scholarly journals Docking studies of Physalis peruviana ethanol extract using molegro virtual docker on insulin tyrosine kinase receptor as antidiabetic agent

2014 ◽  
Vol 3 (5) ◽  
pp. 265-269 ◽  
Author(s):  
Ayik Rosita Puspaningtyas
Keyword(s):  
Tyrosine Kinase ◽  
Ethanol Extract ◽  
Pharmaceutical Journal ◽  
Docking Studies ◽  
In Vivo Studies ◽  
Tyrosine Kinase Receptor ◽  
Molegro Virtual Docker ◽  
Physalis Peruviana ◽  
Urban People

Physalis peruviana Linn in Indonesia was better known as ciplukan, based on information from urban people in Indonesia is as antidiabetic. In the previeous studies, the levels of blood glucose in animals experimental of Physalis peruviana quantified with glucometer and compared with oral antidiabetic drugs gliclazide, showed that Gliclazide was decrease more levels of glucose significantly than ethanol extract of Physalis peruviana. We have done molecular docking using Molegro Virtual Docker (MVD) on ethanol extract of Physalis peruviana and gliclazide to compare between in silico and in vivo studies. Based on studies before the main content of the ethanol extract of Physalis peruviana were withanolide, 4-OH-withanolide, and perulactone. In this study the results showed that gliclazide had been better bond in insulin tyrosine kinase receptor than main content of Physalis peruviana which can be seen from Moldock score 105.217 and Rerank score -68,2931 means that the energy was lower and more stable binding. Moldock Score of main content Physalis peruviana (withanolide, 4-OH-withanolide, and perulactone) were -93.5472; 70.5843; 88.7881, respectively. Rerank score of main content Physalis peruviana (withanolide, 4-OH-withanolide, and perulactone) were -61.5149; -67.5345; -65.7979, respectively. The hydrogen bonds of withanolide, 4-OH-withanolide, perulactone and gliclazide with amino acid of insulin tyrosine kinase receptor were Phe 1186 and Thr 1186. Finally, in the 3D MVD visualization between main content of ethanol extract of Physalis peruviana and gliclazide can be concluded that interaction of gliclazide was more harmonious than main content of ethanol extract Physalis peruviana.DOI: http://dx.doi.org/10.3329/icpj.v3i5.18534 International Current Pharmaceutical Journal, April 2014, 3(5): 265-269

In-silico Studies of Isolated Phytoalkaloid Against Lipoxygenase: Study Based on Possible Correlation

2018 ◽  
Vol 21 (3) ◽  
pp. 215-221
Author(s):  
Haroon Khan ◽  
Muhammad Zafar ◽  
Helena Den-Haan ◽  
Horacio Perez-Sanchez ◽  
Mohammad Amjad Kamal
Keyword(s):  
In Silico ◽  
Docking Studies ◽  
In Vivo Studies ◽  
In Vitro Assays ◽  
Chronic Obstructive ◽  
Lipoxygenase Inhibitors ◽  
Lipoxygenase Inhibition ◽  
In Silico Studies

Aim and Objective: Lipoxygenase (LOX) enzymes play an important role in the pathophysiology of several inflammatory and allergic diseases including bronchial asthma, allergic rhinitis, atopic dermatitis, allergic conjunctivitis, rheumatoid arthritis and chronic obstructive pulmonary disease. Inhibitors of the LOX are believed to be an ideal approach in the treatment of diseases caused by its over-expression. In this regard, several synthetic and natural agents are under investigation worldwide. Alkaloids are the most thoroughly investigated class of natural compounds with outstanding past in clinically useful drugs. In this article, we have discussed various alkaloids of plant origin that have already shown lipoxygenase inhibition in-vitro with possible correlation in in silico studies. Materials and Methods: Molecular docking studies were performed using MOE (Molecular Operating Environment) software. Among the ten reported LOX alkaloids inhibitors, derived from plant, compounds 4, 2, 3 and 1 showed excellent docking scores and receptor sensitivity. Result and Conclusion: These compounds already exhibited in vitro lipoxygenase inhibition and the MOE results strongly correlated with the experimental results. On the basis of these in vitro assays and computer aided results, we suggest that these compounds need further detail in vivo studies and clinical trial for the discovery of new more effective and safe lipoxygenase inhibitors. In conclusion, these results might be useful in the design of new and potential lipoxygenase (LOX) inhibitors.

Promising Anti-stroke Signature of Voglibose: Investigation through In- Silico Molecular Docking and Virtual Screening in In-Vivo Animal Studies

2020 ◽  
Vol 20 (3) ◽  
pp. 223-235
Author(s):  
Pooja Shah ◽  
Vishal Chavda ◽  
Snehal Patel ◽  
Shraddha Bhadada ◽  
Ghulam Md. Ashraf
Keyword(s):  
Molecular Docking ◽  
Virtual Screening ◽  
In Silico ◽  
Reductase Activity ◽  
Infarct Volume ◽  
Docking Studies ◽  
Serum Glucose ◽  
In Vivo Studies ◽  
In Silico Molecular Docking

Background: Postprandial hyperglycemia considered to be a major risk factor for cerebrovascular complications. Objective: The current study was designed to elucidate the beneficial role of voglibose via in-silico in vitro to in-vivo studies in improving the postprandial glycaemic state by protection against strokeprone type 2 diabetes. Material and Methods: In-Silico molecular docking and virtual screening were carried out with the help of iGEMDOCK+ Pymol+docking software and Protein Drug Bank database (PDB). Based on the results of docking studies, in-vivo investigation was carried out for possible neuroprotective action. T2DM was induced by a single injection of streptozotocin (90mg/kg, i.v.) to neonates. Six weeks after induction, voglibose was administered at the dose of 10mg/kg p.o. for two weeks. After eight weeks, diabetic rats were subjected to middle cerebral artery occlusion, and after 72 hours of surgery, neurological deficits were determined. The blood was collected for the determination of serum glucose, CK-MB, LDH and lipid levels. Brains were excised for determination of brain infarct volume, brain hemisphere weight difference, Na+-K+ ATPase activity, ROS parameters, NO levels, and aldose reductase activity. Results: In-silico docking studies showed good docking binding score for stroke associated proteins, which possibly hypotheses neuroprotective action of voglibose in stroke. In the present in-vivo study, pre-treatment with voglibose showed a significant decrease (p<0.05) in serum glucose and lipid levels. Voglibose has shown significant (p<0.05) reduction in neurological score, brain infarct volume, the difference in brain hemisphere weight. On biochemical evaluation, treatment with voglibose produced significant (p<0.05) decrease in CK-MB, LDH, and NO levels in blood and reduction in Na+-K+ ATPase, oxidative stress, and aldose reductase activity in brain homogenate. Conclusion: In-silico molecular docking and virtual screening studies and in-vivo studies in MCAo induced stroke, animal model outcomes support the strong anti-stroke signature for possible neuroprotective therapeutics.

scholarly journals High-Throughput Identification of Organic Compounds from Polygoni Multiflori Radix Praeparata (Zhiheshouwu) by UHPLC-Q-Exactive Orbitrap-MS

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3977
Author(s):  
Shaoyun Wang ◽  
Xiaozhu Sun ◽  
Shuo An ◽  
Fang Sang ◽  
Yunli Zhao ◽  
...  
Keyword(s):  
High Performance ◽  
Chemical Constituents ◽  
Water Extract ◽  
Ethanol Extract ◽  
In Vivo Studies ◽  
Polygonum Multiflorum ◽  
Q Exactive ◽  
Orbitrap Ms

Polygoni Multiflori Radix Praeparata (PMRP), as the processed product of tuberous roots of Polygonum multiflorum Thunb., is one of the most famous traditional Chinese medicines, with a long history. However, in recent years, liver adverse reactions linked to PMRP have been frequently reported. Our work attempted to investigate the chemical constituents of PMRP for clinical research and safe medication. In this study, an effective and rapid method was established to separate and characterize the constituents in PMRP by combining ultra-high performance liquid chromatography with hybrid quadrupole-orbitrap mass spectrometry (UHPLC-Q-Exactive Orbitrap-MS). Based on the accurate mass measurements for molecular and characteristic fragment ions, a total of 103 compounds, including 24 anthraquinones, 21 stilbenes, 15 phenolic acids, 14 flavones, and 29 other compounds were identified or tentatively characterized. Forty-eight compounds were tentatively characterized from PMRP for the first time, and their fragmentation behaviors were summarized. There were 101 components in PMRP ethanol extract (PMRPE) and 91 components in PMRP water extract (PMRPW). Simultaneously, the peak areas of several potential xenobiotic components were compared in the detection, which showed that PMRPE has a higher content of anthraquinones and stilbenes. The obtained results can be used in pharmacological and toxicological research and provided useful information for further in vitro and in vivo studies.

scholarly journals Effect of Harmine against Parkinson’s Disease Protein (PARK7) through Molecular Docking Studies

2021 ◽  
Vol 9 (VI) ◽  
pp. 5479-5485
Author(s):  
Love Kumar
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Molecular Docking ◽  
Neurodegenerative Disorder ◽  
Docking Studies ◽  
In Vivo Studies ◽  
Receptor Protein ◽  
Unknown Etiology

Parkinson’s disease (PD) is a common known neurodegenerative disorder with unknown etiology. It was estimated about 0.3% prevalence in the U.S population and enhance to 4 to 5% in older than 85 years. All studies were depending on the molecular docking where all ligands and protein PARK7 (PDB ID: 2RK3) were interacted by docked process. Some natural compounds was selected such as Harmine, Alloxan, Alpha spinasterol, Myrcene, and Vasicinone and PARK7 (PDB ID: 2RK3) protein. According to the PyRx and SWISS ADME result, Harmine was the only ligand which was showing minimum binding affinity. AutoDock Vina software was used for docking process between ligand (Harmine) and receptor protein PARK7 (PDB ID: 2RK3). The result was visualized under PyMol. Harmine was inhibiting the activity of PARK7 (PDB ID: 2RK3) and it may be used for the treatment of PD in future prospect after its in vitro and in vivo studies.

scholarly journals In vivo Neurological, Analgesic and In vitro Antioxidant and Cytotoxic Activities of Ethanolic Extract of Leaf and Stem Bark of Wedelia chinensis

2019 ◽  
Vol 22 (1) ◽  
pp. 18-26
Author(s):  
Sayema Khanum ◽  
Md Shahid Sarwar ◽  
Mohammad Safiqul Islam
Keyword(s):  
Body Weight ◽  
Oral Administration ◽  
Radical Scavenging ◽  
Ethanolic Extract ◽  
Ethanol Extract ◽  
Pharmaceutical Journal ◽  
Stem Bark ◽  
Cytotoxic Activities

Wedelia chinensis is a widely used anti-inflammatory and hepatoprotective medicinal plant in Bangladesh. In this study, analgesic, neurological, antioxidant and cytotoxic activities of the ethanolic extract of leaf and stem bark of W. chinensis were investigated. Oral administration of the ethanolic extract of W. chinensis (200- and 300-mg/kg body weight) was investigated on animal model for neurological activity using open field test and hole cross test. Acetic acid induced writhing method was used to assess the analgesic activity. DPPH (1,1-diphenyl, 2-picryl hydrazyl) radical scavenging assay was used for determining the antioxidant activity, while brine shrimp lethality bioassay was used for investigating cytotoxicity. The ethanol extract of the plant produced significant reduction (P<0.05) of locomotion in both doses (200- and 300-mg/kg body weight) indicating pronounced neurological activity. Oral administration of alcoholic leaves and stem extracts significantly (p < 0.05) inhibited writhing response in mice. The percentage of scavenging of DPPH free radical was found to be concentration dependent with IC50 value of 44.10 ± 0.65 and 38.96 ± 0.50 μg/ml for leaves and stem extracts, respectively. Our findings indicate that W. chinensis may be a source of natural antioxidant with potent analgesic, neurological and cytotoxic activities. Bangladesh Pharmaceutical Journal 22(1): 18-26, 2019

scholarly journals SUN-087 FGFR-Selective Tyrosine Kinase Inhibitors, Such as Infigratinib, Show Potency and Selectivity for FGFR3 at Pharmacologically Relevant Doses for the Potential Treatment of Achondroplasia

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Katherine Dobscha ◽  
Ge Wei ◽  
Carl L Dambkowski ◽  
Daniela Rogoff
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Kinase Inhibitor ◽  
Survival Advantage ◽  
In Vivo Studies ◽  
Low Doses ◽  
Skeletal Dysplasias ◽  
The Past ◽  
Preclinical Efficacy

Abstract BACKGROUND: Germline mutations in fibroblast growth factor receptor (FGFR) genes 1-3 can cause skeletal dysplasias and craniosynostoses. Achondroplasia (ACH), the most common form of disproportionate short stature, is caused primarily by an autosomal dominant G380R substitution in FGFR3 [Horton WA et al. Lancet 2007]. Infigratinib (BGJ398), a potent and selective FGFR1-3 tyrosine kinase inhibitor (TKI), demonstrated preclinical efficacy at low doses in an ACH mouse model [Demuynck et al. 2019; Komla-Ebri et al. 2016]. The objective of this analysis is to evaluate the dose dependency and toxicity profiles of FGFR-selective TKIs like infigratinib in preclinical skeletal dysplasia models. Methods: A review of the literature was performed to investigate non-clinical data from studies of infigratinib and other FGFR-selective TKIs relevant to FGFR-driven skeletal dysplasias. Major databases (e.g., PubMed, Medline [NLM Catalog]) were searched for relevant articles from the past 10 years and conference archives (e.g., ENDO, ESPE, ISDS, ASHG, ASBMR) for relevant abstracts from the past 5 years. Full text was included where possible. Key words included in the searches were based on the following: achondroplasia, FGFR inhibition, infigratinib, BGJ398, tyrosine kinase inhibitor. Results: Of the 683 publications identified, 10 relevant articles and 2 abstracts were selected for review. Due to direct relevance, 2 additional articles were included, bringing the total to 14 publications. Key results from studies of infigratinib, the most commonly identified TKI, included: FGFR3 IC50 1.0 nM, FGFR3-K650E IC50 4.9 nM. In vitro data showed inhibition of FGFR1-3 activity at concentrations of 5 to 100 nM, including reversal of established growth arrest in chondrocytes at 7 nM. In vivo studies revealed dose-dependent improvements in foramen magnum and long bone length in Fgfr3Y367C/+ mice at doses of 0.2-2 mg/kg/day. No studies reported a survival disadvantage and one showed a significant survival advantage for infigratinib-treated ACH mice. In relation to other FGFR TKIs, one study showed that AZD4547 decreased survival in mice treated at doses of 1x106 to 2x106 nM, and another showed limb malformation in chicken embryos treated with PD173074 at doses of 1x106 to 50x106 nM. While one study suggested toxicity with infigratinib and other FGFR-selective TKIs, the results were not produced at pharmacologically relevant doses for ACH nor were they replicated in the literature. Furthermore, in vivo studies reporting treatment in mice with low doses of infigratinib did not result in any of the abnormal findings observed in this study. Conclusions: Recent studies indicate preclinical efficacy of infigratinib, including a survival advantage in Fgfr3Y367C/+ mice. Given the totality of evidence, low-dose infigratinib appears to be a potentially safe option for further development in children with ACH.

ANTI-HYPERCHOLESTEROLEMIA ACTIVITY OF ETHANOL EXTRACT Peperomia pellucida

2016 ◽  
Vol 12 (1) ◽  
Author(s):  
Chasanah Mazroatul
Keyword(s):  
Total Cholesterol ◽  
Ethanol Extract ◽  
Positive Control ◽  
Diet Group ◽  
In Vivo Studies ◽  
Control Group ◽  
Antioxidant Compounds ◽  
Control Group Design ◽  
White Rats

<p>Hypercholesterolemia is a major cause of cardiovascular disease such as coronary heart disease. Betel water (Peperomia pellucida) is a type of plants that have antioxidant compounds that could delay, retard and prevent the oxidation of lipids, both enzymatic and non-enzymatic. This study aimed to determine the effect of ethanol extract Peperomia pellucida against total cholesterol, HDL, LDL, and triglycerides in the serum of white rats (Wistar) were given a diet aterogenetik, so it can be used as prevention of atherosclerosis. The active compounds contained in the water after screnning betel phytochemicals includes flavonoids, tannins, alkaloids, steroids and quinones. In vivo studies conducted by true experimental method with pre and post test with control group design. Rats were divided into 3 groups: group A positive control is given aterogenetik diet, group B and C were given diet Peperomia Pellucida aterogenetik and extract orally at a dose of 150 mg/kg and 300 mg/kg. Diet aterogenetik given as much as 20 grams per day for 14 days. Data obtained include total cholesterol, HDL, LDL, and triglycerides were analyzed by statistical methods Paired T Test oneway ANOVA (P &lt; 0,05). The study of total cholesterol, HDL, LDL and triglycerides showed ethanol extract of Peperomia pellucida at a dose of 300 mg/kg body weight can lower total cholesterol and LDL significantly, but there was no significant decline in triglycerides and can increase HDL levels.</p>

scholarly journals ANTI-HYPERCHOLESTEROLEMIA ACTIVITY OF ETHANOL EXTRACT Peperomia pellucid

2016 ◽  
Vol 12 (1) ◽  
pp. 88 ◽  
Author(s):  
Chasanah Mazroatul ◽  
Glar Donia Deni ◽  
Nur Ahmad Habibi ◽  
Gita Febri Saputri
Keyword(s):  
Total Cholesterol ◽  
Ethanol Extract ◽  
Positive Control ◽  
Diet Group ◽  
In Vivo Studies ◽  
Control Group ◽  
Antioxidant Compounds ◽  
Control Group Design ◽  
White Rats

Hypercholesterolemia is a major cause of cardiovascular disease such as coronary heart disease. Betel water (Peperomia pellucida) is a type of plants that have antioxidant compounds that could delay, retard and prevent the oxidation of lipids, both enzymatic and non-enzymatic. This study aimed to determine the effect of ethanol extract Peperomia pellucida against total cholesterol, HDL, LDL, and triglycerides in the serum of white rats (Wistar) were given a diet aterogenetik, so it can be used as prevention of atherosclerosis. The active compounds contained in the water after screnning betel phytochemicals includes flavonoids, tannins, alkaloids, steroids and quinones. In vivo studies conducted by true experimental method with pre and post test with control group design. Rats were divided into 3 groups: group A positive control is given aterogenetik diet, group B and C were given diet Peperomia Pellucida aterogenetik and extract orally at a dose of 150 mg/kg and 300 mg/kg. Diet aterogenetik given as much as 20 grams per day for 14 days. Data obtained include total cholesterol, HDL, LDL, and triglycerides were analyzed by statistical methods Paired T Test oneway ANOVA (P &lt; 0.05). The study of total cholesterol, HDL, LDL and triglycerides showed ethanol extract of Peperomia pellucida at a dose of 300 mg/kg body weight can lower total cholesterol and LDL significantly, but there was no significant decline in triglycerides and can increase HDL levels.

scholarly journals In Silico, In Vitro, and In Vivo Antitumor and Anti-Inflammatory Evaluation of a Standardized Alkaloid-Enriched Fraction Obtained from Boehmeria caudata Sw. Aerial Parts

Molecules ◽  
2020 ◽  
Vol 25 (17) ◽  
pp. 4018
Author(s):  
Paula P. de Paiva ◽  
Julia H. B. Nunes ◽  
Fabiana R. Nonato ◽  
Ana L. T. G. Ruiz ◽  
Rafael R. T. Zafred ◽  
...  
Keyword(s):  
Human Tumor ◽  
Antitumor Agent ◽  
Docking Studies ◽  
In Vivo Studies ◽  
Myeloperoxidase Activity ◽  
Aerial Parts ◽  
M Phase ◽  
Anti Inflammatory

In the context of the cancer-inflammation relationship and the use of natural products as potential antitumor and anti-inflammatory agents, the alkaloid-enriched fraction of Boehmeriacaudata (BcAEF) aerial parts was evaluated. In vitro antiproliferative studies with human tumor cell lines showed high activity at low concentrations. Further investigation on NCI-H460 cells showed an irreversible effect on cell proliferation, with cell cycle arrest at G2/M phase and programmed cell death induction. Molecular docking studies of four alkaloids identified in BcAEF with colchicine’s binding site on β-tubulin were performed, suggesting (−)-C (15R)-hydroxycryptopleurine as the main inductor of the observed mitotic death. In vivo studies showed that BcAEF was able to reduce Ehrlich tumor volume progression by 30 to 40%. Checking myeloperoxidase activity, BcAEF reduced neutrophils migration towards the tumor. The in vivo anti-inflammatory activity was evaluated by chemically induced edema models. In croton oil-induced ear edema and carrageenan (CG)-induced paw edema models, BcAEF reduced edema around 70 to 80% together with inhibition of activation and/or migration of neutrophils to the inflammatory area. All together the results presented herein show BcAEF as a potent antitumor agent combining antiproliferative and anti-inflammatory properties, which could be further explored in (pre)clinical studies.

New Benzodioxole-based Pyrazoline Derivatives: Synthesis and Anticandidal, In silico ADME, Molecular Docking Studies

2018 ◽  
Vol 16 (1) ◽  
pp. 82-92 ◽  
Author(s):  
Ahmet Özdemir ◽  
Belgin Sever ◽  
Mehlika Dilek Altıntop
Keyword(s):  
In Silico ◽  
Fungal Infections ◽  
Computational Study ◽  
Docking Studies ◽  
In Vivo Studies ◽  
Heme Group ◽  
In Silico Studies ◽  
Nih 3T3

Background: Azoles are commonly used in the treatment and prevention of fungal infections. They suppress fungal growth by acting on the heme group of lanosterol 14α-demethylase enzyme (CYP51), thus blocking the biosynthesis of ergosterol. </P><P> Objectives: Due to the importance of pyrazolines in the field of antifungal drug design, we aimed to design and synthesize new pyrazoline-based anticandidal agents. Methods: New pyrazoline derivatives were synthesized via the reaction of 1-(chloroacetyl)-3-(2- thienyl)-5-(1,3-benzodioxol-5-yl)-2-pyrazoline with aryl thiols. These compounds were evaluated for their in vitro antifungal effects on Candida species. Docking studies were performed to predict the affinity of the most effective anticandidal agents to substrate binding site of CYP51. Furthermore, MTT assay was performed to determine the cytotoxic effects of the compounds on NIH/3T3 mouse embryonic fibroblast cell line. A computational study for the prediction of ADME properties of all compounds was also carried out. Results: Compounds 5, 8, 10 and 12 were found as the most potent anticandidal agents against Candida albicans and Candida glabrata in this series with the same MIC values of ketoconazole and they also exhibited low toxicity against NIH/3T3 cells. Docking results indicated that all these compounds showed good binding affinity into the active site of CYP51. In particular, chloro substituted compounds 8 and 12 bind to CYP51 through direct coordination with the heme group. According to in silico studies, compound 8 only violated one parameter of Lipinski’s rule of five, making it a potential orally bioavailable agent. Conclusion: Compound 8 was defined as a promising candidate for further in vitro and in vivo studies.

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