Cangxitongbi capsule protects articular cartilage of the knee in rats by regulating ADAMTS-5

Abstract

Background: Knee osteoarthritis (KOA) is a disease with a high incidence in elderly patients and traditional Chinese medicine has a significant effect on the treatment of KOA. Cangxitongbi capsule (CXTB) is a traditional Chinese medicine for KOA treatment and has a remarkable curative effect. The purpose of this article is to investigate the mechanism of CXTB in protecting joint cartilage on KOA rats.Methods: A total of 30 male Sprague-Dawley rats were randomly assigned into five groups: control group; model group; low-, mid-, and high-dose CXTB groups (17.5, 35, and 70 mg/mL). KOA models were made by modified Hulth method except the control group. After pharmacological administration for 4 weeks, knee articular cartilages were observed by hematoxylin and eosin (HE) staining and evaluated by Mankin score. Western blot and reverse transcription-polymerase chain reaction (RT-PCR) were used to detect the concentration of ADAMTS-5. The peripheral blood of the rats was collected to detect content of interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) by enzyme-linked immunosorbent assay (ELISA). Results:The morphological structure of cartilage in the 3 CXTB groups was significantly improved compared with the model group, and the improvement positively correlated with the drug dosage (P<0.05).Compared with the model group, the expression levels of ADAMTS-5 of the 3 CXTB groups was obviously decreased (P<0.05). Furthermore, the upstream targets of ADAMTS-5, including IL-1β and TNF-α were down-regulated in the 3 CXTB groups (P<0.05).Conclusions: Knee joint cartilage on KOA model rats is protected by CXTB via down-regulation of ADAMTS-5. The upstream targets of ADAMTS-5, IL-1β and TNF-α, were also down-regulated by CXTB.

Osthole Suppresses Knee Osteoarthritis Development by Enhancing Autophagy Activated via the AMPK/ULK1 Pathway

“…After 1 week of adaptive feeding, the rats were randomly assigned into five groups: control group (gavage equivalent volumes of normal saline once a day; n = 8); model group (gavage equivalent volumes of normal saline once a day; n = 8); low- (50 mg/kg/day; gavage once a day; n = 8), mid- (75 mg/kg/day; gavage once a day; n = 8), and high-dose osthole groups (100 mg/kg/day; gavage once a day; n = 8) [ 42 , 43 ]. With the exception of the control group, rats were subjected to the modified Hulth method [ 11 ] to establish experimental KOA. Briefly, the left knee anterior cruciate and medial collateral ligaments were transected, and the medial meniscus was resected.…”

“…As a widely used herbal medicine for dispelling wind, removing dampness, and relieving pain, APR has been applied in East Asian countries for thousands of years [ 9 ]. Our previous studies have shown that the Cangxitongbi (CXTB) capsule, a Chinese patent medicine mainly composed of APR, can protect articular cartilage by enhancing autophagy, suppressing inflammation, and inhibiting cartilage extra-cellular matrix (ECM) degradation [ 10 , 11 ]. Given the high content of osthole in CXTB, it is necessary to further verify the mechanism of osthole in inhibiting KOA cartilage degeneration.…”

Polydatin Protects Against Articular Cartilage Degeneration by Regulating Autophagy Mediated by AMPK/Mtor Signaling Pathway

“…All the rats were fed and drank freely and normally. After modeling 4 weeks [13], the KOA + polydatin rats were intraperitoneally injected with polydatin (4 mg/kg, dissolved in saline), while normal rats and model rats intraperitoneally injected with same volume normal saline and continued for 30 d.…”