Abstract

Guava leaf extract and ellagic acid, one of its polyphenolic components, inhibit the activity of a disintegrin and metalloproteinase with thrombospondin type 5 (ADAMTS‐5), which is associated with aggrecan degeneration during the early stage of osteoarthritis (OA). To investigate the efficacy of guava leaf extract for preventing OA, we examined the effect of its dietary intake on cartilage destruction in anterior cruciate ligament‐transected (ACLT) rats. Rats were randomly assigned to four groups: ACLT control rats fed with control diet, ACLT rats fed with diet containing 0.2% guava leaf extract, ACLT rats fed with diet containing 0.5% guava leaf extract, and sham‐operated rats fed with control diet. Mankin's scores, an index of cartilage damage, were higher in rats that underwent ACLT. Guava leaf extract treatment dose‐dependently led to lower Mankin's scores and higher concentrations of ellagic acid in the serum and synovial membrane. Ellagic acid levels in the synovial membrane negatively correlated with cartilage destruction scores. These results suggest that dietary guava leaf extract suppresses OA progression in ACLT rats through ellagic acid‐mediated inhibition of early joint destruction.

Highlights

  • Japan is currently facing a “super-­aged” society, with disability-­free life expectancy of the population estimated to be ten years shorter than the average life expectancy for both sexes (Nakamura, 2009)

  • We evaluated the ADAMTS-­5 inhibitory activity of guava leaf extract by measuring aggrecan fragments produced by ADAMTS-­5 in a reaction mixture containing the substrate, enzyme, and test sample (Karai et al, 2012)

  • Ellagic acid concentrations in the serum and synovial membranes were only measured in rats that underwent anterior cruciate ligament-­transected (ACLT), as ellagic acid was not detected in normal rats during preliminary experiments

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Summary

| INTRODUCTION

Japan is currently facing a “super-­aged” society, with disability-­free life expectancy of the population estimated to be ten years shorter than the average life expectancy for both sexes (Nakamura, 2009). Osteoarthritis (OA), the most common type of joint disease, is prevalent in developed countries, especially among the elderly. No significant progress has been achieved in the development of daily functional foods or therapeutic medicines to address OA. We discovered that guava leaf extract among natural plant extracts strongly suppresses ADAMTS-­5 activity (data not shown). Guava has been reported to contain various polyphenols including ellagic acid (Anand, Kumar, Kumar, & Hedina, 2016; Arshiya, 2013; Lin & Yin, 2012), which has strong ADAMTS-­5 inhibitory activity. Guava leaves have been used to prepare tea in those regions, and it has been used as a functional food in Japan. We demonstrate the suppressive effects of guava leaf extract on OA using a rat model of anterior cruciate ligament transection (ACLT)

| MATERIALS AND METHODS
Findings
| DISCUSSION
| CONCLUSIONS
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