Traditional chinese medicine compound delivery system for treatment of osteoarthritis

S Grad, M Alini, M Stoddart

Background

Osteoarthritis (OA) is the most prevalent degenerative joint disorder that affects millions of patients worldwide. There is currently no effective and standardised treatment available, neither for repair nor for prevention of onset or progression of this disease. In this study, 40 Traditional Chinese Medicine (TCM) compounds were screened for potential anabolic and anti-inflammatory properties on human OA chondrocytes 

 

Histological and immunohistochemical characterization of cell pellets from OA chondrocytes in the inflammatory model. Safranin-O staining, collagen II and aggrecan immunostaining of pellets after 14 days of treatment with compounds. Scale bars = 100 µm

 

Results

After induction of inflammation in our in vitro model, pro-inflammatory and catabolic genes were upregulated, and extracellular matrix content was decreased. After two weeks of treatment with certain compounds (Vanilic acid, Epimedin C, Psoralidin, Protocatechuicaldehyde, 4-Hydroxybenzoicacid and 5-Hydroxymethylfurfural), extracellular matrix was restored compared with the negative control group. Immunohistochemistry and Safranin-O staining confirmed superior amounts of cartilaginous matrix in treated pellets. 

The compounds also exhibited anti-catabolic and anti-inflammatory effects and prevented the upregulation of pro-inflammatory markers including metalloproteinases and cyclooxygenase 2. Pathway analysis by bioinformatics tools, analyzing the most potent compounds, showed that osteoarthritic and inflammatory pathways tended to be downregulated. In conclusion, Vanilic acid and Epimedin C showed promising anti-inflammatory and anabolic effects in our inflammatory model on human OA chondrocytes. A local drug delivery system for the bioactive compound is envisioned and their efficacy for cartilage repair will be tested.

Fund:

Swiss-China Joint project (SNF) ARI funding: CHF 250'000, Period: 2015-2019

 

  • Publication

    Cao H-J, Li C-R, Wang L-Y, Ziadlou R, Grad S, Zhang Y, Cheng Y, Lai Y-X, Yao X-S, Alini M, Qin L, Wang X-L. Effect and mechanism of psoralidin on promoting osteogenesis and inhibiting adipogenesis. Phytomedicine 152860, 2019.

    Zhang S, Hu P, Liu T, Li Z, Huang Y, Liao J, Hamid MR, Wen L, Wang T, Mo C, Alini M, Grad S, Wang T, Chen D, Zhou G. Kartogenin hydrolysis product 4-aminobiphenyl distributes to cartilage and mediates cartilage regeneration. Theranostics. 21;9(24):7108-7121, 2019.

    Ziadlou R, Barbero A, Stoddart MJ, Wirth M, Li Z, Martin I, Wang XL, Qin L, Alini M, Grad S. Regulation of Inflammatory Response in Human Osteoarthritic Chondrocytes by Novel Herbal Small Molecules. Int J Mol Sci. 20(22). pii: E5745, 2019.

    Ziadlou R, Rotman S, Teuschl A, Salzer E, Barbero A, Martin I, Alini M, Eglin D, Grad S. Optimization of hyaluronic acid-tyramine/silk-fibroin composite hydrogels for cartilage tissue engineering and delivery of anti-inflammatory and anabolic drugs. Mater Sci Eng C Mater Biol Appl. 2020;epub Nov 5:111701

     

    Meng X, Li L, Huang C, Shi K, Zeng Q, Wen C, Grad S, Alini M, Qin L, Wang X. Anti-inflammatory and anabolic biphasic scaffold facilitates osteochondral tissue regeneration in osteoarthritic joints.  J Mater Sci Technol. 2023;156:20-31. https://doi.org/10.1016/j.jmst.2023.01.035 

  • Presentation

    Ziadlou R, Grad S, Stoddart M, Wang X, Qin L, Barbero A, Martin I, Alini M. Regulation of Inflammatory Response by Novel Herbal Small Molecules in Human Osteoarthritic Chondrocytes. TERMIS-EU 2019, Rhodes, GR

  • Partner

    Martin I (Prof), University of Basel, CH

    Wang X (PhD), Shenzhen University, PR China

    Qin L (Prof), The Chinese University of Hong Kong, HK

    Lai Y (PhD), Shenzhen University, PR China

    Huang Y (PhD), Shanghai Institute for Biological Sciences, PR China

Completed