Anti-Inflammatory Effect of Carprofen Is Enhanced by Avocado/Soybean Unsaponifiables, Glucosamine and Chondroitin Sulfate Combination in Chondrocyte Microcarrier Spinner Culture.

Cartilage. 2018 Jun 1:1947603518783495. doi: 10.1177/1947603518783495. [Epub ahead of print] Grzanna MW1, Secor EJ1,2, Fortuno LV1, Au AY1, Frondoza CG1,3,4. Author information 1 1 Department of Research and Development, Nutramax Laboratories, Inc., Edgewood, MD, USA. 2 2 College of Veterinary Medicine, Cornell University, Ithaca, NY, USA. 3 3 Department of Orthopaedic Surgery, School of Medicine, Johns Hopkins University, Baltimore, MD, USA. 4 4 Department of Clinical Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS, USA. Abstract Objective Osteoarthritis is a painful, chronic joint disease affecting man and animals with no known curative therapies. Palliative nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used but they cause adverse side effects prompting the search for safer alternatives. To address this need, we evaluated the anti-inflammatory activity of avocado/soybean unsaponifiables (ASU), glucosamine (GLU), and chondroitin sulfate (CS) with or without the NSAID carprofen. Design Canine chondrocytes were propagated in microcarrier spinner culture and incubated with (1) control medium, (2) ASU (8.3 µg/mL) + GLU (11 µg/mL) + CS (20 µg/mL) combination for 24 hours; and/or carprofen (40 ng/mL). Cultures were next incubated with control medium alone or IL-1β (10 ng/mL) for another 24 hours. Production of PGE2, IL-6, IL-8, and MCP-1 (also known as CCL-2) were measured by ELISA. Results Chondrocytes proliferated in microcarrier spinner culture and produced type II collagen and aggrecan. Stimulation with IL-1β induced significant increases in PGE2, IL-6, IL-8, and MCP-1 production. The increases in production were suppressed by carprofen as well as [ASU+GLU+CS]. The combination of carprofen and [ASU+GLU+CS] reduced PGE2 production significantly more than either preparation alone. The inhibitory effect of carprofen on IL-6, IL-8, and MCP-1 production was significantly less than that of [ASU+GLU+CS], whereas the combination did not reduce the production of these molecules significantly more than [ASU+GLU+CS] alone. Conclusions The potentiating effect of [ASU+GLU+CS] on low-dose carprofen was identified in chondrocyte microcarrier spinner cultures. Our results suggest that the combination of low-dose NSAIDs like carprofen with [ASU+GLU+CS] could offer a safe, effective management for joint pain. KEYWORDS: avocado/soybean unsaponifiables; carprofen; chondrocytes; chondroitin sulfate; glucosamine PMID: 29938530 DOI: 10.1177/1947603518783495