Artemisia scoparia Waldst.et Kit.
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Scoparone is a biologically active constituent isolated from Artemisia capillaris and possesses a variety of pharmacological activities, such as anti-inflammatory, anti-tumor, anti-allergic and anti-cardiovascular activities. However, there are no studies focusing on the effects of scoparone against cardiac fibrosis. Therefore, the aim of this study was to investigate the effects of scoparone on Angiotensin II (Ang II)-induced extracellular matrix (ECM) remodeling and its possible mechanism in cardiac fibroblasts (CFs). Our results demonstrated that scoparone effectively attenuated CFs proliferation in Ang II-stimulated CFs. Scoparone also prevented the differentiation of CFs to myofibroblasts and ECM proteins (type I collagen and fibronectin) expression in Ang II-stimulated CFs. Furthermore, scoparone prevented Ang II-induced the activation of TGF-β1/Smad signalling in CFs. Taken together, these studies indicated that scoparone attenuated Ang II-induced ECM remodeling in CFs, at least in part, by inhibiting TGF-β1/Smad signalling. These findings suggest that scoparone may be used a novel therapeutic agent against cardiac fibrosis.
Cardiac fibrosis; Extracellular matrix; Scoparone; TGF-β1/Smad signalling.
Scoparone Attenuates Angiotensin II-induced Extracellular Matrix Remodeling in Cardiac Fibroblasts
Bao Fu 1 , Yi Su 1 , Xin Ma 1 , Chunyan Mu 2 , Fusheng Yu 1
Osteoarthritis (OA) is a degenerative joint disease that is commonly accompanied by inflammation. Scoparone is a biologically active constituent isolated from Artemisia capillaris and possesses anti-inflammatory activity. However, the effect of scoparone on inflammatory response in OA has not been authenticated. The aim of this study was to evaluate the role of scoparone in OA in vitro. Our results showed that IL-1β treatment significantly inhibited the cell viability of chondrocytes, whereas the inhibition effect was attenuated by scoparone in a dose-dependent manner. IL-1β also efficiently induced the production of nitric oxide (NO), prostaglandin E2 (PGE2), MMP-3, MMP-13, ADAMTS-4 and ADAMTS-5 in chondrocytes. However, scoparone dose-dependently suppressed the induction. In addition, scoparone repressed IL-1β-induced the expression of iNOS and COX-2 in chondrocytes. Furthermore, the activation of the PI3K/Akt/NF-κB pathway induced by IL-1β was diminished by scoparone treatment. Taken together, these findings indicated that scoparone inhibited the expression of inflammatory mediators in IL-1β-induced chondrocytes via regulating the PI3K/Akt/NF-κB pathway. Thus, scoparone may be used as a new therapeutic agent for the treatment of OA.
Chondrocytes; IL-1β; Inflammatory responses; Osteoarthritis (OA); PI3K/Akt/NF-κB pathway; Scoparone.
Scoparone Prevents IL-1β-induced Inflammatory Response in Human Osteoarthritis Chondrocytes Through the PI3K/Akt/NF-κB Pathway
Chao Lu 1 , Yanqi Li 2 , Shouye Hu 1 , Yuanzhen Cai 1 , Zhi Yang 1 , Kan Peng 3
Scoparone, a naturally-occurring, bioactive compound isolated from the Chinese herb Artemisia capillaria, has been shown to ameliorate hepatotoxicity and cholestasis in liver diseases. However, the pharmacological effect of scoparone in non-alcoholic steatohepatitis (NASH) has not been elucidated. In this study, we investigated the protective effects and mechanisms of scoparone in NASH. In vivo, the NASH model was established in mice fed a methionine and choline-deficient (MCD) diet for 4weeks, with or without simultaneous scoparone treatment. In vitro, RAW264.7 cells induced by lipopolysaccharide (LPS) were pretreated with or without different concentrations of scoparone. Hepatic triglycerides and serum AST and ALT levels were examined by biochemical assays. Hepatic histology was assessed by H&E, oil red O and Masson’s trichrome staining methods, which were applied to analyze the protective effects of scoparone in NASH. To further explore the underlying mechanism of scoparone, immunohistochemistry, TUNEL, qRT-PCR, and Western blotting assays were applied to liver tissue or LPS-induced RAW264.7 cells. We found that scoparone can effectively improve hepatic steatosis, apoptosis, inflammation, and fibrosis in an MCD diet-induced NASH murine model. Mechanistically, we demonstrated that scoparone treatment alleviates NASH- and lipopolysaccharide (LPS)-induced immune responses in macrophages partly by blocking TLR-4/NF-κB signaling in a dose-dependent manner. Taken together, our results present the potential protective effects and mechanism of scoparone in NASH, suggesting a potentially beneficial drug treatment for NASH.
Apoptosis; Fibrosis; Inflammation; Non-alcoholic steatohepatitis; Scoparone.
Scoparone Alleviates Inflammation, Apoptosis and Fibrosis of Non-Alcoholic Steatohepatitis by Suppressing the TLR4/NF-κB Signaling Pathway in Mice
Beibei Liu 1 , Xiaoling Deng 1 , Qianqian Jiang 1 , Guixin Li 1 , Junli Zhang 1 , Ning Zhang 1 , Shengliang Xin 1 , Keshu Xu 2