Synthesis and biological evaluation of nitrogen-containing benzophenone analogues as TNF-α and IL-6 inhibitors with antioxidant activity

Turkish Scorzonera Species Extracts Attenuate Cytokine Secretion via Inhibition of NF-κB Activation, Showing Anti-Inflammatory Effect in Vitro

“…As visible, with exception of 8, all phenolics identified in Scorzonera aerial part extracts are glycosides, in majority flavonoids. The presence of all these compounds (1)(2)(3)(4)(5)(6)(7)(8) in the most active extracts (Ex. 1 and Ex.…”

“…From the above mentioned, we suggested that chlorogenic acid (8), derivatives of dicaffeoyl-quinic acid (6 and 7), and flavonoids, especially quercetin-3-O-β-D-glucoside (1) and hyperoside (2) could be responsible for the anti-inflammatory activity of tested extracts. Therefore, further experiments were carried out with phenolic compounds previously obtained from Scorzonera species (1)(2)(3)(4)(5)(6)(7)(8), to assay the inhibition of TNF-α and IL-1β production in THP-1 cells, and later also with triterpenes 9-16, because taraxasterol acetate (9) isolated from S. latifolia showed previously analgesic activity in vivo in writhing and tail-flick tests [21] and also other triterpenoid substances like lupeol derivatives (10 and 11), β-sitosterol (12) and other triterpenes (13)(14)(15)(16) could potentially demonstrate anti-phlogistic effect [38,39]. Unfortunately, only weak activity of compounds tested was observed, and no statistically significant activity has been observed in comparison with standard used (prednisone, Supplementary Materials, Figure S1).…”

“…Inflammation is a coordinated and complex biological reaction involving various pro-inflammatory and anti-inflammatory cellular proteins, enzymes, and cytokines [1][2][3][4][5]. Among the pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α) and interleukin 1-β (IL-1β) have a wide range of biological activities on numerous cell types and are reported to be involved in the pathogenesis of various inflammatory disorders, such as rheumatoid arthritis, inflammatory bowel disease, osteoarthritis, psoriasis, endotoxemia, and/or toxic shock syndrome, different types of cancer, and degenerative diseases of the central nervous system [3,6,7].…”

“…Among the pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α) and interleukin 1-β (IL-1β) have a wide range of biological activities on numerous cell types and are reported to be involved in the pathogenesis of various inflammatory disorders, such as rheumatoid arthritis, inflammatory bowel disease, osteoarthritis, psoriasis, endotoxemia, and/or toxic shock syndrome, different types of cancer, and degenerative diseases of the central nervous system [3,6,7]. In response to infection or injury, these cytokines are released by tissue macrophages, and serve to recruit circulating neutrophils to the site of inflammation.…”

“…They may also directly modulate neutrophil functions across the vascular endothelium [6]. TNF-α, which is reported as a key cytokine in the inflammation, has a wide range of functions for maintaining the normal cellular physiology such as triggering of apoptosis, influence on secretion of cytokines e.g., IL-1, IL-6 and IL-10 as well as activation of T cells and other inflammatory cells [3,8]. TNF-α also causes further activation of the transcription factors NF-κB [9] which regulates about 200 immune, growth, and inflammation-related genes [4].…”