Activity-guided fractionation of an ethyl acetate extract of the aerial parts of Tithonia diversifolia, using an antiproliferation bioassay performed with human colon cancer (Col2) cells, led to the isolation of three new sesquiterpenoids, 2alpha-hydroxytirotundin (1), tithofolinolide (2), and 3alpha-acetoxydiversifolol (3), along with eight known sesquiterpene lactones, 3beta-acetoxy-8beta-isobutyryloxyreynosin (4), tagitinin C (5), 1beta,2alpha-epoxytagitinin C (6), 4alpha,10alpha-dihydroxy-3-oxo-8beta-isobutyryloxyguaia-11(13)-en-12,6alpha-olide (7), 3alpha-acetoxy-4alpha-hydroxy-11(13)-eudesmen-12-oic acid methyl ester, 17,20-dihydroxygeranylnerol, tagitinin A, and tirotundin. These isolates were evaluated for their potential as cancer chemopreventive agents, by measuring antiproliferative activity in Col2 cells and induction of cellular differentiation in human promyelocytic leukemia (HL-60) cells. Selected compounds were then investigated for their ability to inhibit 7,12-dimethylbenz[a]anthracene-induced preneoplastic lesions in a mouse mammary organ culture assay. Among these isolates, 5 and 6 showed significant antiproliferative activity, 2, 4, and 7 induced HL-60 cellular differentiation, and 4 significantly inhibited (63.0% at 10 microg/mL) lesion formation in the mouse mammary organ culture assay. The chemical structures of 1-3 were elucidated by spectroscopic analysis. The absolute configurations of 1 and 2 were determined by Mosher ester methodology.

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Extracts of Valeriana officinalis have been used in folkloric medicine for its sedative, hypnotic, tranquilizer and anticonvulsant effects, and may interact with gamma-aminobutyric acid (GABA) and/or benzodiazepine sites. At low concentrations, valerian extracts enhance [3H]flunitrazepam binding (EC50 4.13 x 10(-10) mg/ml). However, this increased [3H]flunitrazepam binding is replaced by an inhibition at higher concentrations (IC50 of 4.82 x 10(-1) mg/ml). These results are consistent with the presence of at least two different biological activities interacting with [3H]flunitrazepam binding sites. Valerian extracts also potentiate K+ or veratridine-stimulated release of radioactivity from hippocampal slices preloaded with [3H]GABA. Finally, inhibition of synaptosomal [3H]GABA uptake by valerian extracts also displays a biphasic interaction with guvacine. The results confirm that valerian extracts have effects on GABA(A) receptors, but can also interact at other presynaptic components of GABAergic neurons.

Vitamin E (VE) tocotrienols (T3), recognized for their cancer-specific anti-proliferative and pro-apoptotic activities, have been previously fabricated into bio-active nanoemulsion (NE) formulations. Here, our viscosity-adapted δ-T3 NE platform was developed to additionally incorporate curcumin (CUR), which is known for its potent suppression of signaling pathways involved in malignant cell growth, survival and metastasis. Thanks to efficient 70:30 wt % surfactant mix of Lutrol F-127:VE-TPGS, in conjunction with optimal CUR loading, a prototype CUR in δ-T3 NE was successfully prepared. Model CUR/δ-T3 NE demonstrated excellent nano-scale aspects (mean particle size = 261 nm, PDI = 0.27, and ζ-potential = −35 mV), pharmaceutical stability, and controlled release properties. Suitability for systemic administration was also verified via standardized in vitro biocompatibility and hemocompatibility assays. In two human cancer cells (MCF-7 and OVCAR-8), our CUR/δ-T3 NE prominently suppressed constitutive NF-κB activation, and significantly induced apoptosis. Finally, the combined CUR/δ-T3 NE produced superior cytotoxicity profiles, in concentration- and time-dependent manners (p ≤ 0.05), at least three to four folds lower IC50 than in closest CUR control. The strong synergism, estimated in both cultured carcinomas, revealed the augmented therapeutic efficacy of our CUR/δ-T3 NE combined platform, supporting its strong potential towards pharmaceutical development for cancer therapy.