• 대한한의학방제학회지
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• 제26권4호
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• pp.283-294
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• 2018

Objectives : Mahaengeuigam-Tang (MHEGT) has been used as a traditional medicine for the treatment of rheumatic aerthritis, rheumatisim, eczema and asthma. The aim of this study was to investigate the molecular mechanisms of MHEGT for cartilage protection in monosodium iodoacetate(MIA)-induced osteoarthritis, particularly focusing on apoptosis. Method : Thirty young male Sprague-Dawley rats were used for the study. Rats were intra-articularly injected with 2 mg MIA in a total volume of 50 ㎕ saline. In MHEGT group, MHEGT extract was orally administered once daily to MIA-induced osteoarthritis rats, and rats of control group were given with saline only. At 4 weeks after MIA injection, all animals were sacrificed, and the histological changes and articular thickness were assessed by hematoxylin and eosin staining. Moreover, the immunohistochemical analyses of BAX and Bcl-2 were carried out. Results : The histomorphological examinations revealed that MHEGT reduced MIA-induced cartilage damage. And, MHEGT ameliorated the severity of cartilage surface damages after MIA injection. Furthermore, MHEGT suppressed the MIA-induced increases of pro-apoptotic BAX protein and increased the protein expression of anti-apoptotic Bcl-2 protein. Conclusion : These findings indicate that MHEGT protects against MIA-induced cartilage damage by inhibition of the apoptotic pathway, demonstrating significant protection of cartilage against osteoarthritis. These results suggest that MHEGT may potentially have clinical applications in the treatment of osteoarthritis.

• 생명과학회지
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• 제33권6호
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• pp.455-462
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• 2023

임신 중 감염에 의한 산모의 면역 활성화는 조현병과 자폐 스펙트럼 장애를 포함한 신경 발달 질환의 위험을 증가시킨다. 여러 연구에서 poly (I:C) 또는 LPS를 사용하여 모체 면역 활성화 유도한 자손에서 비정상적인 행동과 뇌 발달을 관찰하였다. 또한 최근 뇌에 상주하며 면역 세포로 기능하는 미세아교세포가 MIA 유발 자손의 행동 이상과 뇌 발달에 중요한 역할을 한다는 것이 보고되고 있으나 아직 메커니즘은 명확하지 않다. 본 연구에서는 GPCR의 구성원인 GPR56의 미세아교세포 특이적 억제가 행동 이상과 뇌 발달을 유발하는지 여부를 조사하였다. 먼저, MIA 유도는 발달 중인 뇌의 미세아교세포 집단에 영향을 미치지 않으나, 미세아교세포를 분리하여 GRP56의 발현을 조사한 결과, MIA 유도 태아에서 성별에 관계 없이 E14.5와 E18.5 사이에서 GPR56 발현이 억제됨을 관찰하였다. 그리고 미세아교세포 특이적 GPR56 억제는 MIA 유도 자손에게서 나타나는 사교성 결손, 반복적인 행동 패턴 및 증가된 불안 수준과 같은 비정상적인 행동을 관찰하였다. 미세아교세포 GPR56 억제 마우스에서는 MIA 유도 자손과 같은 비정상적인 피질 발달이 관찰되지 않았지만, c-fos 염색을 통해 뇌 활동이 관찰되었다. 따라서 본 연구는 미세아교세포 특이적 GPR56 결핍이 이상 행동을 유발함을 시사하며, 추후 연구를 통해 MIA 자손의 행동 결손 진단 및/ 치료 표적을 위한 바이오마커로 활용될 수 있음을 시사한다.

• Journal of Acupuncture Research
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• 제33권2호
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• pp.35-49
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• 2016

Objectives : This study was designed to investigate the anti-osteoarthritic effects of clematidis radix pharmacopuncture on the MIA-induced osteoarthritis rats. Methods : The subjects were divided into 4 groups ; Normal rat group(N, n=5), MIA-induced osteoarthritis control rat group(C, n=5), MIA-induced osteoarthritis rat group injected with normal saline at ST36(NS, n=5), and MIA-induced osteoarthritis rat group injected with clematidis radix pharmacopuncture at ST36(CR, n=5). The experiment was conducted over a period of 21 days after injecting MIA. We analyzed body weight, hind paw weight distribution, liver and renal function, immunocytes, cykokines, inflammatory mediators, inflammatory proteins and mRNA expressions, as well as histopathological changes. Results : The CR group showed a significant increase in the hind paw weight distribution, and significant decreases in IL-$1{\beta}$, IL-6, $PGE_2$, $LTB_4$, osteocalcin, deoxypyridinoline level, the protein expression of COX2, arachidonate 5 lipoxygenase, and the mRNA expression of COX2, TNF-${\alpha}$, IL-$1{\beta}$, and NOS-II. In terms of the joint damages induced by osteoarthritis, the CR group showed a greater protective effect than group C in histopathologic observation (H&E, Safranin-O staining). Conclusion : These results demonstrated that clematidis radix pharmacopuncture had anti-inflammatory and analgesic effects. In addition, these results showed that it inhibited the progression of osteoarthritis.

• 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.

• 한방재활의학과학회지
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• 제30권2호
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• pp.1-18
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• 2020

Objectives This study intended to evaluate antioxidative, anti-inflammatory effects of Jibaekjihwang-tang on monosodium iodoacetate (MIA)-induced osteoarthritic rat model and investigate the potential mechanism. Methods Jibaekjihwang-tang (100 or 200 mg/kg body weight) was orally administered once daily for 2 weeks days from day 7 after intra-articular MIA injection. And blood analysis, the histologic examinations were performed. Moreover, protein expressions related to anti-oxidant and cartilage degradation and anti-inflammatory cytokines were measured by western blot analysis in cartilaginous tissue. Results Jibaekjihwang-tang reduced serum inflammatory cytokines such as tumor necosis factors-α and interleukin-6. Furthermore, the increase of anti-oxidant enzymes reversed the oxidative stress caused by MIA. Meanwhile, Jibaekjihwang-tang suppressed MIA-induced inflammation and cartilage degradation in cartilaginous tissue. Conclusions Jibaekjihwang-tang alleviated MIA-induced inflammation. Jibaekjihwang-tang was associated with a protective effect on cartilage and by reducing inflammation and cartilage degradation. These findings provide new approaches for understanding osteoarthritis therapy.

• 한방재활의학과학회지
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• 제31권1호
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• pp.17-32
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• 2021

Objectives The present study was designed to find out the therapeutic effects and possible underlying mechanism of Buja-tang, a herbal complex formula on experimental monosodium iodoacetate (MIA)-induced osteoarthritis. Methods Osteoarthritis models were created via intra-joint injection of MIA (50 μL with 80 mg/mL) in rats. Rats were divided into five groups and each group consisted of seven. Normal group was not injected MIA and did a normal diet. Control group injected MIA and received distilled water. Indo injected MIA and oral administration of 5 mg/kg of indomethacin. BJTL injected MIA and oral administration of 100 mg/kg of Buja-tang. BJTH injected MIA and oral administration of 200 mg/kg of Buja-tang. We analyzed weight-bearing ability of hind paws, oxidative stress related factor, antioxidant protein, inflammatory protein, inflammatory messenger and cytokine in joint tissue. Pathological observation of knee cartilage tissue structures was also performed with hematoxylin & eosin and safranin-O chromosomes. Results Weight-bearing ability of hind paws showed a tendency to reduce pain. The incidence of nicotinamide adenine dinucleotide phosphate oxidase and p22phox in articular tissue was significantly reduced, and the incidence of nuclear factor-erythroid 2-related factor 2 and heme oxygenase-1 and superoxide dismutases was significantly increased. The incidence of phosphorylated inhibitor of κBα, nuclear factor-kappa B p65, inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor alpha, interleukin (IL)-6, and IL-1β decreased significantly. In pathological observation, cartilage tissue damaged by MIAs in biopsy has significantly recovered from Buja-tang administration. Conclusions Buja-tang has anti-inflammation, antioxidation and pain relief effects. So this is thought to inhibit the progress of osteoarthritis in rat caused by the MIA.

• 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.

• 대한한의학회지
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• 제40권3호
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• pp.35-58
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• 2019

Objectives: The aim of this study was to investigate the anti-inflammatory effects of Curcuma longa rhizoma extract in an experimental rat model of osteoarthritis. Methods: Osteoarthritis was induced in rats by injecting monosodium iodoacetate (MIA) into the knee joint cavity of rats. The rats were divided into 5 groups (Normal, Control, positive comparison, low (CL) and high (CH) concentration groups). Rats in the low concentration (CL) group had MIA-induced osteoarthritis; they were treated with Curcuma longa rhizoma extract at a dose of 50mg/kg body weight. Rats in the high concentration (CH) group had MIA-induced osteoarthritis; they were treated with Curcuma longa rhizoma extract at a dose of 100mg/kg body weight. Hind paw weight distribution and ROS levels were measured. At the end of all treatments, changes in alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and creatinine levels were analyzed. In addition, inflammatory protein levels were evaluated by western blot analysis. Results: In this study, hind paw weight distribution significantly improved in the CL and CH groups, while. Reactive oxygen species (ROS) production significantly decreased in both. The levels of ALT, AST, BUN, and creatinine did not significantly change in either group. The production of nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4), $p47^{phox}$, and Ras-related C3 botulinum toxin substrate 1 (RAC1) decreased in both. Catalase, heme oxygenase-1 (HO-1) and superoxide dismutase (SOD) significantly increased in the CL and CH groups, respectively. Nuclear factor erythroid 2 (Nrf2) increased, but there were no significant differences between the experimental and control groups. Inflammatory cytokines, including nuclear factor-kappa Bp65 (NF-${\kappa}Bp65$), interleukin-1beta (IL-$1{\beta}$), and tumor necrosis factor-alpha (TNF-${\alpha}$), decreased significantly in both the CL and CH groups. Conclusions: Our results showed that Curcuma longa rhizoma extract has anti-inflammatory effects. Anti-inflammatory activity is regulated by the inhibition of inflammatory cytokines and mediators, such as NF-${\kappa}B$, therefore, it suppresses cartilage damage as well.

• Journal of Nutrition and Health
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• 제46권6호
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• pp.521-530
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• 2013

Protein-energy malnutrition, PEM, and increased hs-CRP level are considered to be associated with increased risk of cardiovascular disease (CVD) in hemodialysis (HD) patients. This is commonly referred to as the vicious circle of malnutrition-inflammation-atherosclerosis cardiovascular disease (MIA syndrome) in chronic kidney disease (CKD). Low protein intake can decrease the serum level of albumin and increase inflammational markers; further, both low serum albumin and high hs-CRP are independent risk factors for all-cause mortality in HD patients. The aim of this study is comparing the serum levels of albumin and hs-CRP in HD patients according to the protein intake levels. The total number of subjects was 60 hemodialysis patients; they were grouped by dietary protein intake: low protein intake group (LPI, protein intake < 1.0 g/kg IBW, 11 men and 19 women) and adequate protein intake group (API, protein intake ${\geq}$ 1.0g/kg IBW, 12 men and 18 women). Blood biochemical parameters, nutrient intake, and dietary behaviors were compared between the LPI and API groups. The LPI group showed a significantly lower serum level of albumin and higher serum level of hs-CRP than the API group (p < 0.05). The LPI group showed a significantly lower intake of most nutrients than the API group (p < 0.05). Index of Nutritional Quality of most nutrients of the LPI and API groups were lower than 1.0. Dietary protein intake was positively correlated with the serum level of albumin (r = 0.306, p < 0.05) and negatively correlated with the serum level of hs-CRP (r = -0.435, p < 0.01). The serum level of hs-CRP was negatively correlated with that of albumin (r = -0.393, p < 0.01). According to these result, serum albumin and hs-CRP in HD patients were influenced by the protein intake levels. To prevent MIA syndrome, it is necessary to improve nutritional status, especially in protein and energy.

• 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.