• 제목/요약/키워드: network pharmacology

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Characteristic Intracelluar Response to Lidocaine And MK-801 of Hippocampal Neurons: An In Vivo Intracellular Neuron Recording Study

  • Choi, Byung-Ju;Cho, Jin-Hwa
    • 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.

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네트워크 약리학을 활용한 심상성 건선에 대한 인진호(茵蔯蒿)의 잠재적 작용 기전 탐색 연구 (A Network Pharmacology-based Study to Explore the Potential Mechanism of Artemisia capillaris Thunb. for Psoriasis Vulgaris)

  • 김준동;서광일;김병현;이한림;김규석;김윤범
    • 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.

네트워크 약리학을 이용한 소양증을 동반한 피부 염증에 대한 창출(蒼朮) 및 후박(厚朴)의 잠재적 치료기전 탐색 (Analysis of Potential Active Ingredients and Treatment Mechanism of Atractylodes Lancea(Thunb.) D.C and Magnolia Officinalis Rehder et Wilson for Dermatitis Accompanied by Pruritus Using Network Pharmacology)

  • 홍예은;서광일;김병현;김규석;남혜정;김윤범
    • 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.

네트워크 분석기반을 통한 대마 줄기 및 뿌리 추출물의 약리효능 예측연구 (A Study of the Predictive Effectiveness of Stem and Root Extracts of Cannabis sativa L. Through Network Pharmacological Analysis)

  • 신명자;차민호
    • 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.

네트워크 약리학적 분석에 의한 소세포폐암에 대한 청대의 항암기전 연구 (Identifying the Anti-Cancer Effect of Indigo Naturalis in Small Cell Lung Cancer Based on Network Pharmacological Analysis)

  • 김영훈;정우진;정광희;김윤숙;안원근
    • 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.

나복자의 항산화 효과 (Antioxidant effect of Raphani Semen (Raphanus sativus L.))

  • 박선빈;강승호;박광일;이원융
    • 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.

Biotechnology Development Collaboration System and Limitations of Domestic Physician Scientists

  • Yu, Tae Gyu
    • 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.

다계층 상호작용 네트워크 기반 사상처방의 작용 기전과 대상 질환 탐색 연구 (Exploring the Mechanisms and Target Diseases of Sasang Constitutional Prescription based on Multiscale Interactome)

  • 이원융;김지환
    • 사상체질의학회지
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    • 제35권4호
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    • pp.10-22
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    • 2023
  • Objectives The aim of this study is to explore the mechanism of action and target diseases of Sasang constitutional prescriptions using a multiscale interactome approach. Methods The compound and target information of Sasang constitutional prescriptions were retrieved from various databases such as the TM-MC, STITCH, and TTD. Key targets for Sasang constitutional prescriptions were identified by selecting the top 100 targets based on the number of simple paths within the constructed network. Diffusion profiles for Sasang constitutional prescriptions and diseases were calculated based on a biased random walk algorithm. Potential diseases and key mechanisms of Sasang constitutional prescriptions were identified by analyzing diffusion profiles. Results We identified 144 Sasang constitutional prescriptions and their targets, finding 80 herbs with effective biological targets. A cluster analysis based on selecting up to 100 key targets for each prescription revealed a more cohesive grouping of prescriptions according to Sasang constitution. We then predicted potential diseases for 62 Sasang constitutional prescriptions using diffusion profiles calculated on a multiscale interactome. Finally, our analysis of diffusion profiles revealed key targets and biological functions of prescriptions in obesity and diabetes. Conclusions This study demonstrates the effectiveness of a multiscale interactome approach in elucidating the complex mechanisms and potential therapeutic applications of prescriptions in Sasang constitutional medicine.

오령산 구성성분-타겟 네트워크 분석 (Analysis of a Compound-Target Network of Oryeong-san)

  • 김상균
    • 한국지식정보기술학회논문지
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    • 제13권5호
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    • pp.607-614
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    • 2018
  • 오령산은 몸 속의 수분을 순환시키고 소변으로 배출이 잘 되게 하는 효능이 있어 수분이 정체되어 나타나는 질환에 많이 쓰이는 처방이다. 본 연구에서는 시스템 약리학 접근 방법을 이용해서 오령산의 작용 기전을 탐색하기 위해서 오령산의 구성약재의 성분-타겟 네트워크를 구축하고 분석하였다. 우선, 오령산의 475개 성분에 대해서 STITCH 데이터베이스에서 연관된 타겟을 검색하였으며, 성분과 타겟의 상호작용에 대한 검색 결과는 XML 파일로 다운로드하였다. 본 연구에서 성분-타겟 네트워크는 Gephi를 이용해서 시각화하고 탐색하였다. 노드는 성분과 타겟이 되고, 링크는 성분과 타겟들간에 상호작용이 존재하면 연결되며, 상호작용의 신뢰도에 따라 링크에 가중치를 부여하였다. MCL 알고리즘을 이용해서 네트워크를 클러스터링 하였으며, 총 130개의 클러스터가 생성되었다. 가장 많은 노드를 가지는 클러스터에서 노드의 개수는 32개였다. 성분-타겟 네트워크에서 약재의 유효 성분들이 신장의 혈압 조절 기능과 관련된 타겟들과 연결되어 있는 것을 발견할 수 있었다. 향후에는 질병 데이터베이스와 연계해서 보다 명확한 오령산의 작용 기전을 밝힐 수 있도록 할 계획이다.

Cigarette Alternatives: Are they Safe?

  • Shantakumari, Nisha;Muttappallymyalil, Jayakumary;John, Lisha Jenny;Sreedharan, Jayadevan
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권8호
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    • pp.3587-3590
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    • 2015
  • In spite of limited data regarding the safety or effectiveness of electronic cigarette introduced into the market as a healthier alternative to tobacco smoking, its popularity has increased enormously. E-cigarettes have penetrated the market rapidly owing to the elaborate marketing network and attractive marketing strategies. Stated advantages include the claim that they help quit smoking and produce less exposure than conventional smoking. The list of disadvantages is even more elaborate. While the majority of the studies supporting health claims and efficacy for quitting smoking are not scientifically sound, they are also challenged by studies providing contradictory results. Owing to the limited evidence on the potential advantages and disadvantages of e-cigarettes, the debate on their safety continues.