PMID- 28987943 OWN - NLM STAT- MEDLINE DCOM- 20180726 LR - 20180726 IS - 1950-6007 (Electronic) IS - 0753-3322 (Linking) VI - 96 DP - 2017 Dec TI - A standardized extract of Butea monosperma (Lam.) flowers suppresses the IL-1beta-induced expression of IL-6 and matrix-metalloproteases by activating autophagy in human osteoarthritis chondrocytes. PG - 198-207 LID - S0753-3322(17)34003-9 [pii] LID - 10.1016/j.biopha.2017.09.140 [doi] AB - 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 LC3-II by immunoblotting and increased number of autophagosomes in BME treated chondrocytes by transmission electron microscopy and confocal microscopy. BME upregulated the expression of several autophagy related genes and increased the autophagy flux in human OA chondrocytes under pathological conditions. Further analysis revealed that BME activated autophagy in chondrocytes via inhibition of mammalian target of rapamycin (mTOR) pathway. Of importance is our finding that BME-mediated suppression of IL-1beta induced expression of IL-6, MMP-3, -9, and -13 was autophagy dependent and was abrogated by inhibition of autophagy. CONCLUSION: The above results show that the Butea monosperma (Lam.) extract has strong potential to activate autophagy and suppress IL-1beta induced expression of IL-6 and MMP-3, -9 and -13 in human OA chondrocytes. This study shows that BME or compounds derived from BME can be developed as safe and effective chondroprotective agent(s) that function by activating autophagy to suppress the expression of inflammatory and catabolic factors associated with OA pathogenesis. CI - Copyright (c) 2017 Elsevier Masson SAS. All rights reserved. FAU - Ansari, Mohammad Y AU - Ansari MY AD - Department of Anatomy and Neurobiology, Northeast Ohio Medical University, Rootstown, OH, 44272, USA. FAU - Khan, Nazir M AU - Khan NM AD - Department of Anatomy and Neurobiology, Northeast Ohio Medical University, Rootstown, OH, 44272, USA. FAU - Haqqi, Tariq M AU - Haqqi TM AD - Department of Anatomy and Neurobiology, Northeast Ohio Medical University, Rootstown, OH, 44272, USA. Electronic address: thaqqi@neomed.edu. LA - eng PT - Journal Article DEP - 20171006 PL - France TA - Biomed Pharmacother JT - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JID - 8213295 RN - 0 (IL6 protein, human) RN - 0 (Interleukin-1beta) RN - 0 (Interleukin-6) RN - 0 (Plant Extracts) RN - EC 3.4.24.- (MMP13 protein, human) RN - EC 3.4.24.- (Matrix Metalloproteinase 13) RN - EC 3.4.24.- (Matrix Metalloproteinases) RN - EC 3.4.24.17 (MMP3 protein, human) RN - EC 3.4.24.17 (Matrix Metalloproteinase 3) RN - EC 3.4.24.35 (MMP9 protein, human) RN - EC 3.4.24.35 (Matrix Metalloproteinase 9) SB - IM MH - Aged MH - Autophagy/drug effects/physiology MH - *Butea MH - Chondrocytes/drug effects/*metabolism MH - Dose-Response Relationship, Drug MH - Flowers MH - Gene Expression MH - Humans MH - Interleukin-1beta/*pharmacology MH - Interleukin-6/*biosynthesis/genetics MH - Matrix Metalloproteinase 13/biosynthesis/genetics MH - Matrix Metalloproteinase 3/biosynthesis/genetics MH - Matrix Metalloproteinase 9/biosynthesis/genetics MH - Matrix Metalloproteinases/*biosynthesis/genetics MH - Middle Aged MH - Osteoarthritis/*metabolism MH - Plant Extracts/isolation & purification/pharmacology OTO - NOTNLM OT - Autophagy OT - Butea monosperma (Lam.) OT - Nutraceuticals OT - Osteoarthritis OT - mTOR EDAT- 2017/10/11 06:00 MHDA- 2018/07/27 06:00 CRDT- 2017/10/09 06:00 PHST- 2017/08/07 00:00 [received] PHST- 2017/09/12 00:00 [revised] PHST- 2017/09/26 00:00 [accepted] PHST- 2017/10/11 06:00 [pubmed] PHST- 2018/07/27 06:00 [medline] PHST- 2017/10/09 06:00 [entrez] AID - S0753-3322(17)34003-9 [pii] AID - 10.1016/j.biopha.2017.09.140 [doi] PST - ppublish SO - Biomed Pharmacother. 2017 Dec;96:198-207. doi: 10.1016/j.biopha.2017.09.140. Epub 2017 Oct 6.