Toll-like receptor 2 (TLR2) is expressed by several immune cells in the central nervous system and plays an important role in neuroinflammation. TLR2 upregulation has been reported in multiple sclerosis patients and in experimental autoimmune encephalomyelitis (EAE), a mouse model for multiple sclerosis. Therefore, modulating TLR2 signaling can be an effective treatment strategy against MS. Oleanolic acid acetate (OAA) has antiinflammatory and immunomodulatory effects. Hence, this study aimed to examine the effects of OAA on TLR2 signaling and neuroinflammation in EAE. EAE was induced in C57/BL6 mice using synthesized myelin oligodendrocyte glycoprotein (MOG) 35-55 peptide, and OAA was administered daily. Hind limb paralysis and inflammatory cell infiltration were observed in the spinal cords of EAE mice. Moreover, T-cell proliferation was significantly stimulated in splenic cells from EAE mice. The expression of proinflammatory cytokines in the spinal cord was upregulated, and their serum protein levels were increased in EAE mice. Furthermore, upregulation of TLR2 and downstream signaling molecules was observed in the spinal cord. These pathological changes were reversed by OAA treatment. Our results suggest that OAA might have promising therapeutic properties and that the TLR signaling pathway is an effective therapeutic target against multiple sclerosis.
Spiraea prunifolia var. simpliciflora (SP) is traditionally used as an herbal remedy to treat fever, malaria, and emesis. This study aimed to evaluate the anti-oxidative and anti-inflammatory properties of the methanol extract of SP leaves in tumor necrosis factor (TNF)-α-stimulated NCI-H292 cells and in a lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model. SP decreased the number of inflammatory cells and the levels of TNF-α, interleukin (IL)-1β, and IL-6 in the bronchoalveolar lavage fluid, and inflammatory cell infiltration in the lung tissues of SP-treated mice. In addition, SP significantly suppressed the mRNA and protein levels of TNF-α, IL-1β, and IL-6 in TNF-α-stimulated NCI-H292 cells. SP significantly suppressed the phosphorylation of the mitogen-activated protein kinases (MAPKs) and p65-nuclear factor-kappa B (NF-κB) in LPS-induced ALI mice and TNF-α-stimulated NCI-H292 cells. SP treatment enhanced the nuclear translocation of nuclear factor erythroid 2-related factor (Nrf2) with upregulated antioxidant enzymes and suppressed reactive oxygen species (ROS)-mediated oxidative stress in the lung tissues of LPS-induced ALI model and TNF-α-stimulated NCI-H292 cells. Collectively, SP effectively inhibited airway inflammation and ROS-mediated oxidative stress, which was closely related to its ability to induce activation of Nrf2 and inhibit the phosphorylation of MAPKs and NF-κB. These findings suggest that SP has therapeutic potential for the treatment of ALI.
Aster yomena (A. yomena) extract has anti-inflammatory, antioxidant, anti-asthma, and anti-atopic effects. However, the commercial use of A. yomena extract requires a long processing time with specific processing steps (including heat treatment and ethanol precipitation), and there are various environmental problems. We aimed to build a system to produce A. yomena extract by culturing the callus in a bioreactor that can allow rapid process scale-up to test the effect of extract (AYC-CS-E) isolated from culture supernatant of A. yomena callus on photoaging of human keratinocytes (HaCaT) caused by ultraviolet B (UVB) exposure. Through screening analysis based on ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS), 17 major metabolites were tentatively identified from AYC-CS-E for the first time. The suppression of cell proliferation caused by UVB was effectively alleviated in UVB-irradiated HaCaT cells treated with AYC-CS-E. Treatment with AYC-CS-E strongly induced the formation of type I procollagen and the inhibition of elastase in UVB-irradiated HaCaT cells and significantly reduced the expression of matrix metalloproteinase (MMP)-1. In addition, treatment of UVB-irradiated HaCaT cells with AYC-CS-E effectively improved various factors associated with an inflammatory reaction, skin damage recovery, skin moisture retention, and hyper-keratinization caused by photoaging, such as reactive oxygen species (ROS), pro-inflammatory cytokines, transforming growth factor beta (TGF-β), MMP-3, MMP-9, filaggrin, hyaluronic acid synthase 2 (HAS-2), keratin 1 (KRT-1), nuclear factor-kappa B (NF-κB), and nuclear factor erythroid 2-related factor 2 (Nrf2) at the gene and protein levels. These results suggest that AYC-CS-E can be used as a cosmetic ingredient for various skin diseases caused by photoaging, and the current callus culture system can be used commercially to supply cosmetic ingredients.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.