β Boswellic Acid Blocks Articular Innate Immune Responses: An In Silico and In Vitro Approach to Traditional Medicine
Eloi Franco-Trepat,
Ana Alonso-Pérez,
María Guillán-Fresco,
Miriam López-Fagúndez,
Andrés Pazos-Pérez,
Antía Crespo-Golmar,
Susana Belén Bravo,
Verónica López-López,
Alberto Jorge-Mora,
José P. Cerón-Carrasco,
Ana Lois Iglesias,
Rodolfo Gómez
Affiliations
Eloi Franco-Trepat
Musculoskeletal Pathology Group, Institute IDIS, Santiago University Clinical Hospital, 15706 Santiago de Compostela, Spain
Ana Alonso-Pérez
Musculoskeletal Pathology Group, Institute IDIS, Santiago University Clinical Hospital, 15706 Santiago de Compostela, Spain
María Guillán-Fresco
Musculoskeletal Pathology Group, Institute IDIS, Santiago University Clinical Hospital, 15706 Santiago de Compostela, Spain
Miriam López-Fagúndez
Musculoskeletal Pathology Group, Institute IDIS, Santiago University Clinical Hospital, 15706 Santiago de Compostela, Spain
Andrés Pazos-Pérez
Musculoskeletal Pathology Group, Institute IDIS, Santiago University Clinical Hospital, 15706 Santiago de Compostela, Spain
Antía Crespo-Golmar
Musculoskeletal Pathology Group, Institute IDIS, Santiago University Clinical Hospital, 15706 Santiago de Compostela, Spain
Susana Belén Bravo
Musculoskeletal Pathology Group, Institute IDIS, Santiago University Clinical Hospital, 15706 Santiago de Compostela, Spain
Verónica López-López
Musculoskeletal Pathology Group, Institute IDIS, Santiago University Clinical Hospital, 15706 Santiago de Compostela, Spain
Alberto Jorge-Mora
Musculoskeletal Pathology Group, Institute IDIS, Santiago University Clinical Hospital, 15706 Santiago de Compostela, Spain
José P. Cerón-Carrasco
Centro Universitario de la Defensa, Universidad Politécnica de Cartagena, C/Coronel López Peña S/N, Base Aérea de San Javier, Santiago de La Ribera, 30720 Murcia, Spain
Ana Lois Iglesias
Musculoskeletal Pathology Group, Institute IDIS, Santiago University Clinical Hospital, 15706 Santiago de Compostela, Spain
Rodolfo Gómez
Musculoskeletal Pathology Group, Institute IDIS, Santiago University Clinical Hospital, 15706 Santiago de Compostela, Spain
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 Boswellia serrata 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.