Anti-inflammatory and chondroprotective activity of (+)-α-pinene: structural and enantiomeric selectivity.
Previous studies have suggested that α-pinene, a common volatile plant metabolite, may have anti-inflammatory effects in human chondrocytes, thus exhibiting potential antiosteoarthritic activity. The objective of this study was to further characterize the potential antiosteoarthritic activity of selected pinene derivatives by evaluating their ability to modulate inflammation and extracellular matrix remodeling in human chondrocytes and to correlate the biological and chemical properties by determining whether the effects are isomer- and/or enantiomer-selective. To further elucidate chemicopharmacological interactions, the activities of other naturally occurring monoterpenes with the pinane nucleus were also investigated. At noncytotoxic concentrations, (+)-α-pinene (1) elicited the most potent inhibition of the IL-1β-induced inflammatory and catabolic pathways, namely, NF-κB and JNK activation and the expression of the inflammatory (iNOS) and catabolic (MMP-1 and -13) genes. (-)-α-Pinene (2) was less active than the (+)-enantiomer (1), and β-pinene (3) was inactive. E-Pinane (4) and oxygenated pinane-derived compounds, pinocarveol (5), myrtenal (6), (E)-myrtanol (7), myrtenol (8), and (Z)-verbenol (9), were less effective or even completely inactive and more cytotoxic than the pinenes tested (1-3). The data obtained show isomer- and enantiomer-selective anti-inflammatory and anticatabolic effects of α-pinene in human chondrocytes, (+)-α-pinene (1) being the most promising for further studies to determine its potential value as an antiosteoarthritic drug.
Center for Neuroscience and Cell Biology, University of Coimbra , Coimbra, Portugal.
Ana T
AT
Rufino
Madalena
M
Ribeiro
Fernando
F
Judas
Lígia
L
Salgueiro
Maria C
MC
Lopes
Carlos
C
Cavaleiro
Alexandrina F
AF
Mendes
D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D000081008:Bicyclic Monoterpenes; D019902:Chondrocytes / Q000187:drug effects*; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D048670:MAP Kinase Kinase 4 / Q000187:drug effects; D015394:Molecular Structure; D039821:Monoterpenes / Q000737:chemistry / Q000494:pharmacology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D052247:Nitric Oxide Synthase Type II / Q000187:drug effects; D010003:Osteoarthritis / Q000188:drug therapy*; D013237:Stereoisomerism; D013729:Terpenes / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D000081008:Bicyclic Monoterpenes; D053583:Interleukin-1beta; D039821:Monoterpenes; D016328:NF-kappa B; D013729:Terpenes; C061545:myrtenal; D052247:Nitric Oxide Synthase Type II; D048670:MAP Kinase Kinase 4; C009951:verbenol; C005451:alpha-pinene