Attenuation of the degenerative effects of endothelin-1 on cartilaginous end plate cells by the endothelin receptor antagonist BQ-123 via the Wnt/尾-catenin signaling pathway. was written by Yuan, Wei;Li, Zhen-Xi;Zhao, Cheng-Long;Hou, Tian-Hui;Hu, Si-Wang;Liu, Wei-Bo;Yuan, Feng-Lai;Xiao, Jian-Ru. And the article was included in The spine journal : official journal of the North American Spine Society in 2018.COA of Formula: C31H42N6O7 This article mentions the following:
BACKGROUND CONTEXT: Endothelin-1 (ET-1) is an inflammatory mediator associated with cartilage end plate (CEP) degeneration in the intervertebral disc (IVD). SOX9 is downregulated during CEP degeneration, along with its targets, collagen II and aggrecan. Wnt/尾-catenin signaling is associated with CEP degeneration and a downstream target of SOX9; however, the precise mechanism of CEP degeneration and the role of ET-1 are largely unknown. PURPOSE: The purpose of the study was to evaluate the influence of the endothelin-A receptor antagonist, BQ-123, on ET-1-induced effects on cartilaginous end plate cells (CECs) associated with CEP degeneration via the Wnt/尾-catenin signaling pathway. STUDY DESIGN/SETTING: The influence of ET-1 on the expression levels of collagen II, aggrecan, and SOX9 in CECs and the effect of BQ-123 in this context were investigated. METHODS: To establish a model for CEP degeneration, three lumbar discs (L3-L4, L4-L5, and L5-L6 levels) in New Zealand white rabbits were punctured close to the vertebral end plate using a 14G needle. Intervertebral disc degeneration was evaluated by magnetic resonance imaging 4 weeks after vertebral end plate injury. CECs were then isolated from the degenerated CEPs to allow evaluation of the role of ET-1 and BQ-123 and to investigate their effects on the Wnt/尾-catenin signaling pathway. The expression of ET-1 in CECs from degenerated CEPs was analyzed by immunofluorescent staining. Changes in the levels of collagen II, aggrecan, and SOX9 were evaluated in CECs by real-time polymerase chain reaction and by Western blotting. The Wnt/尾-catenin signaling pathway was also investigated by Western blotting. RESULTS: After 4 weeks, IVDs with vertebral end plate injury exhibited clear signs of disc degeneration. Immunofluorescent staining showed that ET-1 was expressed in the cytoplasm of CECs. Endothelin-1 stimulation significantly inhibited the expression of collagen II, aggrecan, and SOX9 in CECs, whereas BQ-123 increased the levels of these three molecules. In addition, ET-1 stimulation increased the expression of 尾-catenin, cyclin D1, and Dvl1 in the Wnt/尾-catenin signaling pathway of CECs from degenerated discs and reduced the expression of GSK-3尾, whereas BQ-123 had the opposite effect. CONCLUSIONS: Endothelin-1 can reduce levels of collagen II, aggrecan, and SOX9 in CECs through activation of the Wnt/尾-catenin signaling pathway, whereas BQ-123 attenuates these negative effects, highlighting a new molecular mechanism with potential for exploitation for treatment of CEP degeneration. In the experiment, the researchers used many compounds, for example, 2-((3R,6S,9R,12R,17aS)-9-((1H-Indol-3-yl)methyl)-6-isobutyl-3-isopropyl-1,4,7,10,13-pentaoxohexadecahydro-1H-pyrrolo[1,2-a][1,4,7,10,13]pentaazacyclopentadecin-12-yl)acetic acid (cas: 136553-81-6COA of Formula: C31H42N6O7).
2-((3R,6S,9R,12R,17aS)-9-((1H-Indol-3-yl)methyl)-6-isobutyl-3-isopropyl-1,4,7,10,13-pentaoxohexadecahydro-1H-pyrrolo[1,2-a][1,4,7,10,13]pentaazacyclopentadecin-12-yl)acetic acid (cas: 136553-81-6) belongs to indole derivatives. Indole exists overwhelmingly in the 1H-indole form as do other simple indoles. They are capable of binding to a variety of receptors with high affinity and thus have applications in a wide range of therapeutic areas.COA of Formula: C31H42N6O7
Referemce:
Indole alkaloid derivatives as building blocks of natural products from聽Bacillus thuringiensis聽and聽Bacillus velezensis聽and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles