• Korean Journal of Oriental Medicine
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• v.17 no.3
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• pp.77-85
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• 2011

Objectives : The purpose of this study was to develop a simulator which can analyze the anti-inflammatory effects of medical herbs based on e-cell concerning p38 MAPK signal pathway. Methods : We collected data concerning medical herbs with anti-inflammatory effects and the active compounds to provide as a fundamental databse and to validate the newly developed algorithm. At this time, we used the target database as pubmed and gathered the data by data mining tool, pathway studio. Also we have developed the web-based search system for confirming database related to anti-inflammation. We researched the mechanism of actions of proteins in p38 MAPK signal pathway when active compound has been inserted into the network. We reduced total network into TAK-MKK3-p38 and made the two types of mathematical model about active compounds' interaction. Results & Conclusion : We constructed the database which have 69 cases of medical herbs, 71 cases of active compounds, about 8,000 cases of URL(Uniform Resource Locator) related to papers and reports. We designed the ordinary differential equations for response of TAK, MKK3, p38 in e-cell's cytosol and nucleus. We used this formular as measure whether an active compound of medicinal plants which is inputted by an user would have an anti-inflammation effects. We developed the visualization program which could show the change of concentration over time.

• Journal of Microbiology and Biotechnology
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• v.31 no.12
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• pp.1615-1623
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• 2021

Picropodophyllotoxin (PPT), an epimer of podophyllotoxin, is derived from the roots of Podophyllum hexandrum and exerts various biological effects, including anti-proliferation activity. However, the effect of PPT on colorectal cancer cells and the associated cellular mechanisms have not been studied. In the present study, we explored the anticancer activity of PPT and its underlying mechanisms in HCT116 cells. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to monitor cell viability. Flow cytometry was used to evaluate cell cycle distribution, the induction of apoptosis, the level of reactive oxygen species (ROS), assess the mitochondrial membrane potential (Δψm), and multi-caspase activity. Western blot assays were performed to detect the expression of cell cycle regulatory proteins, apoptosis-related proteins, and p38 MAPK (mitogen-activated protein kinase). We found that PPT induced apoptosis, cell cycle arrest at the G1 phase, and ROS in the HCT116 cell line. In addition, PPT enhanced the phosphorylation of p38 MAPK, which regulates apoptosis and PPT-induced apoptosis. The phosphorylation of p38 MAPK was inhibited by an antioxidant agent (N-acetyl-L-cysteine, NAC) and a p38 inhibitor (SB203580). PPT induced depolarization of the mitochondrial inner membrane and caspase-dependent apoptosis, which was attenuated by exposure to Z-VAD-FMK. Overall, these data indicate that PPT induced G1 arrest and apoptosis via ROS generation and activation of the p38 MAPK signaling pathway.

• Biomolecules & Therapeutics
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• v.30 no.6
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• pp.501-509
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• 2022

Atopic dermatitis (AD) is a chronic inflammatory skin disorder. Suppression of MAPKs and NF-κB is implicated as a vital mechanism of action of several traditional Chinese medicines for AD therapy. Although overexpression of MAPK mRNA in the skin tissue has been shown in the AD model, the roles of each MAPK in AD pathogenesis have rarely been studied. This study examined the effect of NJK14047, an inhibitor of p38 MAPKs, on AD-like skin lesions induced in BALB/c mice by sensitization and challenges with 1-chloro-2,4-dinitrobenzene (CDNB) on dorsal skin and ears, respectively. After induction of AD, NJK14047 (2.5 mg/kg) or dexamethasone (10 mg/kg) was administrated for 3 weeks via intraperitoneal injection. Following its administration, NJK14047 suppressed CDNB-induced AD-like symptoms such as skin hypertrophy and suppressed mast cell infiltration into the skin lesions. It also reduced CDNB-induced increase in T_H2 cytokine (IL-13) and T_H1 cytokines (interferon-γ and IL-12A) levels but did not decrease serum IgE level. Furthermore, NJK14047 blocked CDNB-induced lymph node enlargement. These results suggest that NJK14047, a p38 MAPK inhibitor, might be an optimal therapeutic option with unique modes of action for AD treatment.

• Journal of Life Science
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• v.16 no.6
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• pp.1066-1070
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• 2006

Smooth muscle cell (SMC) proliferation is important in the pathogenesis of vascular proliferative disorders. Understanding of the molecular mechanism underlying SMC growth after arterial injury would have therapeutic implications. Here we report that receptor activator of $NF-{\kappa}B$ ligand (RANKL), a member of tumor necrosis factor (TNF) family, promotes the proliferation of SMC, leading to decreased expression of p21 and enhancement of SMC growth. ERK and p38 phosphorylation was enhanced after RANKL treatment in SMC. Inhibition of ERK/p38 MAPK activity by PD98059/SB203580 completely abolished RANKL-induced proliferation of SMC, indicating ERK and p38 MAPK are essential for RANKL-induced SMC proliferation. Taken together, our findings demonstrate that RANK-RANKL-ERK/p38 pathway is important for proliferation of SMC and that these molecules may be the new therapeutic targets for the prevention of vascular diseases.

• BMB Reports
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• v.43 no.12
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• pp.824-829
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• 2010

Melanin synthesis is regulated by melanocyte specific enzymes and related transcription factors. $\beta$-carboline alkaloids including harmaline and harmalol are widely distributed in the environment including several plant families and alcoholic beverages. Presently, melanin content and tyrosinase activity were increased in melanoma cells by harmaline and harmalol in concentration- and time-dependent manners. Increased protein levels of tyrosinase, tyrosinase-related protein-1 (TRP-1), and TRP-2 were also evident. In addition, immunofluorescence and Western blot analyses revealed harmaline and harmalol increased cAMP response element binding protein phosphorylation and microphthalmia-associated transcription factor expression. In addition to studying the signaling that leads to melanogenesis, roles of the p38 MAPK pathways by the harmaline and harmalol were investigated. Harmaline and harmalol induced time-dependent phosphorylation of p38 MAPK. Harmaline and harmalol stimulated melanin synthesis and tyrosinase activity, as well as expression of tyrosinase and TRP-1 and TRP-2 indicating that these harmaline and harmalol induce melanogenesis through p38 MAPK signaling.

• Journal of Life Science
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• v.21 no.2
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• pp.183-193
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• 2011

Migration and differentiation of mesenchymal stem cells are crucial for tissue regeneration in response to injury. Sphingosine-1-phosphate (S1P) is a bioactive lipid that regulates a variety of biological processes, including proliferation, survival, differentiation and motility. In the present study, we determined the role of S1P in migration and differentiation of human bone marrow-derived mesenchymal stem cells (BMSCs). S1P stimulated migration of BMSCs in a dose- and time-dependent manner, and pre-incubation of the cells with pertussis toxin completely abrogated S1P-induced migration, suggesting involvement of Gi-coupled receptors in S1P-induced cell migration. S1P elicited elevation of intracellular concentration of $Ca^{2+}$ ($[Ca^{2+}]_i$) and pretreatment with VPC23019, an antagonist of $S1P_1/S1P_3$, blocked S1P-induced migration and increase of $[Ca^{2+}]_i$. Small interfering RNA-mediated knockdown of endogenous $S1P_1$ attenuated S1P-induced migration of BMSCs. Furthermore, S1P treatment induced expression of $\alpha$-smooth muscle actin ($\alpha$-SMA), a smooth muscle marker, and pretreatment with VPC23019 abrogated S1P-induced $\alpha$-SMA expression. S1P induced phosphorylation of p38 mitogen-activated protein kinase (MAPK), and pretreatment of cells with SB202190, an inhibitor of p38 MAPK, or adenoviral overexpression of a dominant-negative mutant of the p38 MAPK blocked S1P-induced cell migration and $\alpha$-SMA expression. Taken together, these results suggest that S1P stimulates migration and smooth muscle differentiation of BMSCs through an $S1P_1$-p38 MAPK-dependent mechanism.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2003.11a
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• pp.76-76
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• 2003

Mast cells accumulation can be causally related with several allergic inflammations. Previous work has demonstrated that glucocorticoids decreased tissue mast cell number and stem cell factor (SCF)-induced migration of mast cells required p38 mitogen-activated protein kinase (MAPK) activation. In the present study, we investigated the effects of dexamethasone on SCF-induced migration of rat peritoneal mast cells (RPMCs). SCF significantly induced migration of RPMCs at 4 h. Dexamethasone dose-dependently inhibited SCF-induced migration of RPMCs (about 90.1% at 100 nM, P<0.05). MAPK p38 inhibitor, SB203580 (20 ${\mu}$M) also inhibited the SCF-induced migration. The ability of SCF to enhance morphological alteration and F -actin formation was also abolished by treatment of dexamethasone. Dexamethasone inhibited SCF-induced p38 MAPK activation to near basal level and induced the MKP-1 expression. In addition, SCF-induced inflammatory cytokine production was significantly inhibited by treatment of dexamethasone or SB203580 (p<0.01). Our results show that dexamethasone potently regulates SCF -induced migration, p38 MAPK activation and inflammatory cytokine production through expression of MKP-l protein in RPMCs. Such modulation may have functional consequences during dexamethasone treatment, especially mast cell-mediated allergic inflammation disorders.

• Journal of dental hygiene science
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• v.14 no.2
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• pp.240-247
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• 2014

Acaiberry (Euterpe oleracea Mart.) is widely diffused in amazon and is known that has high antioxidant capacity and potential anti-inflammatory activities. The aim of this study was to evaluate analgesic effects of acaiberry in formalin-induced orofacial pain through p38 mitogen-activated protein kinases (p38 MAPK) and nicotinamide adenine dinucleotide phosphate 4 (NOX4) pathway. Rats were divided into 5 groups (n=6); formalin (5%, $50{\mu}L$), formalin after saline (vehicle) or acaiberry (16, 80, 160 mg/kg, intraperitoneally). The nociceptive response was investigated all of groups, p38 MAPK or NOX4 were analysed at dose of 80 mg/kg of acaiberry in rat's medulla oblongata and adrenal gland. Results indicated that acai berry produced analgesic effect in a dose-dependent manner and significantly reduced formalin-induced nociceptive response at 15~40 min. Acaiberry (80 mg/kg) decreased the increased p38 MAPK activation and NOX4 expression in medulla oblongata and adrenal gland. Based on these results, acaiberry is believed to be useful for modulation of orofacial pain and its treatments because of its anti-inflammatory and antioxidative effects.

• The Journal of Korean Obstetrics and Gynecology
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• v.18 no.4
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• pp.10-23
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• 2005

Purpose : This study is to examine the ability of Rhizoma Scirpi (RS) to induce HeLa cell viability. Methods : We culture HeLa cell which is human metrocarcinoma cell in D-MEM included 10% fetal bovine serum(Hyclone Laboratories) below $37^{\circ}C$, 5% CO2. Then we observed apoptosis of log phage cell which is changed cultivation liquid 24 Hours periodically. Results : 1. RS induces mitochondria membrane potential collapse. 2. P38 MAPK is involved in RS-induced death in HeLa cells. 3. P38 MAPK is involved in RS-induced apoptosis in HeLa cells. 4. P38 MAPK reguates RS-induced caspase-3, -8 and -9 activation in HeLa cells. 5. The inhibition of caspase regulates RS-induced cell death in HeLa cells. 6. RS induces mitochondria membrane potential collapse in HeLa cells. 7. P38 MPK is involved in the regulation of Bcl-2 and Bfu in HeLa cells.8. RS regulates the expression of Bcl-2 and Bax in HeLa cells. 9. SR induces p38 MAPK activation in HeLa cells. Conclusion : RS induces apoptosis in HeLa cells via p38 MAPK activation.

• IMMUNE NETWORK
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• v.13 no.6
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• pp.283-288
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• 2013

The pro-inflammatory cytokines tumor necrosis factor-${\alpha}$ (TNF${\alpha}$) and interleukin (IL)-$1{\beta}$ are crucial mediators involved in chronic inflammatory diseases. Inflammatory signal pathways regulate inflammatory cytokine expression-mediated by p38 mitogen activated protein kinase (p38MAPK). Therefore, considerable attention has been given to p38MAPK as a target molecule for the development of a novel anti-inflammatory therapeutics. BIRB 796, one of p38MAPK inhibitor, is a candidate of therapeutic drug for chronic inflammatory diseases. In this study, we investigated the effect of BIRB 796 on inflammatory cytokine productions by lipopolysaccharide (LPS) in different immune cell types. BIRB 796 reduced LPS-mediated IL-8 production in THP-1 cells but not in Raw 264.7 cells. Further analysis of signal molecules by western blot revealed that BIRB 796 sufficiently suppressed LPS-mediated phosphorylation of p38MAPK in both cell types whereas it failed to block inhibitor of kappa B (I-${\kappa}B$) degradation in Raw 264.7 cells. Taken together, these results suggest that the anti-inflammatory function of BIRB 796 depends on cell types.