• 대한본초학회지
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• 제38권6호
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• pp.29-44
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• 2023

Objectives : This study was planned to evaluate the therapeutic effectiveness and possible underlying mechanism of TPE (Tetrapanax papyrifer stem(inner part of the stem Extract) and AQE (Akebiae quinata stem Extract) on osteoarthritis. Methods : Osteoarthritis models were induced through intra-articular injection of MIA (monosodium iodoacetate) 50 μL with 80 mg/ml in rats. Excluding the normal group, Osteoarthritis-induced rats were divided into 4 groups (Control, INDO, TPE, AQE). The drug concentrations were indomethacin 5 mg/kg, TPE 200 mg/kg, and AQE 200 mg/kg, and were orally administered once a day for a couple of weeks. After drug supplementation, the effects of TPE and AQE were measured with serum diagnosis, western blotting, and histopathological staining. Results : It was found that the DPPH and ABTS free radical erasure ability of AQE was better than that of TPE. AQE administration improved rear limb overload and it led to relieving pain. Both PTE and AQE significantly reduced the expression of inflammatory mediators COX-2, iNOS, and inflammatory cytokine IL-1β and IL-6 by inhibiting the phosphorylation of IκBα and deactivating the pathway of NF-κBp65. On the other hand, TNF-α was significantly reduced only by administration of AQE. In addition, histopathological analysis showed that the administration of AQE compared to PTE suppressed cartilage degeneration and effectively suppressed damage to proteoglycan, a component of ECM. Conclusion : Reviewing these experimental results, TPE and AQE possessed the effect of delaying the progress of osteoarthritis and protecting cartilage. In addition, the results of this study show that AQE has a better cartilage protection effect than TPE.

• Journal of Microbiology and Biotechnology
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• 제33권8호
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• pp.1057-1065
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• 2023

Inflammatory bowel disease (IBD), a chronic inflammatory disease, results from dysregulation of the immune responses. Some lactic acid bacteria (LAB), including Lactobacillus, alleviate IBD through immunomodulation. In this study, the anti-colitis effect of LAB isolated from human breast milk was investigated in a mouse model induced acute colitis with 2,4,6-trinitrobenzene sulfonic acid (TNBS). TNBS remarkably increased weight loss, colon shortening, and colonic mucosal proliferation, as well as the expression levels of inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-1β. Oral administration of LAB isolated from human breast milk resulted in a reduction in TNBS-induced colon shortening, as well as induced cyclooxygenase (COX)-2, nitric oxide synthase (iNOS), nuclear factor-kappa B (NF-κB). In addition, LAB suppressed inflammatory cytokines such as TNF-α, IL-6, and IL-1β, and thus showed an effect of suppressing the level of inflammation induced by TNBS. Furthermore, LAB alleviated gut microbiota dysbiosis, and inhibited intestinal permeability by increasing the expression of intestinal tight junction protein including ZO-1. Collectively, these results suggest that LAB isolated from human breast milk can be used as a functional food for colitis treatment by regulating NF-κB signaling, gut microbiota and increasing expression of intestinal tight junction protein.

• Journal of Microbiology and Biotechnology
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• 제33권11호
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• pp.1484-1494
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• 2023

NUC1 (Nutraceutical compound 1) is an ethanol extract composed of a formulation based on medicinal herbs traditionally used for the treatment of arthritis in Korea and China. This study investigated the therapeutic effects of NUC1 on osteoarthritis (OA). The protective effect of NUC1 on OA was tested in a rabbit model of collagenase-induced arthritis (CIA) for 4 weeks. Results were compared among four groups (n = 9 per group): the normal group (untreated), the CIA group (vehicle control), the NUC1 group (CIA rabbits treated with 200 mg/kg NUC1), and the JOINS group (positive control, CIA rabbits treated with 200 mg/kg JOINS tablet). NUC1 significantly inhibited NO production (p < 0.05 at 125 ㎍/ml, p < 0.01 at 250 ㎍/ml, and p < 0.001 at 500 ㎍/ml) and iNOS expression in macrophages, in a concentration-dependent manner. NUC1 also inhibited the release and protein expression of MMP-1, 3, and 13, in TNF-α-induced chondrosarcoma cells in a concentration-dependent manner. In vivo, the MMP-1 and MMP-3 levels in synovial fluids were significantly (p < 0.05) lower in NUC1 group (77.50 ± 20.56 and 22.50 ± 7.39 pg/ml, respectively) than in the CIA group (148.33 ± 68.58 and 77.50 ± 20.46 pg/ml, respectively). Also, in histopathological, NUC1 ameliorated articular cartilage damage in OA by increasing the abundance of chondrocytes and proteoglycan in the articular cartilage. Thus, NUC1 showed promise as a potential therapeutic agent, and it can be generalized to a broader study population in different OA animal models.

• 한국식품저장유통학회지
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• 제24권8호
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• pp.1149-1157
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• 2017

본 연구에서는 넓패 에탄올 추출물의 항염증 효과를 알아보기 위해 RAW 264.7 세포에 LPS로 유도된 염증 반응 in vitro 및 in vivo 실험을 실시하였다. RAW 264.7 세포에 LPS와 함께 세포를 배양하였다. 먼저 MTT assay 실험을 통해 넓패 에탄올 추출물이 모든 농도(0.1, 1, 10, 50, $100{\mu}g/mL$)에서 세포독성을 나타내지 않는 것을 학인 하였다. 또한 모든 농도에서 염증억제 효과를 살펴 본 결과, LPS 처리구는 iNOS, COX-2, NF-${\kappa}B$ 그리고 MAPKs의 발현양을 증가 시켰으나, 넓패 에탄올 추출물의 경우 염증 반응에 관여하는 전사인자인 NF-${\kappa}B$와 MAPKs의 활성을 억제함으로써 항염증 효과를 나타내었다. 마지막으로 넓패 에탄올 추출물의 mast cell의 피부 조직학적 변화를 알아본 결과, control의 경우 진피와 경피의 면적이 확장 되어있고, mast cell의 침윤이 정상 군에 비하여 현저하게 증가함을 알 수 있었다. 반면에 넓패 에탄올 추출물의 경우 대조군에 비해 진피와 경피의 두께가 줄었으며 mast cell의 침윤감소에 효과가 있는 것을 확인하였다. 따라서 모든 결과를 종합하였을 때 넓패 에탄올 추출물이 항염증 치료제 뿐만 아니라 더 나아가 항염증에 유용한 기능성 식품소재로써 가치가 높다고 사료된다.

• 한국미생물·생명공학회지
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• 제42권2호
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• pp.170-176
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• 2014

본 연구에서는 Euptelea pleiosperma 에탄올 추출물(EPEE)의 항산화능과 항염증 생리활성을 in vitro assay system 및 cell culture model system을 이용하여 분석하였다. 먼저 EPEE의 항산화능을 DPPH radical scavenging activity로 분석한 결과 radical 소거능의 정도가 양성 대조군으로 사용한 ascorbic acid 보다 높은 활성을 보여 매우 강한 항산화능을 보유함을 확인하였다. 또한 RAW 264.7 세포주를 이용한 $H_2O_2$ 및 LPS의 유도에 의해 생성된 ROS에 대한 소거능을 분석한 결과에서도 농도의존적인 강한 소거능을 보였다. 뿐만 아니라 대표적인 항산화효소 중 하나로 천연물에 의한 항산화능 활성에 의해 주로 발현이 유도되는 hemeoxygenase 1 (HO-1) 및 그 전사 인자인 nuclear factor-E2-related factor 2 (Nrf2)의 단백질 발현이 EPEE의 처리에 의해 유의적으로 증가됨을 보였으며 이러한 HO-1 및 Nrf2의 발현 변화는 상위신호전달계인 MAPKs 및 PI3K/Akt 에 의해 조절될 가능성을 보였다. 한편 EPEE가 LPS에 의해 유도된 NO 생성에 미치는 영향을 분석한 결과 농도의존적인 NO 생성 저해능을 보였으며 이는 NO 생성 단백질인 iNOS의 발현 저해에서 기인함을 확인하였다. 이와 같은 EPEE의 NO 생성 억제 효과는 염증 상위신호전달계인 NF-${\kappa}B$ 및 AP-1의 조절을 통해 일어날 가능성을 보였다. 이러한 결과를 통해 EPEE의 높은 항산화능과 항염증 활성을 처음으로 확인하였으며 향후 기능성 소재로서 유용하게 활용될 수 있을 것으로 판단된다.

• The Korean Journal of Physiology and Pharmacology
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• 제22권2호
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• pp.163-172
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• 2018

PRF001 is a fragmented DNA polymer extracted from the testes of salmon. The purpose of this study was to assess the anti-inflammatory effect of PRF001 in vitro as well as the protective effect of PRF001 intake against arthritis in a rat model. In vitro, cell survival and inflammatory markers after $H_2O_2$ treatment to induce cell damage were investigated in CHON-001 cells treated with different concentrations of PRF001. In vivo, osteoarthritis was induced by intra-articular injection of monosodium iodoacetate (MIA) into the knee joints of rats. After consumption of PRF001 (10, 50, or 100 mg/kg) for 4 weeks, inflammatory mediators and cytokines in articular cartilage were investigated. In vitro, the levels of inflammatory markers, $IL-1{\beta}$, $TNF-{\alpha}$, COX-2, iNOS, and PGE2, were significantly suppressed by PRF001 treatment. In vivo, the inflammatory mediators and cytokines, $IL-1{\beta}$, p-Erk1/2, $NF-{\kappa}B$, $TNF-{\alpha}$, COX-2, and PGE2, as well as MMP3 and MMP7, which have catabolic activity in chondrocytes, were decreased in the MIA-induced osteoarthritic rats following intake of PRF001. Histological analysis revealed that PRF001 had a protective effect on the articular cartilage. Altogether, these results demonstrated that the anti-inflammatory property of PRF001 contributes to its protective effects in osteoarthritis through deregulating $IL-1{\beta}$, $TNF-{\alpha}$, and subsequent signals, such as p-Erk1/2, $NF-{\kappa}B$, COX-2, PGE2, and MMPs.

• 동의생리병리학회지
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• 제21권4호
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• pp.921-933
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• 2007

This experiment was designed to investigate the effects of the KBCMT hot water extract & ultra-fine powder on Alzheimer's Disease Model Induced by ${\beta}A$. The effects of the KBCMT hot water extract on expression of $IL-1{\beta}$, IL-6, $TNF-{\alpha}$, NOS-II, COX-2 mRNA and production of $IL-1{\beta}$, IL-6, $TNF-{\alpha}$, NO in BV2 microglial cell line treated by lipopolysacchaide(LPS). The effects of the KBCMT hot water extract & ultra-fine powder on (1) the behavior (2) expression of $IL-1{\beta}$, $TNF-{\alpha}$, MDA, CD68 and CD11b; (3) AChE in serum (4) the infarction area of the hippocampus, and brain tissue injury in Alzheimer's diseased mice induced with ${\beta}A$ were investigated. The KBCMT hot water extract suppressed the expression of $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$ mRNA in BV2 microglia cell line treated with LPS. The KBCMT hot water extract suppressed the production of $IL-1{\beta}$, IL-6, $TNF-{\alpha}$, NO in BV2 microglial cell line treated with LPS. The KBCMT hot water extract & ultra-fine powder a significant inhibitory effect on the memory deficit was shown for the mice with Alzheimer's disease induced by ${\beta}A$ in the Morris water maze experiment, which measured stop-through latency and distance movemet-through latency The KBCMT ultra-fine powder suppressed the expression of TNF-a protein significantly in the microglial cell of mice with Alzheimer's disease induced by ${\beta}A$. The KBCMT hot water extract & ultra-fine powder reduced the MDA and suppressed the over-expression of CD68, CD11b in the mice with Alzheimer's disease induced by ${\beta}A$. The KBCMT hot water extract & ultra-fine powder decreased AChE significantly in the serum of the mice with Alzheimer's disease induced by ${\beta}A$. The KBCMT hot water extract & ultra-fine powder reduced infarction area of hippocampus, and controlled the injury of brain tissue in the mice with Alzheimer's disease induced by ${\beta}A$. The KBCMT hot water extract & ultra-fine powder reduced the tau protein, GFAP, and presenilin1, 2 of hippocampus in the mice with Alzheimer's disease induced by ${\beta}A$. These results suggest that the KBCMT hot water extract & ultra-fine powder may be effective for the prevention and treatment of Alzheimer's disease. Investigation into the clinical use of the KBCMT hot water extract & ultra-fine powder for Alzheimer's disease is suggested for future research.

• 동의생리병리학회지
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• 제21권3호
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• pp.688-699
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• 2007

This experiment was designed to investigate the effect of the SST hot water extract & ultra-fine Powder on Alzheimer's Disease Model Induced by ${\beta}$A. The effects of the SST hot water extract on expression of IL-1${\beta}$, IL-6, TNF-${\alpha}$, NOS-II, COX-2 mRNA and production of IL-l${\beta}$, IL-6, TNF-${\alpha}$, NO in BV2 microglial cell line treated by lipopolysacchaide(LPS). The effects of the SST hot water extract & ultra-fine powder on (1) the behavior (2) expression of IL-1${\beta}$, TNF-${\alpha}$, MDA, (3) Glucose, AChE in serum (4) the infarction area of the hippocampus, and brain tissue injury in Alzheimer's diseased mice induced with ${\beta}$A were investigated. The SST hot water extract suppressed the expression of IL-1${\beta}$, IL-6 and TNF-a mRNA ${\alpha}$in BV2 microglia cell line treated with LPS. The SST hot water extract suppressed the production of IL-1${\beta}$, IL-6, TNF-${\alpha}$, NO in BV2 microglial cell line treated with LPS. The SST hot water extract & ultra-fine powder a significant inhibitory effect on the memory deficit was shown for the mice with Alzheimer's disease induced by ${\beta}$A in the Morris water maze experiment, which measured stop-through latency. The SST ultra-fine powder suppressed the expression of TNF-a protein significantly in the microglial cell of mice with Alzheimer's disease induced by ${\beta}$A. The SST hot water extract & ultra-fine powder reduced the MDA and suppressed the over-expression of CD68, CD11b in the mice with Alzheimer's disease induced by ${\beta}$A. The SST hot water extract & ultra-fine powder decreased AChE significantly in the serum of the mice with Alzheimer's disease induced by ${\beta}$A. The SST hot water extract & ultra-fine powder reduced infarction area of hippocampus, and controlled the injury of brain tissue in the mice with Alzheimer's disease induced by ${\beta}$A. The SST hot water extract & ultra-fine powder reduced the tau protein, GFAP, and presenilin1, 2 of hippocampus in the mice with Alzheimer's disease induced by ${\beta}$A. These results suggest that the SST hot water extract & ultra-fine powder may be effective for the prevention and treatment of A1zheimer's disease. Investigation into the clinical use of the SST hot water extract & ultra-fine powder for Alzheimer's disease is suggested for future research.

• 대한본초학회지
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• 제37권1호
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• pp.19-29
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• 2022

Objectives : Although the pharmacological effects of anti-inflammatory and antioxidant action of Atractylodes macrocephala Koidzumi water extract (AM) have been proven from many studies, reports on the antioxidant effect of AM on ulcerative colitis (UC) are scarce. Therefore, we aimed at evaluating the anti-oxidant effect of AM on the DSS-induced UC model. Methods : To induce ulcerative colitis, 8-week-old male Balb/c mice received 5% DSS in drinking water for 1 week. After 1 week of adaptation, mice were divided into four groups (n=8 each) for use as normal (Normal), DSS Control (Control), DSS + AM 100 mg/kg (AM100)-treatment, DSS + AM 200 mg/kg (AM200)-treatment. After 1 week of the experiment, the animals were sacrificed, and the extracted colon tissue was analyzed for protein through western blot. Results : As a result of confirming the macroscopic changes in colon tissues to confirm the therapeutic effects of AM, the decrease in colon length was suppressed in the AM treatment group compared to the control group. In addition, as a result of biochemical analysis, AM administration significantly reduced serum glutamic oxalacetic transaminase, glutamic pyruvate transaminase levels and tissue malondialdehyde levels. As a result of confirming the protein expression level through western blot, AM administration significantly decreased the expression of NADPH-related proteins such as NOX2, p22^phox, and iNOS, but significantly increased the expression of SOD, catalase, and GPx-1/2. Conclusions : AM may improve DSS-induced UC in mice by modulating NADPH and antioxidant-related proteins. In conclusion, AM showed an antioxidant effect through the improvement of oxidative stress on UC.

• Biomolecules & Therapeutics
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• 제32권1호
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• pp.154-161
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• 2024

Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disorder that causes progressive paralysis. L-Citrulline is a nonessential neutral amino acid produced by L-arginine via nitric oxide synthase (NOS). According to previous studies, the pathogenesis of ALS entails glutamate toxicity, oxidative stress, protein misfolding, and neurofilament disruption. In addition, L-citrulline prevents neuronal cell death in brain ischemia; therefore, we investigated the change in the transport of L-citrulline under various pathological conditions in a cell line model of ALS. We examined the uptake of [¹⁴C]L-citrulline in wild-type (hSOD1wt/WT) and mutant NSC-34/ SOD1^G93A (MT) cell lines. The cell viability was determined via MTT assay. A transport study was performed to determine the uptake of [¹⁴C]L-citrulline. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis was performed to determine the expression levels of rat large neutral amino acid transported 1 (rLAT1) in ALS cell lines. Nitric oxide (NO) assay was performed using Griess reagent. L-Citrulline had a restorative effect on glutamate induced cell death, and increased [¹⁴C]L-citrulline uptake and mRNA levels of the large neutral amino acid transporter (LAT1) in the glutamate-treated ALS disease model (MT). NO levels increased significantly when MT cells were pretreated with glutamate for 24 h and restored by co-treatment with L-citrulline. Co-treatment of MT cells with L-arginine, an NO donor, increased NO levels. NSC-34 cells exposed to high glucose conditions showed a significant increase in [¹⁴C]L-citrulline uptake and LAT1 mRNA expression levels, which were restored to normal levels upon co-treatment with unlabeled L-citrulline. In contrast, exposure of the MT cell line to tumor necrosis factor alpha, lipopolysaccharides, and hypertonic condition decreased the uptake significantly which was restored to the normal level by co-treating with unlabeled L-citrulline. L-Citrulline can restore NO levels and cellular uptake in ALS-affected cells with glutamate cytotoxicity, pro-inflammatory cytokines, or other pathological states, suggesting that L-citrulline supplementation in ALS may play a key role in providing neuroprotection.