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

Abstract

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.

3-Acetyl-11-keto-β-boswellic Acid-Based Hybrids Alleviate Acetaminophen-Induced Hepatotoxicity in HepG2 by the Regulation of Inflammatory and Oxidative Stress Pathways: An Integrated Approach

“…These elements play an important role in the activation liver’s immune response to mitigate the damage and initiate repair processes. , As the enrichment of ficolin 1-rich granules may indicate a specific immune response associated with hepatotoxicity, targeting innate immunity responses has been investigated to control APAP-related toxicity . There are no previous data addressing the ability of the prepared hybrids or their components to directly regulate this marker; still, the ability of boswellic acids to modulate innate immunity in different tissues has been proven. − …”

“… 66 There are no previous data addressing the ability of the prepared hybrids or their components to directly regulate this marker; still, the ability of boswellic acids to modulate innate immunity in different tissues has been proven. 67 − 69 …”

Non-weight-bearing exercise attenuates papain-induced knee osteoarthritis in rats via the TLR4/MyD88/NF-κB signaling pathway

“…The TLR4/MyD88/NF-κB signaling pathway has been identified in both human and rat articular chondrocytes [ 25 , 26 ]. Previous chondrocyte experiments [ 27 ] revealed that the activation of the TLR4 signaling pathway in human and animal chondrocytes further activated the downstream NF-κB signaling pathway, and p-NF-κB was the main form of NF-κB activation [ 28 ]. This led to the release of inflammatory factors such as IL-1β, IL-6, and TNF-α.…”