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

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

doi:10.3389/fphar.2022.931914

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

Front Pharmacol. 2022 Aug 11:13:931914. doi: 10.3389/fphar.2022.931914. eCollection 2022.

Authors

Christelle Sanchez^{1

2}, Jérémie Zappia^{1

2}, Cécile Lambert^{1

2}, Jacques Foguenne³, Yvan Dierckxsens⁴, Jean-Emile Dubuc^{1

5}, Jean-Pierre Delcour⁶, André Gothot³, Yves Henrotin^{1

2

7}

Affiliations

¹ MusculoSKeletal Innovative Research Lab, Center for Interdisciplinary Research on Medicines, University of Liège, Liège, Belgium.
² Center for Interdisciplinary Research on Medicines, University of Liège, Liege, Belgium.
³ Department of Laboratory Hematology, Liege University Hospital, Liege, Belgium.
⁴ Tilman SA, Baillonville, Belgium.
⁵ Cliniques Universitaires de St Luc, Brussels, Belgium.
⁶ Centre Hospitalier Du Bois de L'Abbaye, Seraing, Belgium.
⁷ Physical Therapy and Rehabilitation Department, Princess Paola Hospital, Marche-en-Famenne, Belgium.

Abstract

Objectives: Curcuma longa (CL) and Boswellia serrata (BS) extracts are used to relieve osteoarthritis symptoms. The aim of this in vitro study was to investigate their mechanisms of action at therapeutic plasmatic concentrations on primary human osteoarthritic (OA) chondrocytes. Methods: 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. Results: 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 Nrf2 pathway. Down-regulated genes were principally pro-inflammatory cytokines and chemokines. Inversely, BS anti-oxidant/detoxifying activities were related to the activation of Nrf1 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. Conclusion: 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.

Keywords: Boswellia; Curcuma; chondrocyte; osteoarthritis; transcriptomic (RNA-seq).