AUTHOR=Sanchez Christelle , Zappia Jérémie , Lambert Cécile , Foguenne Jacques , Dierckxsens Yvan , Dubuc Jean-Emile , Delcour Jean-Pierre , Gothot André , Henrotin Yves 

TITLE=Curcuma longa and Boswellia serrata Extracts Modulate Different and Complementary Pathways on Human Chondrocytes In Vitro: Deciphering of a Transcriptomic Study

JOURNAL=Frontiers in Pharmacology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.931914

DOI=10.3389/fphar.2022.931914

ISSN=1663-9812

ABSTRACT=<p><bold>Objectives:</bold><italic>Curcuma longa</italic> (CL) and <italic>Boswellia serrata</italic> (BS) extracts are used to relieve osteoarthritis symptoms. The aim of this <italic>in vitro</italic> study was to investigate their mechanisms of action at therapeutic plasmatic concentrations on primary human osteoarthritic (OA) chondrocytes.</p><p><bold>Methods:</bold> BS (10–50 μg/ml) and CL (0.4–2 μg/ml corresponding to 1–5 µM of curcumin) were evaluated separately or in combination on primary chondrocytes isolated from 17 OA patients and cultured in alginate beads. Ten patients were used for RNA-sequencing analysis. Proteomic confirmation was performed either by immunoassays in the culture supernatant or by flow cytometry for cell surface markers after 72 h of treatment.</p><p><bold>Results:</bold> Significant gene expression modifications were already observed after 6 h of treatment at the highest dose of CL (2 μg/ml) while BS was significantly effective only after 24 h of treatment irrespective of the concentration tested. The most over-expressed genes by CL were anti-oxidative, detoxifying, and cytoprotective genes involved in the <italic>Nrf2</italic> pathway. Down-regulated genes were principally pro-inflammatory cytokines and chemokines. Inversely, BS anti-oxidant/detoxifying activities were related to the activation of <italic>Nrf1</italic> and PPARα pathways. BS anti-inflammatory effects were associated with the increase in GDF15, decrease in cholesterol cell intake and fatty acid metabolism-involved genes, and down-regulation of Toll-like receptors (TLRs) activation. Similar to CL, BS down-regulated ADAMTS1, 5, and MMP3, 13 genes expression. The combination of both CL and BS was significantly more effective than CL or BS alone on many genes such as IL-6, CCL2, ADAMTS1, and 5.</p><p><bold>Conclusion:</bold> BS and CL have anti-oxidative, anti-inflammatory, and anti-catabolic activities, suggesting a protective effect of these extracts on cartilage. Even if they share some mechanism of action, the two extracts act mainly on distinct pathways, and with different time courses, justifying their association to treat osteoarthritis.</p>