• 동의생리병리학회지
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• 제27권2호
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• pp.202-211
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• 2013

The purpose of this study is to investigate the apoptotic effect of Phellodendri Cortex water extract (PCWE) on pancreatic cancer cells and to find out the regulating mechanisms. Human-derived pancreatic cancer cell line, MIA PaCa-2 cells were treated by PCWE with various concentrations and the cytotoxicity was determined by MTT assay. The activation of Annexin V, DNA fragmentation, cell cycle arrest and caspase activation were observed to investigate the role of PCWE in pancreatic cancer cells. Also, to find out the regulating mechanisms, we examined the ROS production. The treatment of PCWE induced the cell death in both concentration and time dependent manner. The treatment of PCWE also increased the expression of Annexin V, DNA fragmentation, cell cycle arrest, and cleavage of caspase, which means cell-death PCWE induced was apoptosis but not necrosis. The ROS production was increased by PCWE treatment and the blockade of ROS inhibited the PCWE-induced cell death. These results could suggest that PCWE induced apoptosis via ROS release in pancreatic cancer cell.

• Journal of Nutrition and Health
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• 제56권3호
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• pp.231-246
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• 2023

본 연구에서는 MIA로 골관절염을 유도한 SD 흰쥐에서 인도산 보스웰리아 검레진을 주정 추출 후, 헥산으로 지방 제거 공정을 추가하여 제조한 보스웰리아 검레진 추출물인 FJH-UBS의 항골관절염 효능을 평가하기 위해 실시하였다. FJH-UBS는 40 또는 80 mg/kg BW/day 용량으로 5주간 경구투여하였고, FJH-UBS를 2주간 투여 후 MIA (3 mg/50 µL/rat)를 무릎 관절강 내에 주사하여 골관절염을 유도하였다. MIA 유도 골관절염 동물모델에서 FJH-UBS는 무릎 관절의 부종을 감소시키고 연골의 분해를 억제하였으며, 연골 내 type II collagen과 aggrecan 발현을 증가시켰다. FJH-UBS (80 mg/kg BW/day)는 혈청 내 PGE2, LTB4, IL-1β, 및 IL-6 함량을 감소시켰고, MMP-13 함량을 감소시켰다. FJH-UBS (80 mg/kg BW/day)는 연골 활막 내 iNOS, COX-2, 5-LOX, IL-1β, IL-6 및 TNF-α 발현을 감소시켰고, MMP-2, MMP-9 및 MMP-13 발현을 감소시켰다. 이 결과는 FJH-UBS가 염증매개물질과 염증성 cytokine의 발현감소를 통해 염증 반응을 억제하고, MMPs의 발현을 억제하여 연골 기질의 분해를 억제함으로서 항골관절염 효능을 나타냄을 의미하며 이는 관절 및 연골 건강 개선 기능성 원료로 FJH-UBS의 활용 가능성을 제시한다.

• 대한한방내과학회지
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• 제43권6호
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• pp.1089-1104
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• 2022

Objective: The aim of this study was to identify the efficacy and underlying mechanism of cloves as an osteoarthritis (OA) treatment in a monosodium iodoacetate (MIA)-induced rat OA model. Osteoarthritis (OA) is nowadays one of the most prevalent degenerative joint diseases. Methods: Sprague-Dawley rats treated with MIA (50 μL; 80 mg/mL) were used as in vivo OA models. Cloves (100 and 200 mg/kg b.w.) were administered orally once daily for 2 weeks from 7 days after MIA injection. Changes in hindpaw weight distribution (HWD) were measured as a joint discomfort index. Activation markers related to inflammatory responses and cartilage degeneration in the right knee joints were evaluated by serum analysis and western blotting. Results: HWD decreased in the MIA control group but showed a dose-dependent elevation after clove treatment. Clove treatment inhibited inflammatory factors by PI3K/Akt/NF-κB signaling pathways, while also activating antioxidant factors through Sirt1/AMPK signaling pathways. Clove treatment also suppressed matrix metalloproteinase (MMP) overexpression and significantly increased the levels of tissue inhibitors of metalloproteinases (TIMPs). Conclusions: Treatment with cloves effectively reversed MIA-induced effects. Therefore, clove treatment could have the potential to protect against or treat OA.

• 한국식품영양학회지
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• 제32권6호
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• pp.678-686
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• 2019

The purpose of this study was to examine the physiochemical characteristics of hot water extract of Caragana sinica roots and verified its protective effect on MIA-induced osteoarthritis in rats. The contents of total polyphenol and total flavonoid used in this experiment were 0.40 mg/g and 0.22 mg/g respectively. We found that the weight of all experiment groups which ingested Caragana sinica extract for three weeks evenly increased in rats with MIA-induced osteoarthritis without toxicity in the liver or kidney. In the histopathological test through the Mankin score, the extent of damage of knee joint tissue in the experiment groups to which Caragana sinica extract was administered in 5 mL/kg or 10 mL/kg was significantly lower than that of the negative control groups statistically(p<0.05). As for the grade of osteoarthritis, the extent of tissue damage of the experiment groups to which Caragana sinica extract was administered in 5 mL/kg or 10 mL/kg was lower than that of the negative control groups as well.

• 대한물리의학회지
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• 제9권2호
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• pp.151-159
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• 2014

PURPOSE: The purpose of this study was to evaluate whether light-emitting diodes (LED) irradiation could be effective in a noninvasive, therapeutic device for the treatment of osteoarthritis(OA). METHODS: Twenty-four male Sprague-Dawley rats were divided into four groups: Vehicle control (saline); monosodium iodoacetate-injection (MIA); LED irradiation after MIA injection (MIA-LED); indomethacin-treatment after MIA injection (MIA-IMT). OA was induced by intra-articular injection of 3 mg MIA through the patellar ligament of the right knee. Vehicle control rats were injected with an equivalent volume of saline. The LED was irradiated for 15 min/day for a week after 7 days of MIA treatment. To compare with the effect of LED irradiation, the indomethacin was administrated 20 mg/kg twice a week orally after 7 days of MIA treatment. Knee joints were removed and fixed overnight in 10% neutral buffered formalin and decalcified by EDTA for 2 week before being embedded in paraffin. The assessment of OA induction were monitored by knee movement and radiographic finding. Histologic analysis were performed following staining with hematoxylin and eosin, safranin O-fast green, or toluidine blue, picrosirius red, and histologic changes were scored according to a modified Mankin system. Apoptotic cell in tissue sections was detected using TUNEL method. RESULTS: Radiographic examination could not show the differences between the MIA-treated and the MIA-LED-treated rats. In the histologic analysis, however, LED irradiation prevented cartilage damage and subchondral bone destruction, and significantly reduced mononuclear inflammatory cell infiltration and pannus formation. LED irradiation also reduced apoptosis of cartilage cells, but it prevented apoptosis of infiltrated inflammatory cells in synovium. In addition, LED irradiation showed an increase of collagen production in the meniscus. CONCLUSION: These results suggest that the 840 nm LED irradiation would be a suitable non-thermal phototherapy for the treatment of OA, as a cartilage protection and anti-inflammatory modality.

• Journal of Acupuncture Research
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• 제32권1호
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• pp.53-66
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• 2015

Objectives : This study was designed to investigate effects of Curculiginis Rhizoma pharmaco-acupuncture at $ST_{36}$ on monosodium iodoacetate-induced osteoarthritic rats. Methods : Twenty rats were divided into four groups consisting of 5 rats: rats receiving no injection(normal), rats injected with monosodium Iodoacetate(MIA, control), rats injected with MIA and normal saline(N-S), and rats injected with MIA and Curculiginis Rhizoma (CRPA). N-S and CRPA were administered once a day at $ST_{36}$ during 21 days. After that we examined the weight-bearing ability of hind paws, liver and kidney function, immunocell, cytokines, proteins, and gene expression of cytokines. Injury of synovial tissue was measured by H & E, Safranin O immunofluorescence. Results : The weight-bearing ability of the hind paws, Serum TNF-${\alpha}$, IL-$1{\beta}$, IL-6, PGE2, LTB4, DPD, Osteocalcin, Protein COX-2 of CRPA decreased significantly. Protein Arachidonate 5 lipoxygenase of CRPA was decreased, but not significantly. Expression of gene COX-2, TNF-${\alpha}$, IL-$1{\beta}$, IL-6, NOS2 of CRPA decreased. In histological observations, CRPA was improved, compared with other control groups. Conclusions : It can be suggested that Curculiginis Rhizoma pharmaco-acupuncture at $ST_{36}$ has anti-inflammatory and pain relief effects on monosodium iodoacetate-induced osteoarthritic rats.

• 한국약용작물학회지
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• 제24권5호
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• pp.341-350
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• 2016

Background: Prenatal exposure to infectious and/or inflammatory insults can increase the risk of developing neuropsychiatric disorder such as bipolar disorder, autism, and schizophrenia later in life. We investigated whether Valeriana fauriei (VF) treatment alleviates prepulse inhibition (PPI) deficits and social interaction impairment induced by maternal immune activation (MIA). Methods and Results: Pregnant mice were exposed to polyriboinosinic-polyribocytidilic acid (5 mg/kg, viral infection mimic) on gestational day 9. The adolescent offspring received daily oral treatment with VF (100 mg/kg) and injections of clozapine (5 mg/kg) for 30 days starting on the postnatal day 35. The effects of VF extract treatment on behavioral activity impairment and protein expression were investigated using the PPI analysis, forced swim test (FST), open field test (OFT), social interaction test (SIT), and immunohistochemistry. The MIA-induced offspring showed deficits in the PPI, FST, OFT, and SIT compared to their non MIA-induced counterparts. Treatment with the VF extract significantly recovered the sensorimotor gating deficits and partially recovered the aggressive behavior observed in the SIT. The VF extract also reversed the downregulation of protein expression induced by MIA in the medial prefrontal cortex. Conclusions: Our results provide initial evidence of the fact that the VF extract could reverse MIA-induced behavioral impairment and prevent neurodevelopmental disorders such as schizophrenia.

• The Journal of Korean Physical Therapy
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• 제26권6호
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• pp.418-424
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• 2014

Purpose: This study was performed to investigate the effect of joint mobilization on pain relief and cartilage repair in an induced osteoarthritis rat model by analyzing the expression of heat shock protein 70 in articular cartilage. Methods: MIA was injected into SD rats to induce osteoarthritis. These rats were divided into 4 groups: control group (n=30), no further treatment after the MIA injection ; experimental group I(n=30), performed swimming exercise after the MIA injection experimental group II (n=30), underwent joint mobilization after the MIA injection and experimental group III (n=30), performed swimming exercise and underwent joint mobilization after the MIA injection. For the histologic and pathophysiologic evaluation, safranin-O staining and for the immunohistochemical evaluation, the expression of HSP 70 in articular cartilage was analyzed 1, 7, 14, and 21 days after the MIA injection. Results: The inflammatory response and loss of tissue declined in experimental groups I and II over time, whereas the greatest decreases were noted in experimental group III. In the articular cartilage, low expression of HSP 70 was observed in every group on day 1, whereas HSP 70 expression was elevated on days 7 and 14 in experimental groups II and III. After 21 days, experimental group II displayed the strongest positive reaction, whereas HSP 70 was higher in experimental group III at this time point compared to that after 14 days. Conclusion: Our results showed that swimming exercise and joint mobilization had positive effects on pain relief and histologic and functional recovery in an induced osteoarthritis rat model.

• 동의생리병리학회지
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• 제25권1호
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• pp.84-91
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• 2011

This study was to investigate the effects of Gyeonbi-Tang Treatment on the monosodium iodoacetate(MIA)-induced mild osteoarthritis in rats. Arthritis was induced by injection of MIA(0.25 mg) into knee joints of rats. Arthritic rats were divided into control(n=8) and treated(n=8) group. Control group was taken distilled water and treated group was taken extracts of Gyeonbi-Tang by orally for 20days. Body weights were measured at 0, 5, 10, 15, 20 days after MIA injection. At the end of experiment(20day after MIA injection), gross and histopathological examination on the articular structures of knee joints were performed. Proteoglycan(PG) contents in articular cartilages were analysed. And also, tumor necrosis factor-${\alpha}$(TNF-${\alpha}$) and interleukin-1${\beta}$(IL-1${\beta}$) contents in synovial fluids were measured by ELISA method. Body weights of the treated group were significantly increased compared with control group at 15, 20 days after injection. Grossly, the severity of osteoarthritis in the treated group were alleviated compared with control group. PG contents in articular cartilages of the treated group were increased compared with control group. Histopathologically, osteoarthritic scores of the treated group was decreased compared with the control group. TNF-${\alpha}$ contents in synovial fluids of the treated group were significantly decreased compared with control group. On the basis of these results, we concluded that Gyeonbi-Tang Treatment has anti-arthritic effects on the monosodium iodoacetate-induced mild osteoarthritis in rats. And it's effects were related with reduced secretion of TNF-${\alpha}$ from synovial membranes.

• 분석과학
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• 제28권1호
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• pp.72-77
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• 2015

참당귀 추출물의 골관절염에 대한 억제 또는 치료효과를 알고자 monosodium iodoacetate로 유발한 흰쥐의 골관절염 모델을 사용하여 30마리 6주령 SD흰쥐를 정상군(normal), 비처리군(untreated) 및 참당귀 처리군(treated)으로 각각 10마리씩 나누어 실험하였다. 실험기간 동안 실험 개시일부터 4일 간격으로 체중 변화를 측정하였다. 3주간 참당귀 추출물 처리 후 관절연골 내의 glycosaminoglycan (GAG)의 함량 및 proteoglycan (PG) 함량을 측정 비교하였다. 그 결과, 참당귀 추출물은 MIA로 증가한 GAG를 완화시켰으며, PG의 함량을 회복시켰다. 또한, 활액에서의 TNF-a함량은 미약하게 감소하였다. 한편, 경골 관절연골을 분리하여 Safranin-O 염색으로 관절연골 상태를 확인한 결과, MIA 처리로 유발된 관절연골 소실을 억제하였다. 이 참당귀 추출물을 HPLC로 분석한 결과, 주요 성분인 decursin 및 decursinol angelate의 총 함량은 $10.5{\pm}0.2%$이었다.