DISCOVERY OF INTERLEUKIN-6 INHIBITORY PROPERTIES OF THE COMPOUNDS DETECTED FROM METHANOLIC LEAF EXTRACTS OF PLECTRANTHUS AMBOINICUS (LOUR) SPRENG. THROUGH MOLECULAR DOCKING
HTML Full TextDISCOVERY OF INTERLEUKIN-6 INHIBITORY PROPERTIES OF THE COMPOUNDS DETECTED FROM METHANOLIC LEAF EXTRACTS OF PLECTRANTHUS AMBOINICUS (LOUR) SPRENG. THROUGH MOLECULAR DOCKING
Suchita Muthukrishnan and Sathyabhama Muthuswamy *
Department of Biotechnology, PSG College of Arts & Science, Coimbatore, Tamil Nadu, India.
ABSTRACT: Plectranthus amboinicus, locally called Karpooravalli in Tamil Nadu, India, is known for its various traditional therapeutic properties. Rheumatoid arthritis is a chronic autoimmune disease where uncontrolled inflammatory markers are released to induce bone damage and pain. In this study, the methanolic extract of P. amboinicus was characterized phytochemically and subjected to in-silico analysis to evaluate its anti-inflammatory properties. The methanolic extract of P. amboinicus was subjected to gas chromatography-mass spectrometry (GCMS) analysis. The detected compounds were subjected to in-silico analysis with biomarkers specific for rheumatoid arthritis (RA) that is interleukin 6. Of the 86 profiled compounds, three belonging to flavonoid, porphyrin, and heterocyclic triazoles classification had the highest affinities for interleukin-6 and was compared with common DMARs given during RA treatment which had significantly low affinities to above 3 highest affinities bioactive compounds. The ADMET profile, drug-likeness, and bioactivity score were also calculated for all the GCMS profiled compounds, revealing adequate drug-like properties. In-silico analysis of the leaf extract of P. amboinicus compounds showed a promising result for its anti-inflammatory activities and indicates the possible use of P. ambionicus extract in treatment of Rheumatoid arthritis.
Keywords: Plectranthus amboinicus, Gas chromatography-mass spectrometry, In-silico analysis, Rheumatoid arthritis (RA), Anti-inflammatory, Interleukin-6
INTRODUCTION: Plectranthus amboinicus (Lour.) Spreng is a perennial, shrubby herb also called Coleus amboinicus that belongs to the Lamiaceae family originates from tropical and warm regions of Asia, Africa, and Australia 1, 2. Along with beneficial essential oils, this edible herb has an aromatic nature used in folk medicine to treat conditions such as cough, cold, sore throat, nasal congestion, breast milk stimulant 3, asthma, fever, and headache 4.
The extract is also effective against other diseases, such as flu, bronchitis, epilepsy, and skin diseases. A total of 76 volatiles and 30 non-volatile’s of different classes were detected and these plants are also known to contain highly bioactive compounds such as monoterpenoids 1.
In recent years, plants have gained scientific importance in pharmaceutical research for evaluating phytochemicals and discovering potential compounds that can treat various diseases. One study revealed that carvacrol in the ethyl acetate extract of P. amboinicus modulates the expression of inducible nitric oxide synthase, cyclooxygenase 2, interleukin 1β, the histamine 1 receptor gene, and the nuclear factor kappa B protein thus exhibiting anti-inflammatory and antinociception properties 5. Another study demonstrated that high doses of P. amboinicus decrease the production of proinflammatory cytokines 6. Hsu and colleagues also postulated that rosmarinic acid from P. amboinicus inhibits osteoclastogenesis by inhibiting the activity of RANKL, an apoptotic regulatory gene, thus preventing bone destruction 7.
Inflammation is an essential biological response and part of the body’s healing process. One of the first responses of the immune system is inflammatory cells travel to the site of injury or infection 8. When this response occurs for an extended period it leads to chronic inflammation, which is the primary response in most autoimmune diseases. Rheumatoid arthritis (RA) is a chronic autoimmune disease in which inflammation and bone destruction is the primary prognoses 9. It has been presumed that genetically inclined individuals exposed to environmental stimuli acts as triggering factors for the progression of RA. RA is associated with systemic pathology, including (i) triggering stages, including the production of inflammatory cells. The environment also triggers the production of inflammatory cells. (ii) In the maturation stage the inflammatory class activates MHC class II-dependent T-cells in lymphoid tissue, which produce B cells and many additional inflammatory cells that, in turn, induce pain, bone loss, and inflammation. The next step is (iii) targeting, during which leukocytes and proinflammatory cells infiltrate the synovial compartment and interact with synovial fibroblasts to produce an inflammatory cascade. The final stage is called the (iv) fulminant stage and is characterized by a hyperplastic synovium caused by the dysfunction of synovial fibroblasts 10.
The hallmark immune components responsible for the pathogenesis of RA are macrophages, neutrophils, CD4+ and CD8+ T cells and their associated cytokines such as tumor necrosis factor-α (TNF-α), interleukin- IL-1, IL-6, IL-17, and IL-23 11. The administration of non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, and disease-modifying anti-rheumatic medications (DMARDs) are frequently used treatment methods. Physical therapy is also recommended to sustain joint mobility 10. In-silico analysis of phytochemicals tremendously helps rapid screening of the vast amounts of compounds in medicinal plants which could have potential in the pharmaceutical industry. With the ability to treat many diseases, diverse plant kingdoms have gained significant attention from researchers seeking new drugs with the help of computational technologies. In-silico analysis has also provided insight in to the immune response and its interaction with ligands and possible outcomes as well as how to narrow down the target protein, thus helping to modify ligands to improve interactions with targeted proteins and increase disease inhibiting activity.
In this study, we targeted P. amboinicus methanolic leaf extract as an herbal medicine for treating RA. Phytochemical analysis was performed, and an evaluation of the antiarthritic properties via in-silico analysis was performed.
MATERIALS AND METHODS:
Sample Collection, Preparation and Extraction: Plectranthus amboinicus leaves were collected from Coimbatore, Tamil Nadu (Lat. 11.022053⁰, Long. 77.017328⁰). The plants were extracted using a modified protocol from Samad et al., 2019. P. amboinicus leaves were cleaned, shade-dried for 48 hours, and ground using an electric grinder. Then, the dried leaf powder was soaked for 5 hours in 30% methanol, and the solvent to solid ratio was 30mL/g. Then, the samples were irradiated for 2 minutes via microwave-assisted extraction (IFB Solo microwave, 2450MHz) 12.
Gas Chromatography-mass Spectroscopy Analysis: The methanolic plant extract was subjected to GC-MS analysis on an Agilent 7000 D GC/TQ instrument by a DB 35-MS capillary standard nonpolar column using helium gas at a flow rate of 1.0 mL/min and an initial temperature of 70°C after which the temperature increased to 260°C at a rate of 6°C to identify the compounds present.
In-silico Analysis (Molecular Docking):
Docking: Compounds identified by GC-MS analysis were downloaded from the PubChem database in SDF format. Similarly, protein-interleukin 6 (Protein ID: IL6) was downloaded from the RCSB Protein Data Bank in PDB format. The compounds were converted to PDBQT formatted using Open Babel GUI software 2006 v3.1.1. In contrast, after docking parameters such as deleting the water molecule, adding Kollman charges, computing Gasteiger, and assigning the AD4 type were applied, the proteins were converted to the PDBQT format in the AutoDock tool.
Docking was performed using AutoDock vina 1.5.7 via the command prompt method. A dock file was created in which ligand and protein files in PDBQT format were saved with the configuration file. The configuration file consists of the protein and ligand file names with the grid box configuration, the log output file name, and the exhaustiveness of the number of docking runs. A grid box was generated and set at 80 × 80 × 80 with the coordinates X-0.166 Y-0.191 Z-0.438 for the protein IL6. Ligand efficiency 13 was calculated using the following formula:
Ligand efficiency =∆G / (Heavy atoms)
Moreover, the inhibition constant (Ki) 14 was calculated using the following formula:
Inhibiton constant Ki = Exp × (∆G / RT)
Where ∆G is the binding energy, R is the universal gas constant (1.985× 10-3 kcal/mol/K), and T is the temperature (298.15 K).
FIG. 1: BIOMARKER OF RA RETRIEVED FROM THE RCSB PDB; INTERLEUKIN 6 (IL6)
Receptor-ligand Interaction: Docking results and receptor-ligand interaction, such as the number of H-bonds formed with amino acid residue, were visualized using the BIOVIA Discovery Studio visualizer 2021V21.1.0.20298.
ADMET Profile: The parameters for ADMET (absorption, distribution, metabolism, excretion, and toxicity) were Human intestinal absorption (HIA) for absorption, blood-brain barrier (BBB), Plasma protein binding (PPB) for distribution, cytochrome P substrate/inhibition for metabolism, Time ½ (half-life) for excretion, and AMES, Carcinogenity, LD50 in rats for toxicity were profiled for the ligand derived from Pubchem using ADMETSAR 2.0 website(http://lmmd.ecust.edu.cn/admetsar2). The half-life was predicted using ADMETLab 2.0 (https://admet.scbdd.com/calcpre/index_sys/) and the LD50 toxicity in rats were determined using the Gusar-Way2Drug (http://way2drug.com/Gusar/acutoxpredict/).
Drug-likeness: SwissADME (http://www.swissadme.ch/index.php) was used to predict the drug-likeness of the ligands. The topological polar surface area (TPSA), solubility log S, C log P, molecular weight (MW), and Lipinski’s rule for the drug-likeness of the given ligands was predicted.
Bioactivity Score: The molinspiration online predictor tool (https://www.molinspiration.com/cgi-bin/properties) was used to calculate the predicted values of various bioactivities such as G-protein-coupled receptor (GPCR), ion channel modulator, kinase inhibitor, nuclear receptor inhibitor, protease inhibitor, and enzyme inhibitor for the given ligands.
RESULTS:
GC-MS Analysis: The identified compounds were further functionally characterized to determine their pharmacological activity and were subjected to in-silico analysis. GC-MS profiling of the extracts revealed a total of 86chemical compounds. Table 1 shows the compound list, retention time classification, and pharmacological characteristics.
Fig. 2 shows the chromatogram of methanolic P. amboinicus extract. The compounds are classified as terpenoids, alkaloids, phenols, and flavonoids. Pteridinone, thymol, diphenhydramine, α-farnesene, hydropapaveroline, and β-Bergamotene are some of the major compounds. A study revealed the presence of α-bergamotene, carvacrol, caryophyllene, ρ-cymene, and γ-terpinene as major constituents 15.
FIG. 2: MASS SPECTRA OF P. AMBOINICUS EXTRACTS
TABLE 1: P. AMBOINICUS COMPOUNDS IDENTIFIED BY GC-MS ANALYSIS
In-silico Analysis:
Docking: The compounds were subjected to molecular docking with the biomarker IL6 in AutoDock Vina via the command prompt method. The results show that the binding energies of the compounds ranged from -1.8 to -9.3. The compounds with the highest binding energy were Bis [(2.3) paracyclophano] [1,2-b:1’,2’-i] anthraquinone, Tetraphenyl porphyrin, 2-Morpholin – 4 – yl - 1, 5 – diphenyl -7-p-tolylimino-5-trifluoromethyl-1, 5, 6, 7-tetrahydro-[1,2,4] triazolo[1,5-c]pyrimidine-8-carbonitrile which had affinities of -9.3, -7.9, and -7.0 respectively. The DMAR, hydroxychloroquine sulfate (HCQs) had a -5.3 affinity for IL6. The further binding energies of the other compounds and their ligand efficiencies and inhibition constants are summarized in Table 2. A study in 2014 targeted IL-6, as it has a profound role in treating RA, and performed docking with 5 compounds, out of which margaric acid exhibited good affinity 87. Another study conducted in silico studies on the ability of the database-derived phytochemicals of Murraya koenigii to treat TNF-α of RA, revealed two compounds with high binding scores 88. Maste and colleagues screened P. ambionicus against COVID-19 and showed two compounds in combination, i.e., plectranthol A and B had high viral anti-inflammatory activity 88. (See supplementary data for the docking profiles of the remaining 76 compounds).
TABLE 2: LIGAND BINDING EFFICIENCY OF GC-MS PROFILED COMPOUNDS WITH INTERLEUKIN-6 DERIVED FROM AUTODOCK
S. no. | Compound Name | Pubchem Id | Kcal/Mol | Ligand Efficiency | Ki (μM) |
1 | Bis[(2.3)paracyclophano][1,2-b:1’,2’-i]anthraquinone | 636069 | -9.3 | -0.20 | 0.147 |
2 | Tetraphenylporphyrin | 86280046 | -7.9 | -0.16 | 1.576 |
3 | 2-Morpholin-4-yl-1,5-diphenyl-7-p-tolylimino-5-trifluoromethyl-1,5,6,7-tetrahydro-[1,2,4]triazolo[1,5-c]pyrimidine-8-carbonitrile | 6426583 | -7.0 | -0.17 | 7.210 |
4 | 1,2,3-Triphenyl-3-methyl-cyclopropene | 624783 | -6.6 | -0.30 | 14.23 |
5 | Flufenamic acid | 3371 | -6.5 | -0.32 | 16.86 |
6 | diphenhydramine | 3100 | -6.4 | -0.33 | 19.99 |
7 | Cyclotetracosene | 5379442 | -6.3 | -0.24 | 23.70 |
8 | 3',4'-Desoxy-3,4-dihydropapaveroline | 619942 | -6.2 | -0.32 | 27.81 |
9 | 2-(2,4-dihydroxyphenyl)-5-(e)-propenylbenzofuran | 10355545 | -6.2 | -0.31 | 27.81 |
10 | Chromeno(4,3-c)chromene-5,11-dione | 622026 | -6.1 | -0.30 | 32.96 |
DMARs | |||||
11 | Hydroxychloroquine sulphate | 12947 | -5.3 | -0.18 | 128.4 |
Kcal/mol= Binding efficiency, Ki= Inhibition constant |
Receptor-ligand Interaction: BIOVIA Discovery Studio helps to visualize the position of compounds interacting with the targeted protein. It also provides a 2D diagram of interactions at the amino acid level. Van der Waal formation was the primary bond found in the docking results. The amino acids found in most of the interactions were ARG, TRP, VAL, PHE, TYR, MET, GLN, ASN, and LYS. The significant bonds that formed were Pi-alkyl and conventional hydrogen bonds. (See supplementary data for the rest of the figures). A study was conducted on flavonoid compounds from Glycyrrhiza glabra as anti-inflammatory drugs against the inflammatory marker interleukin 1 in periodontitis using Autodock tools and the BIOVIA Discovery Studio Visualizer 90.
FIG. 3: A: BIS[(2.3)PARACYCLOPHANO][1,2-B:1’,2’-I]ANTHRAQUINONE B: TETRAPHENYLPORPHYRIN, C: 2-MORPHOLIN-4-YL-1, 5-DIPHENYL-7-P-TOLYLIMINO-5-TRIFLUOROMETHYL - 1, 5, 6, 7 - TETRAHYDRO-[1,2,4]TRIAZOLO[1,5-C]PYRIMIDINE-8-CARBONITRILE, D: 1,2,3-TRIPHENYL-3-METHYL-CYCLOPROPENE, E: FLUFENAMIC ACID, F: DIPHENHYDRAMINE, G: CYCLOTETRACOSENE, H: 3',4'-DESOXY-3,4-DIHYDROPAPAVEROLINE, I: CHROMENO(4,3-C)CHROMENE-5,11-DIONE, J: 2-(2,4-DIHYDROXYPHENYL)-5-(E)-PROPENYLBENZOFURAN
ADMET Profile: ADMET was predicted using the ADMETSAR online tool, which is freely available. An HIA below 0.3 indicates low or no absorption, but the values of all the compounds are high; hence, the compounds have high intestinal adsorption. Compounds with a value greater than 0.1 are positive for the BBB. All the other compounds had a positive blood-brain barrier except for6-demethoxytangeretin, chromeno (4,3-c) chromene-5,11-dione, and flufenamic acid. Cytochrome P plays a role in drug metabolism. Table 3 (the 10 compounds with the highest binding efficiency remaining available in supplementary data) shows whether the compounds are substrates or inhibitors. A positive value indicates a substrate and inhibitor, while a negative value indicates a non-substrate and non-inhibitor. Positive/negative indicates substrate/non-inhibitor, whereas negative/positive indicates non-substrate/ inhibitor. The time ½ (ADMETLab) indicates the rate of elimination or excretion; all of the compounds have values less than 3hours and hence have a low elimination rate. PPB signifies that compounds with high protein-bound efficiency have a low therapeutic index; only 10 among the other compounds have low plasma-protein binding values. AMES predicts the mutagen city of the compound; 20 compounds are predicted to be mutagenic, and 33 are predicted to be carcinogenics. Acute toxicity prediction for the compounds was done using LD50 on Gusar- online way 2 drugs tool and subcutaneous administration of the compounds to rats was chosen because the hydrogel will be applied onto the skin. A recent study of the anti-inflammatory activity of lavender (Lavandula officinalis) essential oil bioactive compounds against COX-1 and COX-2, inflammatory markers, used the ADMETSAR tool to predict the drug-likeness and risk assessment of the compounds with high affinities for these compounds.91Another study used ADMETLab 2.0 for further analysis to evaluate potential candidates against SARS-CoV-2. This study designed 1389 protease inhibitors among which one compound was selected to be most favourable 92. A study used GUSAR software to predict the toxicity of xenobiotic metabolites using quantitative structure–activity relationship (QSAR) models created for acute rat toxicity after the intravenous administration 93.
TABLE 3: ADMET PROFILE OF THE COMPOUNDS FROM PLECTRANTHUS AMBOINICUS EXTRACT
S. no. | Compound Name | HIA | BBB | CYP | T 1/2 (Half Life) | Plasma protein binding % | Ames | Carcin-genicity | LD50 in rats log10 (mmol/kg) |
1 | Bis[(2.3)paracyclophano][1,2-b:1’,2’-i]anthraquinone | + | + | + | 2.324 | 0.736 | + | - | 0.067 |
2 | Tetraphenylporphyrin | + | + | -/+ | 2.541 | 0.901 | - | - | 0.09 |
3 | 2-Morpholin-4-yl-1,5-diphenyl-7-p-tolylimino-5-trifluoromethyl-1,5,6,7-tetrahydro-[1,2,4]triazolo[1,5-c]pyrimidine-8-carbonitrile | + | + | + | 1.951 | 0.934 | - | + | 0.261 |
4
5 |
1,2,3-Triphenyl-3-methyl-cyclopropene | + | + | -/+ | 2.529 | 0.898 | - | + | 0.526 |
6 | Flufenamic acid | + | - | - | 1.259 | 0.939 | - | - | 0.198 |
7 | diphenhydramine | + | + | - | 1.843 | 0.716 | - | + | 0.115 |
8 | Cyclotetracosene | + | + | + | 1.859 | 0.775 | - | - | 0.673 |
9 | 3',4'-Desoxy-3,4-dihydropapaveroline | + | + | -/+ | 1.601 | 0.812 | - | - | 0.337 |
10 | Chromeno(4,3-c)chromene-5,11-dione | + | - | -/+ | 2.268 | 0.854 | - | + | 0.943 |
11 | 2-(2,4-dihydroxyphenyl)-5-(e)-propenylbenzofuran | + | + | -/+ | 1.573 | 0.908 | + | + | 0.624 |
HIA: Human intestinal absorption; BBB: Blood brain barrier; CYP: Cytochrome P, + is substrate and inhibitor, - is non-substrate and non-inhibitor. +/- is substrate/non-inhibitor, and -/+ is non-substrate/inhibitor. |
Druglikness: Drug-likeness refers to qualitative concepts such as the structure and physio-chemical properties of a compound and is used to assess its bioavailability as a drug. The TPSA represents the quality of the transport of compounds into the cell membrane; molecules with high TPSA are transported more easily than are those with low TPSA. Pimelic acid, di (2-nitro-5-fluorophenyl) ester, 3,4-Bis (methoxycarbonyl) benzoic acid, Semioxamazide, 3-(4-nitrophyenyl-4,5-dihyro-1.2.4-oxadiazol-5-onehad the highest TPSA value compared to the others. C Log P represents the hydrophilicity of the compound; high logP values indicate low hydrophillicity and poor absorption and permeation. 5-Aminotetrazole and semioxamazide are the compounds that were predicted to have low logP values. Solubility is an important parameter for the absorption of compounds and their subsequent distribution in the body, and is measured using solubility logS. The lower the value of logS is, the greater the solubility. Among the 86 compounds, hexacosane, diphenhydramine highly soluble compounds and rest are moderately soluble. The molecular weight is directly related to the absorption rate; the lower the molecular weight is, the greater the absorption rate. The average molecular weight of the drug is between 160 and 480 g/mol and only seven compounds have molecular weights above the average. Lipinski’s rule states that a compounds is drug-like if it has no more than one violation 94, and in Table 4 (the 10 highest binding efficiency compounds remaining available in supplementary data), yes indicates that it passes the rule, whereas no means it does not, and the number indicates how many rules are not passed out of five; hence all the other six compounds pass this rule. A study conducted using the SwissADME tool for pharmacological and pharmacognostical profiling of Butea momosperma Lam. Taub 95.
TABLE 4: DRUGLIKENESS PREDICTION OF THE COMPOUNDS FROM PLECTRANTHUS AMBOINICUS EXTRACT
S. no. | Compound Name | TPSA | C Log P | Solubility Log S | Mw | Lipinski |
1 | Bis[(2.3)paracyclophano][1,2-b:1’,2’-i]anthraquinone | 34.14 | 8.76 | -11.05 | 592.72 | no;2 |
2 | Tetraphenylporphyrin | 56.3 | 7.23 | -6.26 | 614.74 | NO;2 |
3 | 2-Morpholin-4-yl-1,5-diphenyl-7-p-tolylimino-5-trifluoromethyl-1,5,6,7-tetrahydro-[1,2,4]triazolo[1,5-c]pyrimidine-8-carbonitrile | 83.4 | 4.6 | -6.8 | 557.57 | yes;1 |
4 | 1,2,3-Triphenyl-3-methyl-cyclopropene | 0 | 5.44 | -5.43 | 282.38 | YES:1 |
5 | Flufenamic acid | 49.33 | 3.69 | -5.07 | 281.23 | yes |
6 | diphenhydramine | 24.72 | 3.07 | -3.27 | 204.72 | yes |
7 | Cyclotetracosene | 0 | 8.56 | -9.67 | 362.68 | yes;1 |
8 | 3',4'-Desoxy-3,4-dihydropapaveroline | 52.82 | 2.61 | -3.34 | 253.30 | YES |
9 | Chromeno(4,3-c)chromene-5,11-dione | 60.42 | 3.01 | -3.88 | 264.23 | yes |
10 | 2-(2,4-dihydroxyphenyl)-5-(e)-propenylbenzofuran | 46.53 | 3.34 | -4.37 | 266.29 | yes |
Topological polar surface area (TPSA), molecular weight (MW), numbers in Lipinski= no. of violations |
Bioactivity Score: The bioactivity score was calculated using the free tool from Molinspiration. Table 5 (other 76 compounds; supplementary data) lists of the compounds with bioactivity scores for GPCRs, ion channel modulators, kinase inhibitors, nuclear receptor inhibitors, protease inhibitors, and enzyme inhibitors; yellow indicates a moderate score, whereas green indicates a high score. The compounds that had good bioactivity scores were Carbamic acid, N-(3-oxo-4-isoxazolidinyl)-, benzyl ester, β-Bergamotene, gamma atlantone, Carbonic acid, octadecyl vinyl ester, Amphetamine, N-pentafluoropropionyl, 9-Oxo-10(9H)-acridineacetic acid, 3-(3,5-di-tert-butylphenyl) pentanedioic acid. A study conducted in Cassia auriculata reported bioactivity scores for phytochemicals predicted via Molinspiration software, which resulted in high scores for to copherol compounds across all parameters 96. In another study in which Molinspiration software was used to predict bioactivity scores of terpenoids and fatty acid esters extracted from the Tiliaceae shrub Triumfetta pentandra 97.
TABLE 5: BIOACTIVITY SCORE OF THE COMPOUNDS FROM PLECTRANTHUS AMBOINICUS EXTRACT
S. no. | Compound Name | GPCR | Ion Channel Modulator | Kinase Inhibitor | Nuclear Receptor Inhibitor | Protease Inhibitor | Enzyme Inhibitor |
1 | Bis[(2.3)paracyclophano][1,2-b:1’,2’-i]anthraquinone | -0.13 | -0.84 | -0.39 | -0.39 | -0.04 | -0.34 |
2 | Tetraphenylporphyrin | -0.36 | -0.99 | -0.58 | -0.77 | -0.21 | -0.55 |
3 | 2-Morpholin-4-yl-1,5-diphenyl-7-p-tolylimino-5-trifluoromethyl-1,5,6,7-tetrahydro-[1,2,4]triazolo[1,5-c]pyrimidine-8-carbonitrile | -0.28 | -0.6 | -0.25 | -0.62 | -0.26 | -0.44 |
4
|
1,2,3-Triphenyl-3-methyl-cyclopropene | 0.11 | -0.02 | -0.05 | -0.02 | -0.06 | -0.02 |
5 | Flufenamic acid | -0.02 | 0.6 | 0.18 | 0.16 | -0.21 | 0.06 |
6 | diphenhydramine | -0.18 | -0.06 | -0.67 | -0.4 | -0.45 | -0.02 |
7 | Cyclotetracosene | -0.08 | 0.02 | -0.11 | 0.14 | -0.01 | 0.06 |
8 | 3',4'-Desoxy-3,4-dihydropapaveroline | -0.03 | 0.10 | -0.48 | -0.16 | -0.14 | 0.22 |
9 | Chromeno(4,3-c)chromene-5,11-dione | -0.37 | -0.32 | -0.25 | 0.06 | -0.35 | -0.03 |
10 | 2-(2,4-dihydroxyphenyl)-5-(e)-propenylbenzofuran | -1.22 | -1.37 | -0.61 | -0.62 | -1.25 | -0.26 |
Yellow= Moderate activity, GREEN= High activity |
DISCUSSION: P. amboinicus has potential therapeutic phytocompounds which is supported by published research. In a recent study on the anti-inflammatory potential of a Coleus amboinicus-based gel formulation, a good inhibitory effect was detected via an albumin denaturation assay 98. A study conducted in 2019 investigates the anti-inflammation effects of Plectranthus amboinicus extract (PA-F4) on THP-1 monocytic leukemia cells. PA-F4 inhibited ATP-induced caspase-1, IL-1β, and IL-18 release from LPS-primed cells, blocking p65 NF-κB activation and ATP-induced signaling pathways. The constituents rosmarinic acid, cirsimaritin, salvinorin, and carvacrol may explain PA-F4's inhibitory activity 99. Another study evaluates the antioxidant in a murine macrophage model, showing that PaE reduces nitric oxide production and inhibits DPPH free radicals and anti-inflammatory using the in-silico method of Indian borage (Plectranthus amboinicus) ethanol extract 100.
The hallmark inflammatory markers involved in RA are interleukins (IL-1, IL-6, IL-17, and IL-23) 11. These inflammatory markers are also responsible for inflammation and detrimental activities in fibroblast-like synoviocytes (FLSs) among which IL-6 is involved, and other cells regulate fibroblast activated protein-α (FAP-α) in FLSs during RA 101. IL-6 also plays a critical role in B cell differentiation into plasma cells and is a potent growth factor for plasmacytoma and myeloma 102, and it induces excess production of VEGF, leading to enhanced angiogenesis and increased vascular permeability 103. Another critical role of IL-6is to cause bone resorption by inducing osteoclast formation via the induction of RANKL in synovial cells, and cartilage degeneration 104. Hence IL-6 was targeted for this study to evaluate anti-inflammatory effects of phytocompounds from P. amboinicus extract on IL-6 via an in-silico method. In this investigation, the constituents of P. amboinicus methanolic extract were profiled using GC-MS analysis and the anti-inflammatory effects of the compounds were analyzed via molecular docking with the IL-6 of RA. The analysis revealed that the extract had significant anti-inflammatory effects on IL-6 and had a greater binding energy than the prescription medication for RA. Thus these compounds are potential agents for treating RA.
CONCLUSION: We subjected methanolic leaf extracts of P. amboinicus to microwave-assisted extraction and used analyzed phytochemical compounds via GC-MS, revealing many bioactive compounds belonging to terpenoids, alkaloids, and phenols classification. Furthermore, the 87 chemical compounds identified were analyzed via the in-silico method.
Molecular docking revealed that three compounds namely Bis[(2.3) paracyclophano] [1,2-b:1’,2’-i] anthraquinone, Tetraphenylporphyrin, 2 – Morpholin – 4 -yl-1,5-diphenyl-7-p-tolylimino-5-trifluoromethyl-1, 5, 6,7-tetrahydro-[1,2,4] triazolo [1,5-c] pyrimidine-8-carbonitrile, had high binding affinities, with affinities of -9.3, -7.9, and -7.0, respectively. Hydroxychloroquine sulphate, a common DMAR, was also docked for comparative purposes with IL6, resulting in a lower binding score (-5.3) than that of the above mentioned compounds. The ADMET profile and drug-likeness scores showed that in addition to Bis[(2.3) paracyclophano] [1,2-b:1’,2’-i] anthraquinone, Hexacosane, 1,26-bis(4'-benzoylphenyl), Tetraphenylporphyrin, Thiophene, 3-methyl-5-octadecyl-2-pentadecyl, α-Farnesene, all the other compounds had adequate drug-like properties. Finally, it can be concluded that phytochemicals from P. amboinicus have potent anti-inflammatory effects on rheumatoid arthritis.
ACKNOWLEGGEMENTS: The authors are thankful to the management of the PSG College of Arts & Science, Coimbatore, India for providing the required infrastructure support.
Author Contribution: The experiments were designed out by SMK and MS. The in-silico analysis was performed by SMK. The article was framed by MS and SMK.
Funding: The author(s) received no financial support for the research.
CONFLICTS OF INTEREST: The authors express no conflicts of interest.
REFERENCES:
- Arumugam G, Swamy MK & Sinniah UR: Plectranthus amboinicus (Lour.) Spreng: botanical, phytochemical, pharmacological and nutritional significance. Molecules 2016; 21(4): 369.
- Roshan P, Naveen M, Manjul PS, Gulzar A, Anita S & Sudarshan S: Plectranthus amboinicus (Lour) Spreng: an overview. Pharm Res 2010; 4: 1-15. ISSN 0975-8216.
- Ashaari NS, Ab. Rahim MH, Sabri S, Lai KS, Song AAL, Abdul Rahim R & Ong Abdullah J: Functional characterization of a new terpene synthase from Plectranthus amboinicus. PloS one 2020; 15(7): e0235416.
- Punet Kumar S & Kumar N: Plectranthus amboinicus: a review on its pharmacological and pharmacognostical studies. American Journal of Physiology 2020; 10(2): 55-62.
- Duraisamy P, Manikandan B, Koodalingam A, Munusamy A & Ramar M: Anti-inflammatory, anti-nociceptive and anti-oxidant activities of carvacrol containing leaf extracts of edible Indian borage plant Plectranthus amboinicus: an in-vivo and in-vitro Comparative Clinical Pathology 2021; 30(3): 397-4.
- Chang JM, Cheng CM, Hung LM, Chung YS & Wu RY: Potential Use of Plectranthus amboinicus in the Treatment of Rheumatoid Arthritis. Evidence-based complementary and alternative medicine: eCAM 2010; 7(1): 115–120.
- Hsu YC, Cheng CP & Chang DM: Plectranthus amboinicus attenuates inflammatory bone erosion in mice with collagen-induced arthritis by downregulation of RANKL-induced NFATc1 expression. The Journal of Rheumatology, 2011; 38(9): 1844–1857.
- Janakiraman D & Somasundaram C: Evaluation of Anti inflammatory effect of Plectranthus amboinicus leaf extract-An in-vitro Journal of Advanced Pharmacy Education & Research 2014; 4(2): 229-232.
- Huber LC, Distler O and Tarner I: Synovial fibroblasts: key players in rheumatoid arthritis. Rheumatology 2006; 45: 669–675.
- Guo Q, Wang Y, Xu D, Nossent J, Pavlos NJ & Xu J: Rheumatoid arthritis: pathological mechanisms and modern pharmacologic therapies. Bone Research 2018; 6(1): 1-14.
- Cecchi I, Arias de la Rosa I, Menegatti E, Roccatello D, Collantes-Estevez E, Lopez-Pedrera C & Barbarroja N: Neutrophils: Novel key players in Rheumatoid Arthritis. Current and future therapeutic targets. In Autoimmunity Reviews 2018; 17(11): 1138–1149). Elsevier B.V.
- Samad NA, Zaidel DNA, Salleh E, Yusof AHM, Dailin DJ & Zaidel DNA: Optimization of Plectranthus amboinicus (Lour.) Spreng extraction process using microwave-assisted technique. Chemical Engineering Transactions 2019; 72: 397-402.
- Orita M, Ohno K, Warizaya M, Amano Y & Niimi T: Lead generation and examples: opinion regarding how to follow up hits. In Methods in enzymology 2011; 493: 383-419). Academic Press.
- Ortiz CLD, Completo GC, Nacario RC & Nellas RB: Potential inhibitors of galactofuranosyltransferase 2 (GlfT2): molecular docking, 3D-QSAR, and in-silico ADMETox studies. Scientific reports 2019; 9(1): 17096.
- Ashaari NS, Ab. Rahim MH, Sabri S, Lai KS, Song AAL, Abdul Rahim R & Ong Abdullah J: Functional characterization of a new terpene synthase from Plectranthus amboinicus. PloS one 2020; 15(7): e0235416.
- Mahmoud AB, Danton O, Kaiser M, Khalid S, Hamburger M & Mäser P: HPLC-based activity profiling for antiprotozoal compounds in Croton gratissimus and Cuscuta hyalina. Frontiers in Pharmacology 2020; 1246.
- Sicari V: Zabbo CP. Diphenhydramine. [Updated 2022 Jul 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK526010/
- Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P and Steinbeck C: ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res 2016.
- de Carvalho Gustavo SG, MP. Dias Rafael, R. Pavan Fernando, Q. F. Leite Clarice, L. Silva Vania, G. Diniz Claudio, T. S. de Paula Daniela, S. Coimbra Elaine, Retailleau Pascal and D. da Silva Adilson: Synthesis, cytotoxicity, antibacterial and antileishmanial activities of imidazolidine and hexahydropyrimidine derivatives, Medicinal Chemistry 2013; 9(3).
- Zhang J: Potential Anti-Proliferative Natural Products from Bidens biternata (Lour.) Merr. & Sherff and Austrobuxus sanii (Beuzev. & CT White) Airy Shaw 2018.
- National Center for Biotechnology Information (2022). PubChem Bioassay Record for AID 1047, Source: SRMLSC. Retrieved August 11, 2022 from https://pubchem.ncbi.nlm.nih.gov/bioassay/1047.
- Jacobsson M, Ellervik U, Belting M & Mani K: Selective antiproliferative activity of hydroxynaphthyl-beta-D-xylosides. Journal of Medicinal Chemistry 2006; 49(6): 1932–1938.
- Geethalakshmi R & Sarada DVL: Evaluation of antimicrobial and antioxidant activity of essential oil of Trianthema decandra Journal of Pharmacy Research, 2013; 6(1): 101-106.
- Vlad IM, Nuță DC, Ancuceanu RV, Caproiou MT, Dumitrascu F, Marinas IC & Limban C: New o-aryl-carbamoyl-oxymino-fluorene derivatives with microbicidal and antibiofilm activity enhanced by combination with iron oxide nanoparticles. Molecules 2021; 26(10): 3002.
- Samant BS & Chakaingesu C: Novel naphthoquinone derivatives: synthesis and activity against human African trypanosomiasis. Bioorganic & Medicinal Chemistry Letters 2013; 23(5): 1420–1423.
- National Center for Biotechnology Information (2022). PubChem Compound Summary for CID 14161, 2-Anilino-3-chloro-1,4-naphthoquinone. Retrieved August 13, 2022 from https://pubchem.ncbi.nlm.nih.gov/compound/14161.
- Sebestik J, Hlavacek J & Stibor I: A role of the 9-aminoacridines and their conjugates in a life science. Current Protein and Peptide Science 2007; 8(5): 471-483.
- National Center for Biotechnology Information (2022). PubChem Compound Summary for CID 7720, 2-Ethylhexanol. Retrieved June 6, 2022 from https://pubchem.ncbi.nlm.nih.gov/compound/2-Ethylhexaonl
- Lasekan O & Teoh LS: Contribution of aroma compounds to the antioxidant properties of roasted white yam (Dioscorea rotundata). BMC Chemistry 2019; 13(1): 1-8.
- Muhsin T: Antibacterial, antitumor and antioxidant of bioactive compounds extracted from secondary metabolites of the fungus Rhizoctonia solani In Qatar Foundation Annual Research Forum 2013; 1: 2013, No. 1, pp. BIOP-01). Hamad bin Khalifa University Press (HBKU Press).
- Isidorov VA & Vinogorova V: GC-MS analysis of compounds extracted from buds of Populus balsamifera and Populus nigra. Zeitschrift für Naturforschung C 2003; 58(5-6): 355-360.
- Senerovic L, Opsenica D, Moric I, Aleksic I, Spasić M and Vasiljevic B: Quinolines and Quinolones as Antibacterial, Antifungal, Anti-virulence, Antiviral and Anti-parasitic Agents. In: Donelli, G. (eds) Advances in Microbiology, Infectious Diseases and Public Health. Advances in Experimental Medicine and Biology, vol 1282. Springer, Cham 2019.
- Wilhelm EA, Ferreira AT, Pinz MP, REIS AS, Vogt AG, Stein AL & Luchese C: Antioxidant effect of quinoline derivatives containing or not selenium: Relationship with antinociceptive action quinolines are antioxidant and antinociceptive. Anais da Academia Brasileira de Ciências, 2017; 89: 457-467.
- Tang X, Zhou Q, Zhan W, Hu D, Zhou R, Sun N & Xue W: Synthesis of novel antibacterial and antifungal quinoxaline derivatives. RSC advances 2022; 12(4): 2399-2407.
- Montana M, Montero V, Khoumeri O & Vanelle P: Quinoxaline derivatives as antiviral agents: a systematic review. Molecules 2020; 25(12): 2784.
- Pinheiro C, AC Mendonça Nogueira T & VN de Souza, M: Quinoxaline nucleus: a promising scaffold in anti-cancer drug discovery. Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Anti-Cancer Agents) 2016; 16(10): 1339-1352.
- Butnariu M & Butu A: Chemical composition of vegetables and their products. Handbook of Food Chemistry 2015; 627-692.
- Ziemska J, Guśpiel A, Jarosz J, Nasulewicz-Goldeman A, Wietrzyk J, Kawęcki R & Solecka J: Molecular docking studies, biological and toxicity evaluation of dihydroisoquinoline derivatives as potential anticancer agents. Bioorganic & Medicinal Chemistry 2016; 24(21): 5302-5314.
- Biernacki K, Daśko M, Ciupak O, Kubiński K, Rachon J & Demkowicz S: Novel 1, 2, 4-oxadiazole derivatives in drug discovery. Pharmaceuticals 2020; 13(6): 111.
- National Center for Biotechnology Information (2022). PubChem Compound Summary for CID 1663, 3-Hydroxybenzylhydrazine. Retrieved August 12, 2022 from https://pubchem.ncbi.nlm.nih.gov/compound/1663#section=ChemIDplus
- Ubaid JM, Hussein HM & Hameed IH: Determination of bioactive chemical composition of Callosobruchus maculutus and investigation of its anti-fungal activity. International Journal of Pharmcognosy and Phytochemical Research 2016; 8(8): 1293-1299.
- Aljari SM, Abutaha N, Al-Keridis LA, Al-Doaiss AA, Fahd AM & Wadaan MA: Acute and subacute toxicity studies of a new herbal formula induced apoptosis in the highly metastatic MDA-MB-231 cells. Journal of King Saud University-Science 2021; 33(8): 101646.
- Baumgartner L, Sosa S, Atanasov AG, Bodensieck A, Fakhrudin N, Bauer J, Favero GD, Ponti C, Heiss EH, Schwaiger S, Ladurner A, Widowitz U, Loggia RD, Rollinger JM, Werz O, Bauer R, Dirsch VM, Tubaro A & Stuppner H: Lignan derivatives from Krameria lappacea roots inhibit acute inflammation in-vivo and pro-inflammatory mediators in-vitro. Journal of Natural Products 2011; 74(8): 1779–1786.
- Ajima U, Onah JO, Kuje MT, Umar DM, Mzozoyana V, & Ojerinde SO: Synthesis, characterization and cytotoxic activity of 5-aminotetrazole Schiff bases. Journal of Pharmacy & Bioresources 2021; 18(1): 32-39.
- Kim YM, Chae HS, Lee EJ, Yang MH, Park JH, Yoon KD, Kim J, Ahn HC, Choi YH & Chin YW: A citrus flavonoid, 6-demethoxytangeretin, suppresses production and gene expression of interleukin-6 in human mast cell-1 via anaplastic lymphoma kinase and mitogen-activated protein kinase pathways. Biological & Pharmaceutical Bulletin 2014; 37(5): 871–876.
- Li ZH, Zhao TQ, Liu XQ, Zhao B, Wang C, Geng PF & Liu HM: Synthesis and preliminary antiproliferative activity of new pteridin-7 (8H)-one derivatives. European Journal of Medicinal Chemistry 2018; 143: 1396-1405.
- Kumar R & Kumari M: Chemistry of acridone and its analogues: a review. J Chem Pharm Res 2011; 3(1): 217-230.
- Kalix P: Cathinone, a natural amphetamine. Pharmacology & Toxicology 1992; 70(2): 77-86.
- Ali A, Khalil AAK, Khuda F, Nazir N, Ullah R, Bari A & Jan S: Phytochemical and Biological Screening of Leaf, Bark and Fruit Extracts from Ilex dipyrena Wall. Life 2021; 11(8): 837.
- Bayala B, Bassole IHN, Gnoula C, Nebie R, Yonli A, Morel L & Simpore J: Chemical composition, antioxidant, anti-inflammatory and anti-proliferative activities of essential oils of plants from Burkina Faso. PLoS one 2014; 9(3): e92122.
- National Center for Biotechnology Information (2022). PubChem Compound Summary for CID 5311017, Benzphetamine. Retrieved August 12, 2022 from https://pubchem.ncbi.nlm.nih.gov/compound/Benzphetamine.
- Malik EM & Müller CE: Anthraquinones As Pharmacological Tools and Drugs. Medicinal Research Reviews 2016; 36(4): 705–748.
- Mahmood R, Kayani WK, Ahmed T, Malik F, Hussain S, Ashfaq M & Rasheed F: Assessment of antidiabetic potential and phytochemical profiling of Rhazya stricta root extracts. BMC Complementary Medicine and Therapies 2020; 20(1): 1-17.
- Tania AD, Kalalo MJ, Kepel BJ, Niode NJ, Kusumawaty D & Idroes R: Evaluation of the Potential for Immunomodulatory and Anti-inflammatory Properties of Phytoconstituents Derived from Pineapple [Ananas comosus (L.) Merr.] Peel Extract Using an In-silico Philippine Journal of Science 2022; 151(1): 397-410.
- Boness H, de Oliveira MS, Batista C, Almeida LS, Boffo EF, Villarreal CF & Cruz FG: Anti-Inflammatory and Antinociceptive Properties of Kielmeyerone A, a Chromenone Isolated from the Roots of Kielmeyera reticulata. Journal of Natural Products 2021; 84(8): 2157–2164.
- Xie G, Jin S, Li H, Ai M, Han F, Dai Y & Qin M: Chemical constituents and antioxidative, anti-inflammatory and anti-proliferative activities of wild and cultivated Corydalis saxicola. Industrial Crops and Products 2021; 169: 113647.
- Mitsiogianni M, Koutsidis G, Mavroudis N, Trafalis DT, Botaitis S, Franco R & Panayiotidis MI: The role of isothiocyanates as cancer chemo-preventive, chemo-therapeutic and anti-melanoma agents. Antioxidants 2019; 8(4): 106.
- Burčul F, Generalić Mekinić I, Radan M, Rollin P & Blažević I: Isothiocyanates: Cholinesterase inhibiting, antioxidant, and anti-inflammatory activity. Journal of Enzyme Inhibition and Medicinal Chemistry 2018; 33(1): 577-582.
- Dufour V, Alazzam B, Ermel G, Thepaut M, Rossero A, Tresse O & Baysse C: Antimicrobial activities of isothiocyanates against Campylobacter jejuni isolates. Frontiers in Cellular and Infection Microbiology 2012; 2: 53.
- Baky MH, Shawky EM, Elgindi MR & Ibrahim HA: Comparative Volatile Profiling of Ludwigia stolonifera Aerial Parts and Roots Using VSE-GC-MS/MS and Screening of Antioxidant and Metal Chelation Activities. ACS Omega 2021; 6(38): 24788-24794.
- Tonisi S, Okaiyeto K, Hoppe H, Mabinya LV, Nwodo UU & Okoh AI: Chemical constituents, antioxidant and cytotoxicity properties of Leonotis leonurus used in the folklore management of neurological disorders in the Eastern Cape, South Africa. 3 Biotech 2020; 10(3): 1-14.
- Yuan FS, Guo SL, Qiu ZX, Deng SH & Huang GH: Effect of dibutyl phthalate on demodicidosis. Zhongguo ji Sheng Chong xue yu ji Sheng Chong Bing za zhi= Chinese Journal of Parasitology & Parasitic Diseases 2001; 19(3): 160-162.
- Li X, Zhang J, Gao W & Wang H: Study on chemical composition, anti-inflammatory and anti-microbial activities of extracts from Chinese pear fruit (Pyrus bretschneideri). Food and Chemical Toxicology, 2012; 50(10): 3673-3679.
- Yusuf-Babatunde AM, Osuntokun OT, Ige OO & Solaja OO: Secondary metabolite constituents, antimicrobial activity and gas chromatography-mass spectroscopy profile of Bombax buonopozense Beauv. (Bombacaceae) stem bark extract. Research Journal of Pharmacognosy and Phytochemistry 2019; 11(2): 87-92.
- Fodale V & Santamaria LB: Laudanosine, an atracurium and cisatracurium metabolite. European Journal of Anaesthesiology 2002; 19(7): 466–473.
- Vanita K, Megh T and Shivam D: Perilla frutescens – a review on pharmacological activities, extraction procedure and applications Asian Jornal of Pharmaceutical and Clinical Research 2022; 15(8): 34-40.
- Zhou JX, Braun MS, Wetterauer P, Wetterauer B & Wink M: Antioxidant, cytotoxic, and antimicrobial activities of Glycyrrhiza glabra, Paeonia lactiflora Pall., and Eriobotrya japonica (Thunb.) Lindl. extracts. Medicines 2019; 6(2): 43.
- Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P and Steinbeck C: ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res 2016.
- Chai WM, Liu X, Hu YH, Feng HL, Jia YL, Guo YJ, Zhou HT & Chen QX: Antityrosinase and antimicrobial activities of furfuryl alcohol, furfural and furoic acid. International Journal of Biological Macromolecules 2013; 57: 151–155.
- Braga ME, Leal PF, Carvalho JE & Meireles MAA: Comparison of yield, composition, and antioxidant activity of turmeric (Curcuma longa) extracts obtained using various techniques. Journal of Agricultural and Food Chemistry 2003; 51(22): 6604-6611.
- Bagad AS, Joseph JA, Bhaskaran N & Agarwal A: Comparative evaluation of anti-inflammatory activity of curcuminoids, turmerones, and aqueous extract of Curcuma longa. Advances in Pharmacological Sciences 2013.
- Arazi H, Taati B & Suzuki K: A review of the effects of leucine metabolite (β-hydroxy-β-methylbutyrate) supplementation and resistance training on inflammatory markers: A new approach to oxidative stress and cardiovascular risk factors. Antioxidants 2018; 7(10): 148.
- Maruyama CR, Guilger M, Pascoli M, Bileshy-José N, Abhilash PC, Fraceto LF & De Lima R: Nanoparticles based on chitosan as carriers for the combined herbicides imazapic and imazapyr. Scientific Reports 2016; 6(1): 1-15.
- Chiacchio MA, Giofrè SV, Romeo R, Romeo G & Chiacchio U: Isoxazolidines as biologically active compounds. Current Organic Synthesis 2016; 13(5): 726-749.
- Lapoint J & Welker KL: Synthetic amphetamine derivatives, benzofurans, and benzodifurans. Novel Psychoactive Substances 2022; 247-278.
- Celik H, Maman M & Babagil A: Cinnamaldehyde and pmethoxycinnamaldehyde derived Schiff bases antibacterial activities. Int J Sci Eng Res 2018; 9: 640-651.
- Nguyen NTT, Nguyen LTN, Danh Sy T, Nguyen QH, Tu TQ, Van Pham K & Chu MH: Chemical composition and cytotoxic effects of essential oils from Capparis trinervia Hook. F. & Thomson on cancer cell lines. Biotechnology & Biotechnological Equipment 2021; 35(1): 1926-1933.
- Oulaï AC, Djè KM, Eba KP, Adima AA & Kouadio EJP: Chemical composition, antioxidant and antimicrobial activities of Capsicum annuum annuum concentrated extract obtained by reverse osmosis. GSC Biological and Pharmaceutical Sciences 2018; 5(2): 116-125.
- Huang L, Zhu X, Zhou S, Cheng Z, Shi K, Zhang C & Shao H: Phthalic acid esters: Natural sources and biological activities. Toxins 2021; 13(7): 495.
- Rhetso T, Shubharani R, Roopa MS & Sivaram V: Chemical constituents, antioxidant, and antimicrobial activity of Allium chinense Don. Future Journal of Pharmaceutical Sciences 2020; 6(1): 1-9.
- Paprocka R, Wiese M, Eljaszewicz A, Helmin-Basa A, Gzella A, Modzelewska-Banachiewicz B & Michalkiewicz J: Synthesis and anti-inflammatory activity of new 1,2,4-triazole derivatives. Bioorganic & Medicinal Chemistry Letters 2015; 25(13): 2664–2667.
- Alonso-Castro AJ, Zapata-Morales JR, Hernández-Munive A, Campos-Xolalpa N, Pérez-Gutiérrez S & Pérez-González C: Synthesis, antinociceptive and anti-inflammatory effects of porphyrins. Bioorganic & Medicinal Chemistry 2015; 23(10): 2529-2537.
- Escobar A, Perez M, Romanelli G & Blustein G: Thymol bioactivity: A review focusing on practical applications. Arabian Journal of Chemistry 2020; 13(12): 9243-9269.
- Staurengo-Ferrari L, Ruiz-Miyazawa KW, Pinho-Ribeiro FA, Fattori V, Zaninell TH, Badaro-Garcia S, Borghi SM, Carvalho, T. T., Alves-Filho, J. C., Cunha, T. M., Cunha, FQ, Casagrande R & Verri WA: Trans-Chalcone Attenuates Pain and Inflammation in Experimental Acute Gout Arthritis in Mice. Frontiers in Pharmacology 2018; 9: 1123.
- Tang KS: Antioxidant and Anti-inflammatory Properties of Yttrium Oxide Nanoparticles: New Insights into Alleviating Diabetes. Current Diabetes Reviews 2021; 17(4): 496–502.
- Topkara KÇ, Toğar B, Türkez H & Taşpınar N: In-vitro cytotoxic, genotoxic, and oxidative effects of acyclic sesquiterpene farnesene. Turkish Journal of Biology 2014.
- Zhou W, Cai JF, Yuan F, Ma M & Yin F: In-silico targeting of interleukin-6 by natural compounds. Bangladesh Journal of Pharmacology 2014; 9(3): 371-376.
- Kaloni D, Chakraborty D, Tiwari A & Biswas S: In silico studies on the phytochemical components of Murraya koenigii targeting TNF-α in rheumatoid arthritis. Journal of Herbal Medicine 2020; 24: 100396.
- Maste MM & Saxena A: Screening of Plectranthus amboinicus against COVID-19 in-silico Journal of Applied Pharmaceutical Science 2020; 10(12): 090â-097.
- Auerkari EI, Andriawan SR & Auerkari P: Molecular Docking Analysis of Flavonoid Compounds from Glycyrrhiza glabra on the Interleukin–1 Receptor (IL-1R) as a Candidate for Anti-Inflammatory Drug in Periodontitis 2023.
- Boukhatem BS & Belhadj AE: In-silico anti-inflammatory activity of lavender (Lavandula officinalis) essential oil bioactive compounds: Molecular docking analysis of COX-1 and COX-2, and ADMET prediction. AIMS Allergy & Immunology 2023; 7(2).
- Cruz K & Taukolo K: Designing Potential Inhibitors of SARS-CoV-2’s Main Protease from (2S)-N-(4-carbamoylphenyl) oxolane-2-carboxamide. Illinois Mathematics and Science Academy 2022.
- Rudik AV, Bezhentsev VM, Dmitriev AV, Druzhilovskiy DS, Lagunin AA, Filimonov DA & Poroikov VV: MetaTox: web application for predicting structure and toxicity of xenobiotics’ metabolites. Journal of Chemical Information and Modeling, 2017; 57(4): 638-642.
- Lipinski CA: Lead-and drug-like compounds: the rule-of-five revolution. Drug discovery today: Technologies 2004; 1(4): 337-341.
- Mahanthesh MT, Ranjith D, Yaligar R, Jyothi R, Narapp G & Ravi MV: Swiss ADME prediction of phytochemicals present in Butea monosperma (Lam.) Taub. J of Pharma and Phytochemistry 2020; 9(3): 1799-1809.
- Mohan AC, Geetha S, Gajalakshmi R, Divya SR & Dhanarajan MS: Determination of molecular property, bioactivity score and binding energy of the phytochemical compounds present in Cassia auriculata by molinspiration and DFT method. Texila International Journal of Basic Medical Science 2017; 2(2): 1-15.
- Jilani MR and Packirisamy ASB: Terpenoids and Fatty Acid Esters from Underutilized Tiliaceae Shrub Exhibit in-silico Bioactivity and Protein Targets. Top Catal 20230.
- Sekar P, Natarajan V, Shanmugam N & Kandasamy T: Preliminary phytochemical analysis, formulation and evaluation of in-vitro anti-inflammatory potential of the formulated gel obtained from an Ethanolic leaves extract of Coleus amboinicus International Journal of Pharmaceutical Chemistry and Analysis 2023; 10(20): 125-132.
- Leu WJ, Chen JC & Guh JH: Extract from Plectranthus amboinicus inhibit maturation and release of interleukin 1β through inhibition of NF-κB nuclear translocation and NLRP3 inflammasome activation. Frontiers in Pharmacology 2019; 10: 446300.
- Puspitarini S, Dwijayanti DR, Wicaksono ST, Lestari ND, Rahayu RP & Widodo N: Antioxidant Activity and Anti-inflammatory Effect of Indian Borage Against Lipopolysaccharide-Induced Inflammation in Murine Macrophage (RAW 264.7) Cell Line. Tropical Journal of Natural Product Research 2023; 7(12).
- Mousavi MJ, Farhadi E, Vodjgani M, Karami J, Tahmasebi MN, SharafatVaziri A, Asgari M, Rezaei N, Mostafaei S, Jamshidi A & Mahmoudi M: Role of Fibroblast Activation Protein Alpha in Fibroblast-like Synoviocytes of Rheumatoid Arthritis. Iranian Journal of Allergy, Asthma and Immunology 2021.
- Hirano T: Interleukin 6 (IL-6) and its receptor: their role in plasma cell neoplasias. International Journal of Cell Cloning 1991; 9(3): 166–184.
- Tanaka T, Narazaki M & Kishimoto T: IL-6 in Inflammation, Immunity, and Disease. Cold Spring Harbor Perspectives in Biology 2014; 6(10): 16295–16296.
- Misato Hashizume MM: The role of interleukin-1 in the pathogenesis of rheumatoid arthritis. Rheumatology (Oxford, England) 2011; 43: 3.
How to cite this article:
Muthukrishnan S and Muthuswamy S: Discovery of interleukin-6 inhibitory properties of the compounds detected from methanolic leaf extracts of Plectranthus amboinicus (lour) spreng. Through molecular docking. Int J Pharm Sci & Res 2024; 15(8): 2463-83. doi: 10.13040/IJPSR.0975-8232.15(8).2463-83.
All © 2024 are reserved by International Journal of Pharmaceutical Sciences and Research. This Journal licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License.
Article Information
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2464-2483
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English
IJPSR
Suchita Muthukrishnan and Sathyabhama Muthuswamy *
Department of Biotechnology, PSG College of Arts & Science, Coimbatore, Tamil Nadu, India.
msathyabhama@gmail.com
10 March 2024
04 April 2024
17 May 2024
10.13040/IJPSR.0975-8232.15(8).2463-83
01 August 2024