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BMC Complementary Medicine and Therapies
Published in: BMC Complementary Medicine and Therapies 1/2019

Open Access 01-12-2019 | Osteoarthrosis | Research article

Cartilage protective and anti-analgesic effects of ALM16 on monosodium iodoacetate induced osteoarthritis in rats

Authors: Doo Jin Choi, Soo-Im Choi, Bo-Ram Choi, Young-Seob Lee, Dae Young Lee, Geum Soog Kim

Published in: BMC Complementary Medicine and Therapies | Issue 1/2019

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Abstract

Background

Osteoarthritis (OA) is an age-related joint disease with characteristics that involve the progressive degradation of articular cartilage and resulting chronic pain. Previously, we reported that Astragalus membranaceus and Lithospermum erythrorhizon showed significant anti-inflammatory and anti-osteoarthritis activities. The objective of this study was to examine the protective effects of ALM16, a new herbal mixture (7:3) of ethanol extracts of A. membranaceus and L. erythrorhizon, against OA in in vitro and in vivo models.

Methods

The levels of matrix metalloproteinase (MMP)-1, −3 and − 13 and glycosaminoglycan (GAG) in interleukin (IL)-1β or ALM16 treated SW1353 cells were determined using an enzyme-linked immunosorbent and quantitative kit, respectively. In vivo, the anti-analgesic and anti-inflammatory activities of ALM16 were assessed via the acetic acid-induced writhing response and in a carrageenan-induced paw edema model in ICR mice, respectively. In addition, the chondroprotective effects of ALM16 were analyzed using a single-intra-articular injection of monosodium iodoacetate (MIA) in the right knee joint of Wister/ST rat. All samples were orally administered daily for 2 weeks starting 1 week after the MIA injection. The paw withdrawal threshold (PWT) in MIA-injected rats was measured by the von Frey test using the up-down method. Histopathological changes of the cartilage in OA rats were analyzed by hematoxylin and eosin (H&E) staining.

Results

ALM16 remarkably reduced the GAG degradation and MMP levels in IL-1β treated SW1353 cells. ALM16 markedly decreased the thickness of the paw edema and writhing response in a dose-dependent manner in mice. In the MIA-induced OA rat model, ALM16 significantly reduced the PWT compared to the control group. In particular, from histological observations, ALM16 showed clear improvement of OA lesions, such as the loss of necrotic chondrocytes and cartilage erosion of more than 200 mg/kg b.w., comparable to or better than a positive drug control (JOINS™, 200 mg/kg) in the cartilage of MIA-OA rats.

Conclusions

Our results demonstrate that ALM16 has a strong chondroprotective effect against the OA model in vitro and in vivo, likely attributed to its anti-inflammatory activity and inhibition of MMP production.
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Literature
1.
Aigner T, McKenna L. Molecular pathology and pathobiology of osteoarthritic cartilage. Cell Mol Life Sci. 2002;59(1):5–18.PubMedCrossRef
2.
Park JS, Lee HJ, Lee DY, Jo HS, Jeong JH, Kim DH, Nam DC, Lee CJ, Hwang SC. Chondroprotective effects of wogonin in experimental models of osteoarthritis in vitro and in vivo. Biomol Ther. 2015;23(5):442–8.CrossRef
3.
Mandelbaum B, Waddell D. Etiology and pathophysiology of osteoarthritis. Orthopedics. 2005;28(2 suppl):s207–14.PubMed
4.
Braza-Boils A, Ferrandiz ML, Terencio MC, Alcaraz MJ. Analysis of early biochemical markers and regulation by tin protoporphyrin IX in a model of spontaneous osteoarthritis. Exp Gerontol. 2012;47(5):406–9.PubMedCrossRef
5.
Tanaka S, Hamanishi C, Kikuchi H, Fukuda K. Factors related to degradation of articular cartilage in osteoarthritis: a review. Semin Arthritis Rheum. 1998;27(6):392–9.PubMedCrossRef
6.
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.PubMedCrossRef
7.
8.
Murphy G, Knäuper V, Atkinson S, Butler G, English W, Hutton M, Stracke J, Clark I. Matrix metalloproteinases in arthritic disease. Arthritis Res. 2002;4(3 suppl):S39–49.PubMedPubMedCentralCrossRef
9.
Li NG, Shi ZH, Tang YP, Wang ZJ, Song SL, Qian LH, Qian DW, Duan JA. New hope for the treatment of osteoarthritis through selective inhibition of MMP-13. Curr Med Chem. 2011;18(7):977–1001.PubMedCrossRef
10.
Fu J, Wang Z, Huang L, Zheng S, Wang D, Chen S, Zhang H, Yang S. Review of the botanical characteristics, phytochemistry, and pharmacology of Astragalus membranaceus (Huangqi). Phytother Res. 2014;28(9):1275–83.PubMedCrossRef
11.
Bedir E, Pugh N, Calis I, Pasco DS, Khan IA. Immunostimulatory effects of cycloartane-type triterpene glycosides from astragalus species. Biol Pharm Bull. 2000;23(7):834–7.PubMedCrossRef
12.
Chan JY, Lam FC, Leung PC, Che CT, Fung KP. Antihyperglycemic and antioxidative effects of an herbal formulation of Radix Astragali, Radix Codonopsis and Cortex Lycii in a mouse model of type 2 diabetes mellitus. Phytother Res. 2009;23(5):658–65.PubMedCrossRef
13.
Shi R, He L, Hu Y, Yi N, Weng S, Cao Y. The regulatory action of Radix Astragali on M-cholinergic receptor of the brain of senile rats. J Tradit Chin Med. 2001;21(3):232–5.PubMed
14.
Cho WC, Leung KN. In vitro and in vivo anti-tumor effects of Astragalus membranaceus. Cancer Lett. 2007;252(1):43–54.PubMedCrossRef
15.
Nigorikawa K, Yoshikawa K, Sasaki T, Iida E, Tsukamoto M, Murakami H, Maehama T, Hazeki K, Hazeki O. A naphthoquinone derivative, shikonin, has insulin-like actions by inhibiting both phosphatase and tensin homolog deleted on chromosome 10 and tyrosine phosphatases K. Mol Pharmacol. 2006;70(3):1143–9.PubMedCrossRef
16.
Choi YH, Kim GS, Choi JH, Jin SW, Kim HG, Han Y, Lee DY, Choi SI, Kim SY, Ahn YS, Lee KY, Jeong HG. Ethanol extract of Lithospermum erythrorhizon Sieb. et Zucc. promotes osteoblastogenesis through the regulation of Runx2 and Osterix. Int J Mol Med. 2016;38(2):610–8.PubMedCrossRef
17.
Han J, Weng X, Bi K. Antioxidants from a Chinese medicinal herb-Lithospermum erythrorhizon. Food Chem. 2008;106(1):2–10.CrossRef
18.
Staniforth V, Wang SY, Shyur LF, Yang NS. Shikonins, phytocompounds from Lithospermum erythrorhizon, inhibit the transcriptional activation of human tumor necrosis factor α promoter in vivo. J Biol Chem. 2004;279(7):5877–85.PubMedCrossRef
19.
Andújar I, Recio MC, Giner RM, Ríos JL. Traditional chinese medicine remedy to jury: the pharmacological basis for the use of shikonin as an anticancer therapy. Curr Med Chem. 2013;20(23):2892–8.PubMedCrossRef
20.
Choi SI, Park SR, Heo TR. Inhibitory effect of Astragali radix on matrix degradation in human articular cartilage. J Microbiol Biotechnol. 2005;15(6):1258–66.
21.
Choi SI, Heo TR, Min BH, Cui JH, Choi BH, Park SR. Alleviation of osteoarthritis by calycosin-7-O-beta-D-glucopyranoside (CG) isolated from Astragali radix (AR) in rabbit osteoarthritis (OA) model. Osteoarthr Cartil. 2007;15(9):1086–92.PubMedCrossRef
22.
Kim GS, Kim HJ, Lee DY, Choi SM, Lee SE, Noh HJ, Choi JG, Choi SI. Effects of supercritical fluid extract, shikonin and acetylshikonin from Lithospermum erythrorhizon on chondrocytes and MIA-induced osteoarthritis in rats. Korean J Medicinal Crop Sci. 2013;21(6):466–73.CrossRef
23.
Mok SS, Masuda K, Hauselmann HJ, Aydelotte MB, Thonar EJ. Aggrecan synthesized by mature bovine chondrocytes suspended in alginate; identification of two distinct metabolic matrix pools. J Biol Chem. 1994;269(52):33021–7.PubMed
24.
Mishra D, Ghosh G, Kumar PS, Panda PK. An experimental study of analgesic activity of selective COX-2 inhibitor with conventional NSAIDs. Asian J Pharm Clin Res. 2011;4(1):78–81.
25.
Obiri DD, Osafo N. Aqueous ethanol extract of the fruit of Xylopia aethiopica (Annonaceae) exhibits anti-anaphylactic and anti-inflammatory actions in mice. J Ethnopharmacol. 2013;148(3):940–5.PubMedCrossRef
26.
Bove SE, Calcaterra SL, Brooker RM, Huber CM, Guzman RE, Juneau PL, Schrier DJ, Kilgore KS. Weight bearing as a measure of disease progression and efficacy of anti-inflammatory compounds in a model of monosodium iodoacetate-induced osteoarthritis. Osteoarthr Cartil. 2003;11(11):821–30.PubMedCrossRef
27.
Chaplan SR, Bach FW, Pogrel JW, Chung JM, Yaksh TL. Quantitative assessment of tactile allodynia in the rat paw. J Neurosci Methods. 1994;53(1):55–63.PubMedCrossRef
28.
Guzman RE, Evans MG, Bove S, Morenko B, Kilgore K. Mono-iodoacetate-induced histologic changes in subchondral bone and articular cartilage of rat femorotibial joints: an animal model of osteoarthritis. Toxicol Pathol. 2003;31(6):619–24.PubMedCrossRef
29.
Huh JE, Kim SJ, Kang JW, Nam DW, Choi DY, Park DS, Lee JD. The standardized BHH10 extract, a combination of Astragalus membranaceus, Cinnamomum cassia, and Phellodendron amurense, reverses bone mass and metabolism in a rat model of postmenopausal osteoporosis. Phytother Res. 2015;29(1):30–9.PubMedCrossRef
30.
Matkovic Z, Zivkovic V, Korica M, Plavec D, Pecanic S, Tudoric N. Efficacy and safety of Astragalus membranaceus in the treatment of patients with seasonal allergic rhinitis. Phytother Res. 2010;24(2):175–81.PubMed
31.
32.
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.PubMedCrossRef
33.
Takahashi K, Goomer RS, Harwood F, Kubo T, Hirasawa Y, Amiel D. The effects of hyaluronan on matrix metalloproteinase-3 (MMP-3), interleukin-1β (IL-1β), and tissue inhibitor of metalloproteinase-1 (TIMP-1) gene expression during the development of osteoarthritis. Osteoarthr Cartil. 1999;7(2):182–90.PubMedCrossRef
34.
Wang M, Sampson ER, Jin H, Li J, Ke QH, Im HJ, Chen D. MMP13 is a critical target gene during the progression of osteoarthritis. Arthritis Res Ther. 2013;15(1):R5.PubMedPubMedCentralCrossRef
35.
Gebauer M, Saas J, Sohler F, Haag J, Soder S, Pieper M, Bartnik E, Beninga J, Zimmer R, Aigner T. Comparison of the chondrosarcoma cell line SW1353 with primary human adult articular chondrocytes with regard to their gene expression profile and reactivity to IL-1β. Osteoarthr Cartil. 2005;13(8):697–708.PubMedCrossRef
36.
Choi DJ, Choi BR, Lee DY, Choi SI, Lee YS, Kim GS. Inhibitory Effect of Mixed Extracts Obtained from Astragali Radix and Lithospermi Radix on Matrix Metalloproteinases in IL-1β-induced SW1353 Cells and Quantitative Analysis of Active Compounds. Korean J Medicinal Crop Sci. 2019;27(4):247–58.CrossRef
37.
Liu XY, Xu L, Wang Y, Li JX, Zhang Y, Zhang C, Wang SS, Zhang XM. Protective effects of total flavonoids of Astragalus against adjuvant-induced arthritis in rats by regulating OPG/RANKL/NF-κB pathway. Int Immunopharmacol. 2017;44:105–14.PubMedCrossRef
38.
Liu X, Chen R, Shang Y, Jiao B, Huang C. Lithospermic acid as a novel xanthine oxidase inhibitor has anti-inflammatory and hypouricemic effects in rats. Chem Biol Interact. 2008;176(2-3):137–42.PubMedCrossRef
39.
Yoo HG, Lee BH, Kim W, Lee JS, Kim GH, Chun OK, Koo SI, Kim DO. Lithospermum erythrorhizon extract protects keratinocytes and fibroblasts against oxidative stress. J Med Food. 2014;17(11):1189–96.PubMedCrossRef
40.
Wood DD, Ihrie EJ, Dinarello CA, Cohen PL. Isolation of an interleukin-1-like factor from human joint effusions. Arthritis Rheum. 1983;26(8):975–83.PubMedCrossRef
41.
Moon MH, Jeong JK, Lee YJ, Seol JW, Park SY. Sphingosine-1-phosphate inhibits interleukin-1β-induced inflammation in human articular chondrocytes. Int J Mol Med. 2012;30(6):1451–8.PubMedCrossRef
42.
Lee JH, Shehzad O, Ko SK, Kim YS, Kim HP. Matrix metalloproteinase-13 downregulation and potential cartilage protective action of the Korean Red Ginseng preparation. J Ginseng Res. 2015;39(1):54–60.PubMedCrossRef
43.
Bighetti EJ, Hiruma-Lima CA, Gracioso JS, Brito AR. Anti-inflammatory and antinociceptive effects in rodents of the essential oil of Croton cajucara Benth. J Pharm Pharmacol. 1999;51(12):1447–53.PubMedCrossRef
44.
Gordo AC, Walker C, Armada B, Zhou D. Efficacy of celecoxib versus ibuprofen for the treatment of patients with osteoarthritis of the knee: A randomized double-blind, non-inferiority trial. J Int Med Res. 2017;45(1):59–74.PubMedPubMedCentralCrossRef
45.
Jeong JH, Moon SJ, Jhun JY, Yang EJ, Cho ML, Min JK. Eupatilin exerts antinociceptive and chondroprotective properties in a rat model of osteoarthritis by downregulating oxidative damage and catabolic activity in chondrocytes. PLoS One. 2015;10(6):e0130882.PubMedPubMedCentralCrossRef
46.
Posadas I, Bucci M, Roviezzo F, Rossi A, Parente L, Sautebin L, Cirino G. Carrageenan-induced mouse paw oedema is biphasic, age-weight dependent and displays differential nitric oxide cyclooxygenase-2 expression. Br J Pharmacol. 2004;142(2):331–8.PubMedPubMedCentralCrossRef
47.
Gupta AK, Parasar D, Sagar A, Choudhary V, Chopra BS, Garg R, Ashish, Khatri N. Analgesic and anti-inflammatory properties of gelsolin in acetic acid induced writhing, tail immersion and carrageenan induced paw edema in mice. PLoS One. 2015;10(9):e0135558.PubMedPubMedCentralCrossRef
48.
Mondal H, Saha S, Awang K, Hossain H, Ablat A, Islam MK, Jahan IA, Sadhu SK, Hossain MG, Shilpi JA, Uddin SJ. Central-stimulating and analgesic activity of the ethanolic extract of Alternanthera sessilis in mice. BMC Complement Altern Med. 2014;14:398.PubMedPubMedCentralCrossRef
49.
Kim J, Yang S, Choi CY. The Evaluation of the effect of herbal extract on osteoarthritis: In vitro and in vivo study. Prev Nutr Food Sci. 2016;21(4):310–6.PubMedPubMedCentralCrossRef
50.
Bahtiar A, Nurazizah M, Roselina T, Tambunan AP, Arsianti A. Ethanolic extracts of babandotan leaves (Ageratum Conyzoides L.) prevents inflammation and proteoglycan degradation by inhibiting TNF-alpha and MMP-9 on osteoarthritis rats induced by monosodium iodoacetate. Asian Pac J Trop Med. 2017;10(3):270–7.PubMedCrossRef
51.
Orita S, Ishikawa T, Miyagi M, Ochiai N, Inoue G, Eguchi Y, Kamoda H, Arai G, Toyone T, Aoki Y, Kubo T, Takahashi K, Ohtori S. Pain-related sensory innervation in monosodium iodoacetate-induced osteoarthritis in rat knees that gradually develops neuronal injury in addition to inflammatory pain. BMC Musculoskelet Disord. 2011;12:134.PubMedPubMedCentralCrossRef
52.
Choi JH, Choi JH, Kim DY, Yoon JH, Youn HY, Yi JB, Rhee HI, Ryu KH, Jung K, Han CK, Kwak WJ, Cho YB. Effects of SKI 306X, a new herbal agent, on proteoglycan degradation in cartilage explant culture and collagenase-induced rabbit osteoarthritis model. Osteoarthr Cartil. 2002;10(6):471–8.PubMedCrossRef
Metadata
Title
Cartilage protective and anti-analgesic effects of ALM16 on monosodium iodoacetate induced osteoarthritis in rats
Authors
Doo Jin Choi
Soo-Im Choi
Bo-Ram Choi
Young-Seob Lee
Dae Young Lee
Geum Soog Kim
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2019
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-019-2746-7

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