Chemical profiling and identification of anti-osteoporosis chemical-markers of Cinnamomum cassia (L.) presl extracts using GC-MS and spectrum-activity analyses.

Cinnamomum cassia (L.) Presl (cinnamon), an important folk medicine is widely used to prevent osteoporosis for long time in China. Our study aimed to investigate the anti-osteoporosis activity and mechanisms of cinnamon extracts obtained by supercritical CO2 extraction (SFE) and identify activity associated chemical components by gas chromatography-mass spectrometry. The cinnamon SFE exhibited superior anti-osteoporosis efficacy in an ovariectomised mice model to common alcohol extracts. It could induce calcified nodules and ALP activity, upregulate the mRNA expression of ALP, BMP-2, and RUNX2 in MC3T3-E1 cells. The major chemical classes of cinnamon extracts were alcohol esters (28.2%), and terpenes (16.1%). The spectrum-activity analysis indicated that the potential chemical-markers of extracts could be (E)-Cinnamaldehyde, γ-Sitosterol, and (Z, Z)-9,12-Octadecadienoic acid, which could induce the proliferation and ALP activity in MC3T3-E1 cells. Our study revealed the promising applications of the cinnamon SFE in prevention of osteoporosis, and identified its anti-osteoporosis associated compounds.

Valtrate as a novel therapeutic agent exhibits potent anti-pancreatic cancer activity by inhibiting Stat3 signaling.

BACKGROUND: Valtrate is a novel epoxy iridoid ester isolated from Chinese herbal medicine Valeriana jatamansi Jones with anti-proliferative activity against various human cancer cell lines. However, its efficacy and molecular mechanisms against pancreatic cancer (PC) cells are largely unclear. PURPOSE: To investigate the anti-cancer effects of valtrate on PC cell lines and its underlying mechanisms. METHODS: MTT assay was first performed to detect the effect of valtrate on cell viability in human PC cell lines and normal pancreatic epithelial cells HPDE. Cell apoptosis and cycle phase assay were detected by flow cytometry. The relative mRNA expressions of Bax, Bcl-2, c-Myc, and CyclinB1 were tested by quantitative PCR (qPCR) assay. The expression of relative proteins was detected by Western blotting (WB). A PANC-1luc cells xenograft mouse model in nu/nu female mice was used to elucidate the effect of valtrate on tumor growth in vivo. RESULTS: Valtrate significantly inhibited the growth of PC cells without affecting the growth of normal pancreatic epithelial cells HPDE, induced significant apoptosis and cell cycle arrest in G2/M phase. Moreover, valtrate inhibited the tumor growth of PC cell PANC-1 in xenograft mice by 61%. Further mechanism study demonstrated that valtrate could increase the expression level of Bax, suppress Bcl-2 as well as c-Myc and Cyclin B1, inhibit the transcriptional activity of Stat3, while valtrate decreased the expression level of Stat3 and phosphated-Stat3 (Tyr705) and induced the high molecular aggregation of Stat3. Molecular docking analysis predicted that valtrate might interact with Cys712 of Stat3 protein. Valtrate could also induce a transient depleted intracellular glutathione (GSH) level and increased reactive oxygen species (ROS). NAC (N-acetylcysteine), a reducer reversed valtrate-induced the depletion of Stat3, p-Stat3, c-Myc, and Cyclin B1. CONCLUSION: Valtrate exerts anti-cancer activity against PC cells by directly targeting Stat3 through a covalent linkage to inhibit Stat3 activity, which causes apoptosis and cell cycle arrest.

Coix seed emulsion synergistically enhances the antitumor activity of gemcitabine in pancreatic cancer through abrogation of NF-κB signaling.

Clinical outcomes in patients with pancreatic cancer (PC) continue to be dismal, in part due to de novo and acquired chemoresistance. In the present study, we provide preclinical evidence that pre-treatment with coix seed emulsion, an injectable agent extracted from coix seeds, synergistically sensitized PC cell lines (BxPC-3, PANC-1 and AsPC-1) to gemcitabine, both in vitro and in vivo. Such pretreatment led to significant induction of pro-apoptosis proteins, including caspase-3, cleaved-PARP and Bax (P<0.05), after lower doses of gemcitabine compared to monotherapy. We also showed that coix seed emulsion suppressed the constitutive and gemcitabine-induced activation of nuclear factor-κB (NF-κB), as shown with the use of electrophoretic mobility shift, reporter and immunoblotting analyses. Coix seed emulsion pretreatment also downregulated the NF-κB-dependent anti­apoptotic molecules Bcl-2, survivin and cyclooxygenase-2. In vivo, coix seed emulsion combined with gemcitabine had a much greater antitumor effect than the effect of either agent alone, consistent with the downregulation of the proliferation index, and the results of immunostaining for Ki-67, or for the NF-κB subunit p65. Overall, our data demonstrated that coix seed emulsion abrogated gemcitabine-induced activation of NF-κB, and synergistically sensitized PC cells to gemcitabine therapy.