Intra-Articular Injection of Fructus Ligustri Lucidi Extract Attenuates Pain Behavior and Cartilage Degeneration in Mono-Iodoacetate Induced Osteoarthritic Rats.

Bo Yan,Li Zhou,Caiwei Wang,Qiang Yuan,Guangping Yu,Thomas Efferth,Letian Shan,Rongrong Wang,Wenxi Du,Li Yan,Peijian Tong,Fucun Liu,Lingying Yu

doi:10.3389/fphar.2018.01360

Abstract

Fructus Ligustri Lucidi (FLL) has been widely used as a traditional Chinese medicine (TCM) for treating soreness and weakness of waist and knees. It has potential for treating OA owing to its kidney-tonifying activity with bone-strengthening effects, but there is so far no report of its anti-OA effect. This study established a rat OA model by intra-articular (IA) injection of mono-iodoacetate (1.5 mg) and weekly treated by IA administration of FLL at 100 μg/mL for 4 weeks. Thermal withdrawal latency, mechanical withdrawal threshold, and spontaneous activity were tested for evaluation of pain behavior, and histopathological (HE, SO, and ABH staining) and immunohistochemical (Col2, Col10, and MMP13) analyses were conducted for observation of cartilage degradation. In vitro effect of FLL on chondrocytes was evaluated by MTT assay and qPCR analysis. Moreover, HPLC analysis was performed to determine its chemoprofile. The pain behavioral data showed that FLL attenuated joint pain hypersensitivity by increasing thresholds of mechanical allodynia and thermal hyperalgesia as well as spontaneous activity. The histopathological result showed that FLL reversed OA cartilage degradation by protecting chondrocytes and extracellular matrix in cartilage, and the immunohistochemical analysis revealed its molecular actions on protein expressions of MMP13, Col2, and Col10 in cartilage. The MTT assay showed its proliferative effects on chondrocytes, and qPCR assay clarified its mechanism associated with gene expressions of Mmp13, Col2, Col10, Adamts5, Aggrecan, and Runx2 in TNF-α treated chondrocytes. Our results revealed an anti-OA effect of FLL on pain behavior and cartilage degradation in OA rats and clarified a molecular mechanism in association with the suppression of chondrocyte hypertrophy and catabolism. IA FLL can be regarded as novel and promising option for OA therapy.

Highlights

As the most common joint disease worldwide, osteoarthritis (OA) affects an estimated 15–40% populations aged 60 years or older (Zhang and Jordan, 2010; Cross et al, 2014)
After the OA modeling, MWT, TWL, and spontaneous activity were significantly decreased in comparison with the normal control
As compared to the model, Fructus Ligustri Lucidi (FLL) significantly increased the levels of MWT, TWL, and spontaneous activity after 28 days intra-articular treatment

Summary

Introduction

As the most common joint disease worldwide, osteoarthritis (OA) affects an estimated 15–40% populations aged 60 years or older (Zhang and Jordan, 2010; Cross et al, 2014). The prevalence of OA is increasing year by year with rising rates in aged people (Nguyen et al, 2011). It occurs with synovial inflammation, cartilage breakdown and bone remodeling, developing to a syndrome of chronic pain, stiffness and impaired movement. The medical costs of OA account for 1–2.5% of the gross domestic product in developed countries and increase by years with increasing prevalence of OA, leading to large resultant socioeconomic burden (Bitton, 2009). The current therapies do not satisfy the clinical needs due to their insufficiency and limitations, urgently demanding a new cost-effective approach to treat OA

Methods

Results

Discussion

Conclusion