[논문]영선제통음(靈仙除痛飮)이 Monosodium Iodoacetate로 유도한 흰쥐의 골관절염에 미치는 효과

안성후; 정영진; 김수학; 이학송; 염승룡; 권영달

doi:10.18325/jkmr.2023.33.4.1

영선제통음(靈仙除痛飮)이 Monosodium Iodoacetate로 유도한 흰쥐의 골관절염에 미치는 효과
Effects of Youngseonjeatonguem on Monosodium Iodoacetate-Induced Osteoarthritis in Sprague-Dawley Rats 원문보기

Journal of Korean Medicine Rehabilitation : JKMR = 한방재활의학과학회지, v.33 no.4, 2023년, pp.1 - 14

안성후 (원광대학교 광주한방병원 한방재활의학과) , 정영진 (원광대학교 광주한방병원 한방재활의학과) , 김수학 (원광대학교 광주한방병원 한방재활의학과) , 이학송 (학송한의원) , 염승룡 (원광대학교 광주한방병원 한방재활의학과) , 권영달 (원광대학교 광주한방병원 한방재활의학과)

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Objectives The anti-inflammatory and anti-arthritic effects of Youngseonjeatonguem (靈仙除痛飮, YSJTU) was evaluated in a cellular model using RAW264.7 macrophages, which are involved in osteoarthritis (OA), and an animal model using Sprague-Dawley (SD) rats, and a possible mechanism of anti-arthritic actions of YSJTU was presented. Methods RAW264.7 macrophages were activated by lipopolysaccharide (LPS). The production of pro-inflammatory cytokines (tumor necrosis factor [TNF]-𝛼, interleukin [IL]-1𝛽, and IL-6) and inflammatory mediators (nitric oxide [NO] and prostaglandin E2 [PGE2]) was determined by ELISA and Griess assay, respectively. Western blot was performed to determine inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression. OA was induced by intra-articular injection of monosodium iodoacetate (MIA) into the right knee joint of SD rats. Results In RAW264.7 macrophages, YSJTU reduced LPS-induced production of TNF-𝛼, IL-1𝛽, and IL-6. In addition, YSJTU inhibited LPS-induced production of NO and PGE2 by suppressing iNOS and COX-2 expression. In SD rats, YSJTU improved MIA-induced OA by reducing swelling, skin heat, and cartilage degradation. In addition, YSJTU reduced serum levels of TNF-𝛼, IL-1𝛽, and IL-6, along with its significant decrease in serum levels of NO and PGE2. Conclusions These results suggest that YSJTU may exert anti-arthritic effect, at least in part, by inhibiting macrophage-mediated joint inflammation.

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표/그림 (19)

표 Table Ⅰ. The Prescription of Youngseonjeatonguem
표 Table Ⅱ. Arthritis Score for Clinical Symptom
그림 Fig. 1. Effect of Youngseonjeatonguem (YSJTU) on cell viability of RAW264.7 macrophages. RAW264.7 macrophages were incubated for 24 hours with vehicle (control, Con) or indicated concentrations of YSJTU. MTT assay for cell viability of RAW264.7 macrophages was carried out. Data are the mean±standard deviation (n=6). *p<0.05.
그림 Fig. 2. Effect of Youngseonjeatonguem (YSJTU) on lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-α secretion in RAW264.7 macrophages. RAW264.7 macrophages were pre-incubated for 1 hour with medium alone or indicated concentrations of YSJTU, and then activated for 20 hours with LPS (1 μg/mL). ELISA for TNF-α secreted by LPS-stimulated RAW264.7 macrophages was carried out. Bars are the mean± standard deviation (n=6). *p<0.05.
그림 Fig. 3. Effect of Youngseonjeatonguem (YSJTU) on lipopolysaccharide (LPS)-induced interleukin (IL)-1β secretion in RAW264.7 macrophages. RAW264.7 macrophages were pre-incubated for 1 hour with medium alone or indicated concentrations of YSJTU, and then activated for 20 hours with LPS (1 μg/mL). ELISA for IL-1β secreted by LPS-stimulated RAW264.7 macrophages was carried out. Bars are the mean±standard deviation (n=6). *p<0.05.
그림 Fig. 5. Effects of Youngseonjeatonguem (YSJTU) on inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression in RAW264.7 macrophages. RAW264.7 macrophages were pre-incubated for 1 hour with medium alone or indicated concentrations of YSJTU, and then activated for 12 hours with lipopolysaccharide (LPS) (1 μg/mL). Western blotting analysis for iNOS and COX-2 was carried out. The bolts are representative of 3 independent experiments.
그림 Fig. 4. Effect of Youngseonjeatonguem (YSJTU) on lipopolysaccharide (LPS)-induced interleukin (IL)-6 secretion in RAW264.7 macrophages. RAW264.7 macrophages were pre-incubated for 1 hour with medium alone or indicated concentrations of YSJTU, and then activated for 20 hours with LPS (1 μg/mL). ELISA for IL-6 secreted by LPS-stimulated RAW264.7 macrophages was carried out. Bars are the mean±standard deviation (n=6). *p<0.05.
그림 Fig. 6. Effect of Youngseonjeatonguem (YSJTU) on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW264.7 macrophages. RAW264.7 macrophages were pre-incubated for 1 hour with medium alone or indicated concentrations of YSJTU, and then activated for 20 hours with LPS (1 μg/mL). Griess assay for NO production was carried out. Bars are the mean± standard deviation (n=6). *p<0.05.
그림 Fig. 7. Effect of Youngseonjeatonguem (YSJTU) on lipopolysaccharide (LPS)-induced prostaglandin E2 (PGE2) production in RAW264.7 macrophages. RAW264.7 macrophages were preincubated for 1 hour with medium alone or indicated concentrations of YSJTU, and then activated for 20 hours with LPS (1 μg/mL). ELISA for PGE2 production was carried out. Bars are the mean± standard deviation (n=6). *p<0.05.
그림 Fig. 8. Effect of Youngseonjeatonguem (YSJTU) on swelling of left knee in monosodium iodoacetate (MIA)-treated Sprague- Dawley (SD) rats. Normal (Nor) rats were neither injected with MIA nor treated with YSJTU. SD rats were injected with MIA. After 7 days, MIA-treated rats orally received distilled water (control, Con), 300 mg/kg YSJTU or 500 mg/kg YSJTU once a day for 4 weeks. The thickness o f lef t knee joint was evaluated. Bars show the mean±standard deviation (n=5). *p<0.05.
그림 Fig. 9. Effect of Youngseonjeatonguem (YSJTU) on skin temperature of left knee in monosodium iodoacetate (MIA)-treated Sprague- Dawley (SD) rats. Normal (Nor) SD rats were neither injected with MIA nor treated with YSJTU. SD rats were injected with MIA. After 7 days, MIA-treated rats orally received distilled water (control, Con), 300 mg/kg YSJTU or 500 mg/kg YSJTU once a day for 4 weeks. Knee skin temperature was measured by a thermal imaging camera. Bars show the mean±standard deviation (n=5). *p<0.05.
그림 Fig. 10. Representative pictures showing the left knee joints of Sprague-Dawley (SD) rats. Normal (Nor) SD rats were neither injected with monosodium iodoacetate (MIA) nor treated with Youngseonjeatonguem (YSJTU). SD rats were injected with MIA. After 7 days, MIA-treated rats orally received distilled water (control, Con), 300 mg/kg YSJTU or 500 mg/kg YSJTU once a day for 4 weeks. The pictures are representative of more than 5 observations.
그림 Fig. 12. Effect of Youngseonjeatonguem (YSJTU) on clinical severity in monosodium iodoacetate (MIA)-treated Sprague- Dawley (SD) rats. Normal (Nor) SD rats were neither injected with MIA nor treated with YSJTU. SD rats were injected with MIA. After 7 days, MIA-treated rats orally received distilled water (control, Con), 300 mg/kg YSJTU or 500 mg/kg YSJTU once a day for 4 weeks. Scores for the clinical severity were evaluated. Bars show the mean±standard deviation (n=5). *p<0.05.
그림 Fig. 11. Safranin-O-stained histopathological observation of the sections o f the lef t knee joints o f Sprague-Dawley (SD) rats. Normal (Nor) SD rats were neither injected with monosodium iodoacetate (MIA) nor treated with Youngseonjeatonguem (YSJTU). SD rats were injected with MIA. After 7 days, MIA-treated rats orally received distilled water (control, Con), 300 mg/kg YSJTU or 500 mg/kg YSJTU once a day for 4 weeks. Safranin-O staining for the sections of the left knee joints was carried out. Sections (×100) are representatives of more than 5 observations. Arrows indicate stained cartilage areas.
그림 Fig. 13. Effect of Youngseonjeatonguem (YSJTU) on serum tumor necrosis factor (TNF)-α levels in monosodium iodoacetate (MIA)-treated Sprague-Dawley (SD) rats. Normal (Nor) SD rats were neither injected with MIA nor treated with YSJTU. SD rats were injected with MIA. After 7 days, MIA-treated rats orally received distilled water (control, Con), 300 mg/kg YSJTU or 500 mg/kg YSJTU once a day f or 4 weeks. ELISA for serum TNF-α was carried out. Bars show the mean±standard deviation (n=5). *p<0.05.
그림 Fig. 14. Effect of Youngseonjeatonguem (YSJTU) on serum interleukin (IL)-1β levels in monosodium iodoacetate (MIA)- treated Sprague-Dawley (SD) rats. Normal (Nor) SD rats were neither injected with MIA nor treated with YSJTU. SD rats were injected with MIA. After 7 days, MIA-treated rats orally received distilled water (control, Con), 300 mg/kg YSJTU or 500 mg/kg YSJTU once a day for 4 weeks. ELISA for serum IL-1β was carried out. Bars show the mean±standard deviation (n=5). *p<0.05.
그림 Fig. 16. Effect of Youngseonjeatonguem (YSJTU) on serum nitric oxide (NO) (nitrite) levels in monosodium iodoacetate (MIA)-treated Sprague-Dawley (SD) rats. Normal (Nor) SD rats were neither injected with MIA nor treated with YSJTU. SD rats were injected with MIA. After 7 days, MIA-treated rats orally received distilled water (control, Con), 300 mg/kg YSJTU or 500 mg/kg YSJTU once a day for 4 weeks. Griess assay for serum nitrite was carried out. Bars show the mean± standard deviation (n=5). *p<0.05.
그림 Fig. 17. Effect of Youngseonjeatonguem (YSJTU) on serum prostaglandin E2 (PGE2) levels in monosodium iodoacetate (MIA)-treated Sprague-Dawley (SD) rats. Normal (Nor) SD rats were neither injected with MIA nor treated with YSJTU. SD rats were injected with MIA. After 7 days, MIA-treated rats orally received distilled water (control, Con), 300 mg/kg YSJTU or 500 mg/kg YSJTU once a day f or 4 weeks. ELISA for serum PGE2 was carried out. Bars show the mean±standard deviation (n=5). *p<0.05.
그림 Fig. 15. Effect of Youngseonjeatonguem (YSJTU) on serum interleukin (IL)-6 levels in monosodium iodoacetate (MIA)- treated Sprague-Dawley (SD) rats. Normal (Nor) SD rats were neither injected with MIA nor treated with YSJTU. SD rats were injected with MIA. After 7 days, MIA-treated rats orally received distilled water (control, Con), 300 mg/kg YSJTU or 500 mg/kg YSJTU once a day for 4 weeks. ELISA for serum IL-6 was carried out. Bars show the mean±standard deviation (n=5). *p<0.05.

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