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

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

doi:10.3389/fphar.2022.931914

Article (Scientific journals)

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

Sanchez, Christelle; Zappia, Jérémie; Lambert, Cécile et al.

2022 • In Frontiers in Pharmacology, 13

Peer Reviewed verified by ORBi

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https://hdl.handle.net/2268/294498

DOI
10.3389/fphar.2022.931914

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Keywords :

Pharmacology (medical); Pharmacology; Osteoarthritis; Curcuma; Boswellia; RNA-seq; chondrocytes; Toll-like receptors

Abstract :

[en] 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.

Research Center/Unit :

CIRM - Centre Interdisciplinaire de Recherche sur le Médicament - ULiège
d‐BRU - Dental Biomaterials Research Unit - ULiège

Disciplines :

Rheumatology

Author, co-author :

Sanchez, Christelle ; Université de Liège - ULiège > Unités de recherche interfacultaires > Centre Interdisciplinaire de Recherche sur le Médicament (CIRM)

Zappia, Jérémie ; Université de Liège - ULiège > Unités de recherche interfacultaires > Centre Interdisciplinaire de Recherche sur le Médicament (CIRM)

Lambert, Cécile ; Université de Liège - ULiège > Unités de recherche interfacultaires > Centre Interdisciplinaire de Recherche sur le Médicament (CIRM)

FOGUENNE, Jacques ; Centre Hospitalier Universitaire de Liège - CHU > > Service d'hématologie biologique et immuno-hématologie

Dierckxsens, Yvan

Dubuc, Jean-Emile

Delcour, Jean-Pierre

Gothot, André ; Centre Hospitalier Universitaire de Liège - CHU > > Service d'hématologie biologique et immuno-hématologie

Henrotin, Yves ; Université de Liège - ULiège > Unités de recherche interfacultaires > Centre Interdisciplinaire de Recherche sur le Médicament (CIRM)

Language :

English

Title :

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

Publication date :

11 August 2022

Journal title :

Frontiers in Pharmacology

ISSN :

1663-9812

Publisher :

Frontiers Media SA

Volume :

Peer reviewed :

Peer Reviewed verified by ORBi

Additional URL :

https://www.frontiersin.org/articles/10.3389/fphar.2022.931914/full

Funders :

SPW DGO6 - Service Public de Wallonie. Economie, Emploi, Recherche

Available on ORBi :

since 11 September 2022

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