• 한방재활의학과학회지
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• 제24권2호
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• pp.15-29
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• 2014

Objectives We have studied to know effects of Bangkeehwangkee-tang on the monosodium iodoacetate (MIA) induced osteoarthritis in rats. Methods Osteoarthritis was induced by injection of monosodium iodoacetate into knee joint cavity of rats. Rats are devided into 4 groups; Sham, control, Bangkeehwangkee-tang, Shinbaro. Sham group was injected by normal saline into knee joint cavity only. Control group was taken no treatment and Experimental groups were taken extracts of Bangkeehwangkee-tang and Shinbaro by orally once a day for 4 weeks. The content of TNF-$\alpha$, IL- $1{\beta}$ and IL-6 in synovial fluids were analysed. COX-2 in chondrocytes and blood PGE2 concentration were analysed. Histopathological examination was performed by Safranin-O fast green staining and Mankins score checking. Results The content of TNF-$\alpha$, IL-$1{\beta}$ in experimental groups were decreased compared with control group. COX-2 in chondrocytes and blood PGE2 concentration in experimental groups were decreased compared with control group. Histopathologically, osteoarthritic scores of experimental groups were decreased compared with control group. But the content of IL-6 in synovial fluids was not significantly compared with control group. Conclusions According to these results, it can be suggested that Bangkeehwangkee-tang has anti-arthritic effects on the MIA induced osteoarthritis in rats.

• Journal of Acupuncture Research
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• 제40권1호
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• pp.35-43
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• 2023

Background: This study aimed to examine the effect of Scutellaria baicalensis extract (SBE) on ameliorating pain response and inflammation in an animal model. Methods: The effects of SBE on joint inflammation-induced rats and pain writhing response were measured. In rats with monosodium iodoacetate (MIA)-induced knee osteoarthritis (OA), the weight-bearing distribution of the hind legs was measured, the actual joint condition was visually confirmed, and serum cytokines were extracted from whole blood and measured. In addition, the acetic acid-induced pain was measured by the number of abdominal wall contractions and writhing responses. Results: 1. The weight-bearing distribution of the hind limbs of the SBE group was remarkably improved compared with that of the control group 7 days after MIA treatment, and the SBE 300 group was improved similarly to that of the indomethacin group. 2. Cartilage erosion was significantly recovered in the SBE and indomethacin groups, and the degree of healing of cartilage erosion by SBE was similar to that by indomethacin. 3. The serum levels of cytokines interleukin-1β, tumor necrosis factor-α, and interleukin-6 were significantly decreased in the SBE group compared with that in the control group, and the SBE 300 group had reduced levels of cytokines similar to the indomethacin group. 4. As regards acetic acid-induced writhing response, the number of writhes was significantly reduced in the SBE and ibuprofen groups, and the SBE 600 group had fewer writhes than the ibuprofen group. Conclusion: SBE significantly improves knee OA and pain and is expected to show similar therapeutic effects to indomethacin and ibuprofen.

• 동의생리병리학회지
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• 제21권6호
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• pp.1483-1490
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• 2007

This study was carried out to investigate the effects of GCP treatment on the expression of NOS, c-fos, serotonin and substance P in central nerve system of monosodium iodoacetate(MIA)-induced osteoarthritic pain model. Arthritis was induced by injection of MIA(0.5 mg) into knee joint cavities of rats. Arthritic rats were divided into control(n=8) and treated(n=8) group. Control group was taken distilled water for 20 days. Treated group was taken extracts of GCP by oraly for same duration. Normal group(n=8) was infected with normal saline and was taken distilled water for 20 days. The numbers of NADPH-d positive cells in superficial dorsal horn of spinal cord of treated group($21{\pm}5$) was significantly (p<0.01) decreased compared with control($33{\pm}5$). The numbers of NADPH-d positive cell in dorsolateral periaqueductal gray matter of treated group($111{\pm}16$) was significantly(p<0.01) decreased compared with control($143{\pm}14$). The numbers of c-fos positive cells in dorsal periaqueductal gray matter of treated group($57{\pm}16$) was significantly(p<0.01) decreased compared with control($78{\pm}13$). The numbers of c-fos positive cells in paraventricular thalamic nucleus of treated group($60{\pm}15$) was significantly decreased compared with control($88{\pm}27$). The numbers of serotonin positive cells in median raphe nucleus of treated group($171{\pm}31$) was significantly(p<0.05) decreased compared with control($217{\pm}48$). On the basis of these results, we concluded that GCP treatment has inhibiting effects on the pain transmission in monosodium iodoacetate-induced osteoarthritic pain model in rat.

• 분석과학
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• 제28권6호
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• pp.361-369
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• 2015

골관절염에 대한 참당귀 추출분말 (AGE)의 치료효과를 검토하고자 토끼연골세포와 흰쥐의 monosodium iodoacetate (MIA)로 유발된 골관절염 부위에서 시료를 채취하여 MMPs의 발현에 대한 AGE의 억제 효능을 검토하였다. 고 농도의 AGE (50 μg/mL) 투여에서 세포독성은 관찰되지 않았으며 면역 및 염증반응과 관련된 여러 인자의 전사인자인 NF-κB 활성화를 효과적으로 억제시켰다. 토끼연골 세포에서 MMP-2와 MMP-9의 활성을 확인해본 결과 AGE는 MMP-9의 활성을 효과적으로 억제시키는 것을 확인하였다. AGE를 토끼연골세포에 처리하여 분석한 결과, 주요성분인 decursin과 decursinol angelate가 3.62±0.47 μg/mg protein와 2.14±0.36 μg/mg protein으로 검출되었다. 동물실험을 위하여, 골관절염은 MIA를 흰쥐 무릎관절에 처리하여 동물모델을 만들었으며, 매일 25, 50와 100 mg/kg의 AGE를 3주 동안 먹인 결과 흰쥐의 연골 조직에서 MMPs가 억제되는 것을 확인하였다. 연골조직으로부터 RT-PCR을 통해 collagen Type I, collagen Type II, aggrecan 및 MMPs (MMP-3, MMP-9, MMP-13)의 mRNA를 확인해본 결과 AGE는 collagen Type I, collagen Type II, aggrecan은 증가시키며 MMPs는 감소시키는 효과를 얻었다. 결론적으로 AGE는 MMPs 억제를 통하여 골관절염의 발생을 억제한다.

• 한방재활의학과학회지
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• 제25권2호
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• pp.15-35
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• 2015

Objectives This study was performed to investigate the effects of Bujasasim-tang ethanol extract (BST) on oxidative stress, inflammation and osteoarthritic rat model. Methods To ensure safety of BST, heavy metal levels were measured and cytotoxicity test was done. In vitro, To evaluate antioxidative effects of BST, total phenolic contents, 1,1-diphenyl-2-picryl-hydrazyl (DPPH), 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) scavenging activity, reactive oxygen species (ROS) levels were measured. Also, to evaluate anti-inflammatory effects of BST treated group, total nitric oxide (NO) and pro-inflammatory cytokines (IL-$1{\beta}$, IL-6, TNF-${\alpha}$) levels were measured in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. In vivo, We injected MIA $50{\mu}l$ (60 mg/ml) into knee joints of rats to induce osteoarthritis. Rats were divided into total 3 groups (normal, control, BST treated group, each n=7). Normal group was not treated at all without inducing osteoarthritis and taken normal diet. Control group was induced osteoarthritis by MIA and taken with 2 ml of distilled water once a day for 4 weeks. BST treated group was induced osteoarthritis by MIA and taken BST 2 ml (200 mg/kg/mouse) once a day for 4 weeks. We evaluated dynamic weight bearing with the Incapacitance Test Meter. At the end of experiment, the rats were sacrificed to observe the functions of liver and kidney, changes of WBC, neutrophil, lymphocyte, monocyte levels in blood, to evaluate the levels of pro-inflammatory cytokines, tissue inhibitor of metallopreteinases-1 (TIMP-1), matrix metalloproteinase-9 (MMP-9), prostaglandin $E_2$ ($PGE_2$), leukotriene $B_4$ ($LTB_4$) within serum. We observed change of articular structures by Hematoxylin & Eosin (H&E), safranin-O staining method and measured amount of cartilage by micro CT-arthrography. Statistical analysis was done by unpaired student's t-test with significance level at p<0.05 in SPSS 11.0 for windows. Results 1. Safety of the BST was identified. 2. AST, ALT, BUN, creatinine levels of BST treated group were within normal limit. In vitro, 1. DPPH and ABTS free radical scavenging activities of BST showed dose-dependent increase. 2. ROS production were significantly decreased. 3. Total nitric oxide (NO) and IL-$1{\beta}$ production were decreased. 4. IL-6 and TNF-${\alpha}$ production were significantly decreased. In vivo, 1. Weight bearing ability was significantly increased. 2. WBC, neutrophil, lymphocyte, monocyte levels in blood were decreased. 3. IL-$1{\beta}$ and TNF-${\alpha}$ levels in serum were significantly decreased. and the IL-6 level was decreased. 4. TIMP-1, MMP-9, $LTB_4$, $PGE_2$ levels in serum were significantly decreased. 5. Cartilage volume of BST treated group was significantly increased. Also changes of cartilage, synovial membrane, fibrous tissue were suppressed. Conclusions The results obtained in this study Bujasasim-tang have effects of antioxidative, anti-inflammatory, relieve pain and protection of cartilage. Therefore we expect that Bujasasim-tang is effective treatment for osteoarthritis.

• 생명과학회지
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• 제27권10호
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• pp.1207-1214
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• 2017

노화에 따른 퇴행성관절염은 삶의 질을 저하시키는 가장 큰 병리학적 현상 중의 하나이다. 오미자 열매(Schisandrae Fructus)는 오랫동안 전통의학에서 여러 가지 만성질환 치료를 위해 널리 사용되어 왔다. 오미자 추출물이 SW1353 인간 연골세포에서 $IL-1{\beta}$에 의해 유발된 염증 반응을 감소시키는 것으로 최근 보고된 바 있으나, primary culture된 연골세포 및 동물 모델에서의 퇴행성관절염에 대한 보호 및 치료 잠재력은 여전히 명확하지 않다. 따라서 본 연구에서는 $IL-1{\beta}$에 의해 유도된 primary culture된 쥐의 연골세포와 MIA에 의해 유도된 골관절염에 대한 matrix metalloproteinases (MMPs)의 활성에 미치는 오미자 에탄올 추출물의 영향을 조사하였다. 오미자 추출물 처리는 $IL-1{\beta}$로 유도된 연골세포에서 MMP-1, -3 및 -13의 mRNA 발현 및 효소 활성을 유의하게 감소시켰다. 또한 오미자 추출물은 MIA에 의해 증가된 MMP-1 및 -3의 발현을 유의적으로 억제시켰다. 따라서 오미자 추출물은 퇴행성관절염 예방과 치료를 위한 기능성 소재로서의 잠재적 가능성이 있음을 알 수 있었다.

• 한국자원식물학회지
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• 제33권6호
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• pp.638-644
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• 2020

Lilium lancifolium (LL) is widely cultivated in East Asia and used to attenuate airway diseases. Our current study aimed to investigate the therapeutic effect of LL on pain level and inflammatory response in a rat model of monosodium iodoacetate (MIA)-induced osteoarthritis (OA). We first examined the effect of LL on inflammatory cytokines and inflammatory mediators in IL-1β-treated HTB-94 cells. The LL extract was found to significantly inhibit the levels of Interleukin-6 (IL-6), Interleukin-8 (IL-8), and prostaglandin-E2 (PGE-2) in Interleukin-1 β (IL-1β)-stimulated HTB-94 cells in a dose-dependent manner. Moreover, chronic oral administration of LL effectively restored the weight-bearing distribution in the rat model of MIA-induced OA. In addition, administration of LL inhibited inflammatory cytokines and inflammatory mediators, such as C-reactive protein (CRP), IL-6, leukotriene B4 (LTB-4), PGE-2, and matrix metalloproteinase-9 (MMP-9). Our findings collectively suggested LL as one of the potential therapeutic agents for OA, owing to its properties of reducing pain and inflammatory responses.

• IMMUNE NETWORK
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• 제14권1호
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• pp.45-53
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• 2014

Osteoarthritis (OA) is a degenerative joint disease characterized by a progressive loss of cartilage. And, increased oxidative stress plays a relevant role in the pathogenesis of OA. Ursodeoxycholic acid (UDCA) is a used drug for liver diseases known for its free radical-scavenging property. The objectives of this study were to investigate the in vivo effects of UDCA on pain severity and cartilage degeneration using an experimental OA model and to explore its mode of actions. OA was induced in rats by intra-articular injection of monosodium iodoacetate (MIA) to the knee. Oral administration UDCA was initiated on the day of MIA injection. Limb nociception was assessed by measuring the paw withdrawal latency and threshold. Samples were analyzed macroscopically and histologically. Immunohistochemistry was used to investigate the expression of interleukin-$1{\beta}$ (IL-$1{\beta}$), IL-6, nitrotyrosine and inducible nitric oxide synthase (iNOS) in knee joints. UDCA showed an antinociceptive property and attenuated cartilage degeneration. OA rats given oral UDCA significantly exhibited a decreased number of osteoclasts in subchondral bone legion compared with the vehicle-treated OA group. UDCA reduced the expression of IL-$1{\beta}$, IL-6, nitrotyrosine and iNOS in articular cartilage. UDCA treatment significantly attenuated the mRNA expression of matrix metalloproteinase-3 (MMP-3), -13, and ADAMTS5 in IL-$1{\beta}$-stimulated human OA chondrocytes. These results show the inhibitory effects of UDCA on pain production and cartilage degeneration in experimentally induced OA. The chondroprotective properties of UDCA were achieved by suppressing oxidative damage and inhibiting catabolic factors that are implicated in the pathogenesis of cartilage damage in OA.

• 한방재활의학과학회지
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• 제25권4호
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• pp.1-20
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• 2015

Objectives This study was intended to clarify the anti-inflammation and anti-oxidation effects of gamikyejakjimo-tang herbal acupuncture (GKHA) for osteoarthritis. Methods Osteoarthritis was induced by injection of MIA into right knee joint cavities of rats. Rats were divided into a total of 4 groups (n=8). The 4 groups were normal group, control group, positive comparison group and expeimental group. Indomethacin and GKHA were medicated for a total of 4 weeks. After that, functions of liver and kidney by AST, ALT, creatinine, BUN, DPPH and ABTS free radical scavenging activity, ROS (reactive oxygen species) production, NO (Total Nitric oxide), IL-$1{\beta}$, IL-6, TNF-${\alpha}$ production, weight changes in the hind legs of MIA-induced osteoarthritis rat, serum PGE2, TIMP-1, MMP-2, MMP-9, LTB4, hs-CRP, and white blood cells, neutrophils, lymphocytes, monocytes were measured. The volume of cartilage was observed by micro CT arthrography. H&E and Safranin-O staining were used to examine the injury of synovial tissue. Results 1. In the hind leg weight bearing measurement, level of weight was increased. 2. AST, ALT, BUN, creatinine were decreased. 3. The production of total white blood cell was decreased, and the production of neutrophils, lymphocytes, monocytes were significantly decreased. 4. The production of NO, PGE2, TIMP-1, MMP-2, MMP-9, LTB4 were significantly decreased, and the production of hs-CRP was also decreased but with no significance. 5. The cartilage volume was significantly increased. 6. In H&E staining and Safranin-O staning, the cartilage cell appeared to be proliferated, and proteoglycans appeared to be increased. Conclusions Based on the results above, Gamikyejakjimo-tang Herbal Acupuncture has anti-oxidation and anti-inflammation effects, which leads to suppressing the underlying causes and the progression of osteoarthritis.

• 분석과학
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• 제28권4호
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• pp.260-269
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• 2015

골관절염에 대한 참당귀 추출분말의 치료효과를 검토하고자 흰쥐의 monosodium iodoacetate(MIA)로 유발된 골관절염 부위에서 시료를 채취하여 염증관련 효소 및 염증성 cytokines의 발현에 대하여 참당귀 추출분말의 억제효능을 검토하였다. 고농도의 참당귀 추출분말 (50 μg/mL) 투여에서도 독성이 관찰되지 않았으며, 동일조건하에서 interleukin-1α (IL-1α)로 유발된 nitric oxide (NO)의 생성을 효과적으로 억제하였다. 특히, 관절연골 조직의 inducible nitric oxide synthase (iNOS) 및 cyclooxygenase-2(COX-2)의 발현을 농도 의존적으로 억제하였다. 따라서 참당귀 추출분말은 항염증 효능을 나타내는 농도에서 독성 없이 사용할 수 있으며, iNOS발현을 억제하여 방출되는 신호전달 물질인 NO의 생성을 억제하였다. 또한 참당귀 추출분말의 처리로 염증유발 부위에서 염증성 cytokines으로 알려진 tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) 및 interleukin-6 (IL-6)의 발현이 억제됨을 확인하였다. 참당귀 추출분말의 항 염증효과는 TNF-α, IL-1β 및 IL-6의 혈중농도를 낮추어 염증부위뿐만 아니라 전체적으로 항염증효과를 나타내었다. 본 실험결과, 참당귀 추출분말의 투여는 MIA 또는 IL-1α로 유발되는 골관절염 동물모델에서 염증인자, 관련 효소의 발현 및 관련 신호전달 물질의 생성을 효과적으로 억제하여, 슬관절의 활액 내 glycosaminoglycan (GAG) 및 관절연골의 proteoglycan (PG)의 분해를 방지하여 골관절염의 발생을 억제할 것으로 추정되었다. 한편, 참당귀 추출분말의 주성분인 decursin은 혈중에서 2시간이내에 decursinol로 전환되어 8시간이상 LC-MS/MS로 검출되었다, 따라서 참당귀 추출분말에 의한 염증성 사이토카인 TNF-α, IL-1β 및 IL-6의 억제활성은 항염증활성이 큰 decursinol에 의한 것으로 추정된다.