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

정재인; 김룡; 김은지

doi:10.4163/jnh.2023.56.3.231

[국내논문] 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
AI-Helper

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.

Keyword

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).

참고문헌 (34)

Chen D, Shen J, Zhao W, Wang T, Han L, Hamilton JL, et al. Osteoarthritis: toward a comprehensive？understanding of pathological mechanism. Bone Res 2017; 5(1): 16044.
Oh J, Yi M. [Structural equation modeling on quality of life in older adults with osteoarthritis]. J Korean？Acad Nurs 2014; 44(1): 75-85.
Man GS, Mologhianu G. Osteoarthritis pathogenesis - a complex process that involves the entire joint. J？Med Life 2014; 7(1): 37-41.
Sirse M. Effect of dietary polyphenols on osteoarthritis-molecular mechanisms. Life (Basel) 2022; 12(3): 436.

상세보기
Nam DE, Kim OK, Shim TJ, Kim JH, Lee J. Effect of Boswellia serrata extracts on degenerative？osteoarthritis in vitro and in vivo models. J Korean Soc Food Sci Nutr. 2014; 43(5): 631-940.
Fibel KH, Hillstrom HJ, Halpern BC. State-of-the-art management of knee osteoarthritis. World J Clin？Cases 2015; 3(2): 89-101.
Trelle S, Reichenbach S, Wandel S, Hildebrand P, Tschannen B, Villiger PM, et al. Cardiovascular safety of？non-steroidal anti-inflammatory drugs: network meta-analysis. BMJ 2011; 342: c7086.

상세보기
Mannino G, Occhipinti A, Maffei ME. Quantitative determination of 3-O-acetyl-11-keto-β-boswellic acid？(AKBA) and other boswellic acids in Boswellia sacra Flueck (syn. B. carteri Birdw) and Boswellia serrata？Roxb. Molecules 2016; 21(10): 1329.
Zhang J, Zhao J, Sun Y, Liang Y, Zhao J, Zou H, et al. GR-mediated anti-inflammation of α-boswellic acid:？insights from in vitro and in silico studies. Food Chem Toxicol 2021; 155: 112379.
Zimmermann-Klemd AM, Reinhardt JK, Nilsu T, Morath A, Falanga CM, Schamel WW, et al. Boswellia？carteri extract and 3-O-acetyl-alpha-boswellic acid suppress T cell function. Fitoterapia 2020; 146: 104694.

상세보기
Bharat KT, Manhas NS, Gutcho J, Lin J, Bhattacharyya S, Kounang R. Ingredients of a natural oral？nutritional supplement and their role in the treatment of osteoarthritis. Clin Med Insights Arthritis？Musculoskelet Disord 2022; 15: 11795441211063365.
Chopra A, Saluja M, Tillu G, Sarmukkaddam S, Venugopalan A, Narsimulu G, et al. Ayurvedic？medicine offers a good alternative to glucosamine and celecoxib in the treatment of symptomatic knee？osteoarthritis: a randomized, double-blind, controlled equivalence drug trial. Rheumatology (Oxford)？2013; 52(8): 1408-1417.
Lee J, Jeong I, Kim GW, Son T, Kim Y, Jun W, et al. Standardized ethanolic extracts of Boswellia serrata？ameliorate symptoms of osteoarthritis by direct effects on chondrocytes. J Food Nutr Res 2021; 9(12): 614-625.
Majeed M, Majeed S, Narayanan NK, Nagabhushanam K. A pilot, randomized, double-blind, placebo-controlled trial to assess the safety and efficacy of a novel Boswellia serrata extract in the management of？osteoarthritis of the knee. Phytother Res 2019; 33(5): 1457-1468.
Notarnicola A, Maccagnano G, Moretti L, Pesce V, Tafuri S, Fiore A, et al. Methylsulfonylmethane and？boswellic acids versus glucosamine sulfate in the treatment of knee arthritis: Randomized trial. Int J？Immunopathol Pharmacol 2016; 29(1): 140-146.

상세보기
Borner F, Werner M, Ertelt J, Meins J, Abdel-Tawab M, Werz O. Analysis of boswellic acid contents？and related pharmacological activities of frankincense-based remedies that modulate inflammation.？Pharmaceuticals (Basel) 2021; 14(7): 660.

상세보기
Meins J, Artaria C, Riva A, Morazzoni P, Schubert-Zsilavecz M, Abdel-Tawab M. Survey on the quality of？the top-selling european and american botanical dietary supplements containing boswellic acids. Planta？Med 2016; 82(6): 573-579.

상세보기
Jung JI, Lee HS, Kim R, Kim EJ. Anti-osteoarthritis effect of enriched Boswellia serrata gum resin extract？in SW1353 chondrocytes. J Korean Soc Food Sci Nutr 2023; 52(5): 460-472.
Lim SM, Lee HS, Jung JI, Kim SM, Kim NY, Seo TS, et al. Cyanidin-3-O-galactoside-enriched Aronia？melanocarpa extract attenuates weight gain and adipogenic pathways in high-fat diet-induced obese？C57BL/6 mice. Nutrients 2019; 11(5): 11.

상세보기
Wojdasiewicz P, Poniatowski LA, Szukiewicz D. The role of inflammatory and anti-inflammatory？cytokines in the pathogenesis of osteoarthritis. Mediators Inflamm 2014; 2014: 561459.
Sheu SY, Ho SR, Sun JS, Chen CY, Ke CJ. Arthropod steroid hormone (20-Hydroxyecdysone) suppresses？IL-1β-induced catabolic gene expression in cartilage. BMC Complement Altern Med 2015; 15(1): 1.
Lin Z, Wu D, Huang L, Jiang C, Pan T, Kang X, et al. Nobiletin inhibits IL-1β-induced inflammation in？chondrocytes via suppression of NF-κB signaling and attenuates osteoarthritis in mice. Front Pharmacol？2019; 10: 570.
Zhang M, Zhang R, Zheng T, Chen Z, Ji G, Peng F, et al. Xanthohumol attenuated inflammation and ECM？degradation by mediating HO-1/C/EBPβ pathway in osteoarthritis chondrocytes. Front Pharmacol 2021;？12: 680585.
Amalinei C, Caruntu ID, Giusca SE, Balan RA. Matrix metalloproteinases involvement in pathologic？conditions. Rom J Morphol Embryol 2010; 51(2): 215-228.
Jenei-Lanzl Z, Meurer A, Zaucke F. Interleukin-1β signaling in osteoarthritis - chondrocytes in focus. Cell？Signal 2019; 53: 212-223.
Liu CC, Zhang Y, Dai BL, Ma YJ, Zhang Q, Wang Y, et al. Chlorogenic acid prevents inflammatory？responses in IL-1β-stimulated human SW-1353 chondrocytes, a model for osteoarthritis. Mol Med Rep？2017; 16(2): 1369-1375.
Zeng L, Rong XF, Li RH, Wu XY. Icariin inhibits MMP-1, MMP-3 and MMP-13 expression through MAPK？pathways in IL-1β-stimulated SW1353 chondrosarcoma cells. Mol Med Rep 2017; 15(5): 2853-2858.
Yamamoto K, Okano H, Miyagawa W, Visse R, Shitomi Y, Santamaria S, et al. MMP-13 is constitutively？produced in human chondrocytes and co-endocytosed with ADAMTS-5 and TIMP-3 by the endocytic？receptor LRP1. Matrix Biol 2016; 56: 57-73.
Zhang H, Ji L, Yang Y, Wei Y, Zhang X, Gang Y, et al. The therapeutic effects of treadmill exercise on？osteoarthritis in rats by inhibiting the HDAC3/NF-kappaB pathway in vivo and in vitro. Front Physiol 2019;？10: 1060.

상세보기
Sondergaard BC, Schultz N, Madsen SH, Bay-Jensen AC, Kassem M, Karsdal MA. MAPKs are essential？upstream signaling pathways in proteolytic cartilage degradation--divergence in pathways leading to？aggrecanase and MMP-mediated articular cartilage degradation. Osteoarthritis Cartilage 2010; 18(3): 279-288.
Saklatvala J. Inflammatory signaling in cartilage: MAPK and NF-kappaB pathways in chondrocytes and？the use of inhibitors for research into pathogenesis and therapy of osteoarthritis. Curr Drug Targets 2007;？8(2): 305-313.

상세보기
Xu F, Zhao LJ, Liao T, Li ZC, Wang LL, Lin PY, et al. Ononin ameliorates inflammation and cartilage？degradation in rat chondrocytes with IL-1β-induced osteoarthritis by downregulating the MAPK and NF-κB pathways. BMC Complement Med Ther 2022; 22(1): 25.
Mariano A, Bigioni I, Misiti F, Fattorini L, Scotto D'Abusco A, Rodio A. The nutraceuticals as modern key to？achieve erythrocyte oxidative stress fighting in osteoarthritis. Curr Issues Mol Biol 2022; 44(8): 3481-3495.
Abdel-Tawab M, Werz O, Schubert-Zsilavecz M. Boswellia serrata: an overall assessment of in vitro,？preclinical, pharmacokinetic and clinical data. Clin Pharmacokinet 2011; 50(6): 349-369.

상세보기

저자의 다른 논문 :

활용도 분석정보

상세보기

다운로드

내보내기

활용도 Top5 논문

해당 논문의 주제분야에서 활용도가 높은 상위 5개 콘텐츠를 보여줍니다.
더보기 버튼을 클릭하시면 더 많은 관련자료를 살펴볼 수 있습니다.

표제어: PCR

동의어: Packet Collision Rate

용어 설명 출처 목록 (6)

용어 설명: PCR은 세균 특이성이 있는 primer를 이용하여 적은 수의 세균이 있을지라도 쉽게 검출할 수 있는 유용한 방법이며, 이를 이용하여 구강 내 치면세균막이나 타액에서 직접 세균을 검출할 수 있게 되었다[8].

내보내기 구분	파일저장 인쇄 메일전송
구성항목	기본정보 상세정보 관리번호, 논문명, 저널/프로시딩명, 저자 , 발행년, 권, 호, 시작페이지, 끝페이지, 발행기관 관리번호, 논문명, 대등논문명, 저자 , 저널/프로시딩명, 발행기관, 발행년, 발행언어, 권, 호, 시작페이지, 끝페이지, ISBN, ISSN, 주제분야, 키워드, 초록(한글), 초록(영문), 저자(소속기관)
저장형식	Text(ASCII format) Excel format RefWorks Direct Export RIS format (for Reference Manager, ProCite, EndNote), Scholar's Aids, Mendeley
메일정보	받는사람 (필수) @ 보내는사람 (선택) @ 제목 내용 KISTI 검색결과 이메일 서비스
안내	총 건의 자료가 검색되었습니다. 다운받으실 자료의 인덱스를 입력하세요. (1-10,000) 검색결과의 순서대로 최대 10,000건 까지 다운로드가 가능합니다. 데이타가 많을 경우 속도가 느려질 수 있습니다.(최대 2~3분 소요) 다운로드 파일은 UTF-8 형태로 저장됩니다. 파일의 내용이 제대로 보이지 않을실 때는 웹브라우저 상단의 보기 -> 인코딩 -> 자동선택 여부를 확인하십시오. ~ Text(ASCII format) Excel format

연합인증