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Computational Molecular Docking and Simulation-Based Assessment of Anti-Inflammatory Properties of Nyctanthes arbor-tristis Linn Phytochemicals.

ABSTRACT: The leaves, flowers, seeds, and bark of the Nyctanthes arbor-tristis Linn plant have been pharmacologically evaluated to signify the medicinal importance traditionally described for various ailments. We evaluated the anti-inflammatory potentials of 26 natural compounds using AutoDock 4.2 and Molecular Dynamics (MDS) performed with the GROMACS tool. SwissADME evaluated ADME (adsorption, distribution, metabolism, and excretion) parameters. Arb_E and Beta-sito, natural compounds of the plant, showed significant levels of binding affinity against COX-1, COX-2, PDE4, PDE7, IL-17A, IL-17D, TNF-α, IL-1β, prostaglandin E2, and prostaglandin F synthase. The control drug celecoxib exhibited a binding energy of -9.29 kcal/mol, and among the tested compounds, Arb_E was the most significant (docking energy: -10.26 kcal/mol). Beta_sito was also observed with high and considerable docking energy of -8.86 kcal/mol with the COX-2 receptor. COX-2 simulation in the presence of Arb_E and control drug celecoxib, RMSD ranged from 0.15 to 0.25 nm, showing stability until the end of the simulation. Also, MM-PBSA analysis showed that Arb_E bound to COX-2 exhibited the lowest binding energy of -277.602 kJ/mol. Arb_E and Beta_sito showed interesting ADME physico-chemical and drug-like characteristics with significant drug-like effects. Therefore, the studied natural compounds could be potential anti-inflammatory molecules and need further in vitro/in vivo experimentation to develop novel anti-inflammatory drugs.

SUBMITTER: Ahmad V

PROVIDER: S-EPMC10820488 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Computational Molecular Docking and Simulation-Based Assessment of Anti-Inflammatory Properties of <i>Nyctanthes arbor-tristis Linn</i> Phytochemicals.

Ahmad Varish V Khan Mohammad Imran MI Jamal Qazi Mohammad Sajid QMS Alzahrani Faisal A FA Albiheyri Raed R

Pharmaceuticals (Basel, Switzerland) 20231222 1

The leaves, flowers, seeds, and bark of the <i>Nyctanthes arbor-tristis Linn</i> plant have been pharmacologically evaluated to signify the medicinal importance traditionally described for various ailments. We evaluated the anti-inflammatory potentials of 26 natural compounds using AutoDock 4.2 and Molecular Dynamics (MDS) performed with the GROMACS tool. SwissADME evaluated ADME (adsorption, distribution, metabolism, and excretion) parameters. Arb_E and Beta-sito, natural compounds of the plant ...[more]

PMID: 38256852

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Project description:BackgroundAn unceasing threat of drug resistance continuously poses demand for new antimalarial drugs. A scientific assessment of traditionally used antimalarial plants through reverse pharmacology is crucial for a fast track drug discovery. An Ayurvedic plant Nyctanthes arbor-tristis Linn. - (Parijat) is being used in clinical practice and had shown antimalarial activity, with a parasite clearance in 76.6% of 120 patients, in an earlier clinical study.ObjectiveTo further explore antimalarial potential of the plant through additional objective markers.Materials and methodsAn open-labelled observational study was conducted at M.A. Podar Hospital - Ayurveda (MAPH-A) after ethics committee approval. Administration of a paste of 5 fresh leaves, thrice a day for a week was a standard practice for management of malaria at MAPH-A. Clinical activity of N. arbor-tristis was evaluated by monitoring pyrexia, parasitemia and morbidity score (MS) in twenty patients. In addition, immune and biochemical markers and organ functions were monitored for objective markers of response. Student's paired-'t' test was applied to assess statistical significance.ResultsTen out of 20 patients showed both fever and parasite clearance, which was confirmed by polymerase chain reaction. Remaining ten patients had persistent but decreasing parasitemia. Four of them needed chloroquine as a fail-safe procedure. Irrespective of the degree of parasitemia all the patients showed decrease in MS. There was also an increase in platelet count and normalization of plasma lactic acid. There was a good clinical tolerability and an improvement in organ function. The inflammatory cytokines showed a reduction; particularly in TNF-α within a day.ConclusionsAt the given dosage, N. arbor-tristis showed disease-modifying activity; early clinical recovery with a decline of TNF-α and a gradual parasite clearance. Further studies with a standardised formulation for dose-searching and optimizing the treatment schedule are needed in a larger sample size.Clinical trial registration noThe process of trial registration had not begun when the study was conducted in 2000.

Project description:Background and aim Orange colored tubular calyx of the flowers of Nyctanthes arbor-tristis contains an apocarotenoid crocin as a major ingredient, which is originally detected to be major colouring principle of saffron stigma. Saffron stigma exhibits good wound healing activity owing to the presence of crocin. The present study is aimed at isolation of crocetin, from tubular calyx of N. arbortristis and improve stability through entrapping in vesicles followed by evaluation of wound healing activity of the topical formulation thereof. Experimental procedure Crocetin was isolated by treating ethanolic extract of tubular calyx of N. arbor-tristis with sodium bicarbonate followed by regeneration of crocetin using hydrochloric acid. The phytosomes were prepared by lipid film hydration technique. The gel containing phytosomes equivalent to crocetin 1% w/w, was then evaluated for wound healing activity through applications on incision and excision wounds inflicted in Wister albino rats. Results Stability of crocetin was found to be increased due to entrapment into phytosomes. The studies revealed that both types of wounds upon treatment with gel containing crocetin phytosomes, indicated good wound healing potential, as the epithelization period was significantly (P < 0.001)decreased as compared to the control group from 26 to 9 days, in excision wound model and significant (P < 0.001)increase in breaking strength of repaired skin, as compared to control from 328.8 to 857.0 gm in incision wound model. Conclusion Crocetin from tubular calyx of Nyctanthes arbor-tristis indicated to be potential wound healing phytoconstituent. Graphical abstract Image 1 Highlights • Significant (P < 0.01) increase in entrapment (71.4%) as compared to the crocin enriched extract (34.4%)• Improved stability with retention of crocetin content in the range of 97–98% w/w in accelerated stability studies• Significant (P < 0.001) reduction period of epithelization (18 days) of excision wound, as compared to control group (26 days).• Significant increase (P < 0.01) in hydroxyproline content in granulation tissue• Significant (P < 0.01) increase in the breaking load of the repaired skin, in case of incision wound• Accelerated healing of both the incision and excision wounds due to topical application of the gel

Project description:BackgroundMalassezia commensal yeasts along with multitude of antigens have been found to be associated with various skin disorders including Pityriasis versicolor (PV). Amongst them Mala s1, a 37 kDa protein has been proved to be a major allergen reacting with a large panel of sera. However, there exists no therapeutic alternative to combat such problems in form of plant based natural compounds. The purpose of this study is in the first place, to determine the anti-Malassezia activity of Nyctanthes arbor-tristis L. (NAT) ethanolic leaf extract through turbidimetric growth curves, disruption of plasma membrane and secondly, it aims to present in silico validation of its active constituents over Mala s1a novel allergen.MethodsThe antifungal susceptibility 50 % ethanolic extract of NAT was determined by broth microdilution method according to CLSI guidelines. Further MICs and IC50 were determined spectrophotometrically using the software SoftMax® Pro-5 (Molecular Devices, USA). Active constituents mediated disruption of plasma membrane was studied through flowcytometry by permeabilization of fluorescent dye Propidium Iodide (PI). Antioxidant activity of the extract was determined using the DPPH stable radical. Molecular validation of fungal DNA from the extract was observed using PCR amplification. In silico analysis of its active constituents over Mala s1 was performed using HEX software and visualized through Pymol.ResultsThe anti-Malassezia potential of NAT leaf extracts reflected moderate MIC 1.05 μg/μl against M. globosa, while least effective against M. restricta with MIC 1.47 μg/μl. A linear correlation coefficient R (2) = 0.866 was obtained in case of M. globosa while minimum was observed in M. restricta with R (2) = 0.732. The flow cytometric data reveal ~ 75 % cell death when treated with active constituents β-Sitosterol and Calceolarioside A. The docking confirmations and the interaction energies between Mala s1 and the active constituents (β-Sitosterol and Calceolarioside A) from extracts showed an effective binding which suggests Mala s1 as efficient allergen for site specific targeting.ConclusionsThis study revealed that Nyctanthes arbor-tristis L. (NAT) extracts possess high anti-Malassezia potential which is driven mainly by disruption of plasma membrane. Also in silico validation and molecular modeling studies establishes Mala s1 as a novel allergen that could be a potential target in disease treatment. Our results would also provide a foundation for the development of new therapeutic approach using NAT extract as lead compound with high antioxidant property as an added trait for skin care.

Project description:Plants and their derived molecules have been traditionally used to manage numerous pathological complications, including male erectile dysfunction (ED). Mimosa pudica Linn. commonly referred to as the touch-me-not plant, and its extract are important sources of new lead molecules in drug discovery research. The main goal of this study was to predict highly effective molecules from M. pudica Linn. for reaching and maintaining penile erection before and during sexual intercourse through in silico molecular docking and dynamics simulation tools. A total of 28 bioactive molecules were identified from this target plant through public repositories, and their chemical structures were drawn using Chemsketch software. Graph theoretical network principles were applied to identify the ideal target (phosphodiesterase type 5) and rebuild the network to visualize the responsible signaling genes, proteins, and enzymes. The 28 identified bioactive molecules were docked against the phosphodiesterase type 5 (PDE5) enzyme and compared with the standard PDE5 inhibitor (sildenafil). Pharmacokinetics (ADME), toxicity, and several physicochemical properties of bioactive molecules were assessed to confirm their drug-likeness property. Molecular dynamics (MD) simulation modeling was performed to investigate the stability of PDE5-ligand complexes. Four bioactive molecules (Bufadienolide (-12.30 kcal mol-1), Stigmasterol (-11.40 kcal mol-1), Isovitexin (-11.20 kcal mol-1), and Apigetrin (-11.20 kcal mol-1)) showed the top binding affinities with the PDE5 enzyme, much more powerful than the standard PDE5 inhibitor (-9.80 kcal mol-1). The four top binding bioactive molecules were further validated for a stable binding affinity with the PDE5 enzyme and conformation during the MD simulation period as compared to the apoprotein and standard PDE5 inhibitor complexes. Further, the four top binding bioactive molecules demonstrated significant drug-likeness characteristics with lower toxicity profiles. According to the findings, the four top binding molecules may be used as potent and safe PDE5 inhibitors and could potentially be used in the treatment of ED.

Dataset Information

Computational Molecular Docking and Simulation-Based Assessment of Anti-Inflammatory Properties of Nyctanthes arbor-tristis Linn Phytochemicals.

Publications

Computational Molecular Docking and Simulation-Based Assessment of Anti-Inflammatory Properties of <i>Nyctanthes arbor-tristis Linn</i> Phytochemicals.

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