Discovery of Phenolic Glycoside from Hyssopus cuspidatus Attenuates LPS-Induced Inflammatory Responses by Inhibition of iNOS and COX-2 Expression through Suppression of NF-κB Activation

Abstract

It seems quite necessary to obtain effective substances from natural products against inflammatory response (IR) as there are presently clinical problems regarding accompanying side effects and lowered quality of life. This work aimed to investigate the abilities of hyssopuside (HY), a novel phenolic glycoside isolated from Hyssopus cuspidatus (H. cuspidatus), against IR in lipopolysaccharide (LPS)-induced RAW 264.7 cells and mouse peritoneal macrophages. The results indicated that HY could reduce nitric oxide (NO) production and inhibit the production and secretion of pro-inflammatory mediators including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in LPS-stimulated macrophages. Moreover, data from the immunofluorescence study showed that HY suppressed nuclear translocation of nuclear factor-kappa B (NF-κB) upon LPS induction. The Western blot results suggested that HY reversed the LPS-induced degradation of IκB (inhibitor of NF-κB), which is normally required for the activation of NF-κB. Meanwhile, the overexpression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) diminished significantly with the presence of HY in response to LPS stimulation. On the other hand, HY had a negligible impact on the activation of mitogen-activated protein kinase (MAPK) pathways. Moreover, an in silico study of HY against four essential proteins/enzymes revealed that COX-2 was the most efficient enzyme for the interaction, and binding of residues Phe179, Asn351, and Ser424 with HY played crucial roles in the observed activity. The structure analysis indicated the typical characterizations with phenylethanoid glycoside contributed to the anti-inflammatory effects of HY. These results indicated that HY manipulated its anti-inflammatory effects mainly through blocking the NF-κB signal transduction pathways. Collectively, we believe that HY could be a potential alternative phenolic agent for alleviating excessive inflammation in many inflammation-associated diseases.

Anti-Inflammatory Effect of Sulfated Polysaccharides Isolated from Codium fragile In Vitro in RAW 264.7 Macrophages and In Vivo in Zebrafish

“…Anti-inflammatory effects of the algal sulfated polysaccharides were related to their sulfated content and proportion of monosaccharides. Previous reports suggested that the polysaccharides contain high amounts of the sulfate group, fucose, and galactose, which could inhibit the LPS-induced inflammatory response in RAW 264.7 cells [23][24][25][26][27]. CFCE-PS contains 21.06% sulfate and 70.19% galactose, and significantly inhibited the production of the inflammatory molecules in LPS-stimulated RAW 264.7 cells.…”

Based on network pharmacology and molecular docking to explore the protective effect of Epimedii Folium extract on cisplatin-induced intestinal injury in mice

“…In addition to direct toxicity to the body, ROS can also induce the expression of the nuclear transcription factor NF-κB, thereby increasing the production of cell adhesion molecules, chemokines, and proinflammatory cytokines, and further enhancing the cytotoxicity of cisplatin ( Li et al, 2017 ). Transcription of inflammatory markers such as iNOS, COX-2, TNF-α, and IL-1β can be triggered explicitly by activation of NF-κB ( Liu et al, 2021 ). According to literature reports, Epimedii Folium can significantly reduce the expression of nuclear transcription factor NF-κB and the secretion of proinflammatory cytokines TNF-α and IL-1β ( Huang et al, 2018 ; Yan et al, 2018 ).…”

CXCR1 and its downstream NF-κB inflammation signaling pathway as a key target of Guanxinning injection for myocardial ischemia/reperfusion injury

“…This study not only revealed that CXCR1 is a key target for the treatment of AMI and is regulated by GXNI, but also found that the high expression of CXCR1 in myocardial tissue caused by MIRI exacerbated the inflammatory response via activating the downstream COX-2/ICAM-1/VCAM-1 through the NF-κB pathway. As an inflammatory mediator, COX-2 is induced by NF-κB under certain conditions, which promotes the release of inflammatory cytokine ( 64 , 65 ). It is known that ICAM-1 and VCAM-1 not only play important roles in angiogenesis, but also closely related to leukocyte infiltration ( 66 , 67 ).…”