Regulation of Inflammatory Response in Human Osteoarthritic Chondrocytes by Novel Herbal Small Molecules.

Abstract

In this study, 34 Traditional Chinese Medicine (TCM) compounds were screened for potential anabolic and anti-inflammatory properties on human osteoarthritic (OA) chondrocytes. The anabolic effects were assessed by measuring the glycosaminoglycan (GAG) relative to the DNA content using a 3D pellet culture model. The most chondrogenic compounds were tested in an inflammatory model consisting of 3 days of treatment with cytokines (IL-1β/TNF-α) with or without supplementation of TCM compounds. The anti-inflammatory effects were assessed transcriptionally, biochemically and histologically. From the 34 compounds, Vanilic acid (VA), Epimedin A (Epi A) and C (Epi C), 2''-O-rhamnosylicariside II (2-O-rhs II), Icariin, Psoralidin (PS), Protocatechuicaldehyde (PCA), 4-Hydroxybenzoic acid (4-HBA) and 5-Hydroxymethylfurfural (5-HMF) showed the most profound anabolic effects. After induction of inflammation, pro-inflammatory and catabolic genes were upregulated, and GAG/DNA was decreased. VA, Epi C, PS, PCA, 4-HBA and 5-HMF exhibited anti-catabolic and anti-inflammatory effects and prevented the up-regulation of pro-inflammatory markers including metalloproteinases and cyclooxygenase 2. After two weeks of treatment with TCM compounds, the GAG/DNA ratio was restored compared with the negative control group. Immunohistochemistry and Safranin-O staining confirmed superior amounts of cartilaginous matrix in treated pellets. In conclusion, VA, Epi C, PS, PCA, 4-HBA and 5-HMF showed promising anabolic and anti-inflammatory effects.

• Authors: Reihane Ziadlou, Andrea Barbero, Martin J Stoddart, Michael Wirth, Zhen Li, Ivan Martin, Xin-Luan Wang, Ling Qin, Mauro Alini, Sibylle Grad
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 20 Issue 22 (Nov 15 2019) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 31731767 (Publication Type: Journal Article)

Chemical References

• Interleukin-1beta
• Tumor Necrosis Factor-alpha

Topics

• Chondrocytes (drug effects, metabolism)
• Humans
• Inflammation (drug therapy, immunology)
• Interleukin-1beta (therapeutic use)
• Medicine, Chinese Traditional (methods)
• Osteoarthritis (drug therapy, immunology)
• Tumor Necrosis Factor-alpha (therapeutic use)