Sclareol exerts anti-osteoarthritic activities in interleukin-1β-induced rabbit chondrocytes and a rabbit osteoarthritis model.

Abstract

Sclareol is a natural product initially isolated form Salvia sclarea which possesses immune-regulation and anti-inflammatory activities. However, the anti-osteoarthritic properties of sclareol have not been investigated. The present study is aimed at evaluating the potential effects of sclareol in interleukin-1β (IL-1β)-induced rabbit chondrocytes as well as an experimental rabbit knee osteoarthritis model induced by anterior cruciate ligament transection (ACLT). Cultured rabbit chondrocytes were pretreated with 1, 5 and 10 μg/mL sclareol for 1 h and followed by stimulation of IL-1β (10 ng/mL) for 24 h. Gene expression of matrix metalloproteinase-1 (MMP-1), MMP-3, MMP-13, tissue inhibitors of metalloproteinase-1 (TIMP-1), inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 was determined by quantitative real-time polymerase chain reaction (qRT-PCR). MMP-3, TIMP-1, iNOS and COX-2 proteins were measured by Western blotting. Enzyme-linked immunosorbent assay (ELISA) was applied for nitric oxide (NO) and prostaglandin E2 (PGE2) assessment. For the in vivo study, rabbits received six weekly 0.3 mL sclareol (10 μg/mL) intra-articular injections in the knees four weeks after ACLT surgery. Cartilage was harvested for measurement of MMP-1, MMP-3, MMP-13, TIMP-1, iNOS and COX-2 by qRT-PCR, while femoral condyles were used for histological evaluation. The in vitro results we obtained showed that sclareol inhibited the MMPs, iNOS and COX-2 expression on mRNA and protein levels, while increased the TIMP-1 expression. And over-production of NO and PGE2 was also suppressed. For the in vivo study, both qRT-PCR results and histological evaluation confirmed that sclareol ameliorated cartilage degradation. Hence, we speculated that sclareol may be an ideal approach for treating osteoarthritis.

• Authors: Ying Zhong, Yi Huang, Marcel B Santoso, Li-Dong Wu
• Journal: International journal of clinical and experimental pathology (Int J Clin Exp Pathol) Vol. 8 Issue 3 Pg. 2365-74 ( 2015) ISSN: 1936-2625 [Electronic] United States
• PMID: 26045743 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Diterpenes
• IL1B protein, human
• Interleukin-1beta
• RNA, Messenger
• Tissue Inhibitor of Metalloproteinase-1
• Nitric Oxide
• sclareol
• Nitric Oxide Synthase Type II
• Cyclooxygenase 2
• Matrix Metalloproteinases
• Dinoprostone

Topics

• Animals
• Anti-Inflammatory Agents (administration & dosage, pharmacology)
• Cartilage, Articular (drug effects, immunology, metabolism, pathology)
• Cells, Cultured
• Chondrocytes (drug effects, immunology, metabolism, pathology)
• Cyclooxygenase 2 (genetics, metabolism)
• Dinoprostone (metabolism)
• Disease Models, Animal
• Diterpenes (administration & dosage, pharmacology)
• Dose-Response Relationship, Drug
• Gene Expression Regulation
• Humans
• Injections, Intra-Articular
• Interleukin-1beta (pharmacology)
• Joints (drug effects, immunology, metabolism, pathology)
• Matrix Metalloproteinases (genetics, metabolism)
• Nitric Oxide (metabolism)
• Nitric Oxide Synthase Type II (genetics, metabolism)
• Osteoarthritis (drug therapy, genetics, immunology, metabolism, pathology)
• RNA, Messenger (metabolism)
• Rabbits
• Signal Transduction (drug effects)
• Tissue Inhibitor of Metalloproteinase-1 (genetics, metabolism)