• CELLMED
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• v.11 no.3
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• pp.15.1-15.9
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• 2021

The chemical constitution of a drug has been accepted as an important basis for pharmacological action in Unani medicine. Various dosage forms have been developed on this concept, such as decoctions (Joshanda), infusions (Khesanda), extract (Rub / Usara), and syrup. Zarawand Mudaharaj (ZM.) / Aristolochia rotunda L. root was subjected to extraction process using Soxhlet's apparatus by using Response Surface Methodology (RSM) to design the number of random runs of the extracts with variation in the factors of temperature, the concentration of ethanol in water, time for extraction, for optimizing and maximizing the yield concentration. The data obtained, was analyzed with regression equation and ANOVA two-way summary to interpret the interaction of the factors for yield maximization. Minitab version 18 was used to design and analyze data. Validation of the optimum conditions for maximum yield of the whole extract of ZM. Root was carried out by re-run of the extract using the optimized conditions. The maximum yield percentage thus obtained using RSM was 20.87% whereas using these optimum conditions 21.35 % yield was obtained thereby validating the method. The association between the response functions and the process variables was identified by a three-factor recorded Box-Behnken design. In the present study RSM is used because itis a cheap and affordable method to optimize maximum yield percentage which may be reliably used by researchers. The study set in the surface conditions for ZM. root extraction by the Soxhlet apparatus for maximizing the yield percentage.

• Korean Journal of Veterinary Service
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• v.44 no.4
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• pp.185-194
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• 2021

Polyglutamine extension in the coding sequence of mutant huntingtin causes neuronal degeneration associated with the formation of insoluble polyglutamine aggregates in Huntington's disease (HD). Mutant huntingtin can form aggregates within the nucleus and processes of neurons possibly due to misfolding of the proteins. To better understand the mechanism by which an elongated polyglutamine causes aggregates, we have developed an in vitro binding assay system of polyglutamine tract from truncated huntingtin. We made GST-HD exon1 fusion proteins which have expanded polyglutamine epitopes (e.g., 17, 23, 32, 46, 60, 78, 81, and 94 CAG repeats). In the present emergence of new study adjusted nanotechnology on protein chip such as surface plasmon resonance strategy which used to determine the substance which protein binds in drug discovery platform is worth to understand better neurodegenerative diseases (i.e., Alzheimer disease, Parkinson disease and Huntington disease) and its pathogenesis along with development of therapeutic measures. Hence, we used strengths of surface plasmon resonance (SPR) technology which is enabled to examine binding specificity and explore targeted molecular epitope using its electron charged wave pattern in HD pathogenesis utilize conjugated mutant epitope of HD protein and its interaction whether wild type GST-HD interacts with mutant GST-HD with maximum binding affinity at pH 6.85. We found that the maximum binding affinity of GST-HD17 with GST-HD81 was higher than the binding affinities of GST-HD17 with other mutant GST-HD constructs. Furthermore, our finding illustrated that the mutant form of GST-HD60 showed a stronger binding to GST-HD23 or GST-HD17 than GST-HD60 or GST-HD81. These results indicate that the binding affinity of mutant huntingtin does not correlate with the length of polyglutamine. It suggests that the aggregation of an expanded polyglutamine might have easily occurred in the presence of wild type form of huntingtin.

• Genomics & Informatics
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• v.19 no.4
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• pp.46.1-46.11
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• 2021

Moringa oleifera is nowadays raising as the most preferred medicinal plant, as every part of the moringa plant has potential bioactive compounds which can be used as herbal medicines. Some bioactive compounds of M. oleifera possess potential anti-cancer properties which interact with the apoptosis protein p53 in cancer cell lines of oral squamous cell carcinoma. This research work focuses on the interaction among the selected bioactive compounds derived from M. oleifera with targeted apoptosis protein p53 from the apoptosis pathway to check whether the bioactive compound will induce apoptosis after the mutation in p53. To check the toxicity and drug-likeness of the selected bioactive compound derived from M. oleifera based on Lipinski's Rule of Five. Detailed analysis of the 3D structure of apoptosis protein p53. To analyze protein's active site by CASTp 3.0 server. Molecular docking and binding affinity were analyzed between protein p53 with selected bioactive compounds in order to find the most potential inhibitor against the target. This study shows the docking between the potential bioactive compounds with targeted apoptosis protein p53. Quercetin was the most potential bioactive compound whereas kaempferol shows poor affinity towards the targeted p53 protein in the apoptosis pathway. Thus, the objective of this research can provide an insight prediction towards M. oleifera derived bioactive compounds and target apoptosis protein p53 in the structural analysis for compound isolation and in-vivo experiments on the cancer cell line.

• Journal of Microbiology and Biotechnology
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• v.32 no.10
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• pp.1262-1274
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• 2022

Cholangiocarcinoma (CCA) is a complex and refractor type of cancer with global prevalence. Several barriers remain in CCA diagnosis, treatment, and prognosis. Therefore, exploring more biomarkers and therapeutic drugs for CCA management is necessary. CCA gene expression data was downloaded from the TCGA and GEO databases. KEGG enrichment, GO analysis, and protein-protein interaction network were used for hub gene identification. miRNA were predicted using Targetscan and validated according to several GEO databases. The relative RNA and miRNA expression levels and prognostic information were obtained from the GEPIA. The candidate drug was screened using pharmacophore-based virtual screening and validated by molecular modeling and through several in vitro studies. 301 differentially expressed genes (DEGs) were screened out. Complement and coagulation cascades-related genes (including AHSG, F2, TTR, and KNG1), and cell cycle-related genes (including CDK1, CCNB1, and KIAA0101) were considered as the hub genes in CCA progression. AHSG, F2, TTR, and KNG1 were found to be significantly decreased and the eight predicted miRNA targeting AHSG, F2, and TTR were increased in CCA patients. CDK1, CCNB1, and KIAA0101 were found to be significantly abundant in CCA patients. In addition, Molport-003-703-800, which is a compound that is derived from pharmacophores-based virtual screening, could directly bind to CDK1 and exhibited anti-tumor activity in cholangiocarcinoma cells. AHSG, F2, TTR, and KNG1 could be novel biomarkers for CCA. Molport-003-703-800 targets CDK1 and work as potential cell cycle inhibitors, thereby having potential for consideration for new chemotherapeutics for CCA.

• Herbal Formula Science
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• v.31 no.3
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• pp.171-182
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• 2023

Objectives : Saposhnikoviae Radix (SR) and Glehniae Radix (GR) have been frequently used in traditional medicine to treat diseases related to 'wind' syndrome, but there have been cases where it has been mixed in a state where the plant of origin is not clear. In this study, to select materials for conducting preclinical cerebral infarction research, the network pharmacology analysis method was used to select suitable medicinal materials for the study. Methods : In this study, a Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) based network pharmacology analysis method was used, and oral bioavailability (OB), drug likeness (DL), Caco-2 and BBB permeability were utilized to select compounds with potential activity. For the values of each variable used in this study, OB ≥ 20%, DL ≥ 0.18, Caco-2 ≥ 0, and BBB ≥ -0.3 were applied, then networks of bioactive compounds, target proteins, and target diseases was constructed. STRING database was used to construct a protein-protein interaction network. Results : It was confirmed that SR rather than GR has various target proteins and target diseases based on network pharmacological analysis using TCMSP database. And it was analyzed that the bioactive compounds only in SR act more on neurovascular diseases, and both drugs are expected to be effectively used for cardiovascular diseases. Conclusions : In our future study, SR will be used in an ischemic stroke mouse model, and the mechanism of action will be explored focusing on apoptosis and cell proliferation.

• Genomics & Informatics
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• v.21 no.2
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• pp.17.1-17.12
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• 2023

Coronavirus has left severe health impacts on the human population, globally. Still a significant number of cases are reported daily as no specific medications are available for its effective treatment. The presence of the CD147 receptor (human basigin) on the host cell facilitates the severe acute respiratory disease coronavirus 2 (SARS-CoV-2) infection. Therefore, the drugs that efficiently alter the formation of CD147 and spike protein complex could be the right drug candidate to inhibit the replication of SARS-CoV-2. Hence, an e-Pharmacophore model was developed based on the receptor-ligand cavity of CD147 protein which was further mapped against pre-existing drugs of coronavirus disease treatment. A total of seven drugs were found to be suited as pharmacophores out of 11 drugs screened which was further docked with CD147 protein using CDOCKER of Biovia discovery studio. The active site sphere of the prepared protein was 101.44, 87.84, and 97.17 along with the radius being 15.33 and the root-mean-square deviation value obtained was 0.73 Å. The protein minimization energy was calculated to be -30,328.81547 kcal/mol. The docking results showed ritonavir as the best fit as it demonstrated a higher CDOCKER energy (-57.30) with correspond to CDOCKER interaction energy (-53.38). However, authors further suggest in vitro studies to understand the potential activity of the ritonavir.

• Korean Journal of Psychosomatic Medicine
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• v.14 no.1
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• pp.62-66
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• 2006

Introduction: Unexpected serious and lethal drug interactions can be occurred by polypharmacy for treatment-resistant psychiatric disorders. We report a case who has suspected upper gastrointestinal bleeding after the combination of clozapine and buspirone. Case : A 69-year-old woman with DSM-IV schizophrenia who was admitted to our hospital had no previous medical problems. Findings on physical exam, laboratory values, EEG, and a magnetic reso-nance imaging scans were no abnormality, except for slightly low level of hemoglobin at admission. Because of aggravating anxiety symptom, a trial of buspirone was begun from 15mg, in addition to olanzapine 30mg. And then olanzapine was switched to clozapine due to her treatment-refractory his-tory and poor response on this admission. Moreover, At the admission 11 weeks later, after 4 weeks of starting buspirone and clozapine, she was placed on a regimen of clozapine 300mg and buspirone 60mg. At this point, she started to complaint nonspecific abdominal pain for 4 days and then hematemesis, melena and hypotension were developed suddenly with negative findings in gastroduodenoscopy. After stopping all medication, the suspected upper gastrointestinal bleeding was subsided. After the regimen was switched back to clozapine only, psychotic symptoms were improved without the recurrence of the adverse events. Conclusion : We concluded that the upper gastrointestinal bleeding in this case was attributed to the drug interaction with clozapine and buspirone, although the definite mechanism is not clear. The clini-cians should be very cautious to prescribe the combination of clozapine and buspirone due to a possible lethal adverse effect.

• Journal of Life Science
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• v.23 no.9
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• pp.1126-1132
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• 2013

Cytochrome P450 2J2 (CYP2J2) is an enzyme mainly found in human extrahepatic tissues, with predominant expression in the cardiovascular system. CYP2J2 plays important roles in the metabolism of endogenous metabolites and therapeutic drugs, such as arachidonic acid, astemizole, ebastine, and terfenadine. CYP2J2 is also overexpressed in human cancer tissues and cancer cell lines and may represent a potential target for therapy of human cancers. In this study, 10 natural products obtained from plants and microorganisms were screened as potential CYP2J2 inhibitors. Among them, thelephoric acid showed strong inhibition of astemizole O-demethylation activity ($IC_{50}=3.23{\mu}M$) in a dose-dependent manner. Evaluation of the substrate dependency of the inhibitory activity of thelephoric acid showed that it strongly inhibited CYP2J2-mediated ebastine hydroxylation ($IC_{50}=5.32{\mu}M$) and terfenadine hydroxylation ($IC_{50}=3.27{\mu}M$) in a substrate nondependent manner. The present data suggest that this compound might be a potential candidate for further evaluation for anticancer activity.

• Journal of Life Science
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• v.28 no.7
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• pp.765-771
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• 2018

Peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$) is a key transcription factor that regulates adipogenesis, and epigenetic control of $PPAR{\gamma}$ is of great interest in obesity-inhibition research. Our previous study showed that CACUL1 (CDK2-associated cullin domain 1) acts as a corepressor that inhibits $PPAR{\gamma}$ transcriptional activity and adipocyte differentiation. Here, we investigated the roles of protein arginine methyltransferase 5 (PRMT5), a novel binding partner of CACUL1, in regulating $PPAR{\gamma}$. The interaction between PRMT5 and CACUL1 was shown by immunoprecipitation assay in vivo and GST pulldown assay in vitro. As shown by luciferase reporter assay, PRMT5 and CACUL1 cooperated to inhibit the transcriptional activity of $PPAR{\gamma}$. The suppressive role of PRMT5 in adipogenesis was examined by Oil Red O staining using 3T3-L1 cells, which stably overexpress or deplete PRMT5. Overexpression of PRMT5 suppresses $PPAR{\gamma}$-mediated adipogenesis, whereas PRMT5 knockdown increases lipid accumulation in 3T3-L1 cells. Consistently, PRMT5 attenuates the expression of Lpl and aP2, the target genes of $PPAR{\gamma}$, as demonstrated by RT-qPCR analysis. Overall, these results suggest that PRMT5 interacts with CACUL1 to impair the transcriptional activity of $PPAR{\gamma}$, leading to the inhibition of adipocyte differentiation. Therefore, the regulation of PRMT5 enzymatic activity may provide a clue to develop an anti-obesity drug.

• The Korea Journal of Herbology
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• v.22 no.4
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• pp.253-260
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• 2007

Objectives : Intracerebral hemorrhage (ICH) is characterized by breakdown of blood vessels within the brain parenchyma. Fundamental therapeutic strategies for ICH, particularly those aimed at neuroprotection, have to be established. So in this experiment, the effects of Woowhangchongshim-won, a traditional prescription formula for treating Cerebral Apoplexy in Asian countries, were investigated. Methods : After intraperitoneal injection of chloralhydrate, rats were placed in a stereotaxic frame. ICH was induced by injection of 1 U collagenase type IV and drug was administered orally for 10 days. The molecular profile of cerebral hemorrhage in rat brain tissue was measured using micro array technique to identify up- or down- regulated genes in brain tissue. These genes induced by brain damage were mainly concerned with general metabolic process such as primary metabolic process, cellular metabolic process, macromolecule metabolic process, and biosynthetic process. Results : The number of genes increased in control and not-changed in experiment was 374, and decreased in control and not-changed in experiment was 527. We are concerned with genes that can be recovered by treatment with medicine, it is especially interesting to above types of genes. Conclusions : Upon medicine treatment to the rat having cerebral hemorrhage, expressions of some genes were restored to normal level. Further analysis using protein interaction database identified some key molecules that can be used for elucidation of therapeutical mechanism of medicine in future.