• Title/Summary/Keyword: Receptor methods

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A network pharmacology approach to explore the potential role of Panax ginseng on exercise performance

  • Kim, Jisu;Lee, Kang Pa;Kim, Myoung-Ryu;Kim, Bom Sahn;Moon, Byung Seok;Shin, Chul Ho;Baek, Suji;Hong, Bok Sil
    • Korean Journal of Exercise Nutrition
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    • v.25 no.3
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    • pp.28-35
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    • 2021
  • [Purpose] As Panax ginseng C. A. Meyer (ginseng) exhibits various physiological activities and is associated with exercise, we investigated the potential active components of ginseng and related target genes through network pharmacological analysis. Additionally, we analyzed the association between ginseng-related genes, such as the G-protein-coupled receptors (GPCRs), and improved exercise capacity. [Methods] Active compounds in ginseng and the related target genes were searched in the Traditional Chinese Medicine Database and Analysis Platform (TCMSP). Gene ontology functional analysis was performed to identify biological processes related to the collected genes, and a compound-target network was visualized using Cytoscape 3.7.2. [Results] A total of 21 ginseng active compounds were detected, and 110 targets regulated by 17 active substances were identified. We found that the active compound protein was involved in the biological process of adrenergic receptor activity in 80%, G-protein-coupled neurotransmitter in 10%, and leucocyte adhesion to arteries in 10%. Additionally, the biological response centered on adrenergic receptor activity showed a close relationship with G protein through the beta-1 adrenergic receptor gene reactivity. [Conclusion] According to bioavailability analysis, ginseng comprises 21 active compounds. Furthermore, we investigated the ginseng-stimulated gene activation using ontology analysis. GPCR, a gene upregulated by ginseng, is positively correlated to exercise. Therefore, if a study on this factor is conducted, it will provide useful basic data for improving exercise performance and health.

Involvement of the spinal γ-aminobutyric acid receptor in the analgesic effects of intrathecally injected hypertonic saline in spinal nerve-ligated rats

  • Myong-Hwan Karm;Hyun-Jung Kwon;Euiyong Shin;Honggyoon Bae;Young Ki Kim;Seong-Soo Choi
    • The Korean Journal of Pain
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    • v.36 no.4
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    • pp.441-449
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    • 2023
  • Background: Hypertonic saline is used for treating chronic pain; however, clinical studies that aid in optimizing therapeutic protocols are lacking. We aimed to determine the concentration of intrathecally injected hypertonic saline at which the effect reaches its peak as well as the underlying γ-aminobutyric acid (GABA) receptor-related antinociceptive mechanism. Methods: Spinal nerve ligation (SNL; left L5 and L6) was performed to induce neuropathic pain in rats weighing 250-300 g. Experiment 1: one week after implanting the intrathecal catheter, 60 rats were assigned randomly to intrathecal injection with 0.45%, 0.9%, 2.5%, 5%, 10%, and 20% NaCl, followed by behavioral testing at baseline and after 30 minutes, 2 hours, 1 day, and 1 week to determine the minimal concentration which produced maximal analgesia. Experiment 2: after determining the optimal intrathecal hypertonic saline concentration, 60 rats were randomly divided into four groups: Sham, hypertonic saline without pretreatment, and hypertonic saline after pretreatment with one of two GABA receptor antagonists (GABAA [bicuculline], or GABAB [phaclofen]). Behavioral tests were performed at weeks 1 and 3 following each treatment. Results: Hypertonic saline at concentrations greater than 5% alleviated SNL-induced mechanical allodynia and had a significant therapeutic effect, while showing a partial time- and dose-dependent antinociceptive effect on thermal and cold hyperalgesia. However, pretreatment with GABA receptor antagonists inhibited the antinociceptive effect of 5% NaCl. Conclusions: This study indicates that the optimal concentration of hypertonic saline for controlling mechanical allodynia in neuropathic pain is 5%, and that its analgesic effect is related to GABAA and GABAB receptors.

Ginsenoside F2 Restrains Hepatic Steatosis and Inflammation by Altering the Binding Affinity of Liver X Receptor Coregulators

  • Kyurae Kim;Myung-Ho Kim;Ji In Kang;Jong-In Baek;Byeong-Min Jeon;Ho Min Kim;Sun-Chang Kim;Won-Il Jeong
    • Journal of Ginseng Research
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    • v.48 no.1
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    • pp.89-97
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    • 2024
  • Background: Ginsenoside F2 (GF2), the protopanaxadiol-type constituent in Panax ginseng, has been reported to attenuate metabolic dysfunction-associated steatotic liver disease (MASLD). However, the mechanism of action is not fully understood. Here, this study investigates the molecular mechanism by which GF2 regulates MASLD progression through liver X receptor (LXR). Methods: To demonstrate the effect of GF2 on LXR activity, computational modeling of protein-ligand binding, Time-resolved fluorescence resonance energy transfer (TR-FRET) assay for LXR cofactor recruitment, and luciferase reporter assay were performed. LXR agonist T0901317 was used for LXR activation in hepatocytes and macrophages. MASLD was induced by high-fat diet (HFD) feeding with or without GF2 administration in WT and LXRα-/- mice. Results: Computational modeling showed that GF2 had a high affinity with LXRα. LXRE-luciferase reporter assay with amino acid substitution at the predicted ligand binding site revealed that the S264 residue of LXRα was the crucial interaction site of GF2. TR-FRET assay demonstrated that GF2 suppressed LXRα activity by favoring the binding of corepressors to LXRα while inhibiting the accessibility of coactivators. In vitro, GF2 treatments reduced T0901317-induced fat accumulation and pro-inflammatory cytokine expression in hepatocytes and macrophages, respectively. Consistently, GF2 administration ameliorated hepatic steatohepatitis and improved glucose or insulin tolerance in WT but not in LXRα-/- mice. Conclusion: GF2 alters the binding affinities of LXRα coregulators, thereby interrupting hepatic steatosis and inflammation in macrophages. Therefore, we propose that GF2 might be a potential therapeutic agent for the intervention in patients with MASLD.

A Case Report of Anti-NMDA Receptor Encephalitis with Ovarian Teratoma Improved by Korean Medicine (난소기형종을 동반한 항 NMDA 수용체 뇌염 환자 1례에 대한 한방치료 증례 보고)

  • Irang Nam;Min-hwa Kim;Mariah Kim;Ki-beom Ku;Se-yeon Lee;So-yeon Kim;So-jung Park;Jun-yong Choi;Chang-woo Han;Jin-woo Hong;Ji-won Kang;In Lee
    • The Journal of Internal Korean Medicine
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    • v.44 no.6
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    • pp.1337-1345
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    • 2023
  • Objectives: This study reports on the improvement of anti-N-methyl-D-aspartate (NMDA) receptor encephalitis with ovarian teratoma after Korean medicine treatment. Methods: A patient was treated with Korean medicine treatments, such as acupuncture and herbal medications (Gami-ondam-tang and Samulanshin-tang-gamibang). The patient's improvement was evaluated using manual muscle testing (MMT), the Mini-Mental State Exam-Korea (MMSE-K), the modified Barthel index (MBI), and the Clinical Assessment Scale in Autoimmune Encephalitis (CASE). Results: After using Korean medicine treatments, the patient's MMT, MMSE-K, and MBI scores increased, and the CASE score decreased. Conclusion: This case suggests that Korean medicine can be effective in treating the symptoms of anti-NMDA receptor encephalitis.

Analgesic and anti-inflammatory effects of galangin: a potential pathway to inhibit transient receptor potential vanilloid 1 receptor activation

  • Kaiwen Lin;Datian Fu;Zhongtao Wang;Xueer Zhang;Canyang Zhu
    • The Korean Journal of Pain
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    • v.37 no.2
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    • pp.151-163
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    • 2024
  • Background: Galangin, commonly employed in traditional Chinese medicine for its diverse medicinal properties, exhibits potential in treating inflammatory pain. Nevertheless, its mechanism of action remains unclear. Methods: Mice were randomly divided into 4 groups for 7 days: a normal control group, a galangin-treated (25 and 50 mg/kg), and a positive control celecoxib (20 mg/kg). Analgesic and anti-inflammatory effects were evaluated using a hot plate test, acetic acid-induced writhing test, acetic acid-induced vascular permeability test, formalin-induced paw licking test, and carrageenan-induced paw swelling test. The interplay between galangin, transient receptor potential vanilloid 1 (TRPV1), NF-κB, COX-2, and TNF-α proteins was evaluated via molecular docking. COX-2, PGE2, IL-1β, IL-6, and TNF-α levels in serum were measured using ELISA after capsaicin administration (200 nmol/L). TRPV1 expression in the dorsal root ganglion was analyzed by Western blot. The quantities of substance P (SP) and calcitonin gene-related peptide (CGRP) were assessed using qPCR. Results: Galangin reduced hot plate-induced licking latency, acetic acid-induced contortions, carrageenan-triggered foot inflammation, and capillary permeability in mice. It exhibited favorable affinity towards TRPV1, NF-κB, COX-2, and TNF-α, resulting in decreased levels of COX-2, PGE2, IL-1β, IL-6, and TNF-α in serum following capsaicin stimulation. Galangin effectively suppressed the upregulation of TRPV1 protein and associated receptor neuropeptides CGRP and SP mRNA, while concurrently inhibiting the expression of NF-κB, TNF-α, COX-2, and PGE2 mRNA. Conclusions: Galangin exerts its anti-inflammatory pain effects by inhibiting TRPV1 activation and regulating COX-2, NF-κB/TNF-α expression, providing evidence for the use of galangin in the management of inflammatory pain.

Assessment of antinociceptive property of Cynara scolymus L. and possible mechanism of action in the formalin and writhing models of nociception in mice

  • Pegah Yaghooti;Samad Alimoahmmadi
    • The Korean Journal of Pain
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    • v.37 no.3
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    • pp.218-232
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    • 2024
  • Background: Cynara scolymus has bioactive constituents and has been used for therapeutic actions. The present study was undertaken to investigate the mechanisms underlying pain-relieving effects of the hydroethanolic extract of C. scolymus (HECS). Methods: The antinociceptive activity of HECS was assessed through formalin and acetic acid-induced writhing tests at doses of 50, 100 and 200 mg/kg intraperitoneally. Additionally, naloxone (non-selective opioid receptors antagonist, 2 mg/kg), atropine (non-selective muscarinic receptors antagonist, 1 mg/kg), chlorpheniramine (histamine H1-receptor antagonist, 20 mg/kg), cimetidine (histamine H2-receptor antagonist, 12.5 mg/kg), flumazenil (GABAA/BDZ receptor antagonist, 5 mg/kg) and cyproheptadine (serotonin receptor antagonist, 4 mg/kg) were used to determine the systems implicated in HECS-induced analgesia. Impact of HECS on locomotor activity was executed by open-field test. Determination of total phenolic content (TPC) and total flavonoid content (TFC) was done. Evaluation of antioxidant activity was conducted employing 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assay. Results: HECS (50, 100 and 200 mg/kg) significantly indicated dose dependent antinociceptive activity against pain-related behavior induced by formalin and acetic acid (P < 0.001). Pretreatment with naloxone, atropine and flumazenil significantly reversed HECS-induced analgesia. Antinociceptive effect of HECS remained unaffected by chlorpheniramine, cimetidine and cyproheptadine. Locomotor activity was not affected by HECS. TPC and TFC of HECS were 59.49 ± 5.57 mgGAE/g dry extract and 93.39 ± 17.16 mgRE/g dry extract, respectively. DPPH free radical scavenging activity (IC50) of HECS was 161.32 ± 0.03 ㎍/mL. Conclusions: HECS possesses antinociceptive activity which is mediated via opioidergic, cholinergic and GABAergic pathways.

High Resolution Melting Analysis for Epidermal Growth Factor Receptor Mutations in Formalin-fixed Paraffin-embedded Tissue and Plasma Free DNA from Non-small Cell Lung Cancer Patients

  • Jing, Chang-Wen;Wang, Zhuo;Cao, Hai-Xia;Ma, Rong;Wu, Jian-Zhong
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.11
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    • pp.6619-6623
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    • 2013
  • Background:The aim of the research was to explore a cost effective, fast, easy to perform, and sensitive method for epidermal growth factor receptor (EGFR) mutation testing. Methods: High resolution melting analysis (HRM) was introduced to evaluate the efficacy of the analysis for dectecting EGFR mutations in exons 18 to 21 using formalin-fixed paraffin-embedded (FFPE) tissues and plasma free DNA from 120 patients. Results: The total EGFR mutation rate was 37.5% (45/120) detected by direct sequencing. There were 48 mutations in 120 FFPE tissues assessed by HRM. For plasma free DNA, the EGFR mutation rate was 25.8% (31/120). The sensitivity of HRM assays in FFPE samples was 100% by HRM. There was a low false-positive mutation rate but a high false-negative rate in plasma free DNA detected by HRM. Conclusions: Our results show that HRM analysis has the advantage of small tumor sample need. HRM applied with plasma free DNA showed a high false-negative rate but a low false-positive rate. Further research into appropriate methods and analysis needs to be performed before HRM for plasma free DNA could be accepted as an option in diagnostic or screening settings.

Therapeutic effect of Shinkiwhan, herbal medicine, regulates OPG/RANKL/RANK system on ovariectomy-induced bone loss rat

  • Seo, Il-bok;Lee, Kang Pa;Park, Sun-young;Ahn, Sang-hyun
    • Korean Journal of Exercise Nutrition
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    • v.24 no.3
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    • pp.19-24
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    • 2020
  • [Purpose] Although physical activity is required to prevent or ameliorate osteoporosis, medicine prescription should precede it, since it may be limited in severe osteoporosis patients. Furthermore, osteoporosis has a great effect on physical activity disorders that accompany fractures and pain, and therefore, research on treatment or prevention to decrease the number of patients is required. The purpose of this study was to discover candidate substances from natural products with an effective pharmacological action and to prepare basic data to help patients. [Methods] To prepare the osteoporosis model, ovariectomy (OVX) was performed using surgical methods. The prepared prescription [Shinkiwhan (SKH), a Korean medicine] was administered orally at a dose of 210 mg/kg/day for 8 weeks. After completion of the animal experiment, the bone mineral density (BMD) was analyzed using double-energy X-ray absorptiometry. The analysis of the effect of drugs on bones was performed using histological analysis and immunostaining. [Results] SKH increased the BMD in the OVX rats. Furthermore, SKH significantly increased the expression of osteoprotegerin and downregulated receptor activator of nuclear factor kappa B ligand and phosphorylation of c-jun N-terminal kinases in the bones of the OVX model. [Conclusion] Our findings suggest a protective effect of SKH against BMD loss in the OVX model.

WEHI-231 cells are defective in the ligand-induced internalization of B cell antigen receptor

  • Yoon, Sang Soon;Kim, Tae Jin
    • IMMUNE NETWORK
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    • v.1 no.3
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    • pp.196-202
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    • 2001
  • Backgorund: WEHI-231 B cell line is a representative model for $IgM^+$ mature B cells. To understand the signaling differences between mature and immature B cells, we compared the responsiveness of WEHI-231 and Bal 17 B cell lines to BCR cross-linking. Methods: The extents of tyrosine phosphorylation, ligand-induced internalization, and activation-induced cell death upon BCR cross-linking were compared in two cell lines. Results: Despite a higher expression of BCR, cross-linking of BCR on WEHI-231 cell evoked a weaker level of tyrosine phosphorylation and BCR endocytosis than Bal 17 cells. Furthermore, the endocytosed BCR could not enter the lysosomal compartment and stayed as peripheral spots in WEHI-231 cells. Conclusion: WEHI-231 cell showed preferred BCR-mediated signaling pathways leading to a reduced capability of antigen presentation as well as the enhanced apoptosis in comparision with Bal 17 cells. These results might reflect the signaling differences between mature and immature B cells.

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The Effects of Cuscuta japonica Chois on Gene Expression in RANKL-induced RAW 264.7 Cell (도사자(菟絲子)가 RANKL 유도 파골세포(破骨細胞)에 미치는 영향)

  • Kim, Joon-Yeon;Hwang, Gwi-Seo
    • Journal of Society of Preventive Korean Medicine
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    • v.14 no.2
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    • pp.77-89
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    • 2010
  • Objectives : This study was performed to evaluate the effect of CJ(Cuscuta japonica Chois) on osteoclast differentiation and gene expression. Methods : The osteoclastogenesis and gene expression were determined in RANKL(receptor activator of nuclear factor kappa B ligand)-stimulated RAW 264.7. The results were summarized as followes. Results : CJ decreased the number of TRAP positive cell in RANKL-stimulated RAW264.7 cell. CJ decreased the expression of RANK(receptor activator of nuclear factor kappa B), $TNF{\alpha}$, and IL-6 in RANKL-stimulated RAW264.7 cell. CJ decreased the expression of iNOS and COX-2 in RANKL-stimulated RAW264.7 cell. CJ decreased the expression of Cathepsin K in RANKL-stimulated RAW264.7 cell. Conclusions : It is concluded that CJ might decrease the bone resorption resulted from decrease of osteoclast differentiation and it's related gene expression.