Diselaginellin B, an Unusual Dimeric Molecule from Selaginella pulvinata, Inhibited Metastasis and Induced Apoptosis of SMMC-7721 Human Hepatocellular Carcinoma Cells.

Two new unusual dimeric selaginellins, diselaginellins A and B (1 and 2), along with two known derivatives, selaginellin (3) and selaginellin B (4), were isolated from Selaginella pulvinata. Their structures were elucidated by extensive NMR and high-resolution ESIMS data analysis. Compound 2 displayed apoptosis-inducing and antimetastatic activities against the human hepatocellular carcinoma cell line SMMC-7721. A microarray analysis revealed that genes related to metabolism, angiogenesis, and metastasis were altered by 2. The up- and down-regulation of the mRNA levels of related genes was confirmed by RT-qPCR. Metabolism modulation and metastasis inhibition might be the mechanisms of the antitumor properties of diselaginellin B (2).

Flavonoid glycosides from the stem bark of Margaritaria discoidea demonstrate antibacterial and free radical scavenging activities.

One new flavonoid glycoside, along with three known flavonoid glycosides were isolated from the stem bark of Margaritaria discoidea, which is traditionally used in the management of wounds and skin infections in Ghana. The new flavonoid glycoside was elucidated as hydroxygenkwanin-8-C-[α-rhamnopyranosyl-(1 → 6)]-ß-glucopyranoside (1) on the basis of spectroscopic analysis. The isolated compounds demonstrated free-radical scavenging as well as some level of antibacterial activities. Microorganisms including Staphylococcus aureus are implicated in inhibiting or delaying wound healing. Therefore, any agent capable of reducing or eliminating the microbial load present in a wound as well as decreasing the levels of reactive oxygen species may facilitate the healing process. These findings therefore provide some support to the ethnopharmacological usage of the plant in the management of wounds.

Antimicrobial selaginellin derivatives from Selaginella pulvinata.

Six selaginellin derivatives, including three new analogues selaginellins D-F (1-3), were isolated from the EtOAc extract of the whole plant of Selaginella pulvinata (Hook. et Grev.) Maxim. Their structures were determined on the basis of extensive physical and chemical evidence. Compounds 1 and 4 demonstrated antifungal activities against Candida albicans; compounds 4-6 exhibited significant antibacterial activity against Staphylococcus aureus.

Identification and mechanistic characterization of low-molecular-weight inhibitors for HuR.

Careful regulation of mRNA half-lives is a fundamental mechanism allowing cells to quickly respond to changing environmental conditions. The mRNA-binding Hu proteins are important for stabilization of short-lived mRNAs. Here we describe the identification and mechanistic characterization of the first low-molecular-weight inhibitors for Hu protein R (HuR) from microbial broths (Actinomyces sp.): dehydromutactin (1), MS-444 (2) and okicenone (3). These compounds interfere with HuR RNA binding, HuR trafficking, cytokine expression and T-cell activation. A mathematical and experimental analysis of the compounds' mode of action suggests that HuR homodimerizes before RNA binding and that the compounds interfere with the formation of HuR dimers. Our results demonstrate the chemical drugability of HuR; to our knowledge HuR is the first example of a drugable protein within the Hu family. MS-444, dehydromutactin and okicenone may become valuable tools for studying HuR function. An assessment of HuR inhibition as a central node in malignant processes might open up new conceptual routes toward combatting cancer.