• Journal of Ginseng Research
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• 제47권3호
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• pp.420-428
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• 2023

Background: Ginsenoside F2 (GF2), a minor component of Panax ginseng, has been reported to possess a wide variety of pharmacological activities. However, its effects on glucose metabolism have not yet been reported. Here, we investigated the underlying signaling pathways involved in its effects on hepatic glucose. Methods: HepG2 cells were used to establish insulin-resistant (IR) model and treated with GF2. Cell viability and glucose uptake-related genes were also examined by real-time PCR and immunoblots. Results: Cell viability assays showed that GF2 up to 50 μM did not affect normal and IR-HepG2 cell viability. GF2 reduced oxidative stress by inhibiting phosphorylation of the mitogen-activated protein kinases (MAPK) signaling components such as c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase 1/2 (ERK1/2), and p38 MAPK, and reducing the nuclear translocation of NF-κB. Furthermore, GF2 activated PI3K/AKT signaling, upregulated the levels of glucose transporter 2 (GLUT-2) and GLUT-4 in IR-HepG2 cells, and promoted glucose absorption. At the same time, GF2 reduced phosphoenolpyruvate carboxykinase and glucose-6-phosphatase expression as well as inhibiting gluconeogenesis. Conclusion: Overall, GF2 improved glucose metabolism disorders by reducing cellular oxidative stress in IR-HepG2 cells via MAPK signaling, participating in the PI3K/AKT/GSK-3β signaling pathway, promoting glycogen synthesis, and inhibiting gluconeogenesis.

• 대한본초학회지
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• 제36권3호
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• pp.1-8
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• 2021

Objective : Reflux esophagitis (RE), one of gastroesophageal reflux disease (GERD), is a disease that causes inflammation due to reflux of stomach contents such as stomach acid and pepsin due to the unstable gastroesophageal sphincter, and is currently increasing worldwide. The currently used treatment for reflux esophagitis has various side effects. Therefore, in this study the effect of Toosendan Fructus extract on chronic acid reflux esophagitis in rats was evaluated in order to find a new treatment material for reflux treatment. Methods : After inducing reflux esophagitis through surgery, the group was separated and the drug was administered for 2 weeks; Normal rats (Normal, n=8), chronic acid reflux esophagitis rats (Control, n=8), Toosendan Fructus 200 mg/kg body weight/day-treated chronic acid reflux esophagitis rats (TF, n=8). After, we were taken esophageal tissue and esophageal mucosa damage was identified, and analyzed the expression of NADPH oxidase, AP-1/MAPK-related proteins, and tight junction proteins by western blot in esophageal tissue. Results : Toosendan Fructus administration significantly protected the esophageal mucosal damage of reflux esophagitis. Also, Toosendan Fructus significantly reduced the expression of NADPH oxidases (NOX2 and p22^phox) and AP-1/MAPK-related proteins (c-Fos, c-Jun, p-p38, p-ERK, and p-JNK). In addition, it significantly increased the expression of tight junction proteins (Occludin, Claudin-3, and Claudin-4). Conclusions : These results suggest that Toosendan Fructus reduced damage to the esophageal mucosa by protecting the esophageal mucosa by upregulating tight junctions proteins as well as inhibiting the AP-1/MAPK pathway through reducing NADPH oxidases expression.

• 대한한의학방제학회지
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• 제13권2호
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• pp.111-123
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• 2005

The purpose of this study was to investigate the anticancer effects of Caesalpiniae Lignum (Somok) on HepG2 cells, a human liver cancer cell line. To study the cytotoxic effect of Caesalpiniae Lignum methanol extract (CL-MeOH) on HepG2 cells, the cells were treated with various concentrations of CL-MeOH and then cell viability was determined by XTT reduction method and trypan blue exclusion assay. CL-MeOH reduced proliferation of HepG2 cells in a dose-dependent manner. To confirm the induction of apoptosis, HepG2 cells were treated with various concentrations of CL-MeOH. The activation of caspase 3 and the cleavage of poly ADP-ribose polymerase (PARP), a substrate for caspase-3 and a typical sign of apoptosis, was examined by western blot analysis. CL-MeOH decreased procaspase 3 level in a dose-dependent manner and induced the clevage of PARP at concentration> $200{\mu}/ml$. Mitogen-activated protein (MAP) kinase signaling cascades are multi-functional signaling networks that influence cell growth, differentiation, apoptosis, and cellular responses to stress. CL-MeOH-induced MAPK activation was examined by Western blot for phosphorylated ERK, p38 and JNK. CL-MeOH significantly increased p38 phosphorylation and JNK phosphorylation in a dose-dependent manner. Inhibition of p38 function using the selective inhibitor SB20358O results in inhibition of apoptosis by CL-MeOH. These results suggest that CL-MeOH-induced apoptosis is MAP kinase-dependent apoptoric pathway. These results suggest that CL-MeOH is potentially useful as a chemotherapeutic agent in human liver cancer.

• 셀메드
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• 제13권6호
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• pp.7.1-7.6
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• 2023

Raphanus sativus L. has been reported to have anti-inflammatory and anti-tumor activity. However, the anti-inflammatory effect and mechanism of action of the Raphanus sativus L. seeds (RSS) with or without oil are still unknown. This study was undertaken to investigate the in-vitro anti-inflammatory effect with or without oil in the RSS on RAW 264.7 cells stimulated by lipopolysaccharide (LPS). Results showed the suppressed LPS-induced secretion of pro-inflammatory mediators such as nitric oxide (NO), inflammatory cytokine (IL-6, TNF-α). Additionally, a decrease in protein expression of iNOS was observed, but nuclear translocation of NF-κB p65 was not inhibited. To elucidate the underlying mechanism of the anti-inflammatory effect of RSS, the involvement of mitogen-activated protein kinase (MAPK) signaling pathways was examined. We also found that RSS blocked LPS-induced phosphorylation of c-Jun N-terminal kinase/stress-activated protein kinase (JNK) signaling but did not affect the phosphorylation of p38 MAPK and extracellular signal-regulated kinase (ERK) 1/2. These results suggest that RSS may have potential as an anti-inflammatory agent through the inhibition of LPS-induced inflammatory cytokine production via regulation of the JNK pathway.

• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2022년도 추계학술대회
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• pp.107-107
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• 2022

Scrophularia koraiensis Nakai is widely used to remedy fever, edema, and neuritis. S. koraiensis has harpagoside and angoroside C, these compounds have been reported to alleviate inflammation, rheumatic diseases, and analgesic stimulation. We evaluated the anti-inflammatory effects of the ethanol extract of S. koraiensis (SKE) in lipopolysaccharides (LPS)-induced macrophages. At cellular levels, SKE decreased the production of nitric oxide (NO), the expression of inducible nitric oxide synthase (iNOS), and cytokines (IL-1b, TNF-a, and IL-6) under the LPS stimulation. SKE inhibited the phosphorylation of nuclear transcription factor-kappa B (NF-κB) p65 and its inhibitor (IκB-α). In addition, SKE suppressed the phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 in the mitogen-activated protein kinase (MAPK) pathway. In conclusion, SKE could be considered a potential resource for attenuating inflammation response and it may be utilized in the material for cosmetics, food additives, and tea.

• Asian Pacific Journal of Cancer Prevention
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• 제16권7호
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• pp.2909-2914
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• 2015

Objective: To investigate the protective effect of quercetin on radiation induced lung injury (RILI) and related mechanisms. Materials and Methods: Mice treated with radiation and/or quercetin were sacrificed at 1-8 weeks after irradiation under anesthesia. Lung tissues were collected for histological examination. Immunohistochemistry (IHC) and Western blotting were performed to detect the protein expression of nuclear factor-${\kappa}B$ ($NF-{\kappa}B$) and Mitogen-activated protein kinases (MAPK) pathway. Results: Hematoxylin and eosin (HE) staining showed that radiation controls displayed more severe lung damage than quercetin groups, either high or low dose. Results of IHC and Western blotting demonstrated the expression level of $NF-{\kappa}B$ to be decreased and that of an inhibitor of $NF-{\kappa}B$ ($I{\kappa}b-{\alpha}$) to be increased by the quercetin intervention compared with the radiation control group. Numbers of JNK/SAPK, p38 and p44/p42 positive inflammatory cells were decreased in the radiation+quercetin injection group (P<0.05). Conclusions: Quercetin may play a radio-protective role in mice lung via suppression of $NF-{\kappa}B$ and MAPK pathways.

• 생명과학회지
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• 제25권9호
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• pp.976-983
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• 2015

Achyranthoside C dimethyl ester (ACDE)는 우슬에서 분리한 oleanolic acid glycoside이다. 본 연구에서는 RAW264.7 대식세포에서 ACDE의 항염증 효과를 관찰하고 그 작용 기전을 연구하였다. ACDE는 세포에 독성을 유도하지 않으면서 heme oxygenase-1 (HO-1)의 발현을 유도하였다. ACDE 는 HO-1의 발현에 관여하는 전사인자인 nuclear factor E2-related factor 2 (Nrf2)를 핵으로 이동시켰다. 또한 ACDE에 의한 HO-1의 발현은 phosphatidylinositol 3-kinase (PI-3K) 및 mitogen activated protein kinases (MAPK) 억제제에 의해 감소되었으며, ACDE가 Akt, c-Jun kinase (JNK), extracellular signal regulated kinase (ERK), p38 kinase의 인산화를 유도하였다. 한편 ACDE는 lipopolysaccharide (LPS)로 인한 nitric oxide (NO)의 생성과 inducible NO synthase (iNOS) 발현을 억제하였으며 HO-1 siRNA를 처리했을 때 ACDE가 iNOS의 발현을 억제하지 못하였다. 이상의 결과를 종합해보면, ACDE는 대식세포에서 PI3K/Akt 및 MAPK와 Nrf2 신호전달과정을 통해 HO-1의 발현을 유도함으로써 NO와 같은 염증매개물질의 생성을 억제한다는 것을 알 수 있다. 이러한 연구결과는 ACDE가 항염증제로 사용될 수 있음을 시사한다.

• 한방안이비인후피부과학회지
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• 제25권3호
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• pp.1-12
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• 2012

Objectives : Fagopyrum esculentum(FE) has been used for removal of inflammation of internal organs and treatment of sore and ulcer by heat toxin in Korean herbal medicines. In this study, To investigated the protective effect of FE on allergic response, we determined whether FE inhibits allergic response. Methods : The effect of FE was analyzed by ELISA, RT-PCR and Western blot in RBL-2H3 cells. We investigated cell viability, ${\beta}$-hexosaminidase, as a marker of degranulation, cytokne, and intracellular ROS and MAPK and NF-${\kappa}B$ signaling. Results : We found that FE suppressed ${\beta}$-hexosaminidase release, the production of IL-4 and TNF-${\alpha}$ and intracellular ROS level in RBL-2H3 by the anti-DNP IgE plus DNP-HSA stimulation. FE also significantly inhibited cytokine mRNA expressions, such as IL-$1{\beta}$, IL-2, IL-3, IL-4, IL-5, IL-6, IL-13, TNF-${\alpha}$ and GM-CSF in RBL-2H3. In addition, PF suppressed the phospholyation of ERK1/2, JNK1/2, p38 and $I{\kappa}B{\alpha}$ and NF-${\kappa}B$ signal transduction pathway. Conclusions : Our results indicate that FE protects against allergic response and exerts an anti-inflammatory effect through the inhibition of degranulation and production of cytokines and ROS via the suppression MAPK and NF-${\kappa}B$ of signal transduction. Abbrevations : FE, Fagopyrum esculentum; RBL-2H3, rat basophilic leukemia cell line; ROS, reactive oxygen species; MAPK, Mitogen-activated protein kinase; $NF{\kappa}B$, nuclear factor ${\kappa}B$; $TNF{\alpha}$, Tumor necrosis factor alpha; GM-CSF, Granulocyte macrophage colony-stimulating factor; ERK, extracellular-signal-regulated kinase; JNK, c-Jun NH2-terminal kinase; p38, p38 MAP kinase; $I{\kappa}B{\alpha}$, inhibitory-kappa B alpha.

• Asian-Australasian Journal of Animal Sciences
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• 제33권9호
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• pp.1497-1506
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• 2020

Objective: Gamma-aminobutyric acid (GABA) and piperine (PIP) are both nutritional supplements with potential use in animal diets. The purpose of this study is to investigate the effect of GABA and/or PIP treatment on the gene expression pattern of a pig kidney epithelial cell line. Methods: LLCPK1 cells were treated with GABA, PIP, or both, and then the gene expression pattern was analyzed using microarray. Gene ontology analysis was done using GeneOntology (Geneontology.org), and validation was performed using quantitative real-time polymerase chain reaction. Results: Gene ontology enrichment analysis was used to identify key pathway(s) of genes whose expression levels were regulated by these treatments. Microarray results showed that GABA had a positive effect on the transcription of genes related to regulation of erythrocyte differentiation and that GABA and PIP in combination had a synergistic effect on genes related to immune systems and processes. Furthermore, we found that effects of GABA and/or PIP on these selected genes were controlled by JNK/p38 MAPK pathway. Conclusion: These results can improve our understanding of mechanisms involved in the effect of GABA and/or PIP treatment on pig kidney epithelial cells. They can also help us evaluate their potential as a clinical diagnosis and treatment.

• Journal of Nutrition and Health
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• 제50권5호
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• pp.415-425
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• 2017

건 여주로부터 얻은 70%에탄올 추출물의 항산화 효과를 측정하고, $H_2O_2$에 의해 유도된 산화적 스트레스에 대한 신경세포 보호효과를 알아보기 위해 human neuroblastoma cell인 SK-N-MC세포를 이용하여 실험을 수행하였다. 여주 추출물의 총 폴리페놀과 플라보노이드 함량은 각각 28.51 mg gallic acid/extract g과 3.95 mg catechin/extract g 이었고, 추출물의 DPPH 라디칼 소거능 ($IC_{50}$)은 $506.95{\mu}g/ml$ 이었다. 여주추출물을 신경세포에 전 처리한 후 $H_2O_2$을 처리하여 산화적 스트레스를 유도했을 때, 여주추출물에 의해 세포생존율은 증가되었고 세포내 ROS는 감소되는 것을 확인하였다. 그리고 세포내 항산화 방어시스템인 항산화효소 (SOD-1,2와 GPx-1)의 mRNA 발현이 여주추출물 처리에 의해 control 수준으로 회복되거나 control 보다 증가되는 결과를 보였으며, ROS 의존적 세포사멸과 연관 있는 것으로 알려진 MAPK pathway 중 p38과 JNK의 인산화를 여주추출물이 억제하였다. 또한 cleaved caspase-3와 cleaved PARP의 발현도 여주추출물의 처리에 의해 감소되었다. 본 연구 결과에서 70% 에탄올 여주추출물은 항산화효능이 우수하여 ROS를 직접적으로 제거할 뿐 아니라 세포내 ROS 축적을 억제시키는 효과를 보여주었다. 그리고 신경세포 내 항산화효소들의 발현 증가 기전과 p38, JNK의 인산화 억제 및 cleaved caspase-3, cleaved PARP의 발현 억제를 통한 세포사멸 억제 기전을 통해 산화적 스트레스로부터 신경세포를 보호하는 효과가 있음을 제시하고 있다. 따라서 여주추출물은 산화적 스트레스에 의한 알츠하이머병이나 파킨슨병 등과 같은 신경변성질환 (neurodegenerative disease)에 대한 예방 및 치료제의 소재로써 이용가치가 충분한 것으로 사료된다.