Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy.
IRCCS Centro Neurolesi "Bonino-Pulejo", 98124 Messina, Italy.
Biomolecules. 2019 Jul 31;9(8):326. doi: 10.3390/biom9080326.
β-caryophyllene (BCP) is a cannabinoid receptor 2 (CB2) agonist that tempers inflammation. An interaction between the CB2 receptor and peroxisome proliferator-activated receptor gamma (PPAR-γ) has been suggested and PPAR-γ activation exerts anti-arthritic effects. The aim of this study was to characterize the therapeutic activity of BCP and to investigate PPAR-γ involvement in a collagen antibody induced arthritis (CAIA) experimental model. CAIA was induced through intraperitoneal injection of a monoclonal antibody cocktail and lipopolysaccharide (LPS; 50 μg/100 μL/ip). CAIA animals were then randomized to orally receive either BCP (10 mg/kg/100 μL) or its vehicle (100 μL of corn oil). BCP significantly hampered the severity of the disease, reduced relevant pro-inflammatory cytokines, and increased the anti-inflammatory cytokine IL-13. BCP also decreased joint expression of matrix metalloproteinases 3 and 9. Arthritic joints showed increased COX2 and NF-ĸB mRNA expression and reduced expression of the PPARγ coactivator-1 alpha, PGC-1α, and PPAR-γ. These conditions were reverted following BCP treatment. Finally, BCP reduced NF-ĸB activation and increased PGC-1α and PPAR-γ expression in human articular chondrocytes stimulated with LPS. These effects were reverted by AM630, a CB2 receptor antagonist. These results suggest that BCP ameliorates arthritis through a cross-talk between CB2 and PPAR-γ.
β-石竹烯（BCP）是一种大麻素受体 2（CB2）激动剂，可调节炎症。已经提出了 CB2 受体与过氧化物酶体增殖物激活受体γ（PPAR-γ）之间的相互作用，并且 PPAR-γ 的激活具有抗关节炎作用。本研究的目的是表征 BCP 的治疗活性，并研究 PPAR-γ 在胶原抗体诱导的关节炎（CAIA）实验模型中的作用。通过腹腔内注射单克隆抗体鸡尾酒和脂多糖（LPS；50μg/100μL/ip）诱导 CAIA。然后，CAIA 动物被随机分为口服 BCP（10mg/kg/100μL）或其载体（100μL 玉米油）。BCP 显著阻碍了疾病的严重程度，降低了相关的促炎细胞因子，并增加了抗炎细胞因子 IL-13。BCP 还降低了关节中基质金属蛋白酶 3 和 9 的表达。关节炎关节中 COX2 和 NF-ĸB mRNA 的表达增加，而 PPARγ 共激活因子 1α、PGC-1α 和 PPAR-γ 的表达减少。这些情况在 BCP 治疗后得到逆转。最后，BCP 降低了 LPS 刺激的人关节软骨细胞中 NF-ĸB 的激活，并增加了 PGC-1α 和 PPAR-γ 的表达。这些作用被 CB2 受体拮抗剂 AM630 逆转。这些结果表明，BCP 通过 CB2 和 PPAR-γ 之间的串扰改善关节炎。
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