• The Korean Journal of Physiology and Pharmacology
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• 제25권4호
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• pp.261-272
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• 2021

Doxorubicin (Dox) is widely used to the treatment of cancer, however, it could cause damage to gastric mucosa. To investigate the protective effects and related mechanisms of coenzyme Q10 (CoQ10) and vitamin C (VC) on Dox-induced gastric mucosal injury, we presented the survey of the 4 groups of the rats with different conditions. The results showed Dox treatment significantly induced GES-1 apoptosis, but preconditioning in GES-1 cells with VC or CoQ10 significantly inhibited the Dox-induced decrease and other harm effects, including the expression and of IκKβ, IκBα, NF-κB/p65 and tumor necrosis factor (TNF-α) in GES-1 cells. Moreover, high-throughput sequencing results showed Dox treatment increased the number of harmful gut microbes, and CoQ10 and VC treatment inhibited this effect. CoQ10 and VC treatment inhibits Dox-induced gastric mucosal injury by inhibiting the activation of the IkKB/IκBα/NF-κB/p65/TNF-α pathway, promoting anti-inflammatory effects of gastric tissue and regulating the composition of the intestinal flora.

• 동의생리병리학회지
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• 제36권1호
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• pp.28-34
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• 2022

Echinacea purpurea (Asteraceae family) is widely used in the European countries and the United States due to its proven immune enhancement and anti-inflammatory effects. Echinacea purpurea has been reported prevent and treat upper respiratory tract infections and common cold, but the underlying molecular mechanisms are not well understood. In the present study, we examined the anti-inflammatory effects and molecular mechanisms of Echinacea purpurea (EP) extract using lipopolysaccharide (LPS)-stimulated signal pathways in RAW264.7 cells. Our results suggest that EP extract exerts anti-inflammatory effects by down-regulating the expression of LPS-induced toll-like receptor 4 (TLR4), subsequently inhibiting the activation of nuclear factor (NF)-κB and mitogen-activated protein kinase (MAPK) signaling pathways and suppression of the release of pro-inflammatory cytokines. These results suggest that EP extract is a potential therapeutic agent for inflammatory diseases.

• Journal of Microbiology and Biotechnology
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• 제34권4호
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• pp.911-919
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• 2024

Solar UVB irradiation cause skin photoaging by inducing the high expression of matrix metalloproteinase (MMPs) to inhibit the expression of Type1 procollagen synthesis. 1-Kestose, a natural trisaccharide, has been indicated to show a cytoprotective role in UVB radiation-induced-HaCaT cells. However, few studies have confirmed the anti-aging effects. In the present study, we evaluated the anti-photoaging and pathological mechanism of 1-kestose using Human keratinocytes (HaCaT) cells. The results found that 1-kestose pretreatment remarkably reduced UVB-generated reactive oxygen species (ROS) accumulation in HaCaT cells. 1-Kestose suppressed UVB radiation-induced MMPs expressions by blocking MAPK/AP-1 and NF-κB p65 translocation. 1-Kestose pretreatment increased Type 1 procollagen gene expression levels by activating TGF-β/Smad signaling pathway. Taken together, our results demonstrate that 1-kestose may serve as a potent natural trisaccharide for inflammation and photoaging prevention.

• 한국자원식물학회지
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• 제33권5호
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• pp.428-435
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• 2020

본 연구에서 상동나무 가지 추출물(STB-E100)은 대장암 세포에서 세포사멸을 유도하여 세포생육을 억제하였다. 또한 IκB-α 인산화를 통한 IκB-α 단백질 분해를 유도하며 이로 인해 P65 핵내 전이를 유도하여 NF-κB 신호전달을 활성화시킨다. NF-κB 신호전달 활성화는 GSK3β 활성화를 통해 P65 핵내 전이를 유도에 의한 것이지만 IκB-α분해는 GSK3β 의존성이 아니다. 상동나무 가지 추출물은 이러한 신호전달 활성화를 통해 세포사멸을 유도하여 대장암의 세포생육을 억제한다. 본 결과를 바탕으로 상동나무 가지가 암 예방 및 치료를 목적으로 한 표적 요법에서 항암제 개발의 잠재적 활용 소재로서 이용 가능하다고 사료된다. 그러나 대장암 세포에서 상동나무 가지 추출물에 의해 유도된 NF-κB 신호전달 작용기전을 좀더 구체적으로 구명할 필요가 있고 대장암에 대한 세포사멸과 작용기전의 정확한 관련성을 조사하기 위해 추가적인 연구가 필요하다.

• Biomolecules & Therapeutics
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• 제32권5호
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• pp.546-555
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• 2024

Aromadendrin is a phenolic compound with various biological effects such as anti-inflammatory properties. However, its protective effects against acute lung injury (ALI) remain unclear. Therefore, this study aimed to explore the ameliorative effects of aromadendrin in an experimental model of lipopolysaccharide (LPS)-induced ALI. In vitro analysis revealed a notable increase in the levels of cytokine/chemokine formation, nuclear factor kappa B (NF-κB) activation, and myeloid differentiation primary response 88 (MyD88)/toll-like receptor (TLR4) expression in LPS-stimulated BEAS-2B lung epithelial cell lines that was ameliorated by aromadendrin pretreatment. In LPS-induced ALI mice, the remarkable upregulation of immune cells and IL-1β/IL-6/TNF-α levels in the bronchoalveolar lavage fluid and inducible nitric oxide synthase/cyclooxygenase-2/CD68 expression in lung was decreased by the oral administration of aromadendrin. Histological analysis revealed the presence of cells in the lungs of ALI mice, which was alleviated by aromadendrin. In addition, aromadendrin ameliorated lung edema. This in vivo effect of aromadendrin was accompanied by its inhibitory effect on LPS-induced NF-κB activation, MyD88/TLR4 expression, and signal transducer and activator of transcription 3 activation. Furthermore, aromadendrin increased the expression of heme oxygenase-1/ NAD(P)H quinone dehydrogenase 1 in the lungs of ALI mice. In summary, the in vitro and in vivo studies demonstrated that aromadendrin ameliorated endotoxin-induced pulmonary inflammation by suppressing cytokine formation and NF-κB activation, suggesting that aromadendrin could be a useful adjuvant in the treatment of ALI.

• 대한한의학방제학회지
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• 제29권4호
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• pp.205-227
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• 2021

Objectives : Jigal-san (JGS, 止渴散) has been used in East Asia including Korea, Japan and China for the treatment of breast inflammatory disorders and severe thirst. JGS originated from Euimunpalbeob (醫門八法; Yimenbafa) composed of Lonicerae Flos and Taraxaci Herba. According to previous studies Lonicerae Flos and Taraxaci Herba have an anti-inflammatory effect, respectively. But, there is no studies regarding on the effects of JGS in the immunological activities. The present study evaluated the anti-inflammatory effects of JGS in vitro and in vivo. Methods : Cell viability was evaluated by MTT assay, and NO was evaluated by content of the nitrite content in culture medium. TNF-α, IL-1β and IL-6 were quantified by ELISA. The protein expression of NF-κB, MAPKs, and iNOS were assessed by western blot analysis. Furthermore, the effects of JGS on acute inflammation were observed in rat paw edema model. Results : The JGS ameliorates the LPS-activated changes in the protein expression of NF-κB, p-JNK, and iNOS, as well as the production of NO and pro-inflammatory cytokines. In rat paw edema study, administration of 0.3 and 1.0 g/kg of JGS for 4 consecutive days inhibited the carrageenan (CA)-induced increases of edema and iNOS expression. Conclusions : These results demonstrate that JGS has anti-inflammatory effect in LPS-stimulated RAW 264.7 cells through decreasing the production of inflammatory mediators, via suppression of the NF-κB and MAPK pathways (JNK, not p-38 and ERK). In addition, the results of the CA-induced paw edema indicate that JGS ameliorates an inflammatory edema. Therefore, the present study could provide scientific evidence for the anti-inflammatory effect of JGS as well as the underlying mechanisms.

• 생명과학회지
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• 제28권11호
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• pp.1361-1368
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• 2018

염증은 인체에서 가장 흔히 나타나는 증상으로 조직이 손상되면 염증 반응이 발생하고 염증 부위에서 혈관 확장과 혈류가 증가하여 부종이 생긴다. Lipopolysaccharide (LPS)는 Toll-like receptor 4에 의해 인식되고 염증 반응을 일으킨다. 열로 사멸시킨 Enterococcus faecalis 사균체(EF-2001)는 면역 조절 및 예방 활동을 하는 것으로 사전 보고되었고, 항 종양 효과가 있다고 보고되었지만 염증에 미치는 영향에 대해서는 지금까지 연구되지 않았다. 본 연구에서는 LPS에 의한 대식세포 염증 반응에 대한 EF-2001의 효과에 대해 연구하였다. 연구결과에서 EF-2001은 LPS에 의해 유도된 산화 질소의 생성을 감소시켰다. 우리는 EF-2001의 세포 독성이 있는지 확인했으며, 산화 질소의 감소는 세포독성에 의한 것이 아님을 확인하였다. 또한 이러한 EF-2001의 항염증 효과에 대한 분자기전을 연구하였다. LPS에 의한 유도된 iNOS와 COX-2의 발현은 EF-2001에 의해 감소되었다. 더해진 분자기작 분석에서 EF-2001은 LPS로 유도된 ERK, JNK 및 p38 인산화를 농도 의존적으로 억제하였다. 더해진 실험에서 EF-2001은 Akt 인산화를 억제하고 $NF-{\kappa}B$ 억제제인 $I{\kappa}B$ 단백질 발현을 증가시켰다. 또한, EF-2001은 p65의 핵으로의 이동을 억제함을 알수 있었다. 따라서, 이러한 결과는 EF-2001이 항염증 효과를 가지며 염증 질환 치료에 유용 할 수 활용될 수 있음을 시사한다.

• BMB Reports
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• 제41권2호
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• pp.158-163
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• 2008

Hepatitis B virus X protein (HBx) is essential for hepatitis B virus infection and exerts a pleiotropic effect on various cellular machineries. HBx has been also demonstrated as an indirect transcriptional transactivator of various different viral and cellular promoters. In addition, HBx is involved in the development of various liver diseases including hepatocellular carcinoma. However the mechanism of HBx in hepatocellular carcinogenesis remains largely unknown. In this study, to identify possible new cellular proteins interacting with HBx, we carried out yeast two-hybrid assay. We obtained several possible cellular partners including VBP1, a binding factor for VHL tumor suppressor protein. The direct physical interaction between HBx and VBP1 in vitro and in vivo was confirmed by immunoprecipitation assay. In addition, we found that VBP1 facilitates HBx-induced $NF{\kappa}B$ activation and cell proliferation. These results implicate the important role of HBx in the development of hepatocellular carcinoma through its interaction with VBP1.

• Archives of Pharmacal Research
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• 제25권5호
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• pp.691-696
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• 2002

Doxorubicin (DOX) is an active and broad spectrum chemotherapeutic agent. Increased inducible nitric oxide synthase (NOS) expression and/or activity have been reported in several human tumors. While the relationship between DOX treatment and the enzymatic activity of endothelial NOS has been well characterized, little is known about the effects of DOX on the expression of iNOS in human cancer cells. In the present study, we characterized the effects of DOX on the nitric oxide (NO) production by colorectal cancer cells, DLD-1. IFN-${\gamma}$/IL-1$\beta$ (CM) increased the production of NO, whereas pretreatment of DOX inhibited the production of NO in response to CM in a dose dependent manner. The increased expressions of iNOS mRNA and protein by CM were completely blocked by DOX without affecting the iNOS mRNA stability. However, DOX activated nuclear factor-kB (NF-kB) in response to CM. Furthermore, the expression of inhibitor kB$\alpha$ was reduced by DOX in a dose dependent manner. Collectively, DOX inhibited the production of NO by DLD-1 cells, which is not linked to well known transcription factor, NF-kB. Therefore, further studies on the possible mechanisms of inhibitory effects of NO production by DOX would be worth pursuing.

• Journal of Microbiology and Biotechnology
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• 제23권3호
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• pp.414-421
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• 2013

Lactic acid bacteria (LAB) in fermented foods have attracted considerable attention recently as treatment options for immune diseases, the incidence of which has been increasing worldwide. The ability of 500 strains of LAB, isolated from kimchi, to induce TNF-${\alpha}$ production in peritoneal macrophages was investigated. Lactobacillus plantarum HY7712 most strongly induced TNF-${\alpha}$ production as well as NF-${\kappa}B$ activation. However, HY7712 inhibited NF-${\kappa}B$ activation in LPS-stimulated peritoneal macrophages. When HY7712 was orally treated in cyclophosphamide (CP)-immunosuppressed mice for 5 or 15 days, it reversed the body and spleen weights, blood RBC and WBC levels, and splenocyte and bone marrow cells that were reduced by CP. Orally administered HY7712 increased concanavalin A-induced T cell proliferation to 84.5% of the normal group on day 15, although treatment with CP alone markedly reduced it to 53.7% of the normal group. Furthermore, orally administered HY7712 significantly induced the expressions of IL-2 and IFN-${\gamma}$ in ConA-induced splenic cytotoxic T cells of CP-treated mice. Orally administered HY7712 restored the CP-impaired phagocytosis of macrophages in mice. Orally administered HY7712 also restored the cytotoxicity of NK and cytotoxic T cells derived from spleen and bone marrow against YAC-1 in CP-immunosuppressed mice. Based on these findings, orally administered HY7712 may accelerate the recovery of cyclophosphamide-caused immunosuppression, without evident side effects, by immunopotentiating NK and Tc cells, and may provide a mechanistic basis for using HY7712 as an alternative means in lessening chemotherapyinduced immunosuppression in cancer patients.