Rhoifolin Ameliorates Osteoarthritis via Regulating Autophagy.

Jiyuan Yan,Yifan Xiao,Gaohong Sheng,Chang Tu,Yongzhuang Ma,Yingchi Zhang,Bowei Ni,Hua Wu,Hao Li

doi:10.3389/fphar.2021.661072

Abstract

Osteoarthritis (OA) is a common age-related joint disease. Its development has been generally thought to be associated with inflammation and autophagy. Rhoifolin (ROF), a flavanone extracted from Rhus succedanea, has exhibited prominent anti-oxidative and anti-inflammatory properties in several diseases. However the exact role of ROF in OA remains unclear. Here, we investigated the therapeutic effects as well as the underlying mechanism of ROF on rat OA. Our results indicated that ROF could significantly alleviate the IL-1β–induced inflammatory responses, cartilage degradation, and autophagy downregulation in rat chondrocytes. Moreover, administration of autophagy inhibitor 3-methyladenine (3-MA) could reverse the anti-inflammatory and anti-cartilage degradation effects of ROF. Furthermore, P38/JNK and PI3K/AKT/mTOR signal pathways were involved in the protective effects of ROF. In vivo, intra-articular injection of ROF could notably ameliorate the cartilage damage in rat OA model. In conclusion, our work elucidated that ROF ameliorated rat OA via regulating autophagy, indicating the potential role of ROF in OA therapy.

Highlights

Osteoarthritis, featured with cartilage loss, joint pain, and physical disability, has attracted worldwide attention in recent years (Kontio et al, 2020)
CCK-8 assay was performed to evaluate the cytotoxic effects of ROF on rat chondrocytes
We explored the effects of ROF on autophagy in IL-1β–treated rat chondrocytes

Summary

Introduction

Osteoarthritis, featured with cartilage loss, joint pain, and physical disability, has attracted worldwide attention in recent years (Kontio et al, 2020). Most therapeutic strategies targeted for OA focus on relieving the symptom rather than reversing the disease progression. Chronic inflammatory responses and cartilage metabolic imbalances are vital to the progression of OA (Appleton, 2018). Previous study indicated that IL-1β could induce the production of matrix metallo-proteinases (MMPs) and aggrecanase-2 (ADAMTS5), which resulted in the loss of cartilage matrix (Tu et al, 2019). In OA pathological progression, autophagy induction could promote chondrocyte survival and cartilage matrix synthesis (Carames et al, 2010). It is reported that IL-1β could significantly induce the autophagy downregulation in chondrocytes (Wang et al, 2019). Strategies targeting IL-1β may lead to new ideas in OA treatment

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