolium Blume4 is a shrub commonly has been used in Traditional system of Medicine, even though the findings on the phyto-constituents are limited [12,13]. Hence, the present study is carried for computational study on the phyto-constituents present in Myxopyrum smilacifolium Blume’s against inflammatory mediator.

Materials and Methods

In silico study

Receptor and ligand preparation: The PDF files of phyto- constituents of Myxopyrum smilacifolium’s were gathered from PubChem and the protein TNF-α was obtained from Protein Data Bank (PDB ID: 2az5) at www.rcsb.org/ pdb shown in Figure 1. The attributes of ligand i.e., x,y,z coordinates towards selected protein were noted by using Biovia Discovery Visualizer after removing the water molecule. Further with the help of Autodock 4.0 the PDB files of ligand and protein were converted into pdbqt files. By using commands in command prompt the docking is per formed. The interactions between each ligand and protein are analysed by using Biovia Discovery Visualizer. SwissADME programming is used to predict the physiochemical characteristics and pharmacokinetics of the chosen substances.

Figure 1: TNF-α (Protein ID: 2az5).

Results

Computation study of phytocompounds in myxopyrum smilacifolium

To investigate about phytocompounds being reasonable for anti-inflammatory property, docking score was analysed via binding affinity of different ligands behaviour towards the selected protein. Absorption, Distribution, Metabolism, Exertion and Toxicity of phyto constituents were predicted by using SwissADME online tool mentioned in Table 1. 2 out of 5 phytocompounds obeyed Lipinski’s Rule of 5. The phyto compounds are along with their PubChem ID and the canonical smiles were represented in Table 2. Docking studies revealed that phytoconstituents Arenarioside, Verbascoside, Myxopyroside had docking score of -16.4 kcal/ mol, -10.6 kcal/mol and -6.5 kcal/mol which showed hydrogen bonding interactions. No phyto compounds formed hydrophobic interactions. The docking score outcomes were predicted and the interactions between protein and ligand mentioned in Figure 2 and Table 3.

Table 1: M. Smilacifolium phyto-constituents representing Canonical Smiles.

Table 2: Pharmacokinetic Analysis Myxopyrum Smilacifolium B. Phyto-compounds.

Table 3: Docking Simulation between TNF-α and Phytocompounds in Myxopyrum Smilacifolium.

Figure 2: 3D Interactions of Ligands with receptor TNF-α A) Verbascoside B) Arenarioside C) Myxopyroside D) 3-Formylindole E) 5-Hydroxy methyl furfural F) Capsiacin G) Methylpredisolone.

Discussion

Findings of myxopyroside, a substance meant to genus Nyctanthes from single leaf of Myxopyrum. It was evidenced by 13C NMR spectrum for the presence of dihydroxy substituted for sythide dimethyl ester and ester derivatives [13]. Herbs have been tremendous usage from ancient times and still the natural phytochemicals exhibiting their significance in health care for the treatment of various ailments [14]. The overuse of NSAIDs brings an adverse state of disease like Myocardial Infarction [15-17]. Earlier studies were evidenced that the phyto components glycosides, polyphenols, quercetin and kaempferol inhibits the mediators TNF-α, NO, IL-1β and MCP-1 responsible for inflammation [18-21].

The docking studies disclosed a perspective interaction of stated ligands towards receptor TNF-α. The interactions of phytocomponents Arenarioside, Verbascoside, Myxopyroside, 3-Formylindole and 5-Hydroxy Methyl Furfural shown hydrogen bonds to GLY A:121, ALA A: 96, ILE A:118, SER A:95, TYR A:119 illustrated in Table 3. The docking score of Arenarioside, Verbascoside, Myxopyroside, 3-Formylindole, 5-Hydroxy Methyl Furfural is around -5.0, -4.9, -5.1, -3.5, and 3.4, respectively. In current study the 5 ligands of Myxopyrum smilacifolium at the receptor TNF-α site, docking score was analysed by the use of Autodock 4.0. It has shown good docking score of about -5.1 kcal/mol between Myxpyroside and receptor TNF-α, proves that Myxopyroside inhibits the inflammatory mediator, evidenced by strong binding affinity with receptor. By using SwisADME tool, the pharmacokinetic study was studied for the components Arenarioside, Verbascoside, Myxopyroside where it revealed GI absorption is low whereas 3-Formylindole, 5-Hydroxy Methyl Furfural, 3-Formylindole GI absorption is high depicted in Table 3. Myxopyroside had shown high and mere equivalent to docking score around -5.1 kcal/mole when compared to reference natural phyto-constitutent Capsiacin and standard drug Methylprednisolone of about -4.8 kcal/mole and -5.4 kcal/mole.

Conclusion

Inflammatory mediators are responsible for various conditions of diseased state. Researches on phyto constituents were limited against inflammation. It can concluded that the phyto components in Myxopyrum smilacifolium can be explored and by modifying the SAR it may lead to finding of new moiety to treat inflammatory conditions and simultaneously the use of NSAIDs can be limited to overcome their adverse effects.

Acknowledgement

I would like express my acknowledgements to the Management of V. V. Institute of Pharmaceutical Sciences, Gudlavalleru and Prof. G. Rajitha, Professor, Institute of Pharmaceutical Technology, Sri Padmavati Mahila Visvavidyalayam, Tirupati-517502, Andhra Pradesh, India for their support.

Conflict of Interest

No conflict of interest.

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