Development Of Anti-inflammatory Drugs Research Articles

In Vivo and In Silico Molecular Modeling Studies of Newly Synthesized Pyrazoles for Their Anti-Inflammatory and Analgesic Properties

Background: Pyrazole derivatives have gained attention as potential leads for developing anti-inflammatory and analgesic drugs. Chemical modifications of pyrazole structures offer a strategy to enhance their therapeutic properties, while minimizing undesirable effects. Objective: This study aimed to synthesize novel pyrazole derivatives through chemical modifications and assess their anti-inflammatory and analgesic activities. Methods: A series of pyrazole variants were synthesized by reacting various acetophenone derivatives and diethyl oxalate in basic conditions, followed by treatment with glacial acetic acid and hydrazine hydrate. The resulting compounds were further methylated and acetylated. The synthesized compounds were characterized using elemental analysis, 1H NMR, IR, and MASS spectroscopy. The anti-inflammatory activity was evaluated using the rat paw edema technique induced by carrageenan, while the analgesic activity was assessed using the writhing reflux method. Results: Among the newly synthesized pyrazole derivatives, compounds 3b, 3e and 3g′ demonstrated significant anti-inflammatory activity with reduced ulcerogenic potential. Compounds 3d, 3b′ and 3d′ exhibited notable analgesic activity compared to the standard drug. The chemical modifications introduced in these derivatives were confirmed through spectroscopic analyses. Conclusion: The findings of this study highlight the potential of pyrazole derivatives as promising candidates for anti-inflammatory and analgesic drug development. The structural modifications performed in this research improved the therapeutic activities of the compounds, while addressing safety concerns. Further investigations are warranted to elucidate the underlying mechanisms of action and optimize the pharmacological profiles of these novel pyrazole derivatives.

Editorial: Anti-inflammatory drug development focusing on immune mediated diseases

Editorial: Anti-inflammatory drug development focusing on immune mediated diseases

Potential of natural products in inflammation: biological activities, structure-activity relationships, and mechanistic targets.

A balance between the development and suppression of inflammation can always be found in the body. When this balance is disturbed, a strong inflammatory response can damage the body. It sometimes is necessary to use drugs with a significant anti-inflammatory effect, such as nonsteroidal anti-inflammatory drugs and steroid hormones, to control inflammation in the body. However, the existing anti-inflammatory drugs have many adverse effects, which can be deadly in severe cases, making research into new safer and more effective anti-inflammatory drugs necessary. Currently, numerous types of natural products with anti-inflammatory activity and distinct structural features are available, and these natural products have great potential for the development of novel anti-inflammatory drugs. This review summarizes 260 natural products and their derivatives with anti-inflammatory activities in the last two decades, classified by their active ingredients, and focuses on their structure-activity relationships in anti-inflammation to lay the foundation for subsequent new drug development. We also elucidate the mechanisms and pathways of natural products that exert anti-inflammatory effects via network pharmacology predictions, providing direction for identifying subsequent targets of anti-inflammatory natural products.

Structural Characterization and Screening for Anti-inflammatory Activity of Polysaccharides with Different Molecular Weights from Astragali Radix.

Astragali Radix polysaccharides (APSs)exhibit a broad spectrum of biological activity, which is mainly related to immune regulation. At present, most available studies focus on total APSs or a certain component of APSs. However, structuralstructure study and screening for theanti-inflammatory activity of polysaccharides with different molecular weights (MW) have yet to be conducted. In this study, lipopolysaccharide (LPS)-induced RAW264.7 macrophages were used as a model to investigate the anti-inflammatory activity of APSs and its fractions. The results revealed that fractionAPS-I had better anti-inflammatory effectsthan APS-II. After APS-Ⅰ washydrolyzed by trifluoroacetic acid (TFA),the resulting degradation products oligosaccharideswere fully methylated. These derivatizedoligosaccharideswere further analyzed by MALDI-TOF-MS and UPLC-Q-Exactive-MS/MS.The results showed that APS-Ⅰ wasa hetero-polysaccharide with a molecular weight of about2.0 × 106Da, mainly consisting of glucose (46.8%) and galactose (34.4%).The degree of polymerization of Astragali Radixoligosaccharides (APOS)was 2-16. APOSwereidentified as 1,4-glucooligosaccharides and 1,4-galactooligosaccharides. The findings of this study lay the foundation for further elucidation of structure-function relationships of APSs and provide guidance for the development of anti-inflammatory drugs.

Total synthesis/semi-synthesis of natural isopentenyl flavonoids with inhibitory activity on NLRP3 inflammasome

Inflammation is the body's defense response to stimuli. When the homeostatic balance is disturbed, disease may result. Flavonoids have clear anti-inflammatory effects and the isopentenyl group significantly enhances the pharmacological activity of flavonoids. Therefore, isopentenyl flavonoids have the potential to serve as lead compounds for the development of anti-inflammatory drugs. Throughout this research, eight natural compounds were synthesized, including 5,7-dihydroxy-4′-methoxy-8-prenylflavonoid (1), 4′-O-Methylatalantoflavone (2), Kushenol W (3) and Racemoflavone (5), which were totally synthesized for the first time. Additionally, three flavonols: Licoflavonol (6), 3,5,7,3′,4′-pentahydroxy-6-prenylflavonol (7) and Macarangin (8), can be one-step synthesized by direct C-isopentenylation. In the process, an economical and efficient C-isopentenylation method was also simultaneously explored that could facilitate the efficient synthesis of natural products. These compounds were evaluated for their potential anti-inflammatory activities via the NLRP3 signaling pathway. Notably, Macarangin (8) manifested the most potent inhibitory effect. The SAR (Structure-Activity Relationships) also showed the introduction of the isopentenyl group was determined to enhance these effects, whereas simple flavonoid frameworks or cyclization of isopentenyl groups all diminished anti-inflammatory activity.

Anti-Inflammatory Effect of Ethanolic Leaves Extract of <i>Sansevieria trifasciata</i> and <i>Sansevieria liberica</i> in Swiss Mice, (<i>Mus musculus</i>)

The aim of this study was to examine the anti-inflammatory properties of Sansevieria trifasciata, also known as mother-in-law tongue, and Sansevieria liberica ethanolic leaf extract on mice, (Mus musculus). In a scientific setting, plant powder was extracted using 70% ethanol over a 72-hour period. Using the test animals, the extracts’ median lethal dose (LD50) was established. The soluble portion of the extracts was given at working doses of 10, 20, and 30% of the LD50 to the corresponding experimental animal groups (i.e low, middle, and high dosages accordingly). Findings from Sansevieria trifasciata and S. liberica’s phytochemical screening indicated the existence of secondary metabolites like terpenes, alkaloids, cardiac glycosides, and tannins. When given intraperitoneally, the LD50 of S. trifasciata and S. liberica were 387.30 and 353.55 mg/kg, respectively. The plant extracts’ soluble fraction was given intraperitoneally (i.p.) by injection as well as orally. The phlogistic egg-albumin-induced inflammation significantly decreased (p<0.05) according to the results. However, the development of a strong anti-inflammatory drug with low toxicity and an improved therapeutic index may come from the isolation of these bioactive components.

A Strain-Promoted Divergent Chemical Steroidation Unveils Potent Anti-Inflammatory Pseudo-Steroidal Glycosides.

The development of novel agents with immunoregulatory effects is a keen way to combat the growing threat of inflammatory storms to global health. To synthesize pseudo-steroidal glycosides tethered by ether bonds with promising immunomodulatory potential, we develop herein a highly effective deoxygenative functionalization of a novel steroidal donor (steroidation) facilitated by strain-release, leveraging cost-effective and readily available Sc(OTf)3 catalysis. This transformation produces a transient steroid-3-yl carbocation which readily reacts with O-, C-, N-, S-, and P-nucleophiles to generate structurally diverse steroid derivatives. DFT calculations were performed to shed light on the mechanistic details of the regioselectivity, underlying an acceptor-dependent steroidation mode. This approach can be readily extended to the etherification of sugar alcohols to enable the achievement of a diversity-oriented, pipeline-like synthesis of pseudo-steroidal glycosides in good to excellent yields with complete stereo- and regiospecific control for anti-inflammatory agent discovery. Immunological studies have demonstrated that a meticulously designed cholesteryl disaccharide can significantly suppress interleukin-6 secretion in macrophages, exhibiting up to 99% inhibition rates compared to the negative control. These findings affirm the potential of pseudo-steroidal glycosides as a prospective category of lead agents for the development of novel anti-inflammatory drugs.

Novel 1,3,4-oxadiazole derivatives as highly potent microsomal prostaglandin E2 synthase-1 (mPGES-1) inhibitors

Selective inhibition of microsomal prostaglandin E2 synthase-1 (mPGES-1) is implicated as a new therapeutic modality for the development of new-generation anti-inflammatory drugs. Here, we present the discovery of new and potent inhibitors of human mPGES-1, i.e., compounds 13, 15–25, 29–30 with IC50 values in the range of 5.6–82.3 nM in a cell-free assay of prostaglandin (PG)E2 formation. We also demonstrate that 20 (TG554, IC50 = 5.6 nM) suppresses leukotriene (LT) biosynthesis at low µM concentrations, providing a benchmark compound that dually intervenes with inflammatory PGE2 and LT biosynthesis. Comprehensive lipid mediator (LM) metabololipidomics with activated human monocyte-derived macrophages showed that TG554 selectively inhibits inflammatory PGE2 formation over all cyclooxygenase (COX)-derived prostanoids, does not cause substrate shunting towards 5-lipoxygenase (5-LOX) pathway, and does not interfere with the biosynthesis of the specialized pro-resolving mediators as observed with COX inhibitors, providing a new chemotype for effective and safer anti-inflammatory drug development.

Utilization of diamondback puffer (Lagocephalus guentheri) biomass for the production of bioactive oligopeptides and their inflammation suppressing effects invitro

Development of new anti-inflammatory drugs has always been of prime interest due to various side effects exerted by common non-steroidal anti-inflammatory drugs (NSAIDs). Hence, due to the biochemical diversity and efficient anti-inflammatory activities of bioactive peptides from oceanic sources, their demand is increasing. In this study, the common diamondback puffer fish (Lagocephalus guentheri) muscle (PM) and visceral (PV) mass waste was used to produce enzymatic hydrolysates using trypsin, alcalase and papain digestion which were further used to obtain inflammation suppressing peptides. High pressure liquid chromatography (HPLC) analysis showed abundant essential amino acids like arginine, alanine, tyrosine, and glutamic acid in muscle as well as visceral part. The data obtained by the anti-inflammatory assays such as albumin denaturation inhibition and membrane stabilization assay of hydrolysates showed that alcalase 12th hr and 6th hr showed highest activity for PM and PV respectively. Further, out of the fractions obtained through ultrafiltration, 10-3 kDa showed higher anti-inflammatory activity which was subsequently purified with gel filtration chromatography. Moreover, the purified active peaks were analysed using LC-MS/MS to acquire a peptide sequence of MEPLGQG (731 Da) and LLHA (453 Da) for PMpep and PVpep respectively. In vitro studies revealed non-cytotoxic effects of peptide and pro-inflammatory cytokine suppression post LPS-stimulation in RAW264.7 cells. Thus, the puffer fish and other marine waste can be exploited for the isolation of potential nutraceutical and therapeutic compounds.

Development of Anti-Inflammatory Drug from Crataeva Nurvala: In Silico and In Vitro Approach

ABSTRACT Background: Crataeva nurvala, a medicinal plant with potential therapeutic properties, offers a promising avenue for the development of novel anti-inflammatory drugs. This study adopted a combined in silico and in vitro approach to investigate the anti-inflammatory potential of compounds derived from Crataeva nurvala. Materials and Methods: In the in silico phase, virtual screening and molecular docking analyses were conducted to identify bioactive compounds from Crataeva nurvala that could interact with key inflammatory targets. Subsequently, selected compounds were synthesized and subjected to in vitro experimentation. Cellular models were employed to assess the anti-inflammatory effects of Crataeva nurvala-derived compounds, focusing on the modulation of pro-inflammatory cytokine levels and the underlying signaling pathways. Results: Virtual screening and molecular docking led to the identification of several bioactive compounds with favorable interactions with inflammatory targets. In the in vitro experiments, treatment with Crataeva nurvala-derived compounds resulted in a significant reduction in pro-inflammatory cytokine production. Moreover, the compounds exhibited the ability to modulate inflammatory signaling pathways, further substantiating their anti-inflammatory potential. Conclusions: This study not only contributes to the development of effective anti-inflammatory drugs but also underscores the value of harnessing natural sources such as Crataeva nurvala for therapeutic interventions in inflammatory disorders. The dual-phase strategy presented here provides a robust framework for anti-inflammatory drug discovery and validation.

In-vitro and In-vivo Studies of Anti-inflammatory Potential of Compounds Derived from Piper mullesua

The identification and development of new anti-inflammatory drugs continue to benefit greatly from the use of natural substances and their synthetic counterparts. Studies have been conducted on a compounds obtained from the Piper mullesua plant. The current work aims to use in-vitro and in-vivo experiments to investigate these substances’ anti-inflammatory properties. Our investigation’s findings showed that various substances had varying percentages of cell viability on RAW 264.7 cells. These substances were also tested for suppression of nitric oxide. Novel approaches to the creation of pharmaceuticals have demonstrated the potential of natural product derivatives. This study set out to investigate PM208-209’s potential anti-inflammatory properties. The impact of PM208-209 on inhibiting tumor necrosis factor-alpha (TNF-α) and IL-6 in LPS-induced RAW 264.7 cells was examined using enzyme-linked immunosorbent assay (ELISA). Additionally, PM208-209 demonstrated anti-inflammatory effects in mice, as evidenced by the suppression of vascular permeability and migration of leukocytes. The information gathered suggested that PM208-209 should be investigated further in terms of pharmacological research and could be regarded as a possible therapeutic anti-inflammatory option

Molecular docking of quercetin: a promising approach for the development of new anti-inflammatory and analgesic drugs

The aim of this study is to investigate the antinociceptive, anti-inflammatory and antipyretic effects of quercetin. Additionally, molecular docking studies were conducted to evaluate potential interactions between quercetin and various molecular targets. Animal models were used to conduct a comprehensive pharmacological investigation of quercetin. Evaluation of analgesic activity revealed a reduction in the number of abdominal cramps during the twisting test and inhibition of pain during the second phase of the formaldehyde test. Additionally, evaluation of its anti-inflammatory activity showed a reduction in ear oedema. However, it is important to note that quercetin administration has not been shown to significantly reduce yeast-induced hyperthermia. The docking study revealed the high inhibitory potential of quercetin against the COX-2 receptor.

Precise cuts for tailoring chromene-phenyl COX inhibitors with Ligand Designer

Cyclooxygenases 1 and 2 (COX-1/2) are enzymes renowned for inducing inflammatory responses through the production of prostaglandins. Thus, the development of COX inhibitors has been a promising approach for identifying compounds with anti-inflammatory potential. In this study, we designed 27 new compounds (1–27) based on the structure of a previously known COX inhibitor, using the Ligand Designer tool. Our aim was to improve the affinity of the compounds with COX enzymes by inducing interactions with residue Arg120 while retaining the good π-π stacking interactions of the chromene-phenyl scaffold. Through screening based on ligand-binding free energy defined by molecular docking simulations and MM/GBSA technique, compounds 9 and 10 were identified as having the highest ability to inhibit COX proteins. The binding affinities of the two compounds with COX-1/2 were superior to those of the original NAI10 compound and the reference drug indomethacin. Our virtual screening suggests that compounds 9 and 10 have a strong ability to inhibit COX-1/2 and thus could be promising candidates for further anti-inflammatory drug studies. In essence, our study underscores the pivotal role of the N-aryl iminocoumarin scaffold in shaping the future landscape of novel anti-inflammatory drug development.

Synthesis of urolithin derivatives and their anti-inflammatory activity

Two series of urolithin derivatives, totally 38 compounds, were synthesized. Their anti-inflammatory activity was investigated by detecting the inhibitory effects on the expression of TNF-α in bone marrow-derived macrophages (BMDMs), showing that 24 of 38 ones reduced the expression of TNF-α. Compound B2, the ring C opened derivative of urolithin B with a butoxycarbonyl substitution in ring A, showed the strongest inhibitory activity compared with that of indomethacin. Furthermore, B2 treatment decreased the expression of pro-inflammatory factors IL-1β, IL-6, iNOS and COX-2. Mechanically, the anti-inflammatory effect of B2 was related to the inhibition of NF-κB signaling pathway. These results clearly illustrated that B2 hold potential for application as an anti-inflammatory agent. The present study provided a viable approach to modify the gut metabolites for anti-inflammatory drug development.

Antinociceptive effect and anti-inflammatory activity of 1,4-naphthoquinones in mice

Aim: The ability of synthetic 1,4-naphthoquinones (1,4-NQs) to prevent adenosine triphosphate (ATP)-induced and purinergic P2X7 receptor (P2X7R) mediated inflammation in macrophage and neurodegeneration of neuronal cells in vitro was previously established. The aim of the present study was to investigate analgesic-like and anti-inflammatory activity of 1,4-NQs thioglucoside derivatives, compounds U-286 and U-548, in in vivo experiments. Methods: Spectrofluorimetry approach and YO-PRO-1 fluorescent dye uptake determination were applied to study the effect of 1,4-NQs upon ATP-induced P2X7R mediated macropore formation in mouse neuroblastoma Neuro-2a cells and macrophages RAW 264.7 cells. An acetic acid-induced writhing test, hot plate test, and carrageenan-induced paw edema test were used as an in vivo mouse models to study the ability of 1,4-NQs to inhibit pain and inflammation. In the in vivo experiments, compounds were administered to mice intraperitoneally at dosages of 0.1 mg/kg, 1.0 mg/kg and 10.0 mg/kg. A group of animals that received injections of sterile water was used as a control. Each dosage group and the control group consisted of 6 mice. Results: In the present work the analgesic-like and anti-inflammatory activity of 1,4-NQs, U-286 and U-548, was demonstrated. Compound U-548 showed a significant inhibitory effect in antinociceptive tests reducing the number of mouse writhings and eliminating the latent time of mouse hind paw licking, correspondingly. Selected compounds were able to almost completely reduce the size of carrageenan-induced paw edema 24 h after injection and had a potent anti-inflammatory activity. Observed effects were accompanied with aptitude of studied 1,4-NQs to inhibit the formation of purinergic P2X7R macropore associated with inflammation and nociceptive pain. Conclusions: The results obtained allow to consider compounds U-286 and U-548 and as a pharmacological basis for the development of new analgesic-like and anti-inflammatory drugs.

Analgesic and Anti-Inflammatory Potential of the New Tetrahydropyran Derivative (2s,6s)-6-ethyl-tetrahydro-2h-pyran-2-yl) Methanol.

The development of analgesic and anti-inflammatory drugs plays a crucial role in modern medicine, aiming to alleviate pain and reduce inflammation in patients. Opioids and nonsteroidal anti-inflammatory drugs are groups of drugs conventionally used to treat pain and inflammation, but a wide range of adverse effects and ineffectiveness in some pathological conditions leads us to search for new drugs with analgesic and anti-inflammatory properties. In this regard, the authors intend to investigate the ((2s,6s)-6-ethyl-tetrahydro-2h-pyran- 2-yl) methanol compound (LS20) on pain and acute inflammation. Male Swiss mice were evaluated using acetic acid-induced abdominal writhing, formalin, and tail-flick as models of nociceptive evaluation and edema paw, air pouch and cell culture as models of inflammatory evaluation besides the rotarod test for assessment of motor impairment. The compound showed an effect on the acetic acid-induced abdominal writhing, formalin and tail-flick tests. Studying the mechanism of action, reversion of the antinociceptive effect of the compound was observed from previous intraperitoneal administration of selective and non-selective opioid antagonists on the tail flick test. In addition, the compound induced an antiedematogenic effect and reduced leukocyte migration and the production of pro-inflammatory cytokines in the air pouch model. LS20 was able to maintain cell viability, in addition to reducing cell production of TNF-α and IL-6. In summary, the LS20 compound presented an antinociceptive effect, demonstrating the participation of the opioid system and an anti-inflammatory effect related to the inhibition of proinflammatory cytokine production. The compound also demonstrated safety at the cellular level.

Anti-inflammatory ability of licorice (Glycyrrhiza glabra) root extract in cyclooxygenase-2 enzyme inhibition: In silico study

Background: Inflammation represents the body's natural response to injury, which can be induced by chemical, physical, or biological agents. Current approaches to managing inflammatory conditions involve addressing the primary etiological factors and administering anti-inflammatory medications like Nonsteroid Anti Inflammatory Drugs (NSAIDs) in inhibiting cyclooxygenase 2 (COX-2). However, data from 2021 reveals that 78.8% of patients experience gastritis as a side effect of such treatment. Licorice root extract (LRE)-an ayurvedic plants emerges as a promising alternative due to its potent anti-inflammatory properties attributed to the presence of glycyrrhizin, constituting between 2% to 25% of its dry weight. Objectives: To find out and determine the molecular inhibition of compound in LRE against COX-2 enzyme. Method: The process involves isolating the active constituents of LRE using pubchem and BioVia application, isolation active site of COX-2 by exploring RCSB PDB and isolate it using PyMol and engaging in molecular docking simulations using PyRx. Results and discussions: Cyclooxygenase-2 (COX-2) emerges as a pivotal enzymatic orchestrator intricately woven into the fabric of the inflammatory cascade. Licorice root extract stands at the forefront of prospective candidates in the realm of anti-inflammatory drug development, buoyed by its remarkable anti-inflammatory attributes. Regarding to ∆Gbind value, molecular docking tests show LRE compounds inhibit COX-2 better than arachidonic acid and mefenamic acid. Six LRE compounds outperform reference compounds, indicating potential anti-inflammatory capabilities. Other compounds show anti-inflammatory activity, and RMSD values affirm the accuracy of in silico predictions. Conclusion: LRE had potential as oral topical anti-inflammatory drugs through COX-2 inhibition with the best anti-inflammation ability is 18β‐glycyrrhetic acid.

Comparison of supercritical CO2 extraction and pressurized fluid extraction for isolation of alkaloids from Anacardium occidentale with the study of its anti-inflammatory activity

In recent years, there has been a growing interest in the therapeutic potential of natural compounds, particularly of plant origin, owing to their demonstrated anti-inflammatory properties. Among these, Anacardium occidentale, commonly known as cashew, has garnered significant attention due to its reputed health benefits. This study aim to establish a correlation between the bioactive compounds contained in the extracts of Anacardium occidentale and its anti-inflammatory activity. Dried Anacardium occidentale leaves powder was used as the extraction matrix. Extraction techniques are maceration, pressurized fluid extraction (PFE), and supercritical fluid extraction (SFE). The preliminary analysis of extracts was made by LC-MS/MS. The Response Surface Methodology (RSM), Principal Component Analysis (PCA), and heat maps were employed to model the influence of experimental conditions on extraction yield and peak area of specific compounds from the plant. To evaluate anti-inflammatory activity, RAW 264.7 cells were cultured, activated with LPS, and treated with varying concentrations of the plant extracts. Cell proliferation was assessed using the XTT assay. Indeed, Anacardium occidentale extracts contain anacardic acids, cardanols, and cardol, with distinct profiles yielded by SFE and ethanol-based methods. RSM shows that temperature and ethanol, as additives to CO2, significantly affect extraction efficiency in both PFE and SFE. Moreover, this composition with SFE demonstrate higher selectivity for specific group of compounds. The extracts exhibit anti-inflammatory properties without cytotoxicity in macrophages, reducing levels of pro-inflammatory proteins COX-2, COX-1, and TLR4 in activated cells. This suggests their potential as anti-inflammatory agents without adverse effects on cell viability or pro-inflammatory protein levels in non-activated cells. Overall, these findings underscore the promising therapeutic potential of Anacardium occidentale extracts in mitigating inflammation, while also providing crucial insights into optimizing the extraction process for targeted compound isolation. Thus, this makes a good prospect for the development of anti-inflammatory drugs from this plant.

1-Benzylindoles as inhibitors of cytosolic phospholipase A2α: synthesis, biological activity, aqueous solubility, and cell permeability.

Cytosolic phospholipase A2α (cPLA2α) is considered an interesting target for the development of new anti-inflammatory drugs, as it is significantly involved in the formation of pro-inflammatory lipid mediators. Recently, in a ligand-based virtual screening approach, 2,4-dichlorobenzyl-substituted 4-[2-(indol-3-ylmethylene)hydrazineyl]benzoic acid 7 was found to be an inhibitor of cPLA2α with micromolar activity. This compound has now been systematically varied to increase inhibitory potency. The studies performed led to 5-(1-benzylindol-3-ylmethyl)-2H-tetrazol-2-yl)pentanoic acid derivatives that exhibited submicromolar activity against the enzyme. The most potent compounds were also tested for their water solubility and for permeability in a Caco-2 model. Among other things, it was found that in Caco-2 cells, the pentanoic acid chain of the molecules can be metabolised to a considerable extent to propionic acid by β-oxidation.

Exploring the Anti-Inflammatory Potential of Phytochemicals from Anvillea radiata: In Vitro Assay, Molecular Docking, and Molecular Dynamics Simulations

Abstract This study delves into the comprehensive evaluation of phytochemicals extracted from Anvillea radiata, with a focus on their potential anti-inflammatory applications. High-performance liquid Chromatography analysis reveals the dominance of catechin in the aqueous extract, alongside other compounds such as syringic acid, 3,4-dihydroxybenzoic acid, and vanillic acid, as well as quercetin-3-β-D-glucoside and rutin in smaller quantities. An in vitro anti-inflammatory assay demonstrates the superior effectiveness of A. radiata aqueous extract at lower concentrations compared to Aspirin, raising possibilities for reduced side effects and enhanced cost-effectiveness. Drug-likeness predictions emphasize the potential of catechin, syringic acid, and vanillic acid for drug development due to their molecular characteristics. Toxicity risk assessment indicates that catechin, quercetin-3-β-D-glucoside, and rutin exhibit low toxicity risks and favorable drug-likeness properties. Molecular docking analysis highlights promising interactions between the identified compounds and crucial anti-inflammatory (COX-2, MPO, IL1β, IL6, and TNFα.) target proteins. Notably, catechin demonstrates a strong binding affinity to these proteins. Molecular dynamics simulations further support catechin’s potential, revealing significant deformability in complexes with COX-2 and MPO, indicating high structural flexibility. The variance map shows higher cumulative variances and the elastic network map yields satisfactory outcomes, further reinforcing the potential of A. radiata aqueous extract compounds, with catechin as a standout candidate for anti-inflammatory drug development.