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Hepatocellular carcinoma (HCC) spreads further with continuance and increasing incidence due to its high-grade malignancy and metastasis. More effectual strategies on blocking proliferation and metastasis of cancer cells should be studied in HCC. Dulcitol, a natural product extracted from euonymus alatus, was reported that it could induce apoptosis of C6 glioma cells. However, the underlying mechanism of Dulcitol on HCC remains unclea.
In this study, we aimed to reveal the effect and potential mechanisms of Dulcitol on hepatocellular carcinoma in vitro and in vivo. Study design and methods The cell proliferation and apoptosis were evaluated by MTT, Ki-67 and Hoechst 33258/PI double staining. The migratory and invasive abilities of HepG2 cells were measured by wound-healing and transwell assays. Pathological changes of tumor tissue were observed by HE staining and IHC methods. The expression levels of protein were detected using Western Blot analysis.
The results showed that Dulcitol inhibited HepG2 cells proliferation by down-regulating the protein expression of SIRT1, Bcl-2, along with up-regulating p53, acetylated-p53 (K382), cleaved-caspase9, cleaved-caspase3, Bax, and cytochrome c in a dose-dependent manner. Furthermore, Dulcitol surpressed the migration and invasion of HepG2 cells through decreasing the levels of MMP-2, uPA and MMP-9 and increasing E-cadherin associated with tumor invasion. In vivo, Dulcitol distinctly inhibited the growth of HepG2 cancer xenograft tumors via inhibiting SIRT1/p53 pathway.
Our findings suggested that Dulcitol acted as a SIRT1 inhibitor, inducing apoptosis and inhibiting proliferation, migration and invasion of HepG2 cells and its modulatory mechanism seemed to be associated with regulation of MMPs, SIRT1/p53 pathways.
Copyright © 2019 Elsevier GmbH. All rights reserved.
Anti-cancer activity; Apoptosis; Dulcitol; Hepatocellular carcinoma; Migration
Dulcitol suppresses proliferation and migration of hepatocellular carcinoma via regulating SIRT1/p53 pathway.
Lin XL1, Li K2, Yang Z2, Chen B3, Zhang T4.
A gas-phase study on the artificial sweeteners sorbitol and dulcitol has been carried out for the first time by using a combination of chirped-pulse Fourier-transform microwave (CP-FTMW) spectroscopy and laser ablation (LA). The isolation conditions provided by the supersonic expansion reveal the intrinsic conformational structures of these sweeteners. The three and five observed conformers for sorbitol and dulcitol, respectively, are stabilized by networks of cooperative intramolecular hydrogen bonds between vicinal hydroxyl groups in clockwise or counterclockwise arrangements. Suitable places in the structure of seven out of eight conformers identified for both polyalcohols meet the requirements of the glucophore proposed by Shallenberger and Acree’s molecular theory of sweet taste. Present results provide the first linkage between sweetness and structure in sugar alcohols.
© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
artificial sweetener; dulcitol; laser ablation; rotational spectroscopy; sorbitol
The Structural Signs of Sweetness in Artificial Sweeteners: A Rotational Study of Sorbitol and Dulcitol.
Alonso ER1, Leon I1, Kolesnikova L1, Alonso JL1.
2018 Dec 19
Dulcitol was isolated chemically from Celastrus obiculatus Thumb and determined by HPLC. Effects of dulcitol were examined on collagen-induced arthritis (CIA) in DBA/1J mice. From 6 weeks after the first immunization with bovine type II collagen, dulcitol (100 mg/kg body weight/day) was administered orally to immunized mice for 9 weeks. Clinical score of CIA was improved significantly by dulcitol intervention compared with the non-treated CIA mice. Radiographic score of phalangeal destruction was also improved by dulcitol treatment. These findings suggest that dulcitol may play a role in regulation of some inflammatory responses in the present arthritis model. Significant reduction of percentage of CD4+ and CD8+ T cell subsets in the spleen leucocytes of CIA mice was observed by flow cytometry. Almost normal level of CD4+ and CD8+ T cells was observed in dulcitol-treated groups, suggesting T cell-modifying effect of dulcitol in CIA. Weight of spleen was larger in CIA mice and it was not affected by dulcitol. Anti-collagen antibody titer was increased in CIA mice, and it was not affected by dulcitol, either. Improvement of the changes of CD4+ and CD8+ T cells in the spleen by dulcitol may suggest its modulatory effect on cellular immunity.
[Suppressive effects of a plant-origin polyol, dulcitol on collagen-induced arthritis in mice].
Kobayashi Y1, Shen J, Li SH, Kakizoe E, Okunishi H, Chen JF.
Dulcite is a sugar alcohol with a slightly sweet taste which is a metabolic breakdown product of galactose.