Matrine Inhibitory Effect on Self-renewal and Re-sensitization of 5-FU Resistant NSCLC Stem Cells were through Let-7b dependent Downregulation of CCND1.

Matrine is one of the major alkaloids extracted from Sophora flavescens Ait of the traditional Chinese medicine, was the main chemical ingredient of compounds of Kushen injection. The Matrine is considered as a promising therapeutic agent for curing nonsmall cell lung cancer (NSCLC), used either alone or combined with chemotherapeutic agents. In the present study, we focused on the possible roles of Matrine exerted on the self-renewal ability of stem-like cells of the NSCLC group, as well as the cytotoxicity of chemotherapeutic agents, in vitro and in vivo. Here we reported that Matrine inhibits cancer stem-like cell (CSC) properties through upregulation of Let-7b and suppression of the Wnt pathway. Overexpression of Let-7b suppressed the ability of tumorsphere formation, decreased Wnt pathway activation through inhibiting its transcriptional activity in lung CSCs. Further studies revealed that Let-7b directly targeted CCND1 and decreased its expression, whereas Matrine increased Let-7b levels and followed by inactivation of the CCND1/Wnt signaling pathway and inhibition of EMT, which was characterized by loss of epithelial markers and acquisition of a mesenchymal phenotype in lung CSCs. What is more, we found that Matrine increased Let-7b level in an endoribonuclease DICER1-dependent manner. And xenografts in nude mice evidenced that Matrine increased the sensitivity of lung CSCs to 5-FU and inhibited the accumulation of CCND1 in tumor tissues induced by 5-FU. Taken together, these data illustrate the role of Let-7b in regulating lung CSCs traits and DICER1/let-7/CCND1 axis in Matrine or in combination with 5-FU intervention of lung CSCs' expansion, helping to fulfill the anti-cancer action of Matrine.

Magnesium lithospermate B protects neurons from N-methyl-D-aspartic acid injury and attenuates kainic acid-induced neurodegeration in FVB mice.

Magnesium lithospermate B (MLB) is one of the major bioactive components of Radix Salviae miltiorrhizae (Dan Shen), which is a Chinese traditional herbal medicine with therapeutic effects on cardiovascular and cerebrovascular diseases. The aim of this study was to investigate the neuroprotective effects of MLB on N-methyl-D-aspartic acid (NMDA)-injured neurons and against kainic acid (KA)-induced neurodegeneration in mice. In cultured mouse primary hippocampal neurons, MLB significantly reduced NMDA-induced cell death and promoted neurite growth in a dose-dependent manner. In FVB mice, MLB attenuated KA-induced neurodegeneration. Additionally, MLB prevented the decrease in phosphorylated Akt and glycogen synthase kinase-3ß (GSK-3ß) levels both in NMDA-injured neurons and KA-injured mouse brain. This effect was blocked by phosphoinositide 3-kinase (PI3K) inhibitor LY294002 and Akt inhibitor triciribine, thus indicating the neuroprotective effects of MLB are most likely mediated by the PI3K/Akt/GSK-3ß pathway. Taken together, these results show the efficacy and underlying mechanism of MLB against neuronal injury and raise its therapeutic potential in neurodegenerative diseases.

Isolation of a new meroterpene and inhibitors of nitric oxide production from Psoralea corylifolia fruits guided by TLC bioautography.

A new meroterpene, psoracorylifol F (1), was isolated from Psoralea corylifolia fruits, along with two known meroterpenes (2 and 3), guided by TLC bioautography against O(2)(-) radicals. The structure of 1 was elucidated by means of NMR, HRESIMS, and X-ray crystallographic analysis. All the three metroterpenes possessed potential inhibitory activity against LPS-induced NO production in RAW 264.7 cells with IC(50) values ranging from 7.71 to 27.63µM.

Isolation of antioxidants from Psoralea corylifolia fruits using high-speed counter-current chromatography guided by thin layer chromatography-antioxidant autographic assay.

A combinative method using high-speed counter-current chromatography (HSCCC) and thin layer chromatography (TLC) as an antioxidant autographic assay was developed to separate antioxidant components from the fruits of Psoralea corylifolia. Under the guidance of TLC bioautography, eight compounds including five flavonoids and three coumarins were successfully separated from the fruits of P. corylifolia by HSCCC with an optimized two-phase solvent system, n-hexane-ethyl acetate-methanol-water (1:1.1:1.3:1, v/v/v/v). The separation produced 5.91mg psoralen, 6.26mg isopsoralen, 3.19mg psoralidin, 0.92mg corylifol A, and 2.43mg bavachinin with corresponding purities of 99.5, 99.8, 99.4, 96.4, and 99.0%, as well as three sub-fractions, in a single run from 250mg ethyl acetate fraction of P. corylifolia extract. Following an additional clean-up step by preparative TLC, 0.4mg 8-prenyldaidzein (purity 91.7%), 4.18mg neobavaisoflavone (purity 97.4%) and 4.36mg isobavachalcone (purity 96.8%) were separated from the three individual sub-fractions. The structures of the isolated compounds were identified by (1)H NMR and (13)C NMR. The results of antioxidant activity estimation by electron spin resonance (ESR) method showed that psoralidin was the most active antioxidant with an IC50 value of 44.7microM. This is the first report on simultaneous separation of eight compounds from P. corylifolia by HSCCC.