• IMMUNE NETWORK
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• 제20권4호
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• pp.29.1-29.20
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• 2020

The development of refractory tumor cells limits therapeutic efficacy in cancer by activating mechanisms that promote cellular proliferation, migration, invasion, metastasis, and survival. Benzimidazole anthelmintics have broad-spectrum action to remove parasites both in human and veterinary medicine. In addition to being antiparasitic agents, benzimidazole anthelmintics are known to exert anticancer activities, such as the disruption of microtubule polymerization, the induction of apoptosis, cell cycle (G2/M) arrest, anti-angiogenesis, and blockage of glucose transport. These antitumorigenic effects even extend to cancer cells resistant to approved therapies and when in combination with conventional therapeutics, enhance anticancer efficacy and hold promise as adjuvants. Above all, these anthelmintics may offer a broad, safe spectrum to treat cancer, as demonstrated by their long history of use as antiparasitic agents. The present review summarizes central literature regarding the anticancer effects of benzimidazole anthelmintics, including albendazole, parbendazole, fenbendazole, mebendazole, oxibendazole, oxfendazole, ricobendazole, and flubendazole in cancer cell lines, animal tumor models, and clinical trials. This review provides valuable information on how to improve the quality of life in patients with cancers by increasing the treatment options and decreasing side effects from conventional therapy.

• 대한한의학방제학회지
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• 제32권1호
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• pp.11-28
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• 2024

Objectives : GunRyeong-Tang(GRT) is a traditional herbal prescription that combines Oryeongsan and Sagunja-tang. This study employed network analysis methods on the components of GRT and target genes related to diabetes complications to predict the improvement effects of GRT on diabetes complications. Methods : The collection of active compounds of GRT and related target genes involved the utilization of public databases and the PubChem database. We selected diabetes complication-related genes using GeneCards and confirmed their correlation through comparative analysis with the target genes of GRT. We constructed a network using Cytoscape 3.9.1 and conducted topological analysis. To predict the mechanism, we performed functional enrichment analysis based on Gene Ontology (GO) biological processes and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Results : Through network analysis, 234 active compounds and 1361 related genes were collected from GRT. A total of 9,136 genes related to diabetes complications were collected, and 1,039 target genes overlapping with the components of GRT were identified. The core genes of this network were TP53, INS, AKT1, ALB, and EGFR. In addition, GRT significantly reduced the H9c2 cell size and the expression of myocardial hypertrophy biomarkers (ANP, BNP), which were increased by high glucose (HG). Conclusions : Through this study, we were able to predict the activity and mechanism of action of GRT on diabetes and diabetic complications, and confirmed the potential of GRT as a treatment for diabetes complications through the effect of GRT on improving myocardial hypertrophy for diabetic cardiomyopathy.

• 한방안이비인후피부과학회지
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• 제35권4호
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• pp.75-94
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• 2022

Objectives : To identify the active ingredient of Poncirus Trifoliata Immaturus and to explore the mechanism expected to potentially act on dermatitis accompanied by pruritus. Methods : We conducted the network pharmacological analysis. We selected effective ingredients among the active compounds of Poinciri Fructus Immaturus. We found the target protein of the selected active ingredient, disease(dermatitis accompanied by pruritus) and fexofenadine. Then we established the network between the proteins which Poinciri Fructus Immaturus and fexofenadine intersected with disease respectively, and the coregene was also extracted. After that, the active pathways in the human body involving the groups and coregenes were searched. Results : Total of 7 active ingredients were selected, and 202 target proteins were collected. There were 756 proteins related to inflammatory skin disease accompanied by pruritus, and 75 proteins were related to fexofenadine. 42 proteins crossed by Poinciri Fructus Immaturus with a disease, and 31 proteins crossed by fexofenadine with a disease. 12 proteins were found as a coregene from the proteins that cross Poinciri Fructus Immaturus and disease. Coregenes are involved in 'Nitric-oxide synthase regulator activity', 'Epidermal growth factor receptor signaling pathway'. 2 groups that extracted are invloved in 'Fc receptor signaling pathway', 'Central carbon metabolism in cancer', 'Phosphatidylinositol 3-kinase complex, class IB', and 'omega-hydroxylase P450 pathway'. Conclusion : It is expected that Poinciri Fructus Immaturus will be able to show direct or indirect anti-pruritus and anti-inflammatory effects on skin inflammation accompanied by pruritus in the future. And it is also expected to have a synergy effect with fexofenadine on skin disease.

• The Korean Journal of Physiology and Pharmacology
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• 제2권3호
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• pp.297-305
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• 1998

This study used in vivo intracellular recording in rat hippocampus to evaluate the effect of lidocaine and MK-801 on the membrane properties and the synaptic responses of individual neurons to electrical stimulation of the commissural pathway. Cells in control group typically fired in a tonic discharge mode with an average firing frequency of $2.4{\pm}0.9$ Hz. Neuron in MK-801 treated group (0.2 mg/kg, i.p.) had an average input resistance of $3.28{\pm}5.7\;M{\Omega}$ and a membrane time constant of $7.4{\pm}1.8$ ms. These neurons exhibited $2.4{\pm}0.2$ ms spike durations, which were similar to the average spike duration recorded in the neurons of the control group. Slightly less than half of these neurons were firing spontaneously with an average discharge rate of $2.4{\pm}1.1$ Hz. The average peak amplitude of the AHP following the spikes in these groups was $7.4{\pm}0.6$ mV with respect to the resting membrane potential. Cells in MK-801 and lidocaine treated group (5 mg/kg, i.c.v.) had an average input resistance of $3.45{\pm}6.0\;M{\Omega}$ and an average time constant of $8.0{\pm}1.4$ ms. The cells were firing spontaneously at an average discharge rate of $0.6{\pm}0.4$ Hz. Upon depolarization of the membrane by 0.8 nA for 400 ms, all of the tested cells exhibited accommodation of spike discharge. The most common synaptic response contained an EPSP followed by early-IPSP and late-IPSP. Analysis of the voltage dependence revealed that the early-IPSP and late-IPSP were putative $Cl^--and\;K^+-dependent$, respectively. Systemic injection of the NMDA receptor blocker, MK-801, did not block synaptic responses to the stimulation of the commissural pathway. No significant modifications of EPSP, early-IPSP, or late-IPSP components were detected in the MK-801 and/or lidocaine treated group. These results suggest that MK-801 and lidocaine manifest their CNS effects through firing pattern of hippocampal pyramidal cells and neural network pattern by changing the synaptic efficacy and cellular membrane properties.

• 한방안이비인후피부과학회지
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• 제35권3호
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• pp.15-24
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• 2022

Objectives : The purpose of this study is to investigate the potential mechanism of Artemisia capillaris Thunb. for psoriasis vulgaris. Methods : We conducted the network pharmacological analysis. It contains the process that search the compounds of the herb, the target proteins of the compounds, related genes of psoariasis vulgaris and the pathway/terms of the common protein lists between psoriasis vulgaris and Artemisia capillaris Thunb.. Results : 13 compounds and 30 protein targets of Artemisia Capillaris Herba were searched. And 997 psoriasis-related genes were searched. The common proteins were 11, and the core genes were 3; AKT1, CASP3, MAPK8. The related pathway/terms of 11 proteins were analyzed. ω-hydroxylase P450 pathway(60%), nitric oxide(NO) biosynthetic process(20%) were resulted. Also, 19 proteins of Artemisia Capillaris Herba were analyzed, and sterol homeostasis(78.95%), sterol biosynthetic process(15.79%), Type 2 diabetes mellitus(5.26%) were resulted. Conclusion : The Artemisia Capillaris Herba can potentially act through the ω-hydroxylase P450 pathway and nitric oxide(NO) biosynthetic process for psoriasis. Also, the metabolism of sterol biosynthesis and homeostasis can be involved in a roundabout way for psoriasis.

• 한방안이비인후피부과학회지
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• 제36권4호
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• pp.30-50
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• 2023

Objectives : To investigate the active compounds and therapeutic mechanisms of Atractylodes Lancea(Thunb.) D.C. and Magnolia Officinalis Rehder et Wilson in the treatment of dermatitis accompanied by pruritus, as well as their potential to complement or replace standard drugs. Methods : We conducted the network pharmacological analysis. We selected effective ingredients among the active compounds of research target herbs. Then we explore pathway/terms of the common target proteins among research target herbs, fexofenadine and disease. Results : We selected 9 active compounds are selected from Atractylodes lancea and identified 231 target proteins. Among them, 74 proteins are associated with inflammatory skin diseases that cause pruritus. These proteins are involved in various pathways including, 'Nitric-oxide synthase regulator activity', 'Hydroperoxy icosatetraenoate dehydratase activity, Aromatase activity', 'RNA-directed DNA polymerase activity', 'Arachidonic acid metabolism', 'Peptide hormone processing', 'Chemokine binding' and 'Sterol biosynthetic process'. Additionally, coregenes are involved in 'IL-17 signaling pathway'. Similarly, we selected 2 active compounds from Magnolia officinalis and identified 133 target proteins. Among them, 33 proteins are related to inflammatory skin diseases that cause pruritus. These proteins are primarily involved in 'Vascular associated smooth muscle cell proliferation' and 'Arachidonic acid metabolism'. There is no significant difference between the pathways in which coregenes are involved. Conclusions : It is expected that Atractylodes Lancea will be able to show direct or indirect anti-pruritus and anti-inflammatory effects on skin inflammation accompanied pruritus through suppressing inflammation and protecting skin barrier. Meanwhile, it is expected that Magnolia Officinalis will only be able to show indirect anti-inflammation effects. Therefore, Atractylodes Lancea and fexofenadine are believed to complement each other, whereas Magnolia Officialinalis is expected to provide supplementary support on skin disease.

• 생명과학회지
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• 제34권3호
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• pp.179-190
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• 2024

Canabas sativa L. (marijuana and hemp)는 전 세계적으로 널리 재배되는 식물로 식품, 의약품 등의 재료로 사용되었다. 본 연구는 네트워크 약리학을 이용하여 대마 줄기 및 뿌리 추출물의 기능적 효과를 예측하고 이들의 새로운 기능을 알아보고자 하였다. 줄기 및 뿌리 에탄올 추출물의 성분은 GC/MS로 확인하였고, 성분과 단백질 간의 네트워크는 STIHICI 데이터베이스를 이용하여 알아보았다. 성분과 연결된 단백질의 작용기전은 KEGG pathway 분석을 수행하였다. 추출물의 효과는 실시간 PCR을 이용하여 lysophosphatylcholine 유도 THP-1 세포에서 확인하였다. 줄기 및 뿌리 추출물에서 각각 21개 및 32개의 성분이 확인되었다. 줄기 및 뿌리의 성분과 연결된 단백질은 각각 147개, 184개의 단백질이었다. KEGG pathway 분석결과 MAPK signaling pathway를 포함한 69개의 경로가 추출물에 의해 공통적으로 영향을 받는 것으로 나타났다. 경로 네크워크를 이용한 추가 조사 결과, Terpenoid backbone biosynthesis 추출물 및 MVK와 MVD 의해 영향을 받을 가능성이 높으며, 유전자 발현은 추출물에 의해 LPC 유도 THP-1 세포에서 감소하였다. 따라서 본 연구에서는 대마 줄기 및 뿌리 에탄올 추출물이 다양한 경로로 영향을 미칠 수 있음을 보여주었고, 이러한 결과는 대마의 효과를 예측하고 연구하기 위한 기초 정보를 제공할 것으로 사료된다.

• 동의생리병리학회지
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• 제36권6호
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• pp.229-234
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• 2022

Lung cancer is the leading cause of cancer-related deaths worldwide. Indigo Naturalis (IN) is a dark blue powder obtained by processing leaves or stems of indigo plants, its anticancer effects have been reported in several studies. However, the pharmacological mechanism of IN in small cell lung cancer (SCLC) is not elucidated. In this study, to investigate the anticancer efficacy of IN for SCLC, we presented potential active ingredients, SCLC-related targets, and pharmacological mechanisms of IN that are expected to have anticancer activity for SCLC using a network pharmacological analysis. The phytochemical compounds of IN have been collected through TCMSP, SymMap, or HPLC documents. The active ingredients of IN such as indirubin, indican, isatin, and tryptanthrin were selected through ADME parameters or literature investigations for each compound. Using the Compounds, Disease-Target associations Databases, 124 common targets of IN and SCLC were obtained. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway enrichment analysis was carried out. GO biological processes are associated with response to xenobiotic stimulus, positive regulation of protein phosphorylation, regulation of mitotic cell cycle, and regulation of apoptotic signaling pathway. KEGG disease pathways included Gastric cancer, Bladder cancer, SCLC, and Melanoma. The main anticancer targets of the IN for SCLC were analyzed in 14 targets, including BCL2, MYC, and TP53. In conclusion, the results of this study based on the network pharmacology of IN can provide important data for the effective prevention and treatment of SCLC.

• 대한한의학방제학회지
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• 제31권1호
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• pp.41-51
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• 2023

Objectives : Raphani Semen (Raphanus sativus L.) is known for the various beneficial effects in Korean medicine. This study aimed to investigate the effect of Raphani Semen extract (RSE) against arachidonic acid (AA)+iron-induced oxidative stress in cells. Methods : Ingredients, their target information, oxidative stress liver injury-related proteins was obtained from various network pharmacology databases and software. A hypergeometric test and enrichment analysis were conducted to evaluate associations between protein targets of RSE. The cell viability was assessed by MTT assay, and immunoblot analysis was used to confirm the molecular mechanisms. Results : A compound-target network of RSE was constructed, which consisted of 336 edges between 18 ingredients and 123 protein targets. PI3K-Akt signaling pathway, ErbB signaling pathway, HIF-1 signaling pathway, PPAR signaling pathway, and AMPK signaling pathway was significantly associated with protein targets of RSE. RSE protected HepG2 cells against AA+iron-induced oxidative stress as mediated with AMPK signaling. Conclusion : RSE was found to protect the cells against oxidative stress via the AMPK signaling pathway.

• International journal of advanced smart convergence
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• 제11권4호
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• pp.247-252
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• 2022

The purpose of the domestic physician scientist support program is to promote the development of various biotechnology. Therefore, it can be said that examining whether the purpose of support is being faithfully implemented has an important meaning for the future domestic biotechnology development ecosystem. Therefore, this study limited the subject of analysis to 79 MD-PhD experts who participated or participated in doctor scientist programs at major universities in Korea. Among them, a total of 25 researchers, one researcher from each classroom in parasitology, microbiology, pharmacology, biochemistry, physiology, and anatomy, which had the highest paper citations in the last five years (2016-2021), were selected to examine the relationship between joint research. It was selected as the subject of review. As a result, 25 selected pseudo-scientists(MD-PhD) identified domestic and foreign researchers who participated as co-researchers when publishing in overseas academic journals for the last 5 years(2016-2021), and identified the affiliation and name of the top 5 among them, as well as the pseudo-scientist(MD-PhD), it was possible to identify the relationship of a total of 123 co-researchers(excluding 2 missing values) of the top 5 co-researchers with a high degree of cooperation with respect to the researcher(25 in total), and the collaboration of pseudo-scientists. Relationships, major researchers, and research institutes were examined. Nodexl Basic 2018 ver. (Microsof) was used for the analysis, and the relationship between researchers could be visualized by applying network analysis techniques.