Description
BACKGROUND/OBJECTIVE: Osteoarthritis (OA) is a leading cause of joint dysfunction, disability and poor quality of life in the affected population. The underlying mechanism of joint dysfunction involves increased oxidative stress, inflammation, high levels of cartilage extracellular matrix degrading proteases and decline in autophagy-a mechanism of cellular defense. There is no disease modifying therapies currently available for OA. Different parts of the Butea monosperma (Lam.) plant have widely been used in the traditional Indian Ayurvedic medicine system for the treatment of various human diseases including inflammatory conditions. Here we studied the chondroprotective effect of hydromethanolic extract of Butea monosperma (Lam.) flowers (BME) standardized to the concentration of Butein on human OA chondrocytes stimulated with IL-1beta. METHODS: The hydromethanolic extract of Butea monosperma (Lam.) (BME) was prepared with 70% methanol-water mixer using Soxhlet. Chondrocytes viability after BME treatment was measured by MTT assay. Gene expression levels were determined by quantitative polymerase chain reaction (qPCR) using TaqMan assays and immunoblotting with specific antibodies. Autophagy activation was determined by measuring the levels of microtubule associated protein 1 light chain 3-II (LC3-II) by immunoblotting and visualization of autophagosomes by transmission electron and confocal microscopy. RESULTS: BME was non-toxic to the OA chondrocytes at the doses employed and suppressed the IL-1beta induced expression of inerleukin-6 (IL-6) and matrix metalloprotease-3 (MMP-3), MMP-9 and MMP-13. BME enhanced autophagy in chondrocytes as determined by measuring the levels of
Subject
*Butea; Aged; Autophagy; Autophagy/drug effects/physiology; Butea monosperma (Lam.); Chondrocytes/drug effects/*metabolism; Dose-Response Relationship; Drug; Flowers; Gene Expression; Humans; Interleukin-1beta/*pharmacology; Interleukin-6/*biosynthesis/genetics; Matrix Metalloproteinase 13/biosynthesis/genetics; Matrix Metalloproteinase 3/biosynthesis/genetics; Matrix Metalloproteinase 9/biosynthesis/genetics; Matrix Metalloproteinases/*biosynthesis/genetics; Middle Aged; mTOR; Nutraceuticals; Osteoarthritis; Osteoarthritis/*metabolism; Plant Extracts/isolation & purification/pharmacology