β Boswellic Acid Blocks Articular Innate Immune Responses: An In Silico and In Vitro Approach to Traditional Medicine

• Published in: Antioxidants Vol. 12; no. 2; p. 371
• Main Authors: Franco-Trepat, Eloi, Alonso-Pérez, Ana, Guillán-Fresco, María, López-Fagúndez, Miriam, Pazos-Pérez, Andrés, Crespo-Golmar, Antía, Belén Bravo, Susana, López-López, Verónica, Jorge-Mora, Alberto, Cerón-Carrasco, José P, Lois Iglesias, Ana, Gómez, Rodolfo
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 03.02.2023; MDPI
• Subjects: Arthritis; Ayurvedic medicine; Boswellia serrata; Cartilage; Cartilage diseases; Cell culture; Chondrocytes; clinical trials; Computer applications; computer simulation; Cyclooxygenase-2; Cytokines; Extracellular matrix; Gene expression; humans; IL1; Immune response; Inflammation; Innate immunity; Interleukin 1; Interleukin 1 receptors; interleukin-6; Kinases; MAP kinase; Medicine; Metabolism; Metabolomics; mice; NF-κB protein; Nitric oxide; Observations; Osteoarthritis; osteoblasts; Pathophysiology; pharmacology; Proteins; Proteomics; Reactive oxygen species; Rheumatic diseases; ROS; Signal transduction; Synoviocytes; therapeutics; TLR4; TLR4 protein; Toll-like receptor 4; Toll-like receptors; Traditional medicine; Transcriptomics; Germany; United States > US; chondrocytes; osteoarthritis; ROS; synoviocytes; NLRP3; TLR4; IL1
• ISSN: 2076-3921; 2076-3921
• DOI: 10.3390/antiox12020371

Osteoarthritis (OA) is hallmarked as a silent progressive rheumatic disease of the whole joint. The accumulation of inflammatory and catabolic factors such as IL6, TNFα, and COX2 drives the OA pathophysiology into cartilage degradation, synovia inflammation, and bone destruction. There is no clinical available OA treatment. Although traditional ayurvedic medicine has been using extracts (BSE) as an antirheumatic treatment for a millennium, none of the BSE components have been clinically approved. Recently, β boswellic acid (BBA) has been shown to reduce in vivo OA-cartilage loss through an unknown mechanism. We used computational pharmacology, proteomics, transcriptomics, and metabolomics to present solid evidence of BBA therapeutic properties in mouse and primary human OA joint cells. Specifically, BBA binds to the innate immune receptor Toll-like Receptor 4 (TLR4) complex and inhibits both TLR4 and Interleukin 1 Receptor (IL1R) signaling in OA chondrocytes, osteoblasts, and synoviocytes. Moreover, BBA inhibition of TLR4/IL1R downregulated reactive oxygen species (ROS) synthesis and MAPK p38/NFκB, NLRP3, IFNαβ, TNF, and ECM-related pathways. Altogether, we present a solid bulk of evidence that BBA blocks OA innate immune responses and could be transferred into the clinic as an alimentary supplement or as a therapeutic tool after clinical trial evaluations.