一项体外和体内研究：芳樟醇通过抗氧化应激和抗炎作用保护软骨并缓解骨关节炎的进展。

An in vitro and in vivo study: Valencene protects cartilage and alleviates the progression of osteoarthritis by anti-oxidative stress and anti-inflammatory effects.

机构信息

Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.

出版信息

Int Immunopharmacol. 2023 Oct;123:110726. doi: 10.1016/j.intimp.2023.110726. Epub 2023 Aug 2.

DOI:10.1016/j.intimp.2023.110726

PMID:37536183

Abstract

BACKGROUND

Osteoarthritis (OA) is a heterogeneous disease involving the whole joint. The pathogenesis involves oxidative stress levels and chronic inflammation, and Valencene (VA) has excellent anti-inflammatory and antioxidant stress abilities.

PURPOSE

The objective was to study the effects of VA therapy on combating oxidative stress and to evaluate the protective effect of chondrocytes to alleviate the progression of OA.

METHODS

C57BL6J mouse chondrocytes were used as the primary cells in this study. Mouse chondrocytes were stimulated with IL-1β, and VA was administered in different concentrations. Reactive oxygen species (ROS) assay kits, western blotting, cellular immunofluorescence, and scanning microscopy were used to evaluate VA's antioxidant stress mechanism, anti-inflammatory effect, and cartilage protective ability. The mouse arthritis model constructed by destabilization of medial meniscus (DMM) was observed by micro-CT scan and histology after different treatments.

RESULTS

We found that VA can reverse the rise of ROS under IL-1β, the degeneration of the cartilage extracellular matrix, and the production of inflammatory mediators. In terms of mechanism, VA activated NRF2/HO-1/NQO1 pathway, thus enhancing ROS clearance. The phosphorylation of IκBα is inhibited, which further reduces the downstream phosphorylation of P65 in nuclear factor-κB (NF-κB) signaling. In addition, VA inhibited mitogen-activated protein kinase (MAPK) signaling molecules P-JNK, P-ERK, and P-P38, inhibiting the production of inflammatory mediators and thus inhibiting Aggrecan and Collagen Type II （COL2）degeneration. In vivo, VA reduced DMM-induced osteophytes and spurs, suppressed subchondral bone destruction, and reduced articular cartilage erosion.

CONCLUSION

Our study demonstrated that VA is an effective candidate for OA treatment.

摘要

背景

骨关节炎（OA）是一种涉及整个关节的异质性疾病。其发病机制涉及氧化应激水平和慢性炎症，而 Valencene（VA）具有出色的抗炎和抗氧化应激能力。

目的

本研究旨在研究 VA 治疗对抗氧化应激的作用，并评估其对软骨细胞的保护作用，以减轻 OA 的进展。

方法

本研究使用 C57BL6J 小鼠软骨细胞作为原代细胞。用 IL-1β刺激小鼠软骨细胞，并给予不同浓度的 VA。使用活性氧（ROS）测定试剂盒、western blot、细胞免疫荧光和扫描电镜评估 VA 的抗氧化应激机制、抗炎作用和软骨保护能力。通过内侧半月板不稳定（DMM）构建的小鼠关节炎模型，在不同治疗后通过微 CT 扫描和组织学观察。

结果

我们发现，VA 可以逆转 IL-1β 下 ROS 的升高、软骨细胞外基质的退化和炎症介质的产生。在机制上，VA 激活了 NRF2/HO-1/NQO1 通路，从而增强了 ROS 的清除。抑制 IκBα 的磷酸化，进一步降低核因子-κB（NF-κB）信号下游 P65 的磷酸化。此外，VA 抑制丝裂原活化蛋白激酶（MAPK）信号分子 P-JNK、P-ERK 和 P-P38，抑制炎症介质的产生，从而抑制 Aggrecan 和 Collagen Type II（COL2）的退化。在体内，VA 减少了 DMM 诱导的骨赘和骨刺，抑制了软骨下骨破坏，并减少了关节软骨侵蚀。