Background:Epidemiological studies have confirmed that longer exposure to insecticides like cypermethrin(CYP)significantly increases the risk of male reproductive toxicity.Crocus sativus L.has been recognized due to i...Background:Epidemiological studies have confirmed that longer exposure to insecticides like cypermethrin(CYP)significantly increases the risk of male reproductive toxicity.Crocus sativus L.has been recognized due to its therapeutic properties,but its exact role and molecular mechanisms in treatment of reproductive dysfunction remain unclear.Methods:During this study,36 rats were randomly divided into six groups(n=6):control,CYP-induced(60 mg/kg),standard(leuprolide 3 mg/kg)and three treatment groups receiving aqueous,ethanolic,and oil extracts(50 mg/kg or 20 mL/kg)for post-toxicity induction.Results:The finding represented that exposure of CYP significantly increased oxidative stress,disrupted testicular architecture,and markedly reduced testosterone levels(P<0.05).Importantly,Crocus sativus L.treatment alleviated these changes by increasing the expression of Nrf2(nuclear factor erythroid 2-related factor 2),restoring the activity of antioxidant enzymes,and enhancing testicular histomorphology.Surprisingly,molecular docking established a high binding affinity of Crocus sativus L.phytoconstituents such as gallic acid,cinnamic acid and quercetin to the Nrf2-Keap1 complex.It is worth noting that,Crocus sativus L.exhibited a high level of protection against reproductive toxicity caused by CYP in male rats,which was mediated by the activation of Nrf2 pathway,reduction of oxidative damage,and favorable ADMET characteristics.Conclusion:Notably,this research provides a more valid,safe,and effective method of developing new drugs for reproductive disorders,however,further investigation is needed to support the research findings and implement it in clinical practice.展开更多
Still a major worldwide health issue,tuberculosis requires the development of new medicinal drugs.Compu-tational techniques,including QSAR modeling,molecular docking,ADMET analysis,and molecular dynamics simulation,we...Still a major worldwide health issue,tuberculosis requires the development of new medicinal drugs.Compu-tational techniques,including QSAR modeling,molecular docking,ADMET analysis,and molecular dynamics simulation,were used in this work,which examines the antitubercular potential of a nitroimidazole derivative targeting the Ddn protein of Mycobacterium tuberculosis.A multiple linear regression-based QSAR model(R2=0.8313,Q2Lo0=0.7426)created using QSARINS software shows strong prediction accuracy for anti-TB activity.Using molecular docking experiments(AutoDockTool 1.5.7),DE-5 compound was found to be the most prom-ising molecule with a binding affinity of 7.81 kcal/mol and important hydrogen bonding interactions with active site residues PRO A:63,LYS A:79,and MET A:87.High bioavailability,good pharmacokinetics,and low toxicity risk were found by ADMET profiling(SwissADME).A 100 ns molecular dynamics simulation confirmed the stability of the DE-5-Ddn complex,as indicated by minimal Root Mean Square deviation,stable hydrogen bonds,low Root Mean Square Fluctuation,and compact structure reflected in Solvent Accessible Surface Area and radius of gyration values.Furthermore,MM/GBSA computations(-34.33 kcal/mol)confirmed a strong binding affinity and hence supporting DE-5's activity potential.These findings suggest that DE-5 is a suitable potential compound to advance the creation of new tuberculosis therapies targeting the Ddn protein.This work opens the path for logical drug design strategies in the TB battle.展开更多
Background:Hepatitis B virus(HBV)has affected over 300 million people worldwide which causes to induce mostly liver disease and liver cancer.It is a member of the family Hepadnaviridae which is a small DNA virus with ...Background:Hepatitis B virus(HBV)has affected over 300 million people worldwide which causes to induce mostly liver disease and liver cancer.It is a member of the family Hepadnaviridae which is a small DNA virus with unusual characters like retroviruses.Generally,hepatoprotective drugs provoke some side effects in human beings.For the reason,this study aims to identify alternative drug molecules from the natural source of medicinal plants with smaller quantity of side effects than those conventional drugs in treating HBV.Methods:We developed computational methods for calculating drug and target binding resemblance using the Maestro v10.2 of Schrodinger suite.The target and ligand molecules were obtained from recognized databases.Ligand molecules of 40 phytoconstituents were retrieved from variety of plants after we executed crucial analyses such as molecular docking and absorption,distribution,metabolism,and excretion(ADME)analysis.Results:In the docking analysis,the natural analogues repandusinic acid showed better docking scores of-14.768 with good binding contacts.The remaining bioactive molecules corilagin,furosin,nirurin,iso-quercetin and gallocatechin also showed better docking scores.Conclusions:This computational analysis reveals that repandusinic acid is a suitable drug candidate for HBV.Therefore,we recommend that this analogue is suitable in further exploration using in vitro studies.展开更多
Background The detrimental consequences of synthetic pharmaceuticals have generated interest in natural remedies.Balakata baccata(Roxb.)Esser a plant of ethnomedicinal significance,has been conventionally utilized for...Background The detrimental consequences of synthetic pharmaceuticals have generated interest in natural remedies.Balakata baccata(Roxb.)Esser a plant of ethnomedicinal significance,has been conventionally utilized for its anti-inflammatory and analgesic characteristics;nevertheless,its flowers are yet to be thoroughly investigated.Objective The current study examines the pharmacological potential of the methanol extract of B.baccata flowers(MEBBF)for antinociceptive,antipyretic,and anthelmintic effects.Methods MEBBF was assessed utilizing in vivo models,consisting of the acetic acid-induced writhing test,formalin-induced paw-licking test,yeast-induced pyrexia model,and Tubifex tubifex assay.GC-MS analysis was used to affirm the presence of bioactive chemicals,whereas molecular docking and ADMET analysis elucidated their mechanisms and safety profiles.Results The MEBBF demonstrated analgesic,antipyretic,and anthelmintic actions.It noticeably diminished pain responses,decreased temperature,and caused paralysis and mortality in Tubifex tubifex.Phytochemical analysis found flavonoids,phenolic compounds,and glycosides as principal bioactive constituents.Molecular docking of compounds from GC-MS of MEBBF demonstrated robust binding affinities with target proteins,while ADMET analysis suggested beneficial pharmacokinetic characteristics.Conclusion MEBBF has a high therapeutic potential for treating pain,fever,and helminthic diseases.Nevertheless,further research has to be done to substantiate these findings and confirm its curative applications.展开更多
文摘Background:Epidemiological studies have confirmed that longer exposure to insecticides like cypermethrin(CYP)significantly increases the risk of male reproductive toxicity.Crocus sativus L.has been recognized due to its therapeutic properties,but its exact role and molecular mechanisms in treatment of reproductive dysfunction remain unclear.Methods:During this study,36 rats were randomly divided into six groups(n=6):control,CYP-induced(60 mg/kg),standard(leuprolide 3 mg/kg)and three treatment groups receiving aqueous,ethanolic,and oil extracts(50 mg/kg or 20 mL/kg)for post-toxicity induction.Results:The finding represented that exposure of CYP significantly increased oxidative stress,disrupted testicular architecture,and markedly reduced testosterone levels(P<0.05).Importantly,Crocus sativus L.treatment alleviated these changes by increasing the expression of Nrf2(nuclear factor erythroid 2-related factor 2),restoring the activity of antioxidant enzymes,and enhancing testicular histomorphology.Surprisingly,molecular docking established a high binding affinity of Crocus sativus L.phytoconstituents such as gallic acid,cinnamic acid and quercetin to the Nrf2-Keap1 complex.It is worth noting that,Crocus sativus L.exhibited a high level of protection against reproductive toxicity caused by CYP in male rats,which was mediated by the activation of Nrf2 pathway,reduction of oxidative damage,and favorable ADMET characteristics.Conclusion:Notably,this research provides a more valid,safe,and effective method of developing new drugs for reproductive disorders,however,further investigation is needed to support the research findings and implement it in clinical practice.
文摘Still a major worldwide health issue,tuberculosis requires the development of new medicinal drugs.Compu-tational techniques,including QSAR modeling,molecular docking,ADMET analysis,and molecular dynamics simulation,were used in this work,which examines the antitubercular potential of a nitroimidazole derivative targeting the Ddn protein of Mycobacterium tuberculosis.A multiple linear regression-based QSAR model(R2=0.8313,Q2Lo0=0.7426)created using QSARINS software shows strong prediction accuracy for anti-TB activity.Using molecular docking experiments(AutoDockTool 1.5.7),DE-5 compound was found to be the most prom-ising molecule with a binding affinity of 7.81 kcal/mol and important hydrogen bonding interactions with active site residues PRO A:63,LYS A:79,and MET A:87.High bioavailability,good pharmacokinetics,and low toxicity risk were found by ADMET profiling(SwissADME).A 100 ns molecular dynamics simulation confirmed the stability of the DE-5-Ddn complex,as indicated by minimal Root Mean Square deviation,stable hydrogen bonds,low Root Mean Square Fluctuation,and compact structure reflected in Solvent Accessible Surface Area and radius of gyration values.Furthermore,MM/GBSA computations(-34.33 kcal/mol)confirmed a strong binding affinity and hence supporting DE-5's activity potential.These findings suggest that DE-5 is a suitable potential compound to advance the creation of new tuberculosis therapies targeting the Ddn protein.This work opens the path for logical drug design strategies in the TB battle.
文摘Background:Hepatitis B virus(HBV)has affected over 300 million people worldwide which causes to induce mostly liver disease and liver cancer.It is a member of the family Hepadnaviridae which is a small DNA virus with unusual characters like retroviruses.Generally,hepatoprotective drugs provoke some side effects in human beings.For the reason,this study aims to identify alternative drug molecules from the natural source of medicinal plants with smaller quantity of side effects than those conventional drugs in treating HBV.Methods:We developed computational methods for calculating drug and target binding resemblance using the Maestro v10.2 of Schrodinger suite.The target and ligand molecules were obtained from recognized databases.Ligand molecules of 40 phytoconstituents were retrieved from variety of plants after we executed crucial analyses such as molecular docking and absorption,distribution,metabolism,and excretion(ADME)analysis.Results:In the docking analysis,the natural analogues repandusinic acid showed better docking scores of-14.768 with good binding contacts.The remaining bioactive molecules corilagin,furosin,nirurin,iso-quercetin and gallocatechin also showed better docking scores.Conclusions:This computational analysis reveals that repandusinic acid is a suitable drug candidate for HBV.Therefore,we recommend that this analogue is suitable in further exploration using in vitro studies.
文摘Background The detrimental consequences of synthetic pharmaceuticals have generated interest in natural remedies.Balakata baccata(Roxb.)Esser a plant of ethnomedicinal significance,has been conventionally utilized for its anti-inflammatory and analgesic characteristics;nevertheless,its flowers are yet to be thoroughly investigated.Objective The current study examines the pharmacological potential of the methanol extract of B.baccata flowers(MEBBF)for antinociceptive,antipyretic,and anthelmintic effects.Methods MEBBF was assessed utilizing in vivo models,consisting of the acetic acid-induced writhing test,formalin-induced paw-licking test,yeast-induced pyrexia model,and Tubifex tubifex assay.GC-MS analysis was used to affirm the presence of bioactive chemicals,whereas molecular docking and ADMET analysis elucidated their mechanisms and safety profiles.Results The MEBBF demonstrated analgesic,antipyretic,and anthelmintic actions.It noticeably diminished pain responses,decreased temperature,and caused paralysis and mortality in Tubifex tubifex.Phytochemical analysis found flavonoids,phenolic compounds,and glycosides as principal bioactive constituents.Molecular docking of compounds from GC-MS of MEBBF demonstrated robust binding affinities with target proteins,while ADMET analysis suggested beneficial pharmacokinetic characteristics.Conclusion MEBBF has a high therapeutic potential for treating pain,fever,and helminthic diseases.Nevertheless,further research has to be done to substantiate these findings and confirm its curative applications.
