No abstract

A series of C7-O- and C20-O-amidated 2,3-dehydrosilybin (DHS) derivatives ((+/-)-1a-f and (+/-)-2), as well as a set of alkenylated DHS analogues ((+/-)-4a-f), were designed and de novo synthesized. A diesteric derivative of DHS ((+/-)-3) and two C23 esterified DHS analogues ((+/-)-5a and (+/-)-5b) were also prepared for comparison. The cell viability of PC12 cells, Fe(2+) chelation, lipid peroxidation (LPO), free radical scavenging, and xanthine oxidase inhibition models were utilized to evaluate their antioxidative and neuron protective properties. The study revealed that the diether at C7-OH and C20-OH as well as the monoether at C7-OH, which possess aliphatic substituted acetamides, demonstrated more potent LPO inhibition and Fe(2+) chelation compared to DHS and quercetin. Conversely, the diallyl ether at C7-OH and C20-OH was more potent in protection of PC12 cells against H(2)O(2)-induced injury than DHS and quercetin. Overall, the more lipophilic alkenylated DHS analogues were better performing neuroprotective agents than the acetamidated derivatives. The results in this study would be beneficial for optimizing the therapeutic potential of lignoflavonoids, especially in neurodegenerative disorders such as Alzheimer's and Parkinson's disease.

Three new diarylheptanoids and one new monoterpenoid were isolated from the rhizomes of Zingiber officinale together with four known diarylheptanoids, 5-8. Their structures were elucidated mainly by spectroscopic methods, and they were deduced as 5-[4-hydroxy-6-(4-hydroxyphenethyl)tetrahydro-2 H-pyran-2-yl]-3-methoxybenzene-1,2-diol (1), sodium (E)-7-hydroxy-1,7-bis(4-hydroxyphenyl)hept-5-ene-3 S-sulfonate (2), sodium (E)-7-hydroxy-1,7-bis(4-hydroxyphenyl)hept-5-ene-3 R-sulfonate (3), and hydroxycineole-10-O-beta-D-glucopyranoside (4), respectively. Among the isolated compounds, compounds 1, 5, and 8 exhibited strong superoxide anion radical scavenging activities in a phenazine methosulfate-NADH system. In a more biological system, these compounds were demonstrated to exhibit potent protection against lipid peroxidation in mouse liver microsomes exposed to oxidative conditions. These compounds were subsequently tested on primary cultures of rat hepatocytes exposed to oxidative damage, and definitive cytoprotective actions were found.

Background Zinc-finger protein 471 (ZNF471) is a member of the Krüppel-associated box domain zinc finger protein (KRAB-ZFP) family. ZNF471 is methylated in squamous cell carcinomas of tongue, stomach and esophageal. However, its role in breast carcinogenesis remains elusive. Here, we studied its expression, functions, and molecular mechanisms in breast cancer. Methods We examined ZNF471 expression by RT-PCR and qPCR. Methylation-specific PCR determined its promoter methylation. Its biological functions and related molecular mechanisms were assessed by CCK-8, clonogenicity, wound healing, Transwell, nude mice tumorigenicity, flow cytometry, BrdU-ELISA, immunohistochemistry and Western blot assays. Results ZNF471 was significantly downregulated in breast cell lines and tissues due to its promoter CpG methylation, compared with normal mammary epithelial cells and paired surgical-margin tissues. Ectopic expression of ZNF471 substantially inhibited breast tumor cell growth in vitro and in vivo, arrested cell cycle at S phase, and promoted cell apoptosis, as well as suppressed metastasis. Further knockdown of ZNF471 verified its tumor-suppressive effects. We also found that ZNF471 exerted its tumor-suppressive functions through suppressing epithelial-mesenchymal transition, tumor cell stemness and AKT and Wnt/β-catenin signaling. Conclusions ZNF471 functions as a tumor suppressor that was epigenetically inactivated in breast cancer. Its inhibition of AKT and Wnt/β-catenin signaling pathways is one of the mechanisms underlying its anti-cancer effects.