Effects of Pomegranate Concentrate Powder: Eucommiae Cortex: Achyranthis Radix 5:4:1 (w/w) Mixed Formula on Monosodium Iodoacetate-Induced Osteoarthritis in Rats

Abstract

We examined the antiosteoarthritis effect of a mixture of powdered pomegranate concentrate, eucommiae cortex, and achyranthis radix (5:4:1 w/w) (PEA-Mix). After the injection of monosodium iodoacetate (MIA), PEA-Mixs were orally administered. To assess pain-related behaviors, a von Frey filament test and open field test were performed. We also examined the knee thickness, maximum knee extension angle, bone mineral density (BMD), and compressive strength of the knee joint and performed a histopathologic analysis. The number of COX-2, tumor necrosis factor (TNF)-α, poly (ADP-ribose) polymerase (PARP), and 5-bromo-2′-deoxyuridine immunoreactive cells, the prostaglandin E2 (PGE2) and 5-lipoxygenase (LPO) levels, matrix metalloproteinase (MMP) activity, and mRNA levels of chondrogenesis-related genes were analyzed. PEA-Mix significantly inhibited the MIA-induced decrease in the paw-withdrawal threshold and total distance moved, and the MIA-induced increases in the maximum knee extension angle and knee thickness. Also, the MIA-induced loss of the knee joint articular surface region and decrease in the BMD were significantly suppressed by PEA-Mix. The MIA-induced increases in the 5-LPO, PGE2, MMP-2, MMP-9, COX-2, and TNF-α mRNA levels were reduced by PEA-Mix. PEA-Mix increased the MIA-mediated reduction in the SOX-9 and aggrecan mRNA levels. The number of PARP-positive cells was smaller in PEA-Mix-administered rats than in MIA-administered rats, while the number of 5-bromo-2′-deoxyuridine-positive cells was larger. Therefore, PEA-Mix relieved the MIA-induced pain-related behaviors, chondrocyte proliferation, and anti-inflammatory activity.