α-Lipoic Acid Potentiates the Anti-Inflammatory Activity of Avocado/Soybean Unsaponifiables in Chondrocyte Cultures.
- Journal Article
Summary
This research paper investigates whether a combination of avocado/soybean unsaponifiables (ASU) and α-lipoic acid (LA) can suppress chondrocyte (a type of cell found in healthy cartilage) production of prostaglandin E-2 (PGE), a compound that can cause inflammation and contribute to osteoarthritis.
Research Design and Methods
In the study, chondrocytes from the articular cartilage (the smooth, slippery surface that covers the ends of bones) of equine joints were set up in various conditions:
- In control media with no treatment
- With ASU treatment
- With LA treatment
- With a combination of ASU and LA treatment
These cells then underwent activation with lipopolysaccharide (LPS), interleukin 1β (IL-1β), or hydrogen peroxide (HO) for 24 hours. The liquids around the cells were then tested for the presence of PGE, which reveals the level of inflammation in the cells.
The Nuclear factor-kappa B (NF-κB, a protein complex that controls the transcription of DNA) analyses were performed through the use of immunocytochemistry and Western blot after having been activated with IL-1β for an hour.
Results
The results showed that activation with LPS, IL-1β, or HO significantly increased PGE production, and hence inflammation. However, treatment with ASU or LA alone was able to suppress this inflammation in cells activated with LPS and IL-1β. For HO-activated cells, LA alone at 2.5 µg/mL was able to inhibit inflammation.
Importantly, a combination of ASU and LA was able to inhibit inflammation more than either agent alone in all activated cells. Moreover, this combination also inhibited the translocation (movement) of NF-κB induced by IL-1β.
Conclusions
The prevailing results suggest that the combination of ASU and LA effectively inhibits the production of PGE by chondrocytes, more efficiently than when either substance is used alone. The inhibition of PGE production is linked with the suppression of the movement of NF-κB, which reduces inflammation. The potent inhibitory effect of the ASU and LA combination on PGE production potentially makes it an advantageous approach for the combined anti-inflammatory and antioxidant management of osteoarthritis.
Cite This Article
Publication
Researcher Affiliations
- 1 Nutramax Laboratories, Inc., Edgewood, MD, USA.
- 2 Department of Orthopaedic Surgery, Johns Hopkins University, Baltimore, MD, USA.
- 3 College of Veterinary Medicine, Mississippi State University, Mississippi State, MS, USA.
- 1 Nutramax Laboratories, Inc., Edgewood, MD, USA.
- 1 Nutramax Laboratories, Inc., Edgewood, MD, USA.
- 1 Nutramax Laboratories, Inc., Edgewood, MD, USA.
- 1 Nutramax Laboratories, Inc., Edgewood, MD, USA.
- 4 College of Veterinary Medicine, Michigan State University, East Lansing, MI, USA.
MeSH Terms
- Animals
- Anti-Inflammatory Agents / adverse effects
- Anti-Inflammatory Agents / metabolism
- Anti-Inflammatory Agents / pharmacology
- Cartilage, Articular / cytology
- Cartilage, Articular / drug effects
- Cartilage, Articular / metabolism
- Cells, Cultured / drug effects
- Chondrocytes / cytology
- Chondrocytes / drug effects
- Chondrocytes / metabolism
- Combined Modality Therapy / methods
- Dinoprostone / biosynthesis
- Dinoprostone / metabolism
- Disease Models, Animal
- Horses
- Hydrogen Peroxide / metabolism
- Hydrogen Peroxide / pharmacology
- Inflammation / drug therapy
- Interleukin-1beta / metabolism
- Interleukin-1beta / pharmacology
- Lipopolysaccharides / metabolism
- Lipopolysaccharides / pharmacology
- NF-kappa B / metabolism
- NF-kappa B / pharmacology
- Osteoarthritis / drug therapy
- Osteoarthritis / metabolism
- Osteoarthritis / physiopathology
- Persea / adverse effects
- Persea / metabolism
- Plant Extracts / pharmacology
- Soybean Oil / adverse effects
- Soybean Oil / metabolism
- Soybean Oil / pharmacology
- Thioctic Acid / adverse effects
- Thioctic Acid / metabolism
- Thioctic Acid / pharmacology
Conflict of Interest Statement
References
- Arthritis Foundation. Osteoarthritis. 2015.
- Cross M, Smith E, Hoy D, Nolte S, Ackerman I, Fransen M. The global burden of hip and knee osteoarthritis: estimates from the global burden of disease 2010 study. Ann Rheum Dis 2014;73:1323-30.
- Loeser RF, Collins JA, Diekman BO. Ageing and the pathogenesis of osteoarthritis. Nat Rev Rheumatol 2016;12:412-420.
- Yusuf E, Nelissen RG, Ioan-Facsinay A, Stojanovic-Susulic V, DeGroot J, van Osch G. Association between weight or body mass index and hand osteoarthritis: a systematic review. Ann Rheum Dis 2010;69:761-5.
- Lieberthal J, Sambamurthy N, Scanzello CR. Inflammation in joint injury and post-traumatic osteoarthritis. Osteoarthritis Cartilage 2015;23:1825-1834.
- Varady Y, Grodzinsky AJ. Osteoarthritis year in review 2015: mechanics. Osteoarthritis Cartilage 2016;24:27-35.
- Mobasheri A, Henroitin Y. Biomarker of (osteo)arthritis. Biomarkers 2015;20:513-8.
- Berenbaum F, Vandenber WB. Inflammation in osteoarthritis: changing views. Osteoarthritis Cartilage 2015;23:1823-1824.
- Goldring MB, Otero M. Inflammation in osteoarthritis. Curr Opin Rheumatol 2011;23:471-8.
- Kapoor M, Martel-Pelletier J, Lajeunesse D, Pelletier JP, Fahmi H. Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nat Rev Rheumatol 2011;7:33-42.
- Attur M, Al-Mussawir HE, Patel J, Kitay A, Dave M, Palmer G. Prostaglandin E2 exerts catabolic effects in osteoarthritis cartilage: evidence for signaling via the EP4 receptor. J Immunol 2008;181:5082-8.
- Liu-Bryan R. Inflammation and intracellular metabolism: new targets in OA. Osteoarthritis Cartilage 2015;23:1835-42.
- Schaible HG, Ebersberger A, Von Banchet G. Mechanisms of pain in arthritis. Ann N Y Acad Sci 2002;966:343-54.
- Lee A S, Ellman MB, Yan D, Kroin JS, Cole BJ, van Wijnen AJ, Im HJ. Current review of molecular mechanisms regarding osteoarthritis and pain. Gene 2013;527:440-7.
- Miller RE, Miller RJ, Malfait AM. Osteoarthritis joint pain: the cytokine connection. Cytokine 2014;70:185-93.
- Haversath M, Catelas I, Li X, Tassemeier T, Jäger M. PGE2 and BMP-2 in bone and cartilage metabolism: 2 intertwining pathways. Can J Physiol Pharmacol 2012;90:1434-45.
- Wixted JJ, Fanning PF, Rothkopf I, Stein G, Lian J. Arachidonic acid, eicosanoids, and fracture repair. J Orthop Trauma 2010;24:539-42.
- Kalish BT, Kieran MW, Puder M, Panigrahy D. The growing role of eicosanoids in tissue regeneration, repair, and wound healing. Prostaglandins Other Lipid Mediat 2013;104-105:130-8.
- Sharma L. Osteoarthritis year in review 2015: clinical. Osteoarthritis Cartilage 2016;24:36-48.
- Loveless MS, Fry AL. Pharmacologic therapies in musculoskeletal conditions. Med Clin North Am 2016;100:869-90.
- Henrotin YE, Sanchez C, Deberg MA, Piccardi N, Guillou GB, Msika P. Avocado/soybean unsaponifiables increase aggrecan synthesis and reduce catabolic and proinflammatory mediator production by human osteoarthritic chondrocytes. J Rheumatol 2003;30:1825-34.
- Au RY, Al-Talib TK, Au AY, Phan PV, Frondoza CG. Avocado soybean unsaponifiables (ASU) suppress TNF-α, IL-1β, COX-2, and i-NOS gene expression, and prostaglandin E2 and nitric oxide production in articular chondrocytes and monocyte/macrophages. Osteoarthritis Cartilage 2007;15:1249-55.
- Gabay O, Gosset M, Levy A, Salvat C, Sanchez C, Pigenet A. Stress-induced signaling pathways in hyalin chondrocytes: inhibition by avocado soybean unsaponifiables (ASU). Osteoarthritis Cartilage 2008;16:373-84.
- Lippiello L, Nardo JV, Harlan R, Chiou T. Metabolic effects of avocado/soy unsaponifiables on articular chondrocytes. Evid Based Complement Alternat Med 2008;5:191-7.
- du Souich P, Garcia AG, Verges J, Montell E. Immunomodulatory and anti-inflammatory effects of chondroitin sulphate. J Cell Mol Med 2009;13:1451-63.
- Chan PS, Caron JP, Orth MW. Effect of glucosamine and chondroitin sulfate on regulation of gene expression of proteolytic enzymes and their inhibitors in interleukin-1-challanged bovine articular cartilage explants. Am J Vet Res 2005;66:1870-6.
- Grzanna MW, Ownby SL, Heinecke LF, Au AY, Frondoza CG. Inhibition of cytokine expression and prostaglandin E2 production in monocyte/macrophage-like cells by avocado soybean unsaponifiables and chondroitin sulfate. J Complement Integr Med 2010;7:Article 10.
- Heinecke LF, Grzanna MW, Au AY, Mochal CA, Rashmir-Raven A, Frondoza CG. Inhibition of cyclooxygenase-2 expression and prostaglandin E2 production in chondrocytes by avocado soybean unsaponifiables and epigallocatechin gallate. Osteoarthritis Cartilage 2010;18:220-7.
- Ownby SL, Fortuno LV, Au AY, Grzanna MW, Rashmir-Raven AM, Frondoza CG. Expression of pro-inflammatory mediators is inhibited by an avocado/soybean unsaponifiables and epigallocatechin gallate combination. J Inflamm (Lond) 2014;11:8.
- Frondoza CG, Heinecke LF, Grzanna MW, Au AY, Ownby SL. Modulation of cytokine-induced prostaglandin E2 production in cultures of articular chondrocytes obtained from carpal joints of camels (Camelus dromedarius). Am J Vet Res 2011;72:51-8.
- Henrotin Y, Lambert C, Couchourel D, Ripoll C, Chiotelli E. Nutraceuticals: do they represent a new era in the management of osteoarthritis? A narrative review from the lessons taken with five products. Osteoarthritis Cartilage 2011;19:1-21.
- Leffler CT, Philippi AF, Leffler SG. Glucosamine, chondroitin, and manganese ascorbate for degenerative joint disease of the knee or low back: a randomized, double-blind, placebo-controlled pilot study. Mil Med 1999;164:85-91.
- Das A Jr, Hammad TA. Efficacy of a combination of FCHG49 glucosamine hydrochloride, TRH122 low molecular weight sodium chondroitin sulfate and manganese ascorbate in the management of knee osteoarthritis. Osteoarthritis Cartilage 2000;8:343-50.
- Provenza JR, Shinjo SK, Silva JM. Combined glucosamine and chondroitin sulfate, once or three times daily, provides clinically relevant analgesia in knee osteoarthritis. Clin Rheumatol 2015;34:1455-62.
- Navarro SL, White E, Kantor ED. Randomized trial of glucosamine and chondroitin supplementation on inflammation and oxidative stress biomarkers and plasma proteomics profiles in healthy humans. PLoS One 2015;10:e0117534.
- Hochberg MC, Martel-Pelletier J, Monfort J, Möller I, Castillo JR, Arden N. Combined chondroitin sulfate and glucosamine for painful knee osteoarthritis: a multicentre, randomised, double-blind, non-inferiority trial versus celecoxib. Ann Rheum Dis 2016;75:37-44.
- Wildi LM, Raynauld JP, Martel-Pelletier J, Beaulieu A, Bessette L, Morin F. Chondroitin sulphate reduces both cartilage volume loss and bone marrow lesions in knee osteoarthritis patients starting as early as 6 months after initiation of therapy: a randomised, double-blind, placebo-controlled pilot study using MRI. Ann Rheum Dis 2011;70:982-9.
- Dalirfardouei R, Karimi G, Jamialahmadi K. Molecular mechanisms and biomedical applications of glucosamine as a potential multifunctional therapeutic agent. Life Sci 2016;152:21-9.
- Amin AR, Dave M, Attur M, Abramson SB. COX-2, NO, and cartilage damage and repair. Curr Rheumatol Rep 2000;2:447-53.
- Ziskoven C, Jäger M, Zilkens C, Bloch W, Brixius K, Krauspe R. Oxidative stress in secondary osteoarthritis: from cartilage destruction to clinical presentation?. Orthop Rev (Pavia) 2010;2(2):e23.
- Lepetsos P, Papavassiliou AG. ROS/oxidative stress signaling in osteoarthritis. Biochim Biophys Acta 2016;1862:576-91.
- Moura FA, de Andrade KQ, dos Santos JC, Goulart MO. Lipoic acid: its antioxidant and anti-inflammatory role and clinical applications. Curr Top Med Chem 2015;15:458-83.
- Shay KP, Moreau RF, Smith EJ, Smith AR, Hagen TM. Alpha-lipoic acid as a dietary supplement: molecular mechanisms and therapeutic potential. Biochim Biophys Acta 2009;1790:1149-60.
- Rosa FT, Zulet MÁ, Marchini JS, Martínez JA. Bioactive compounds with effects on inflammation markers in humans. Int J Food Sci Nutr 2012;63:749-65.
- Huerta AE, Prieto-Hontoria PL, Sáinz N, Martínez JA, Moreno-Aliaga MJ. Supplementation with α-lipoic acid alone or in combination with eicosapentaenoic acid modulates the inflammatory status of healthy overweight or obese women consuming an energy-restricted diet. J Nutr 2016;146:889S-96S.
- Wang J, Sun H, Fu Z, Liu M. Chondroprotective effects of alpha-lipoic acid in a rat model of osteoarthritis. Free Radic Res 2016;50:767-80.
- Safa J, Ardalan MR, Rezazadehsaatlou M, Mesgari M, Mahdavi R, Jadid MP. Effects of alpha lipoic acid supplementation on serum levels of IL-8 and TNF-α in patient with ESRD undergoing hemodialysis. Int Urol Nephrol 2014;46:1633-8.
- Zhang WJ, Wei H, Hagen T, Frei B. Alpha-lipoic acid attenuates LPS-induced inflammatory responses by activating the phosphoinositide 3-kinase/Akt signaling pathway. Proc Natl Acad Sci U S A 2007;104:4077-82.
- Ying Z, Kampfrath T, Sun Q, Parthasarathy S, Rajagopalan S. Evidence that α-lipoic acid inhibits NF-κB activation independent of its antioxidant function. Inflamm Res 2011;60:219-25.
- McIlwraith CW, Frisbie DD, Kawcak CE. The horse as a model of naturally occurring osteoarthritis. Bone Joint Res 2012;1:297-309.
- Malda J, Benders KEM, Klein TJ, de Grauw JC, Kik MJ, Hutmacher DW. Comparative study of depth-dependent characteristics of equine and human osteochondral tissue from the medial and lateral femoral condyle. Osteoarthritis Cartilage 2012;20:1147-51.
- Marlovits S, Hombauer M, Truppe M, Vècsei V, Schlegel W. Changes in the ratio of type-I and type-II collagen expression during monolayer culture of human chondrocytes. J Bone Joint Surg Br 2004;86:286-95.
- Cheng T, Maddox NC, Wong AW, Rahnama R, Kuo AC. Comparison of gene expression patterns in articular cartilage and dedifferentiated articular chondrocytes. J Orthop Res 2011;30:234-45.
- Na JY, Song K, Kim S, Kwon K. Rutin protects rat articular chondrocytes against oxidative stress induced by hydrogen peroxide through SIRT1 activation. Biochem Biophys Res Commun 2016;473:1301-8.
- Tallarida RJ, Cowan A, Raffa RB. Antinociceptive synergy, additivity, and s뫝itivity with combinations of oral glucosamine plus nonopioid analgesics in mice. J Pharmacol Exp Ther 2003;307:699-704.
- Wardyn JD, Ponsford AG, Sanderson CM. Dissecting molecular cross-talk between Nrf2 and NF-κB response pathways. Biochem Soc Trans 2015;43:621-6.