Therapeutic effect of Huzhangoside D in rats with knee osteoarthritis induced by anterior cruciate ligament transection

Ruo Jing Zhang; Cheng Chen Cai; Jian Pang; Xiao Li Xu; Hai Xin Gou; Guo Wen Li

Articles

Abstract

Pharmacognosy Magazine,2021,17,73,112-119.

DOI:10.4103/pm.pm_298_20

Published:January 2021

Type:Original Article

Authors:

Author(s) affiliations:

Ruo Jing Zhang¹, Cheng Chen Cai², Jian Pang³, Xiao Li Xu², Hai Xin Gou², Guo Wen Li¹
¹ Department of Pharmacy, Shanghai TCM.Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
² Department of Traditional Chinese Medicine, HuaDong Hospital, FuDan University, Shanghai, China
³ Shi's Center of Orthopaedics and Traumatology, ShuGuang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China

Abstract:

Background: Knee osteoarthritis (KOA) is an age-related disease. Huzhangoside D is a saponin isolated from genus Clematis L. (Ranunculaceae). The aim of this study is to explore the anti-inflammatory, apoptotic, and autophagy regulation effects of huzhangoside D on KOA in a rat model. Materials and Methods: The KOA model was established by an anterior cruciate ligament transection surgery. Huzhangoside D was administered for 4 weeks. The weight-bearing assay, morphology observation, and intrinsic mechanism exploration were performed. Results: After administration, the weight-bearing assay showed that huzhangoside D promoted joint function recovery. Hematoxylin-eosin and safranin O-Fast green staining indicated that huzhangoside D ameliorated the structural damage. The Mankin scores were decreased in the huzhangoside D groups. Huzhangoside D enhanced cartilage thickness. Enzyme-linked immunosorbent assay study revealed that huzhangoside D downregulated the proinflammatory cytokine (tumor necrosis factor alpha, interleukin-6, and interleukin-1β) levels, while it upregulated the anti-inflammatory cytokine (interleukin-10) level in rat serum. Terminal deoxynucleotidyl transferase dUTP nick end labeling assay showed that huzhangoside D downregulated the apoptosis ratio of cartilage cells. Immunohistochemical staining showed that huzhangoside D upregulated the autophagy-related protein beclin-1, ATG5, ATG7, and light chain 3 levels and downregulated the p62 level. Moreover, the AKT and mTOR signaling pathway activities were downregulated. The 3-MA combination with huzhangoside D downregulated the weight-bearing function and morphology of the knee and upregulated the proinflammatory cytokines, which showed the role of autophagy as a protective mechanism in the effect of huzhangoside D. Conclusion: This study revealed that huzhangoside D is a promising agent in KOA treatment.