Objective

nnp

Neurology, Neuropsychiatry, Psychosomatics

Неврология, нейропсихиатрия, психосоматика

2074-27112310-1342

"IMA-Press", LLC

10.14412/2074-2711-2018-2-38-44

nnp-883

Research Article

ORIGINAL INVESTIGATIONS

ОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯ И МЕТОДИКИ

Molecular mechanisms of action of glucosamine sulfate in the treatment of degenerative-dystrophic diseases of the joints and spine: results of proteomic analysis

Молекулярные механизмы глюкозамина сульфата при лечении дегенеративно-дистрофических заболеваний суставов и позвоночника: результаты протеомного анализа

Громова

О. А.

Gromova

O. A.

Контакты: Ольга Алексеевна Громова

119333, Москва, ул. Вавилова, 40

Contact: Olga Alekseevna Gromova

40, Vavilov St., Moscow 119333

unesco.gromova@gmail.com

Торшин

И. Ю.

Torshin

I. Yu.

Лила

А. М.

Lila

A. M.

115522, Москва, Каширское шоссе, 34А

Громов

А. Н.

Gromov

A. N.

Федеральный исследовательский центр «Информатика и управление» Российской академии наук, Институт фармакоинформатикиРоссияInstitute of Pharmacoinformatics, Federal Research Center «Informatics and Control», Russian Academy of SciencesRussian Federation

ФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой»РоссияV.A. Nasonova Research Institute of RheumatologyRussian Federation

2018

24062018

1023844

2018

Громова О.А., Торшин И.Ю., Лила А.М., Громов А.Н.

Gromova O.A., Torshin I.Y., Lila A.M., Gromov A.N.

Данная работа распространяется под лицензией Creative Commons Attribution 4.0.

This work is licensed under a Creative Commons Attribution 4.0 License.

https://nnp.ima-press.net/nnp/article/view/883

Objective

Objective: to carry out a systems analysis of the molecular mechanisms of action of the chondroprotector Sustaguard® Arthro based on the microcrystalline pharmaceutical substance glucosamine sulfate (GS) manufactured by Bioiberica S.A.U. (Spain).

Material and methods

Material and methods. The systems analysis of the molecular mechanisms was based on literature data and proteomic databases through machine learning systems.

Results and discussion

Results and discussion. GS interacts with the receptors CD44, TLR4, and ICAM1 on the surface of chondrocytes, inhibits the proinflammatory transcription factor NF-κB and the cytokine signaling pathway JAK/STAT, and regulates the synthesis of IgA, the migration of leukocytes, and the activity of hematopoietin and interferon receptors.

Conclusion

Conclusion. The findings indicate that there are molecular mechanisms of synergism between glucosamine and nonsteroidal anti-inflammatory drugs in the therapy of cartilage tissue pathology.

Цель исследования – систематический анализ молекулярных механизмов действия хондропротектора Сустагард® Артро, производимого на основе микрокристаллической фармацевтической субстанции глюкозамина сульфата – ГС (Биоиберика, С.А.У., Испания).

Материал и методы

Материал и методы. Систематический анализ молекулярных механизмов на основе данных литературы и протеомных баз данных посредством систем машинного обучения.

Результаты и обсуждение

Результаты и обсуждение. ГС взаимодействует с рецепторами CD44, TLR4 и ICAM1 на поверхности хондроцитов, ингибирует провоспалительный транскрипционный фактор NF-кВ, цитокиновый сигнальный путь JAK/STAT, регулирует синтез IgA, миграцию лейкоцитов, активность рецепторов гематопоэтина и интерферонов.

Заключение

Заключение. Полученные результаты указывают на молекулярные механизмы синергизма между глюкозамином и нестероидными противовоспалительными препаратами в терапии патологии хрящевой соединительной ткани.

хондропротекциятаргетные белкимолекулярные механизмыпероральный приемСустагард® Артро

chondroprotectiontarget proteinsmolecular mechanismsoral administrationSustaguard® Arthro

References1

Zhu X, Wu D, Sang L, et al. Comparative effectiveness of glucosamine, chondroitin, acetaminophen or celecoxib for the treatment of knee and/or hip osteoarthritis: a network meta-analysis. Clin Exp Rheumatol. 2018 Jan 31. [Epub ahead of print].

Lu C, Wang L, Zhu X, et al. Glucosamine promotes osteoblast proliferation by modulating autophagy via the mammalian target of rapamycin pathway. Biomed Pharmacother. 2018 Mar;99:271-277. doi: 10.1016/j.biopha.2018.01.066.

Terencio MC, Ferrandiz ML, Carceller MC, et al. Chondroprotective effects of the combination chondroitin sulfate-glucosamine in a model of osteoarthritis induced by anterior cruciate ligament transection in ovariectomised rats. Biomed Pharmacother. 2016 Apr;79:120-8. doi: 10.1016/j.biopha.2016.02.005.

Torshin IYu. Sensing the change from molecular genetics to personalized medicine. New York: Nova Biomedical Books; 2009.

Papatriantafyllou M. Partnerships in European biomolecular research: the EMBLparadigm. FEBS Lett. 2017 Dec;591(24): 3939-3941. doi: 10.1002/1873-3468.12926. PMID: 29226317

The UniProt Consortium. UniProt: the universal protein knowledgebase. Nucleic Acids Res. 2018 Mar 16;46(5):2699. doi: 10.1093/nar/gky092.

Segura V, Garin-Muga A, Guruceaga E, Corrales FJ. Progress and pitfalls in findingthe 'missing proteins' from the human proteome map. Expert Rev Proteomics. 2017 Jan;14(1):9-14. doi: 10.1080/14789450.2017.1265450.

Volpi N. Anti-inflammatory activity of chondroitin sulphate: new functions from an old natural macromolecule. Inflammopharmacology. 2011 Dec;19(6):299-306. doi: 10.1007/s10787-011-0098-0. Epub 2011 Nov 1.

Kim MM, Mendis E, Rajapakse N, Kim SK. Glucosamine sulfate promotes osteoblastic differentiation of MG-63 cells via anti-inflammatory effect. Bioorg Med Chem Lett. 2007 Apr 1; 17(7):1938-42. Epub 2007 Jan 19.

Largo R, Alvarez-Soria MA, Diez-Ortego I, et al. Glucosamine inhibits IL-1-induced NFB activation in human osteoarthritic chondrocytes. Osteoarthritis Cartilage. 2003 Apr; 11(4):290-8.

Calamia V, Ruiz-Romero C, Rocha B, Fernandez-Puente P, Mateos J, Montell E, Verges J, Blanco FJ. Pharmacoproteomic study of the effects of chondroitin and glucosamine sulfate on human articular chondrocytes. Arthritis Res Ther. 2010;12(4):R138. doi: 10.1186/ar3077. Epub 2010 Jul 13.

Navarro SL, White E, Kantor ED, et al. Randomized trial of glucosamine and chondroitin supplementation on inflammation and oxidative stress biomarkers and plasma proteomics profiles in healthy humans. PLoS One. 2015 Feb 26;10(2):e0117534. doi: 10.1371/journal.pone.0117534. eCollection 2015.

Calamia V, Mateos J, Fernandez-Puente P, et al. A pharmacoproteomic study confirms the synergistic effect of chondroitin sulfate and glucosamine. Sci Rep. 2014 Jun 10;4:5069. doi: 10.1038/srep05069.

Kantor ED, Lampe JW, Navarro SL, et al. Associations between glucosamine and chondroitin supplement use and biomarkers of systemic inflammation. J Altern Complement Med. 2014 Jun;20(6):479-85. doi: 10.1089/acm.2013.0323. Epub 2014 Apr 16.

Kantor ED, Lampe JW, Vaughan TL, et al. Association between use of specialty dietary supplements and C-reactive protein concentrations. Am J Epidemiol. 2012 Dec 1;176(11):1002-13. doi: 10.1093/aje/kws186. Epub 2012 Nov 8.

Bottegoni C, Muzzarelli RA, Giovannini F, Busilacchi A, Gigante A. Oral chondroprotection with nutraceuticals made of chondroitin sulphate plus glucosamine sulphate in osteoarthritis. Carbohydr Polym. 2014;109:126-38.

Lee YH, Woo JH, Choi SJ, Ji JD, Song GG. Effect of glucosamine or chondroitin sulfate on the osteoarthritis progression: a meta-analysis. Rheumatol Int. 2010 Jan;30(3):357-63. doi: 10.1007/s00296-009-0969-5. Epub 2009 Jun 21.

Hochberg MC, Zhan M, Langenberg P. The rate of decline of joint space width in patients with osteoarthritis of the knee: a systematic review and meta-analysis of randomized placebo-controlled trials of chondroitin sulfate. Curr Med Res Opin. 2008 Nov;24(11): 3029-35. doi: 10.1185/03007990802434932 . Epub 2008 Oct 2.

Poolsup N, Suthisisang C, Channark P, Kittikulsuth W. Glucosamine long-term treatment and the progression of knee osteoarthritis: systematic review of randomized controlled trials. Ann Pharmacother. 2005 Jun;39(6):1080-7. Epub 2005 Apr 26.

Wu D, Huang Y, Gu Y, Fan W. Efficacies of different preparations of glucosamine for the treatment of osteoarthritis: a meta-analysis of randomised, double-blind, placebo-controlled trials. Int J Clin Pract. 2013 Jun;67(6):585-94. doi: 10.1111/ijcp.12115.

Gruenwald J, Petzold E, Busch R, et al. Effect of glucosamine sulfate with or without omega-3 fatty acids in patients with osteoarthritis. Adv Ther. 2009 Sep;26(9):858-71. doi: 10.1007/s12325-009-0060-3. Epub 2009 Sep 4.

Borisenko OV, Belen'kii DA. Impact of combined therapy using glucosamine sulfate and anti-inflammatory agent on pain severity in patients with osteoarthritis: prospective, noncontrolled postmarketing study. Klin Med (Mosk). 2013;91(5):65-71.

Hochberg MC, Martel-Pelletier J, Monfort J, et al. Combined chondroitin sulfate and glucosamine for painful knee osteoarthritis: a multicentre, randomised, double-blind, non-inferiority trial versus celecoxib. Ann Rheum Dis. 2016 Jan;75(1):37-44. doi: 10.1136/annrheumdis2014-206792. Epub 2015 Jan 14.

Зоткин ЕГ, Харитонова ТВ, Шкиреева СЮ. Возможность клинического применения хондроитин сульфата для парентерального введения у пациентов с остеоартрозом в гериатрической практике. Успехи геронтологии. 2014;(2):366-75.

Zotkin EG, Kharitonova TV, Shkireeva SYu. Possibility of clinical application of chondroitin sulfate for parenteral administration in patients with osteoarthritis in geriatric practice. Uspekhi gerontologii. 2014;(2): 366-75. (In Russ.).

Haghighat A, Behnia A, Kaviani N, Khorami B. Evaluation of Glucosamine sulfate and Ibuprofen effects in patients with temporomandibular joint osteoarthritis symptom. J Res Pharm Pract. 2013 Jan;2(1):34-9. doi: 10.4103/ 2279-042X.114087.

Damlar I, Esen E, Tatli U. Effects of glucosamine-chondroitin combination on synovial fluid IL-1beta, IL-6, TNF-alpha and PGE2 levels in internal derangements of temporomandibular joint. Med Oral Patol Oral Cir Bucal. 2015 May 1;20(3):e278-83.

Persiani S, Roda E, Rovati LC, et al. Glucosamine oral bioavailability and plasma pharmacokinetics after increasing doses of crystalline glucosamine sulfate in man. Osteoarthritis Cartilage. 2005 Dec;13(12):1041-9.Epub 2005 Sep 13.

Tannis AJ, Barban J, Conquer JA. Effect of glucosamine supplementation on fasting and non-fasting plasma glucose and serum insulin concentrations in healthy individuals. Osteoarthritis Cartilage. 2004 Jun;12(6):506-11.

Palma Dos Reis R, Giacovelli G, Girolami F, et al. Crystalline glucosamine sulfate in the treatment of osteoarthritis: evidence of longterm cardiovascular safety from clinical trials. Open Rheumatol J. 2011;5:69-77. doi: 10.2174/1874312901105010069. Epub 2011 Nov 29.

Chan PS, Caron JP, Rosa GJ, Orth MW. Glucosamine and chondroitin sulfate regulate gene expression and synthesis of nitric oxide and prostaglandin E(2) in articular cartilage explants. Osteoarthritis Cartilage. 2005 May; 13(5):387-94.

Bruyere O, Altman RD, Reginster JY. Efficacy and safety of glucosamine sulfate in the management of osteoarthritis: Evidence from real-life setting trials and surveys. Semin Arthritis Rheum. 2016 Feb;45(4 Suppl):S12-7. doi: 10.1016/j.semarthrit.2015.11.011.

Runhaar J, Deroisy R, van Middelkoop M, et al. The role of diet and exercise and of glucosamine sulfate in the prevention of knee osteoarthritis: Further results from the PRevention of knee Osteoarthritis in Overweight Females (PROOF) study. Semin Arthritis Rheum. 2016 Feb;45(4 Suppl):S42-8. doi: 10.1016/j.semarthrit.2015.11.001.

Спиричев ВБ, Громова ОА. Витамин D и его синергисты. Земский врач. 2012;(2): 33-8.

Spirichev VB, Gromova OA. Vitamin D and its synergists. Zemskii vrach. 2012;(2):33-8. (In Russ.).

Громова ОА, Гоголева ИВ. Селен – впечатляющие итоги и перспективы применения. Трудный пациент. 2007;5(14):25-30. [

Gromova OA, Gogoleva IV. Selenium-impressive results and prospects of application. Trudnyi patsient. 2007;5(14):25-30. (In Russ.).

The authors declare that there are no conflicts of interest present.