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

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 PGE, 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 PGE, 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 PGE 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.

Avocado–Soybean Unsaponifiables: A Panoply of Potentialities to Be Exploited

“…Likewise, Grzanna et al (2010), using monocyte/macrophage cell models, determined the inhibitory effects of ASU extract (8.3 µg/mL) in combination with chondroitin sulfate (CS) (20 µg/mL) on both the synthesis and expression of pro-inflammatory stimulators and mediators, such as cytokine expression and PGE-2 production [88]. An addition, Grzanna et al (2018) carried out another study where ASU extract was used with glucosamine (GLU), CS and with or without the presence of carprofen, a nonsteroidal anti-inflammatory drug (NSAID) [89]. The aim of this study was to assess the anti-inflammatory activity using a composite mixture of ASU extract (8.3 µg/mL), GLU (11 µg/mL), CS (20 µg/mL) and/or the NSAID carprofen (40 ng/mL).…”

Effects of Warm Acupuncture Combined with Meloxicam and Comprehensive Nursing on Pain Improvement and Joint Function in Patients with Knee Osteoarthritis

“…DA, 5-HT is a peripheral pain medium, which can stimulate sensory peripheral nerves to make the body feel pain [25]. PGE2 can be produced in large quantities in the early stage of inflammation, reduces the pain threshold in the local area of inflammation, and activates the EP receptors on the peripheral sensory nerve endings to enhance the pain sensation [26]. is study found that warm acupuncture combined with meloxicam and comprehensive nursing could significantly reduce the content of pain mediator (PGE2, SP, DA, and 5-HT) in patients with KOA, indicating that meloxicam combined with warm acupuncture has a good analgesic effect.…”

Therapeutic potential of pyrrole and pyrrolidine analogs: an update

“…Previously, carprofen was used for the treatment of gastrointestinal pain and nausea. Later, it is banned due to its toxicity [ 88 , 89 ].…”

“…Fakhar et al [154] report based on the structure-based pharmacophore modeling, virtual screening workflow, ADMET, and molecular dynamics simulations revealed that compound ABBV-744 (87) has a strong affinity (ΔGbind − 45.43 kcal/mol) to the main protease. Further, this study also considered the other two compounds (88,89) as potential inhibitors of SARS-CoV-2. In the year 2021, by the experimental evidence, Varghese et al [155] have proposed a combination of obatoclax and berberine as possible antiviral drugs for SARS-CoV-2 infection (Fig.…”