Cucurbitane-type triterpenoids from the fruits of Citrullus colocynthis.

A phytochemical investigation of the fruits of Citrullus colocynthis resulted in the isolation of 21 structurally diverse cucurbitane triterpenoids, including 9 previously undescribed ones, colocynins A-I (1-9). Their absolute configurations were elucidated by means of quantum chemical electronic circular dichroism (ECD) calculations, CD exciton chirality method, and single-crystal X-ray crystallography. Colocynins A-C (1-3) represent the first examples of nonanorcucurbitane-type triterpenoids. An anti-acetylcholinesterase activity assay showed that 6, 10, 13, 18, and 20 exhibited inhibitory activities, with IC50 values ranging from 5.0 to 21.7 µM. In addition, 18 and 21 showed significant cytotoxicity against PACA, A431, and HepG2 cells, with IC50 values ranging from 0.042 to 0.60 and 3.6-14.4 µM, respectively.

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.

A cyclic peptide and two pairs of norlignan lignanoside epimers from Selaginella pulvinata.

A new cyclopeptide, pulvpeptin A (1), two pairs of norlignan lignanosides, tamariscinosides G and H (2, 3), together with five known compounds (4-8) were isolated from Selaginella pulvinata. The structures were elucidated by spectroscopic data and chemical degradation. The activity of tamariscinoside G (2) was evaluated by stimulating glucose uptake in 3T3-L1 adipocytes. The results showed 1.49-fold increase in glucose uptake in 3T3-L1 cells relative to basal.

The genus Tripterygium: A phytochemistry and pharmacological review.

The genus Tripterygium belongs to the family Celastraceae, and contains three species, i.e. Tripterygium wilfordii Hook. F, Tripterygium hypoglaucum (Levl.) Hutch. and Tripterygium regelii Sprague et Takeda. All three species are reported to have excellent medicinal properties that help to cure rheumatoid arthritis, nephrotic syndrome, systemic lupus erythematosus and widely used as a folk medicine in China. Phytochemical studies have led to discovering more than 500 secondary metabolites in this genus, including five main types: sesquiterpenoids, diterpenes, triterpenoids, flavonoids, lignans. This work provides structurally grouping statistic of 198 secondary metabolites of Tripterygium species published from 2008 to the present, as well as pharmacological knowledges in the past five years. The information will be helpful for developing the new discoveries of medicinal value related to the genus Tripterygium.

neo-Clerodane diterpenoids from the aerial parts of Teucrium fruticans cultivated in China.

Seven neo-clerodane diterpenes, teufruintins A-G (1-7), together with eight known compounds (8-15) were isolated from the CHCl3-soluble fraction of the aerial parts of Teucrium fruticans cultivated in China. The chemical structures of the isolated compounds were elucidated using different spectroscopic methods. All of the isolated diterpenes were evaluated for their cytotoxic activities on three human cancer cell lines, and for their ability to inhibit LPS-induced nitric oxide production in RAW 264.7 macrophages. None of the compounds displayed cytotoxic activities on the cancer cell lines, and only 15 showed weak NO inhibitory activity.

Antihyperglycemic glucosylated coumaroyltyramine derivatives from Teucrium viscidum.

Eight new glucosylated coumaroyltyramine derivatives, teuvissides A-H (1-8), were isolated from whole plants of Teucrium viscidum. Their structures were elucidated using spectroscopic data and chemical methods. The antihyperglycemic activities of these compounds were evaluated in HepG2 cells and 3T3-L1 adipocytes, and all of the isolates elicited different levels of glucose consumption at a concentration of 2.0 µM. Teuvissides A (1), B (2), and F (6) induced 2.2-, 2.1-, and 2.2-fold changes, respectively, in the levels of glucose consumption in HepG2 cells and 2.5-, 2.1-, and 2.3-fold changes, respectively, in 3T3-L1 adipocytes relative to the basal levels.

A new neo-clerodane diterpene from Ajuga decumbens.

A new neo-clerodane diterpene, named ajugacumbin J (1), together with 13 known compounds (2-14) was isolated from Ajuga decumbens. The structure of ajugacumbin J (1) was elucidated by 1D and 2D NMR spectra and MS. Ajugacumbin J (1) and ajugacumbin D (5) exhibited inhibition of lipopolysaccharide-induced nitric oxide production in RAW 264.7 macrophages with an IC50 value of 46.2 and 35.9 µM, respectively.