In this study, we aimed to determine the synergistic effects of a formula consisting of dried pomegranate concentrate powder, Eucommiae Cortex, and Achyranthis Radix 5:4:1 (g/g) (PCP:EC:AR) in a surgically induced osteoarthritis (OA) rabbit model. PCP:EC:AR was orally administered once per day. Knee thickness, maximum extension of the knee joint, gross articular defect area, and the histopathological appearance of the cartilage were monitored, along with serum collagen type II C-telopeptide (CTX-II), cartilage oligomeric matrix protein (COMP), matrix metalloproteinase (MMP)-3, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and subchondral IL-1β and TNF-α levels. Roentgenographic images were also evaluated. PCP:EC:AR significantly inhibited the surgically induced increase in knee thickness, maximum extension of both knees, knee thickness after capsule exposure, gross femoral and tibial articular defect areas, loss of the knee joint area, serum and synovial COMP, CTX-II, and MMP expression, and synovial IL-1β, and TNF-α expression. In addition, surgically induced narrowing of the knee bones, loss of the joint area, cartilage damage, and osteophyte formation were reduced. PCP:EC:AR suppressed the surgically induced increases in the Mankin score, and subchondral IL-1β and TNF-α immunolabeled cell numbers. PCP:EC:AR exerted potent OA protective effects in a surgically induced OA rabbit model.
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.
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