Cytotoxicity, apoptosis inducing activity and Western blot analysis of tanshinone derivatives from Stachys parviflora on prostate and breast cancer cells.

Cytotoxic activities of methanolic crude extract of Stachys parviflora (Lamiaceae family) and its sub-fractions were primarily evaluated against human breast adenocarcinoma (MCF-7 and MDA-MB-231) and prostate (PC3) cell lines. The methanolic extract exhibited the highest activity, and was chosen for the isolation procedure. Four diterpenoid quinones, namely miltirone [1], tanshinone IIA [2], 1-hydroxy-tanshinone IIA [3], and cryptotanshinone [4] were isolated. Notably, this is the first report on the isolation and/or characterization of the mentioned diterpenoids from the Stachys genus. In this study, 1-hydroxy-tanshinone IIA [3] displayed the highest cytotoxicity among the isolated compounds. The mechanism of the cytotoxicity of methanolic extract and isolated compounds was further investigated by the utilization of propidium iodide staining (PI) assay. The results showed that the methanolic extract and 1-hydroxy-tanshinone IIA [3] enhanced DNA fragmentation in PC3 and MCF-7 cells. Moreover, the western blotting analysis demonstrated increasing and decreasing protein levels of Bax and Bcl2, respectively, and cleaved poly ADP-ribose polymerase (PARP). Further bioassay-guided phytochemical assessments of S. parviflora can be suggested as a promising approach for discovering potent bioactive secondary metabolites.

4,5-Seco-5,10-friedo-abietane-type diterpenoids with anticancer activity from Salvia atropatana Bunge.

The purpose of this study is cytotoxicity-guided isolation of the petroleum ether fraction from the roots of Salvia atropatana for the first time, which has shown to growth inhibition and apoptosis induction in MCF-7 and PC3 cells. Bioassay-guided isolation method was conducted for finding compounds with highest cytotoxicity. Different extracts were prepared from the roots of Salvia atropatana. All extracts were tested for their cytotoxic activity against three cancer cell lines (PC3, MCF-7, and MDA-MB-231). The most cytotoxic extract was chosen for further isolation by column chromatography and HPLC. The chemical structures were determined by spectroscopic methods including 1D and 2D NMR. From the petroleum ether extract, four abietane-type diterpenoids, including a new abietane-type diterpenoid, named atropatanene (1), together with three known diterpenoids, 7α-acetoxyroyleanone (2), and a mixture of two isomers, saprorthoquinone and aethiopinone (3+4), were isolated. The latter exhibited substantial cytotoxicity with IC50 value of 8.73 µg/ml against PC3 cells and led to an increasing number of cells in the subG1 region and an increase in the amount of Bax and cleavage of PARP protein, indicating apoptotic cell death. Owing to its numerous biological activities, Salvia species could be represented as a natural potential source against several cancer cell lines.

Absolute configuration and anti-cancer effect of prenylated flavonoids and flavonostilbenes from Sophora pachycarpa: Possible involvement of Wnt signaling pathway.

A new prenylated flavonostilbene, namely, alopecurone P together with three known compounds sophoraflavanone G, 2-(4-hydroxyphenyl)-2,3-dihydrobenzo[b]furan-3,4,6-triol and alopecurone J were characterized from the roots of Sophora pachycarpa. The absolute configuration of alopecurones J and P were characterized by comparison of experimental electronic circular dichroism (ECD) spectroscopy and simulated data using time-dependent density functional theory (TDDFT) for possible stereoisomers. The cytotoxic properties of isolated compounds have also been evaluated on two breast cancer cell lines (MCF-7 and MDA-MB-231) and normal cell line (NIH/3T3) using AlamarBlue®, flowcytometry and western blot assays. Alopecurone J and P showed cytotoxic effect on MCF-7 cell line through Wnt signaling pathway. It seems that the presence of lavandulyl substitution in C-8 position of flavanone structure increased the cytotoxic effect.

Impact of curcumin on toll-like receptors.

Toll-like receptors (TLRs) have a pivotal role in the activation of innate immune response and inflammation. TLRs can be divided into two subgroups including extracellular TLRs that recognize microbial membrane components (TLR1, 2, 4, 5, 6, and 10), and intracellular TLRs that recognize microbial nucleic acids (TLR3, 7, 8, and 9). Curcumin is a dietary polyphenol from Curcuma longa L. that is reputed to have diverse biological and pharmacological effects. Extensive research has defined the molecular mechanisms through which curcumin mediates its therapeutic effects. One newly defined and important target of curcumin is the TLR, where it exerts an inhibitory effect. In the current study, we focus upon the TLR antagonistic effect of curcumin and curcumin's therapeutic effect as mediated via TLR inhibition. The available evidence indicates that curcumin inhibits the extracellular TLR 2 and 4 and intracellular TLR9 and thereby exerts a therapeutic effect in diseases such as cancer, inflammation, infection, autoimmune, and ischemic disease. Curcumin effectively modulates the TLR response and thereby exerts its potent therapeutic effects.

Biologically active prenylated flavonoids from the genus Sophora and their structure-activity relationship-A review.

The genus Sophora (Fabaceae) has been used in traditional medicine for years. Prenylated flavonoids are one of the constituents of Sophora species that play important roles in their biological properties. Different classes of prenylated flavonoids are produced by Sophora spp. including prenylated flavonol (e.g., sophoflavescenol), prenylated flavanone (e.g., sophoraflavanone G), prenylated flavonostilbene (e.g., alopecurones A and B), and prenylated chalcone (kuraridin). Prenylated flavonoids have a more lipophilic structure, which leads to its high affinity to the cell membranes and enhancement of the biological activity, which includes cytotoxicity, antibacterial, anti-inflammatory, and estrogenic activities. However, it is reported that prenylation decreases the plasma absorption but increases the tissue accumulation. The presence of the prenyl or lavandulyl groups on C8 position of flavonoids plays an important role in the biological activity. It seems that prenylated flavonoids have the potential to be developed as new drugs or supplements for human health.