[논문]Anti-osteoarthritis Effects of the Combination of Boswellia serrata, Curcuma longa, and Terminalia chebula Extracts in Interleukin-1β-stimulated Human Articular Chondrocytes

Kim, Hae Lim; Min, Daeun; Lee, Dong-Ryung; Lee, Sung-Kwon; Choi, Bong-Keun; Yang, Seung Hwan

doi:10.15188/kjopp.2022.04.36.2.79

Anti-osteoarthritis Effects of the Combination of Boswellia serrata, Curcuma longa, and Terminalia chebula Extracts in Interleukin-1β-stimulated Human Articular Chondrocytes 원문보기

동의생리병리학회지 = Journal of physiology & pathology in Korean Medicine, v.36 no.2, 2022년, pp.79 - 87

Kim, Hae Lim (Department of Biotechnology, Chonnam National University) , Min, Daeun (NUON Co., Ltd) , Lee, Dong-Ryung (NUON Co., Ltd) , Lee, Sung-Kwon (NUON Co., Ltd) , Choi, Bong-Keun (NUON Co., Ltd) , Yang, Seung Hwan (Department of Biotechnology, Chonnam National University)

Abstract ▼ AI-Helper

In this study, extracts of Boswellia serrata gum resin, Curcuma longa rhizome, and Terminalia chebula fruit were combined in different ratios, and their anti-osteoarthritis effects were compared to determine which combination had the best synergistic effect. B. serrata, C. longa, and T. chebula extracts in a 2:1:2 ratio exhibited higher antioxidative activity in scavenging DPPH radicals than did the individual extracts alone or the other extract combinations. Additionally, the 2:1:2 combination significantly improved the levels of enzymatic antioxidants and antioxidant-related proteins. Moreover, this same combination ratio decreased the protein levels of matrix metalloproteinase (MMP) 3 and MMP13 in interleukin-1β-stimulated human articular chondrocytes (HCHs) and increased those of aggrecan and collagen type II alpha 1 chain (COL2A1). Analysis of the underlying mechanisms revealed that the 2:1:2 combination significantly inhibited the phosphorylation of nuclear factor kappa B (NF-κB) p65, extracellular regulated protein kinase (ERK), and p38 mitogen-activated protein kinase (MAPK). Therefore, the 2:1:2 combination of these three plant extracts has the best potential for use as an effective dietary supplement for improving joint health compared with the individual extracts and their other combination ratios.

주제어

표/그림 (7)

표 Table 1. Combination ratios of Boswellia serrata gum resin extract (BSE): Curcuma longa extract (CLE): Terminalia chebula extract (TCE) (No. 4-7), and individual extracts (No. 1-3).
그림 Fig. 1. DPPH radical-scavenging activities of the individual B. serrata gum resin, C. longa, and T. chebula extracts alone or in various combination ratios. All values are expressed as the mean ± standard deviation (n = 3).
그림 Fig. 2. Effects of individual B. serrata gum resin, C. longa, and T. chebula extracts alone or in various combinations on human articular chondrocytes (HCHs) viability. The cells were treated with or without IL-1 β and samples, following which their viability was evaluated using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Data are presented as the mean ± standard deviation (n = 3).
그림 Fig. 3. Effects of the individual B. serrata gum resin, C. longa, and T. chebula extracts alone or in various combinations on antioxidant-related protein expression in IL-1β-stimulated HCHs. The cells were treated with IL-1β (10 ng/mL) alone or IL-1β plus the various extracts (50 μg/mL) for 24h. The levels of the target proteins were analyzed using the western blot assay and quantified using the ImageJ program. Data are presented as the mean ± standard deviation (n = 3). #P < 0.05, ##P < 0.01, and ###P < 0.001 compared with the vehicle control group. *P < 0.05, **P < 0.01, and ***P < 0.001 compared with the IL-1β-treated control group.
그림 Fig. 5. Effects of the individual B. serrata gum resin, C. longa, and T. chebula extracts alone or the 2:1:2 combination on the NF-κB signaling pathway in IL-1β-stimulated HCHs. The cells were treated with IL-1β (10 ng/mL) alone or IL-1β plus the various extracts (50 μg/mL) for 15 min. The target protein levels were analyzed using (A) p-p65 immunofluorescence staining and (B) the western blot assay and quantified using the ImageJ program. Data are presented as the mean ± standard deviation (n = 3). ###P < 0.001 compared with the vehicle control group. ***P < 0.001 compared with the IL-1β-treated control group.
그림 Fig. 4. Effects of the individual B. serrata gum resin, C. longa, and T. chebula extracts alone or in various combinations on extracellular matrix degradation-related protein expression in IL-1β-stimulated HCHs. The cells were treated with IL-1β (10 ng/mL) alone or IL-1β plus the various extracts (50 μg/mL). (A) MMP3, MMP13, aggrecan, and COL2A1 protein levels, as analyzed using the western blot assay. The data were quantified using the ImageJ program. Data are presented as the mean ± standard deviation (n = 3). ##P < 0.01, and ###P < 0.001 compared with the vehicle control group. *P < 0.05, **P < 0.01, and ***P < 0.001 compared with the IL-1β-treated control group. (B) Aggrecan expression level, as determined by safranin O staining.
그림 Fig. 6. Effects of the individual B. serrata gum resin, C. longa, and T. chebula extracts alone or the 2:1:2 combination on the MAPK signaling pathway in IL-1β-stimulated HCHs. The cells were treated with IL-1β (10 ng/mL) alone or IL-1β plus the various extracts (50 μg/mL) for 15 min. The target protein levels were analyzed using the western blot assay and quantified using the ImageJ program. Data are presented as the mean ± standard deviation (n = 3). ##P < 0.01 and ###P < 0.001 compared with the vehicle control group. *P < 0.05, **P < 0.01, and ***P < 0.001 compared with the IL-1β-treated control group.

참고문헌 (38)

Lane NE, Shidara K, Wise BL. Osteoarthritis year in review 2016: Clinical Osteoarthr. Cartil 2017;25(2):209-15.
Haroyan A, Mukuchyan V, Mkrtchyan N, Minasyan N, Gasparyan S, Sargsyan A, et al. Efficacy and safety of curcumin and its combination with boswellic acid in osteoarthritis: a comparative, randomized, double-blind, placebo-controlled study. BMC Complement Altern Med. 2018;18(1):1-16.
Olivotto E, Otero M, Marcu KB. Pathophysiology of osteoarthritis: canonical NF-κB/IKKβ-dependent and kinase-independent effects of IKKα in cartilage degradation and chondrocyte differentiation. RMD Open. 2015;1(Suppl 1):e000061.
Van der Kraan PM, Van den Berg WB. Chondrocyte hypertrophy and osteoarthritis: Role in initiation and progression of cartilage degeneration? Osteoarthr Cartil. 2012;20(3):223-32.

상세보기
Dreier R. Hypertrophic differentiation of chondrocytes in osteoarthritis: The developmental aspect of degenerative joint disorders. Arthritis Res Ther. 2010;12(5):216.

상세보기
Goldring SR, Goldring MB. The role of cytokines in cartilage matrix degeneration in osteoarthritis. Clin Orthop Relat Res. 2004;427:s27-s36.
Kelwick R, Desanlis I, Wheeler GN, Edwards DR. The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) family. Genome Biol. 2015;16(1):113.

상세보기
Goldring MB, Otero M. Inflammation in osteoarthritis. Curr Opin Rheumatol. 2011;23(5):471.

상세보기
Santangelo K, Nuovo GJ, Bertone AL. In vivo reduction or blockade of interleukin-1β in primary osteoarthritis influences expression of mediators implicated in pathogenesis. Osteoarthr Cartil. 2012; 20(12):1610-8.
Kimmatkar N, Thawani V, Hingorani L, Khiyani R. Efficacy and tolerability of Boswellia serrata extract in treatment of osteoarthritis of knee-a randomized double-blind placebo-controlled trial. Phytomedicine. 2003;10(1):3-7.

상세보기
Daily JW, Yang M, Park S. Efficacy of Turmeric Extracts and Curcumin for Alleviating the Symptoms of Joint Arthritis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. J Med Food. 2016;19(8):717-29.
Seo JB, Jeong JY, Park JY, Jun EM, Lee SI, Choe SS, et al. Anti-Arthritic and Analgesic Effect of NDI10218, a Standardized Extract of Terminalia chebula, on Arthritis and Pain Model. Biomol Ther. 2012; 20(1):104-12.
Goel A, Kunnumakkara AB, Aggarwal BB. Curcumin as ''Curecumin'': From kitchen to clinic. Biochem Pharmacol. 2008;75(4):787-809.

상세보기
Bag A, Bhattacharyya SK, Chattopadhyay RR. The development of Terminalia chebula Retz. (Combretaceae) in clinical research. Asian Pac J Trop Biomed. 2013;3(3):244-52.

상세보기
Grover AK, Samson SE. Benefits of antioxidant supplements for knee osteoarthritis: Rationale and reality. Nutr J. 2016;15(1):1-13.

상세보기
Kim HL, Lee HJ, Lee DR, Choi BK, Yang SH. Anti-osteoarthritic Effects of an Herbal Composition LI73014F2 on Interleukin-1β-induced Primary Human Articular Chondrocytes. Molecules. 2020;25(9):2033.
Kim HL, Lee HJ, Lee DR, Choi BK, Yang SH. Herbal Composition LI73014F2 Alleviates Articular Cartilage Damage and Inflammatory Response in Monosodium Iodoacetate-Induced Osteoarthritis in Rats. Molecules. 2020;25(22):5467.

상세보기
Lepetsos P, Papavassiliou AG. ROS/oxidative stress signaling in osteoarthritis. Biochim Biophys Acta 2016;1862(4):576-91.
Li D, Wang W, Xie G. Reactive oxygen species: the 2-edged sword of osteoarthritis. Am J Med Sci. 2012;344(6):486-90.

상세보기
Henrotin Y, Kurz B, Aigner T. Oxygen and reactive oxygen species in cartilage degradation: friends or foes? Osteoarthr Cartil. 2005;13(8):643-54.

상세보기
Regan EA, Bowler RP, Crapo JD. Joint fluid antioxidants are decreased in osteoarthritic joints compared to joints with macroscopically intact cartilage and subacute injury. Osteoarthr Cartil. 2008;16(4):515-21.

상세보기
Sharma A, Upadhyay J, Jain A, Kharya MD, Namdeo A, Mahadik KR. Antioxidant activity of aqueous extract of Boswellia serrata. J Chem Biol Phys Sci. 2011;1:60-71.
Tanvir EM, Hossen M, Hossain M, Afroz R, Gan SH, Khalil M, et al. Antioxidant properties of popular turmeric (Curcuma longa) varieties from Bangladesh. J Food Qual. 2017;2017:1-8.

상세보기
Hazra B, Sarkar R, Biswas S, Mandal N. Comparative study of the antioxidant and reactive oxygen species scavenging properties in the extracts of the fruits of Terminalia chebula, Terminalia belerica and Emblica officinalis. BMC Complement Altern Med. 2010;10(1):20.
Kulkarni RR, Patki PS, Jog VP, Gandage SG, Patwardhan B. Treatment of osteoarthritis with a herbomineral formulation: a double-blind, placebo-controlled, crossover study. J Ethnopharmacol. 1991;33(1-2):91-5.
Lekshmi PC, Arimboor R, Raghu KG, Menon AN. Turmerin, the antioxidant protein from turmeric (Curcuma longa) exhibits antihyperglycaemic effects. Nat Prod Res. 2012;26(17):1654-58.

상세보기
Bag A, Kumar Bhattacharyya S, Kumar Pal N, Ranjan Chattopadhyay R. Anti-inflammatory, anti-lipid peroxidative, antioxidant and membrane stabilizing activities of hydroalcoholic extract of Terminalia chebula fruits. Pharm Biol. 2013;51(12):1515-20.

상세보기
Li B, Jiang T, Liu H. Andrographolide protects chondrocytes from oxidative stress injury by activation of the Keap1-Nrf2-Are signaling pathway. J Cell Physiol. 2018;234(1):561-71.
Chen JJ, Huang JF, Du WX, Tong PJ. Expression and significance of MMP3 in synovium of knee joint at different stage in osteoarthritis patients. Asian Pac J Trop Med. 2014;7(4):297-300.

상세보기
Li NG, Shi ZH, Tang YP, Wang ZJ, Song SL, Qian LH, et al. New hope for the treatment of osteoarthritis through selective inhibition of MMP-13. Curr Med Chem. 2011;18(7):977-1001.

상세보기
Wu YS, Hu YY, Yang RF, Wang Z, Wei YY. The matrix metalloproteinases as pharmacological target in osteoarthritis: Statins may be of therapeutic benefit. Med Hypotheses. 2007;69(3):557-9.

상세보기
Mueller MB, Tuan RS. Anabolic/catabolic balance in pathogenesis of osteoarthritis: Identifying molecular targets. PM R. 2011;3(6):s3-s11.

상세보기
Simkin PA. Rethinking the physiology of articular cartilage. Clin Rheumatol. 2009;15(5):260-3.
Fan Z, Bau B, Yang H, Aigner T. IL-1 beta induction of IL-6 and LIF in normal articular human chondrocytes involves the ERK, p38 and NF kappa B signaling pathways. Cytokine 2004;28(1):17-24.
Saklatvala J. Inflammatory signaling in cartilage: MAPK and NF-kappa B pathways in chondrocytes and the use of inhibitors for research into pathogenesis and therapy of osteoarthritis. Curr Drug Targets. 2008;8(2):305-13.
Herrero-Beaumont G, Perez-Baos S, Sanchez-Pernaute O, Roman-Blas JA, Lamuedra A, Largo R. Targeting chronic innate inflammatory pathways, the main road to prevention of osteoarthritis progression. Biochem Pharmacol. 2019;165:24-32.

상세보기
Yang DW, Qian GB, Jiang MJ, Wang P, Wang KZ. Inhibition of microRNA-495 suppresses chondrocyte apoptosis through activation of the NF-kappaB signaling pathway by regulating CCL4 in osteoarthritis. Gene Ther. 2019;26(6):217-29.
Abramson SB. Osteoarthritis and nitric oxide. Osteoarthr Cartil. 2008;16:s15-s20.2004;324(1):432-9.

상세보기

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