Sanse Powder Essential Oil Nanoemulsion Negatively Regulates TRPA1 by AMPK/mTOR Signaling in Synovitis: Knee Osteoarthritis Rat Model and Fibroblast-Like Synoviocyte Isolates

Abstract

Synovitis is the primary driving factor for the occurrence and development of knee osteoarthritis (KOA) and fibroblast-like synoviocytes (FLSs) and plays a crucial role during this process. Our previous works revealed that transient receptor potential ankyrin 1 (TRPA1) ion channels mediate the amplification of KOA synovitis. In recent years, essential oils have been proved to have blocking effect on transient receptor potential channels. Meanwhile, the therapeutic effect of Sanse Powder on KOA synovitis has been confirmed in clinical trials and basic studies; although, the mechanism remains unclear. In the present study, Sanse Powder essential oil nanoemulsion (SP-NEs) was prepared, and then chemical composition, physicochemical properties, and stability were investigated. Besides, both in MIA-induced KOA rats and in LPS-stimulated FLSs, we investigated whether SP-NES could alleviate KOA synovitis by interfering with AMP-activated protein kinase- (AMPK-) mammalian target of rapamycin (mTOR), an energy sensing pathway proved to negatively regulate the TRPA1. Our research shows that the top three substances in SP-NEs were tumerone, delta-cadinene, and Ar-tumerone, which accounted for 51.62% of the total, and should be considered as the main pharmacodynamic ingredient. Less inflammatory cell infiltration and type I collagen deposition were found in the synovial tissue of KOA rats treated with SP-NEs, as well as the downregulated expressions of interleukin (IL)-1β, IL-18, and TRPA1. Besides, SP-NEs increased the phosphorylation level of AMPK and decreased the phosphorylation level of mTOR in the KOA model, and SP-NEs also upregulated expressions of peroxisome proliferator-activated receptor-gamma (PPARγ) and PPARγ coactivator-1α and downstream signaling molecules of AMPK-mTOR in vivo and in vitro. To conclude, a kind of Chinese herbal medicine for external use which is effective in treating synovitis of KOA was extracted and prepared into essential oil nanoemulsion with stable properties in the present study. It may alleviate synovitis in experimental KOA through the negative regulation of TRPA1 by AMPK-mTOR signaling.

Fabrication and Biological Activities of All-in-One Composite Nanoemulsion Based on Blumea balsamifera Oil-Tea Tree Oil

“…Some investigators have also demonstrated the anti-inflammatory activity of EO NE using models of arthritis. Li et al [63] prepared a sanse powder EO NE (SP-NE) and also found less inflammatory cell infiltration in the synovial tissue of osteoarthritis rats treated with SP-NEs. Similar results were reported by Mohammadifar et al [64].…”

Deferoxamine in the Treatment of Hemophilic Synovitis by Inhibiting Macrophage Iron Overload

“…These ndings suggest that deferoxamine can mitigate osteoarthritis caused by iron overload, yet its impact on the M1 polarization of synovial macrophages due to iron overload remains unexplored. Given the crucial role of the mTORC1-p70S6K/4E-BP1 pathway in M1 macrophage polarization and synovitis promotion [25,26], and the potential for intracellular iron to activate this pathway [27], this study aims to demonstrate that deferoxamine can reduce synovial iron overload by inhibiting the mTORC1-p70S6K/4E-BP1 pathway, thereby suppressing M1 macrophage polarization, decreasing pro-in ammatory cytokine secretion, and alleviating hemophilic synovitis.…”

l-carnitine alleviates synovitis in knee osteoarthritis by regulating lipid accumulation and mitochondrial function through the AMPK-ACC-CPT1 signaling pathway

“…A recent study demonstrated that l -carnitine supplementation can reduce synovial inflammation and cartilage destruction and alleviate pain at the central and peripheral levels [ 22 ]. Our previous work also addressed the role of fibroblast-like synoviocytes (FLS) in AMPK signaling during KOA, accordingly suggesting that these cells promote both the onset and the progression of synovitis by regulating AMPK Signaling [ 23 ]. When LPS-induced inflammatory responses in FLS occur, TRPA1-mediated Ca 2+ influx is enhanced and IL-1β, TNF-α expression is increased [ 24 ].…”