Atopic dermatitis (AD) is a rapidly escalating global health concern, affecting up to 20 % of children and 10 % of adults, with current therapies often proving inadequate due to limited efficacy, adverse effects, and lack of multi-target action. This study addresses a significant knowledge gap by investigating a novel, multi-targeted combination strategy involving luteolin, quercetin, and cetirizine to modulate key molecular mechanisms underlying AD, namely oxidative stress, inflammatory signaling, and histamine-mediated immune response. We hypothesized that the combination of these three compounds would exert synergistic anti-inflammatory and antioxidant effects, surpassing their individual performances using computational studies and experimental validation. In silico molecular docking revealed strong binding affinities of luteolin and quercetin with thymic stromal lymphopoietin (TSLP) at -6.2 and -6.4 kcal/mol, respectively, while cetirizine showed the highest affinity for histamine H1 receptor (-9.1 kcal/mol). Molecular dynamics simulations over 100 ns confirmed stable ligand-protein interactions. Network pharmacology analysis further suggested these compounds collectively modulate key signalling pathways in AD pathogenesis. In vitro assays validated these findings, with the combination showing superior DPPH radical scavenging (IC50: 1.5394 ± 0.056 µg/mL), NO• assay (84.1 ± 1.68 %), and anti-inflammatory activity via albumin denaturation (88.2 ± 1.76 %). A synergy value of 35.37±1.52 % confirmed a positive interaction. These results support the therapeutic promise of this flavanoid-antihistamine combination as a multi-targeted strategy for AD management.

Alzheimer's disease (AD) is a commonly occurring neurodegenerative disease in elderly and it is a leading cause of dementia worldwide. Hydroxychavicol (HC), a major phenolic component of Piper betle, has prominent anti-inflammatory and antioxidant properties, and studies have found its role in cognition improvement. Here is a systematic approach to deciphering the potential protein targets of HC in AD through network pharmacology and validation from molecular docking and dynamics simulation study. First, the druglikeliness of HC was predicted using the SwissADME analysis, which showed significant druglikeliness. A total of 88 possible target genes between HC and AD were obtained from the Swiss Target Prediction, HIT Version 2, DisGeNET, and GeneCards database. The pathway analysis was carried out using the STRING database which showed several genes including COMT, HSP90AA1, and GAPDH as the top hub genes on the basis of degree. GO and KEGG analyses demonstrated that the core targets were mainly involved in cAMP, PI3K/AkT, HIF1, Rap1, and Calcium signaling pathways. The molecular docking of HC with top hub genes resulted in the highest binding of HC with COMT (-8.9 kcal/mol), GAPDH (-6.7 kcal/mol), and HSP90AA1 (-6.5 kcal/mol) that showed stable binding in the molecular dynamics simulation study. COMT regulates the dopamine levels in the prefrontal cortex and impairment of the COMT is associated with the rapid progression of AD. HSP90, a ubiquitous molecular chaperone, is involved in regulating tau metabolism and Aβ processing and found to be downregulated in AD. GAPDH has been reported as the disease-susceptible gene in AD and its interaction with amyloid precursor protein and NFTs has also been reported. These findings suggest that HC is a promising therapeutic candidate, targeting multiple AD-related pathways, warranting further investigation into its molecular mechanisms and potential for clinical application.

Neuroblastoma is the extracranial of children characterized by diverse clinical manifestations. The present study aimed to investigate the anti-neuroblastoma activity of hydromethanolic extract of Callistemon viminalis (Sol. ex Gaertn.) flower. The anti-neuroblastoma activity of hydromethanolic extract of C. viminalis flower was analysed in SH-SY5Y cell line using MTT assay. The study also evaluated drug-likeness and pharmacokinetic properties of bioactive compounds of extract using SwissADME tool and conducted in silico analysis to determine the molecular interaction between ascorbic acid and 5-LO for explaining the anti-neuroblastoma effect. Significant cytotoxicity was observed in SH-SY5Y cells in a dose and time dependent manner. The ADMET properties of the analysed bioactive compounds of C. viminalis showed them as a suitable drug candidate with appropriate pharmacokinetic properties. In silico results revealed that ascorbic acid binds into the catalytic domain and interacted with Ser447, Tyr470 and Arg457 of 5-LO with a binding energy of -5.11 Kcal/mol. The total phenol and ascorbate content were found to be 18.71 mg CAE/gm and 16.8 mg/100gm of extract, respectively. Hydromethanolic extract of C. viminalis flower induced cytotoxic effect in human neuroblastoma SH-SY5Y cells via interaction of its constituent ascorbic acid with the 5-LO, one of the important mediators of Neuroblastoma.

Background Diarrhoea has become one of the major areas of concern due to its high mortality rate contributing it to be the second largest cause of death in world. To explore the effectiveness of medicinal plant, the present investigation was undertaken to scientifically justify the traditional claim of the ethanolic root extract of the plant Begonia rubrovenia (EBV) against diarrhoea. Results EBV was standardized using HPLC with quercetin as marker and was further subjected to normal fecal excretion study at 100, 200 and 300 mg/kg, p.o. along with quercetin and loperamide. The study confirmed the effectiveness of EBV at 200 and 300 mg/kg followed by quercetin. In castor oil induced diarrhoea rat model, EBV at 200 and 300 mg/kg significantly delayed onset of diarrhoea, reduced the diarrhoeal faecal output which contributed in higher % protection. The effectiveness of EBV at 200 mg/kg was also confirmed through gastrointestinal motility, fluid accumulation and PGE 2 induced enteropooling tests. EBV and its marker quercetin also reduced the elevated level of NO and cytokines and restored the alterations in antioxidant enzymes, ions and enhanced Na + /K + –ATPase activity. Molecular docking, dynamics and network pharmacology study confirmed the role of quercetin in modulating the inflammatory mediators IL-1β, TNF-α and EP3 prostanoid receptor, where quercetin formed more stable complex with EP3 prostanoid receptor. Conclusion The study has scientifically justified the traditional use of the plants B. rubrovenia in treating diarrhoea, where quercetin played a critical role in the observed antidiarrhoeal potential of B. rubrovenia contributing in maintaining electrolyte balance, antioxidant status and inhibiting inflammatory mediators.

[This corrects the article DOI: 10.1016/j.jtcme.2023.05.001.].

The area of system biology is a combination of experimental large-scale measurement techniques and computational approaches to interrogate, model and understand life at the level of organismal system itself. The applications of system-wide approaches in understanding the factors that affect human health and diseases is opening a novel area with great prospects. In this chapter, the area of system biology has been described with the current status, and its impact on the individual and population. The application of system biology in developing a framework for modelling living systems and diseases is discussed. Further the utility of systems biology in molecular diagnostics, genetic techniques, deletion/duplication analysis, targeted variant analysis, DNA methylation, pathway-based biomarker analysis, gene interaction maps and disease genes identification etc. is described. These current knowledge of significant contribution in the field may stimulate further discussion and debates in other areas in addition to systems biology. In this way, the systems medicine will realize its full potential and promises within societal standards.

The term neurodegenerative disease means the loss of neuronal cells in the brain, including Alzheimer's disease, Parkinson's disease, Multiple sclerosis, and Huntington's disease. It is one of the most common types of disease associated with elevated rates of mortality and morbidity worldwide. At the same time, modern allopathic medicines have a large number of synthetic chemicals for the symptomatic treatment and control of these diseases. These drugs have failed miserably due to clinical insufficiency and debilitating adverse effects. In the past decade, natural ingredients have gained notable interest in the prevention and treatment of neurodegeneration due to their powerful anti-inflammatory and anti-oxidant properties with minimal side effects. However, there is also an issue of safety and effectiveness due to the absence of an ample amount of research findings. The most common cellular mechanism for every neurodegenerative disorder is neuroinflammation and oxidative stress. Several preclinical and clinical studies conducted across the world have demonstrated that different bioactive compounds of herbal origin can potentially arrest these processes to prevent or treat neurodegeneration and can be developed into promising pharmaceutical formulations. This article discusses and analyses the various herbal compounds, such as Allium sativum, Camella sinensis, Centella asiatica, Coriandrum sativum, Crocus sativus, Glycyrrhiza glabra, and Morus alba used for phytotherapy of neurodegenerative diseases by combining recent in vitro and in vivo models.

The plant Begonia roxburghii, widely distributed in North East India, is regularly used as a vegetable and food item in these areas. The plant's roots are traditionally used in treating digestive disorders, diarrhoea, dysentery and various stomach ailments. Therefore, the main objective included scientific justification of the traditional assertions about the edible roots and its marker flavonoids from the plant in the treatment of diarrhoea, followed by deriving its mechanism. HPLC was used to standardize the ethanolic extract of B. roxburghii (EBR) with respective markers luteolin and rutin. The study revealed the similar antibacterial potential of both the markers (luteolin and rutin); however, normal faecal excretion showed the highest antisecretory potential of EBR followed by rutin. EBR at 300 mg/kg, p.o. demonstrated the highest % protection from diarrhoea in both nonpathogenic (castor oil-induced) and pathogenic (enteropathogenic E. coli-induced) diarrhoea rat models, which also restored the altered biochemical parameters, ion concentration and cytokine levels. EBR and rutin also justified their protective nature through histopathology showing less broadening of villus and intact epithelia compared to diarrhoea control rat colons. The in-silico studies validated the contribution of rutin as a major biomarker which enhanced Na+/K+-ATPase activity and stabilized the C-terminal 282-residue fragment of EPEC intimin and was also supported by findings of network pharmacology observations. The present investigation justified the traditional claim of the edible roots of B. roxburghii in treating diarrhoea, where its marker rutin played a significant role in reactivating Na+/K+-ATPase, restored electrolyte balance, and also stabilized the EPEC C-terminal.

This study aimed to assess the efficacy of ethanolic extract of Solanum torvum L. fruit (EESTF) containing solasodine in treating chronic constriction injury (CCI)–induced neuropathic pain in rats. Three-dimensional (3D) simulation studies of solasodine binding were conducted on the TRPV1 receptor, IL-6, and TNF-α structures. For in vivo justification, an assessment of behavioral, biochemical, and histological changes was designed after a CCI-induced neuropathic pain model in rats. On days 7, 14, and 21, CCI significantly increased mechanical, thermal, and cold allodynia while producing a functional deficit. IL-6, TNF-α, TBARS, and MPO levels also increased. SOD levels of catalase and reduced glutathione levels also decreased. Administration of pregabalin (30 mg/kg, oral), solasodine (25 mg/kg, oral), and EESTF (100 and 300 mg/kg, oral) significantly reduced CCI-induced behavioral and biochemical changes ( P < 0.05). The protective nature of EESTF was also confirmed by histological analysis. Capsaicin, a TRPV1 receptor agonist, abolished the antinociceptive effects of EESTF when used previously. From the observations of the docking studies, solasodine acted as an antagonist at TRPV1, whereas the docking scores of solasodine against TNF-α and IL-6 were reported to be −11.2 and −6.04 kcal/mol, respectively. The attenuating effect of EESTF might be related to its antagonistic effects on TRPV1, suppression of cytokines, and anti-inflammatory and antioxidant properties.

In order to determine the present state of knowledge on ethnobotanyEthnobotany, ethnopharmacologyEthnopharmacology, and its application to drugDrugs development, this work reviews a variety of texts and studies in these fields. Traditional medical systems based on plants continue to be crucial to healthcare since the majority of the world's population still relies on them as their primary form of treatment. Many significant development medications, including aspirin, digitoxin, vinblastine, reserpine, ephedrine, ergometrine, and atropine, have been discovered by following leads from traditional usage. The development of novel chemical entities for therapeuticTherapeutics use and potential lead compoundsCompounds for the structural modification of current drugsDrugs to produce new and more powerful ones both rely heavily on natural productsNatural products as a starting point. EthnobotanyEthnobotany has been crucial in the discovery of novel medicines for many years. In light of ethnopharmacological research, the development of modern treatment systems has benefited greatly from the discovery of drugsDrugs from natural sources. The application of current drugDrugs development concepts to the selection, authentication, extractionExtraction, biological screening, and analogue creation of plant-based natural productsNatural products gives a thorough overview of the numerous methods employed in ethnobotanical and ethnopharmacological research.

Since diarrhoea is reportedly the third largest cause of fatality among kids, therefore it is considered to be one of the major areas of concerns among developing nations. The main causative agents of diarrhoea include Escherichia coli, Vibrio cholera, and Shigella spp where E. coli shares the maximum contribution. The roots of the plant Eriosema chinense Vogel. (Fabaceae) are traditionally used by the native tribes of Meghalaya, India to treat diarrhoea. From previous reports, the plant and its marker eriosematin E have been reported to have antidiarrhoeal potential against pathogenic and nonpathogenic diarrhoea. Therefore, the objective of the current investigation was to use in silico studies to determine the efficacy of eriosematin E against different diarrhoeagenic strains of E. coli. Six different pathovars of E. coli i.e. enteropathogenic E. coli (EPEC), enterotoxigenic E. coli (ETEC), enterohaemorrhagic E. coli (EHEC), enteroaggregative E. coli (EAEC), uropathogenic E. coli (UPEC) and enteroinvasive E. coli (EIEC) were subjected to docking simulation studies utilizing Glide module of Schrodinger Maestro 2018-1 MM Share Version. Based on the obtained binding energy and balance between H-bonding, hydrophobic, and salt bridge interactions eriosematin E was found to be most effective against EPEC followed by EAEC and ETEC, while UPEC and EHEC were moderately affected. The molecular dynamics studies suggested a higher affinity of eriosematin E towards heat-labile enterotoxin b-pentamer from ETEC. The in vitro antibacterial studies against the universal strain S. aureus 12981 and E. coli 10418 revealed the effectiveness of eriosematin E showing MIC values of ≥256 µg/mL.Communicated by Ramaswamy H. Sarma.

The "deadly nightshade" family, commonly known as "black nightshades," it's also used as a traditional medicine system in a country like India and China.is known to contain alkaloids, steroids, glycol-Solanum xanthocarpum alkaloids, steroid saponins, glycoproteins, that exhibit antitumor activity.This review explores the phytopharmacological properties of and summarizes its wide range of pharmacological Solanum Xanthocarpum applications to understand and integrate potential image issues as multipurpose medicines.Solanocarpidine and a phytosterol known as Carpesterol are also present.The seed oil contains Carpesterol.Diosgenin, lanosterol, sitosterol.Solasonnine, solamargine, and solasodine have been isolated from the plant.The roots and fruits are used for medicinal purposes.The herb is useful both internally as well as externally.The apoptotic effects and the amount of DNA fragmentation increased in a dose-dependent manner after the treatment with the protein.Authors believe this glycoprotein is a natural anticancer agent due to its potential to induce apoptosis in the HTC29 cell.

Objectives: We aimed to investigate the protective potential of Punica granatum L. fruit rind extract (PFE) containing punicalagin (10.3% W/W), ellagic acid (EA) (2.7%W/W) in vincristine (75 µg/kg i.p.)- induced neuropathic pain in Wistar rats.Methods: Docking simulation studies were done on the three-dimensional (3D) structure of the GABAA and PPAR γ receptor for the binding of EA as well as punicalagin docking studies on TNF-α, and IL-6. The Present Study conceptualized a test battery to evaluate the behavioral, biochemical and histological changes.Results: Vincristine -induced significant cold allodynia, mechanical hyperalgesia, and functional deficit on 12th and 21st days. It also increased in the levels of TNF-α (Tumor necrosis factor-α), IL-6 (Interleukin-6), and MPO (Myeloperoxidase). Administration of PFE (100 and 300 mg/kg, p.o.), EA (50 mg/kg), and gabapentin (100 mg/kg) attenuated Vincristine-induced behavioral and biochemical changes significantly (P < .05). PFE showed better antinociceptive activity to EA. The histopathological evaluation also revealed the protective effects of PFE. Pretreatment of bicuculline (selective antagonist of GABAA receptors) reversed antinociceptive action of PFE, but administration of γ aminobutyric acid potentiated the action of PFE. PPAR-γ antagonist BADGE did not modify the effect of PFE. Docking results revealed that EA properly positioned into GABA and PPARγ binding site and acts as a partial agonist. Docking score of Punicalagin found to be - 9.02 kcal/mol and - 8.32 kcal/mol on IL-6 and TNFα respectively.Discussion: Conclusively, the attenuating effect of PFE may be attributed to the GABAergic system, cytokine inhibition, and anti-inflammatory activities.

Objective: The principal objective of the present investigation was the preparation of several analogs to further evaluate the binding site hypothesis.Aryl semicarbazides have also been reported to display excellent anticonvulsant activity in mice and rats.In this project, the synthesis of semicarbazone derivatives was Matearial and Methods: carried out.All molecules were synthesized using the common starting material -aniline.In all compounds, an intermediate was first formed by substituted phenyl urea using substituted aniline and potassium cyanate, and then it was hydrolyzed to get substituted phenyl semicarbazide, which was directly coupled with ketones.All the synthesized compounds were biologically screened for their anticonvulsant activity by the MES method.Results: Standard error mean was calculated concerning standard and control drug, Phenytoin sodium (25mg/kg.)and DMSO.The synthesized semicarbazone was characterized by using IR Spectroscopy.One another representative molecule compound was characterized using H NMR Spectroscopy.It can be concluded that designed 1 Conclusion: semicarbazones were synthesized and characterized successfully.After synthesis of designed semicarbazones compounds were evaluated for anticonvulsant activity.Finally, two compounds have shown better activity in comparison to the other molecules.

Saikosaponins are major biologically active triterpenoids, usually as glucosides, isolated from Traditional Chinese Medicines (TCM) such as Bupleurum spp., Heteromorpha spp., and Scrophularia scorodonia with their antiviral and immunomodulatory potential. This investigation presents molecular docking, molecular dynamics simulation, and free energy calculation studies of saikosaponins as adjuvant therapy in the treatment for COVID19. Molecular docking studies for 23 saikosaponins on the crystal structures of the extracellular domains of human lnterleukin-6 receptor (IL6), human Janus Kinase-3 (JAK3), and dehydrogenase domain of Cylindrospermum stagnale NADPH–oxidase 5 (NOX5) were performed, and selected protein–ligand complexes were subjected to 100 ns molecular dynamics simulations. The molecular dynamics trajectories were subjected to free energy calculation by the MM-GBSA method. Molecular docking and molecular dynamics simulation studies revealed that IL6 in complex with Saikosaponin_U and Saikosaponin_V, JAK3 in complex with Saikosaponin_B4 and Saikosaponin_I, and NOX5 in complex with Saikosaponin_BK1 and Saikosaponin_C have good docking and molecular dynamics profiles. However, the Janus Kinase-3 is the best interacting partner for the saikosaponin compounds. The network pharmacology analysis suggests saikosaponins interact with the proteins CAT Gene CAT (Catalase) and Checkpoint kinase 1 (CHEK1); both of these enzymes play a major role in cell homeostasis and DNA damage during infection, suggesting a possible improvement in immune response toward COVID-19.

COVID-19 has ravaged the world and is the greatest of pandemics in modern human history, in the absence of treatment or vaccine, the mortality and morbidity rates are very high. The present investigation identifies potential leads from the plant Withania somnifera (Indian ginseng), a well-known antiviral, immunomodulatory, anti-inflammatory and a potent antioxidant plant, using molecular docking and dynamics studies. Two different protein targets of SARS-CoV-2 namely NSP15 endoribonuclease and receptor binding domain of prefusion spike protein from SARS-CoV-2 were targeted. Molecular docking studies suggested Withanoside X and Quercetin glucoside from W. somnifera have favorable interactions at the binding site of selected proteins, that is, 6W01 and 6M0J. The top-ranked phytochemicals from docking studies, subjected to 100ns molecular dynamics (MD) suggested Withanoside X with the highest binding free energy (Delta G(bind) = -89.42kcal/mol) as the most promising inhibitor. During MD studies, the molecule optimizes its conformation for better fitting with the receptor active site justifying the high binding affinity. Based on proven therapeutic, that is, immunomodulatory, antioxidant and anti-inflammatory roles and plausible potential against n-CoV-2 proteins, Indian ginseng could be one of the alternatives as an antiviral agent in the treatment of COVID 19. [GRAPHICS] .

Aim and Objective:: At present, the world is facing a global pandemic threat of SARSCoV- 2 or COVID-19 and to date, there are no clinically approved vaccines or antiviral drugs available for the treatment of coronavirus infections. Studies conducted in China recommended the use of liquorice (Glycyrrhiza species), an integral medicinal herb of traditional Chinese medicine, in the deactivation of COVID-19. Therefore, the present investigation was undertaken to identify the leads from the liquorice plant against COVID-19 using molecular docking simulation studies. Materials and Methods:: A set of reported bioactive compounds of liquorice were investigated for COVID-19 main protease (M pro ) inhibitory potential. The study was conducted on Autodock vina software using COVID-19 M pro as a target protein having PDB ID: 6LU7. Results: Out of the total 20 docked compounds, only six compounds showed the best affinity towards the protein target, which included glycyrrhizic acid, isoliquiritin apioside, glyasperin A, liquiritin, 1-methoxyphaseollidin and hedysarimcoumestan B. From the overall observation, glycyrrhizic acid followed by isoliquiritin apioside demonstrated the best affinity towards M pro representing the binding energy of -8.6 and -7.9 Kcal/mol, respectively. Nevertheless, the other four compounds were also quite comparable with the later one. Conclusion:: From the present investigation, we conclude that the compounds having oxane ring and chromenone ring substituted with hydroxyl 3-methylbut-2-enyl group could be the best alternative for the development of new leads from liquorice plant against COVID-19.

Background Since December 2019, SARS-CoV-2 had been a significant threat globally, which has accounted for about two million deaths. Several types of research are undergoing and have reported the significant role of repurposing existing drugs and natural lead in the treatment of COVID-19. The plant Phyllanthus emblica (Synonym-Emblica officinalis) (Euphorbiaceae) is a rich source of vitamin C, and its use as an antiviral agent has been well established. Purpose The present study was undertaken to investigate the potency of the several components of Phyllanthus emblica against three protein targets of 2019-nCoV viz. NSP15 endoribonuclease, main protease, and receptor binding domain of prefusion spike protein using molecular docking and dynamics studies. Methods The docking simulation studies were carried out using Schrödinger maestro 2018-1 MM share version, while dynamics studies were conducted to understand the binding mechanism and the complexes' stability studies. Results Out of sixty-six tested compounds, Chlorogenic acid, Quercitrin, and Myricetin were most effective in showing the highest binding energy against selected protein targets of SARS-CoV-2. The network pharmacology analysis study confirmed these compounds' role in modulating the immune response, inflammatory cascade, and cytokine storm through different signaling pathways. Conclusion Current pharmacoinformatic approach shows possible role of Phyllanthus emblica in the treatment and management of COVID-19.

•(-) epicatechin showed significant H+, K+-ATPase inhibitory effects which is attributed via. K+ competitive acid blocker.•In silico study, predicted the binding energy of (-) epicatechin which is twofold better as compared to that of omeprazole.•β-sitosterol and five well known fatty acids were reported for the first time from the P. fulgens. root.