Avocado soybean unsaponifiables (ASU) suppress TNF-alpha, IL-1beta, COX-2, iNOS gene expression, and prostaglandin E2 and nitric oxide production in articular chondrocytes and monocyte/macrophages.
OBJECTIVE
To evaluate the effects of avocado soybean unsaponifiables (ASU) on proinflammatory mediators in chondrocytes and monocyte/macrophage-like cells.


METHODS
To determine the dose response of ASU, chondrocytes (5 x 10(5) cells/well) were incubated at 5% CO(2), 37 degrees C for 72 h with (1) control media alone or (2) ASU at concentrations of 0.3, 0.9, 2.7, 8.3, and 25 microg/ml. Cells were activated with 20 ng/ml lipopolysaccharide (LPS) for 24 h and cell supernatants were analyzed for prostaglandin E(2) (PGE(2)) and nitrite content. Chondrocytes and THP-1 monocyte/macrophages (5 x 10(5) cells/well) were incubated at 5% CO(2), 37 degrees C for 72 h with (1) control media alone or (2) ASU (25 mug/ml). One set of cells was activated for 1 h with LPS (20 ng/ml) for both reverse-transcriptase PCR and real-time PCR analysis of tumor necrosis factor-alpha (TNF-alpha), interleukin-1-beta (IL-1beta), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) expression. One set of cells was activated for 24 h to analyze secreted PGE(2) and nitrite levels in the cellular supernatant.


RESULTS
ASU reduced TNF-alpha, IL-1beta, COX-2, and iNOS expression in LPS-activated chondrocytes to levels similar to nonactivated control levels. The suppression of COX-2 and iNOS expression was paralleled by a significant reduction in PGE(2) and nitrite, respectively, in the cellular supernatant. ASU also reduced TNF-alpha and IL-1beta expression in LPS-activated monocyte/macrophage-like cells.


CONCLUSIONS
The present study demonstrates that the anti-inflammatory activity of ASU is not restricted to chondrocytes, but also affects monocyte/macrophage-like cells that serve as a prototype for macrophages in the synovial membrane. These observations provide a scientific rationale for the pain-reducing and anti-inflammatory effects of ASU observed in osteoarthritis patients.
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Nutramax Laboratories, Inc., Edgewood, MD 21040, USA.
Al-Talib
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Phan
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Frondoza
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D000818:Animals; D002358:Cartilage, Articular / Q000201:enzymology / Q000378:metabolism; D002417:Cattle; D019902:Chondrocytes / Q000201:enzymology / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D006801:Humans; D053583:Interleukin-1beta; D008264:Macrophages / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis / Q000235:genetics; D027421:Persea; D010936:Plant Extracts / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013025:Glycine max; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D053583:Interleukin-1beta; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D015232:Dinoprostone