Naringenin regulates production of matrix metalloproteinases in the knee-joint and primary cultured articular chondrocytes and alleviates pain in rat osteoarthritis model.

Inflammation of cartilage is a primary symptom for knee-joint osteoarthritis. Matrix metalloproteinases (MMPs) are known to play an important role in the articular cartilage destruction related to osteoarthritis. Naringenin is a plant-derived flavonoid known for its anti-inflammatory properties. We studied the effect of naringenin on the transcriptional expression, secretion and enzymatic activity of MMP-3 in vivo in the murine monosodium iodoacetate (MIA) osteoarthritis model. The assessment of pain behavior was also performed in the MIA rats. The destruction of knee-joint tissues was analyzed microscopically. Moreover, the effect of naringenin was also studied in vitro in IL-1ß activated articular chondrocytes. The transcriptional expression of MMP-3, MMP-1, MMP-13, thrombospondin motifs (ADAMTS-4) and ADAMTS-5 was also studied in primary cultured chondrocytes of rats. Naringenin caused significant reduction in pain behavior and showed marked improvement in the tissue morphology of MIA rats. Moreover, a significant inhibition of MMP-3 expression in MIA rats was observed upon treatment with naringenin. In the in vitro tests, naringenin caused a significant reduction in the transcriptional expression, secretion and enzymatic activity of the studied degradative enzymes. The NF-κB pathway was also found to be inhibited upon treatment with naringenin in vitro. Overall, the study suggests that naringenin alleviated pain and regulated the production of matrix-metalloproteinases via regulation of NF-κB pathway. Thus, naringenin could be a potent therapeutic option for the treatment of osteoarthritis.

Association of phosphodiesterase 4D gene and interleukin-6 receptor gene polymorphisms with ischemic stroke in a Chinese hypertensive population.

Genetic factors have been shown to be associated with the risk of stroke. However, due to individual differences, the extent of the association between genetic factors and stroke varies widely. Hypertension is considered one of the most important risk factors for stroke, but it remains unknown whether the genetic association with stroke in a hypertensive population is the same as that in a non-hypertensive population. The aim of the present study was to explore the association between the phosphodiesterase 4D gene (PDE4D) and interleukin-6 receptor gene (IL6R) single nucleotide polymorphisms and ischemic stroke in a hypertensive population. The study included 307 ischemic stroke cases with hypertension and 227 controls (simple hypertension). The polymorphic loci rs12188950 and rs918592 in PDE4D, and rs4075015 and rs4537545 in IL6R were selected for analyzing the genotype and allele frequencies between cases and controls. rs12188950 was not found in the study population. In the univariate analysis, the rs918592 polymorphism in PDE4D was found to be significantly associated with ischemic stroke with the recessive model (P = 0.02), whereas no association with ischemic stroke was observed for rs4075015 and rs4537545 in IL6R. Following adjustment for binary logistic regression, the rs918592 polymorphism was not found to be associated with ischemic stroke. While prior studies have found an association between PDE4D and IL6R polymorphisms and ischemic stroke, our results suggest that this association may be different in a hypertensive population. Therefore, the association between PDE4D and IL6R polymorphisms and ischemic stroke among a hypertensive population requires further investigation.