Andrographolide Exerts Chondroprotective Activity in Equine Cartilage Explant and Suppresses Interleukin-1β-Induced MMP-2 Expression in Equine Chondrocyte Culture

Abstract

Cartilage erosion in degenerative joint diseases leads to lameness in affected horses. It has been reported that andrographolide from Andrographis paniculata inhibited cartilage matrix-degrading enzymes. This study aimed to explore whether this compound protects equine cartilage degradation in the explant culture model and to determine its effect on matrix metalloproteinase-2 (MMP-2) expression, a matrix-degrading enzyme, in equine chondrocyte culture. Equine articular cartilage explant culture was induced by 25 ng/mL interleukin-1β, a key inducer of cartilage degeneration, in cultures with or without andrographolide ranging from 10 to 50 μM. After 3–21 days, they were analyzed for the markers of cartilage degradation. It was found that interleukin-1β increased the release of sulfated glycosaminoglycans and hyaluronan from the explants into the culture media consistently with the decrease in uronic acid and collagen content in the cartilage explants. These catabolic effects were inhibited when cotreated with interleukin-1β and andrographolide. In primary equine chondrocytes, andrographolide suppressed interleukin-1β-induced MMP-2 mRNA expression and MMP-2 activity in the culture medium. These results confirmed the in vitro potent chondroprotective activities of this compound which were performed in cartilage explants and on a cellular level. These may indicate the application of andrographolide for therapeutic use in equine degenerative joint diseases.

TGF-β1 upregulates the expression of hyaluronan synthase 2 and hyaluronan synthesis in culture models of equine articular chondrocytes

“…Twenty-four hours prior to treatment, at 80% confluence, the cultured cells were starved and then treated with 2.5 ng/mL TGF-β1 at the indicated times (0, 3, 6, 9, 15, 24, 36, and 48 h) to evaluate the time-effect of TGF-β1 on HAS2 gene expression. Three-hour treatments with different concentrations of TGF-β1 (0, 2.5, 5, and 10 ng/mL) for 3 h were conducted to evaluate the dose-effect of TGF-β1 on HAS2 gene expression as assessed by using semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) [ 31 ].…”

A double‐blind, randomized, placebo‐controlled study to assess the efficacy of Andrographis paniculata standardized extract (ParActin®) on pain reduction in subjects with knee osteoarthritis

“…These observations suggest that andrographolide can be considered as a potential therapeutic agent for the treatment and prevention of osteoarthritis, because it shows potent inhibition of matrix metalloproteinase (MMP) 1, 3, and 13 and iNOS expression, as well as the upregulation of TIMP‐1 in IL‐1β‐stimulated human articular chondrocytes (Ding et al, ; Tangyuenyong, Viriyakhasem, Peansukmanee, Kongtawelert, & Ongchai, ). Using rat chondrocytes injured with H 2 O 2 , andrographolide was effective in increasing antioxidant enzyme activity, including SOD and CAT and was able to reduce Inflammatory factors such as MMP13, tissue inhibitor of metalloproteinase 1 (TIMP1), and interleukin‐6 (Li et al, ).…”

Andrographolide prevents human nucleus pulposus cells against degeneration by inhibiting the NF‐κB pathway

“…ANDRO has been demonstrated in the use of anti‐inflammation and antiapoptosis therapies (Tangyuenyong et al, ). In this study, ANDRO inhibited the augments of ADAMTS4 , ADAMTS5 , COX2 , PGE2 , MMP‐13 , and MMP‐3 induced by LPS in NP cells, indicating the promising therapeutic effect of ANDRO on IDD.…”

“…Traditional Chinese medicine has gained global attention for its promising therapeutic effects in a wide range of diseases, including inflammation, cancer, and age‐related degenerations (Xie, Zhang, Sun, Yan, & Wang, ). Andrographolide (ANDRO) extracted from Andrographis paniculata , a traditional Chinese herb used in clinic for anti‐inflammatory (Z. Zhu, Duan, Jing, Xu, & Yu, ) and anticancer (Khan, Khan, Farooqui, & Ansari, ) utilities, has been widely applied in the treatment of musculoskeletal disorders and degenerative diseases (Jiang et al, ; Tangyuenyong, Viriyakhasem, Peansukmanee, Kongtawelert, & Ongchai, ). For instance, Q. Zhu et al () suggest that ANDRO represses the IL‐23/IL‐17‐axis‐mediated nonspecific intestinal inflammatory disease.…”