[논문]Monosodium iodoacetate 유도 골관절염 동물모델에서 보스웰리아 검레진 추출물의 항골관절염 효과 연구

정재인; 김룡; 김은지

doi:10.4163/jnh.2023.56.3.231

Monosodium iodoacetate 유도 골관절염 동물모델에서 보스웰리아 검레진 추출물의 항골관절염 효과 연구
Anti-osteoarthritis effect of Boswellia serrata gum resin extract in monosodium iodoacetate-induced osteoarthritic Sprague-Dawley rats 원문보기

Journal of nutrition and health, v.56 no.3, 2023년, pp.231 - 246

정재인 (한림대학교 바이오헬스케어소재기업협업센터) , 김룡 (에스알이서비스(주) 연구개발부) , 김은지 (한림대학교 바이오헬스케어소재기업협업센터)

초록
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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.

Abstract ▼ AI-Helper

Purpose: The aim of this study was to investigate the anti-osteoarthritic effect of the ethanol extract of Boswellia serrata gum resin (FJH-UBS) enriched with keto-β-boswellic acid and 3-O-acetyl-11-keto-β-boswellic acid compared to the conventional Boswellia serrata extract by adding the process of removing oil with hexane, in the monosodium iodoacetate (MIA)-induced osteoarthritis rat model. Methods: Sprague-Dawley (SD) rats were orally administered 0, 40, or 80 mg of FJH-UBS/kg body weight (BW)/day for 5 weeks and injected with MIA intra-articularly into right knee joints on day 15 to induce osteoarthritis. Changes in the knee joint microarchitecture, cartilage degradation, the expression of inflammatory mediators, cytokines, and matrix metalloproteinases (MMPs) in serum and synovia were observed. Results: Oral administration of FJH-UBS (80 mg/kg BW/day) reduced MIA-induced knee swelling and cartilage degradation and increased the expression of type II collagen and aggrecan in articular cartilage. Furthermore, FJH-UBS administration reduced MIA-induced increases in the serum levels of prostaglandin E2, leukotriene B4, interleukin (IL)-1β, IL-6, and MMP-13, and MIA-induced increases in the mRNA expressions of inducible nitric oxide synthase, cyclooxygenase-2, 5-lipoxygenase, IL-1β, IL-6, TNF-α, MMP-2, MMP-9, and MMP-13 in the synovia of knee joints. Conclusion: These results indicate that FJH-UBS exerts its anti-osteoarthritic effects by suppressing the expressions of inflammatory cytokines and MMPs and, thus, cartilage degradation. Furthermore, they suggest that FJH-UBS has potential use as a functional food that improves joint and cartilage health.

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표/그림 (9)

표 Table 1. Primer sequences used in this study
표 Table 2. Effect of FJH-UBS on knee thickness in Sprague-Dawley rats with MIA-induced osteoarthritis
그림 Fig. 1. Effect of FJH-UBS osteoarthritis symptoms in SD rats with MIA-induced osteoarthritis. (continued to the next page)
그림 Fig. 2. Effect of FJH-UBS on histological changes in the articular cartilage of SD rats with MIA-induced osteoarthritis. SD rats were administered with FJH-UBS and injected with MIA as described in Fig. 1. Articular cartilage was stained with (A) hematoxylin and eosin and (B) safranin O. Representative staining images are shown (n = 5). Magnification, 40×. NC, normal control group; OC, osteoarthritis (injected with MIA) control group; O+F40, osteoarthritis (injected with MIA) + 40 mg/kg BW/day FJH-UBS-treated group; O+F80, osteoarthritis (injected with MIA) + 80 mg/kg BW/day FJH-UBS-treated group; O+M, osteoarthritis (injected with MIA) + 150 mg/kg BW/day methyl sulfonyl methane (positive control)-treated group; SD, Sprague-Dawley; MIA, monosodium iodoacetate.
그림 Fig. 3. Effect of FJH-UBS on the expression of COL2A1 and aggrecan in the articular cartilage of SD rats with MIA-induced osteoarthritis. SD rats were administered with FJH-UBS and injected with MIA as described in Fig. 1. Articular cartilage was stained with (A) COL2A1 and (B) aggrecan antibodies. Representative staining images are shown (n = 5). Magnification, 100×. NC, normal control group; OC, osteoarthritis (injected with MIA) control group; O+F40, osteoarthritis (injected with MIA) + 40 mg/kg BW/day FJH-UBS-treated group; O+F80, osteoarthritis (injected with MIA) + 80 mg/kg BW/day FJH-UBS-treated group; O+M, osteoarthritis (injected with MIA) + 150 mg/kg BW/day methyl sulfonyl methane (positive control)-treated group; SD, Sprague-Dawley; MIA, monosodium iodoacetate.
표 Table 3. Effect of FJH-UBS on serum levels of inflammatory mediators and cytokines in MIA-induced osteoarthritis rats
표 Table 4. Effect of FJH-UBS on serum levels of MMPs in SD rats with MIA-induced osteoarthritis
그림 Fig. 4. Effect of FJH-UBS on the expression of inflammatory mediators and cytokines in the synovia of SD rats with MIA-induced osteoarthritis. SD rats were administered with FJH-UBS and injected with MIA as described in Fig. 1. Total RNA in the synovia was extracted, reversed transcribed, and real-time polymerase chain reaction was performed. Expression of target mRNA (A-F) was normalized to that of GAPDH and represents relative to that of the NC group. Values are expressed as mean ± SEM (n = 10). iNOS, inducible nitric oxide synthase; NC, normal control group; OC, osteoarthritis (injected with MIA) control group; O+F40, osteoarthritis (injected with MIA) + 40 mg/kg BW/day FJH-UBS-treated group; O+F80, osteoarthritis (injected with MIA) + 80 mg/kg BW/day FJH-UBS-treated group; O+M, osteoarthritis (injected with MIA) + 150 mg/kg BW/day methyl sulfonyl methane (positive control)-treated group; COX-2, cyclooxygenase-2; 5-LOX, 5-lipoxygenase; IL, interleukin; TNF, tumor necrosis factor; SD, Sprague-Dawley; MIA, monosodium iodoacetate. t-test was used to compare the means of the NC and OC groups and ANOVA followed by Duncan’s multiple comparison test was used to compare the means of the four groups (OC, O+F40, O+F80, and O+M). ***p < 0.001 significantly different from the NC group. Different letters indicate differences among OC, O+F40, O+F80, and O+M groups (p < 0.05).
그림 Fig. 5. Effect of FJH-UBS on the expression of MMPs in the synovia of SD rats with MIA-induced osteoarthritis. SD rats were administered with FJH-UBS and injected with MIA as described in Fig. 1. Total RNA in the synovia was extracted, reversed transcribed, and real-time polymerase chain reaction was performed. Expression of target (A-D) mRNA was normalized to that of GAPDH and represents relative to that of the NC group. Values are expressed as mean ± SEM (n = 10). MMP, matrix metalloproteinase; NC, normal control group; OC, osteoarthritis (injected with MIA) control group; O+F40, osteoarthritis (injected with MIA) + 40 mg/kg BW/day FJH-UBS-treated group; O+F80, osteoarthritis (injected with MIA) + 80 mg/kg BW/day FJH-UBS-treated group; O+M, osteoarthritis (injected with MIA) + 150 mg/kg BW/day methyl sulfonyl methane (positive control)-treated group; SD, Sprague-Dawley; MIA, monosodium iodoacetate. t-test was used to compare the means of the NC and OC groups and ANOVA followed by Duncan’s multiple comparison test was used to compare the means of the four groups (OC, O+F40, O+F80, and O+M). **p < 0.01, ***p < 0.001 significantly different from the NC group. Different letters indicate differences among OC, O+F40, O+F80, and O+M groups (p < 0.05).

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