• Proceedings of the Plant Resources Society of Korea Conference
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• 2023.04a
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• pp.47-47
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• 2023

Paeonia lactiflora roots (PLR) are a medicinal plant widely used for treating inflammatory diseases. However, PLR has been recently reported to increase the production of proinflammatory mediators and activates phagocytosis in macrophages. Thus, in this study, we tried to verify the macrophage activation of PLR and elucidate its mechanism of action. PLR upregulated the production of proinflammatory mediators and activated phagocytosis in RAW264.7 cells. However, these effects were reversed by inhibition of TLR2/4. In addition, the inhibition of p38, JNK, and ERK1/2 reduced the PLR-mediated production of proinflammatory mediators, and the PLR-mediated activation of p38, JNK, and ERK1/2 was blocked by the TLR4 inhibition. These findings indicate that PLR may activate macrophages through TLR4-dependent activation of p38, JNK, and ERK1/2. These indicate that PLR has immunostimulatory activity. Thus, it is believed that PLR can be used as a functional food agent that enhances the immune system.

• Korean Journal of Pharmacognosy
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• v.50 no.1
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• pp.18-24
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• 2019

Andrographolide, the main compound of Andrographis paniculata (A. paniculata), shows various biological properties including anti-viral, anti-inflammatory, anti-diabetic, and hepatoprotective effects. Our previous study has shown that A. paniculata extract exerts antiaging effects by activation of stemness in epidermal stem cells (EpSCs). In this study, we investigated the effect of andrographolide as a main compound of A. paniculata on EpSCs and its mechnism of action using several in vitro assays. Andrographolide increased the proliferation of EpSCs and induced cell cycle progression. Additionally, andrographolide increased VEGF production and the expression of stem cell markers integrin ${\beta}1$ and p63. Furthermore, phosphorylation levels of extracellular signal-regulated kinase 1/2 (ERK1/2), S6 ribosomal protein (S6RP) and Akt were increased by andrographolide. Taken together, these results indicate that andrographolide-induced proliferation of EpSCs is mediated by the ERK1/2, Akt-dependent pathway with increased production of VEGF and upregulated stemness through integrin ${\beta}1$ and p63.

• Biomedical Science Letters
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• v.15 no.2
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• pp.141-146
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• 2009

Paclitaxel, an antimicrotubule agent, binds to beta-tubulin in the microtubule and stabilizes the polymer, thereby repressing dynamic instability. Here, we have demonstrated that microtubule cytoskeletal architecture involved in regulation of the COX-2 expression in chondrocyte treated with paclitaxel. Paclitaxel enhanced COX-2 expression and prostaglandin E2 production, as indicated by the Western blot analysis, reverse transcriptase PCR(RT-PCR) and immunofluorescence staining, and $PGE_2$ assay, respectively. In our previous data have shown that paclitaxel treatment stimulated activation of ERK-1/2 and p38 kinase(Im et al., 2009). SB203580, an inhibitor of p38 kinase, blocked the induction of COX-2 expression by paclitaxel. Also PD98059, an inhibitor of ERK-1/2 kinase was blocked the induced COX-2 expression. These results indicate that activation of ERK-1/2 and p38 kinase is required for COX-2 expression induced by paclitaxel in rabbit articular chondrocytes.

• Clinical and Experimental Reproductive Medicine
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• v.33 no.2
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• pp.105-113
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• 2006

Objective: To investigate the role of ERK and $PPAR{\gamma}$ on the $TGF-{\beta}1$ induced human endometrial stromal cell decidualization in vitro. Method: Endometrial stromal cells are cultured under the following condition: DMEM/F12 (10% FBS, 1 nM E2 and 100 nM P4). $TGF-{\beta}1$ (5 ng/ml), Rosiglitazone (50 nM), and PD98059 ($20{\mu}M$) were added according to experimental purposes. Trypan-Blue and hematocytometer were utilized to count cell number. Enzyme-linked immunosorbent assay (ELISA) and western blotting were utilized to detect proteins. Result: $TGF-{\beta}1$ inhibited proliferation of cultured human endometrial stromal cells and induced expression of PGE2 and prolactin. This effect was mediated by Smad and ERK activation. Administration of rosiglitazone, $PPAR{\gamma}$ agonist, prevented $TGF-{\beta}1$ effect on cell proliferation. Furthermore, Rosiglitazone inhibited $TGF-{\beta}1$ induced activation of ERK, consequently reduced PGE2 and prolactin production. Conclusion: $TGF-{\beta}1$ induced decidualization of endometrial stromal cell through Smad and ERK phosphorylation. $PPAR{\gamma}$ acts as a negative regulator of human ndometrial cell decidualization in vitro.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.20
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• pp.8539-8548
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• 2014

Mitogen-activated protein kinase (MAPK) is an important signaling pathway in living beings in response to extracellular stimuli. There are 5 main subgroups manipulating by a set of sequential actions: ERK(ERK1/ERK2), c-Jun N(JNK/SAPK), p38 MAPK($p38{\alpha}$, $p38{\beta}$, $p38{\gamma}$ and $p38{\delta}$), and ERK3/ERK4/ERK5. When stimulated, factors of upstream or downstream change, and by interacting with each other, these groups have long been recognized to be related to multiple biologic processes such as cell proliferation, differentiation, death, migration, invasion and inflammation. However, once abnormally activated, cancer may occur. Several components of the MAPK network have already been proposed as targets in cancer therapy, such as p38, JNK, ERK, MEK, RAF, RAS, and DUSP1. Among them, alteration of the RAS-RAF-MEK-ERK-MAPK(RAS-MAPK) pathway has frequently been reported in human cancer as a result of abnormal activation of receptor tyrosine kinases or gain-of-function mutations in genes. The reported roles of MAPK signaling in apoptotic cell death are controversial, so that further in-depth investigations are needed to address these controversies. Based on an extensive analysis of published data, the goal of this review is to provide an overview on recent studies about the mechanism of MAP kinases, and how it generates certain tumors, as well as related treatments.

• Journal of Digital Convergence
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• v.18 no.3
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• pp.267-273
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• 2020

To determine the biological effects of exercise on hippocampus in mice brain exposed to radiofrequency radiaton (RF), the expression of AMPKα, p-AMPKα, ERK1/2, p-ERK1/2, p38, and p-p38 protein in the mouse exposed to RF were investigated in the hippocampal tissues, Western blot method was used to compare the protein expression levels for each molecule. Significant increases in protein expression of individual and phosphorylated molecules were observed in the spontaneous exercise group, and the expression of these molecules was notably decreased in the RF exposure and spontaneous exercise group. This study shows that neuroplasticity can be increased by exercise in hippocampus that is responsible for memory, but memory and cognitive function may be affected by exposure to RF. We may expect clinically interesting results on dementia or Alzheimer disease if we proceed further investigation on the effect of RF.

• Journal of Acupuncture Research
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• v.23 no.3
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• pp.91-102
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• 2006

목적 : 이 연구에서는 FBS에 의하여 유도되는 혈관 평활근 세포 증식에 대한 봉약침액과 Melittin의 세포 고사효과의 영향 및 작용 기전을 살펴보고자 하였다. 방법 : $I{\kappa}Ba$, p-$I{\kappa}Ba$, p-ERK1/2, p-Akt, p53, Bcl-2, Bax 및 active caspase-3는 Western blotting을, $NF-{\kappa}B$는 EMSA와 immunofluorescence staining을 이용하여 측정하였다. 결과 : 1. Melittin은 $NF-{\kappa}B$ 활성에 대하여 $I{\kappa}Ba$의 인산화를 유의하게 익제하고 $I{\kappa}Ba$를 증가시켰으며, $NF-{\kappa}B$의 DNA 결합과 $NF-{\kappa}B$ p50의 핵 내 유입을 유의하게 감소시켰다. 2. Melittin은 $NF-{\kappa}B$ 활성을 증가시키는 물질인 Akt의 인산화를 유의하게 억제하였고, ERK1/2의 인산화도 억제하였다. 3. Melittin은 세포사멸 전구 단백질인 p53, Bax 및 caspase-3의 발현을 유의하게 증가시켰고, 세포사멸억제 단백질인 Bcl-2의 발현은 감소시켰다. 결론 : 이상의 결과는 $NF-{\kappa}B$ 와 Akt 활성을 억제함으로써 혈관평활근세포 증식을 억제하는 효과가 있음을 입증한 것이며, 향후 안전성 연구를 바탕으로 혈관성형술 후 재발성협착증과 동맥경화증의 치료제로 사용될 수 있을 것으로 기대된다.

• Nutritional Sciences
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• v.7 no.1
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• pp.23-30
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• 2004

As a central component of a novel protein kinase cascade, the activation of the mitogen-activated protein (MAP) kinase cascade has attracted considerable attention. We sought to determine the effect of exercise and diet on the activation of the extracellular-signal regulated protein kinase (ERK) 1/2 and the p38 MAP kinase pathways in rat soleus muscle. Forty-eight Sprague-Dawley rats were assigned to one of two dietary conditions: high-carbohydrate (CHO) or high-fat (FAT). Animals having each dietary condition were further divided into one of three subgroups: a sedentary control group that did not exercise (NT), a group that performed 8 weeks of treadmill running and was sacrificed 48 h after their final treadmill run (CE), and a group that was sacrificed immediately after their final routine exercise training (AE). A high-fat diet did not have any significant effect on phosphorylated and total forms of ERK 1/2 or p38 MAP kinase. In chronically trained muscle that was taken 48 h after the last training, phosphorylated ERK 1/2 significantly increased only in the FAT but not in the CHO groups. In the case of total ERK 1/2, it increased significantly for both groups. In contrast, both phosphorylated and total forms of p38 MAP kinase decreased markedly compared to sedentary muscle. In muscle that was taken immediately after a last bout of exercise, phosphorylated ERK 1/2 increased in both groups but statistical significance was seen only in the CHO group. Total ERK 1/2 in acutely stimulated muscle increased only in the CHO-AE group even though the degree was much lower than the phosphorylated status. Muscle that was taken immediately after the routine training increased in phosphorylation status of p38 MAP kinase for both dietary conditions. However, statistical significance was seen only in the CHO group owing to a large variation with FAT. In conclusion, a high-fat diet per se did not have any notable effect versus a high-carbohydrate diet on MAP kinase pathways. However, when diet (either CHO or FAT) was combined with exercise and/or training, there was differentiated protein expression in MAP kinase pathways. This indicates MAP kinase pathways have diverse control mechanisms in slow-twitch fibers.

• Journal of Food Hygiene and Safety
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• v.34 no.3
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• pp.303-308
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• 2019

L-carnitine is found in high levels in muscle tissues. It has been developed as a nutrient and dietary supplement, and also used as a therapeutic supplement in various diseases including type II diabetes, osteoporosis and metabolic neuropathies. However, it is not fully understood how it affects cellular mechanisms in colorectal cancer. Therefore, we attempted to determine the effect of L-carnitine in HCT116 human colorectal cancer cells. First, the HCT116 cells were exposed to L-carnitine for 24 hours at 0-40 mM, and then analyzed for cellular proliferation, oxidative stress and related mechanisms. In a MTT assay, L-carnitine inhibited cellular proliferation and induced reactive oxygen species (ROS) in HCT116 by DCF-DA analysis. To analyze the mechanism of L-carnitine in colorectal cancer cells, we performed a western blot analysis for pERK1/2 and pp38 MAP kinase. The western blot showed that L-carnitine significantly increased protein levels of pERK1/2 and pp38 compared with control. Taken together, we found that L-carnitine has anti-proliferative function via increased ROS and activation of ERK1/2 and p38 pathway in HCT116. These findings suggest that L-carnitine may have an anti-proliferative role on colorectal cancer.

• Biomedical Science Letters
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• v.15 no.1
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• pp.67-72
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• 2009

Microtubule-interfering agents (MIAs), including paclitaxel, have been attributed in part to interference with microtubule assembly, impairment of mitosis, and changes in cytoskeleton. But the signaling mechanisms that link microtubule disarray to destructive or protective cellular responses are poorly understood. This study investigated the effect of paclitaxel on differentiation such as type II collagen expression and sulfated proteoglycan accumulation in rabbit articular chondrocytes. Paclitaxel caused differentiated chondrocyte phenotype as demonstrated by increment of type II collagen expression and proteoglycan synthesis Paclitaxel treatment stimulated activation of ERK-1/2 and p38 kinase. Inhibition of ERK-1/2 with PD98059 enhanced paclitaxel-induced differentiation, whereas inhibition of p38 kinase with SB203580 suppressed paclitaxel-induced differentiation. Our findings suggest that ERK-1/2 and p38 kinase oppositely regulate paclitaxel-induced differentiation in chondrocytes.