Pterostilbene nanoparticles with small particle size show excellent anti-breast cancer activityin vitroandin vivo.

Pterostilbene (PTE) is known as resveratrol of the next generation and it has attracted extensive attention in recent years. PTE can inhibit the growth of a variety of tumor cells. To overcome the problem of insolubility, PTE was loaded into nanoparticles (NPs) by anti-solvent precipitation technique using soybean lecithin (SPC) and D-α-tocopheryl polyethylene glycol succinate (TPGS) as stabilizers. The obtained PTE-NPs had an average particle size of 71.0 nm, a polydispersity index （PDI） value of 0.258, and a high zeta potential of -40.8 mV. PTE-NPs can maintain particle size stability in various physiological media. The entrapment efficiency of PTE-NPs was 98.24%. And the apparently water solubility of PTE-NPs was about 53 times higher than the solubility of PTE (54.41µg ml-1v-1s-1. 2.89 mg ml-1). M-1T-1T-1assay showed that the antitumor activity of PTE-NPs on 4T1 breast cancer cells, MCF-7 breast cancer cells and Hela cervical cancer cells was significantly increased by 4, 6 and 8 times than that of free PTE, respectively.In vivostudies have shown that PTE-NPs has a certain dose dependence. When injected intraperitoneally, PTE-NPs showed a similar therapeutic effect as paclitaxel injection (TIR was 57.53% versus 57.23%) against 4T1 tumor-bearing mice. This should be due to the improved bioavailability of the drug caused by nano-drug delivery system (nano-DDS). These results indicate that PTE-NPs may be a clinically promising anti-tumor drug for breast cancer treatment.

Combined administration on You-Gui Yin and low-dose Raloxifene partially attenuates the bone loss in ovariectomized mice through the proliferation and osteogenic differentiation of bone marrow stromal cells.

BACKGROUND: Osteoporosis is a systemic skeletal disease of fragility fractures due to the loss of mass and deterioration of the microarchitecture of bone. PURPOSE: The aim of the study was to assess the osteogenic effects and the underlying mechanisms of the combined administration of You-Gui Yin (YGY) and Raloxifene hydrochloride (RLX) in ovariectomized (OVX) mice. METHODS: First, a classic animal model was used to mimic postmenopausal osteoporosis through the removal of the ovary of mice. Second, the OVX mice were administered YGY, RLX, and YGY + RLX for 12 weeks. Next, the bone microtomographic histomorphometry and bone mineral density (BMD) were assessed by micro-CT, and the biochemical markers of procollagen type I N-terminal propeptide (P1NP) and beta-isomerized C-telopeptide (ß-CTX) in serum were assessed. Finally, primary bone marrow stromal cells (BMSCs) were isolated from the tibia and cultured to evaluate cell proliferation and osteogenic differentiation. RESULTS: The results showed that BMD on the YGY + RLX group was higher than that on the RLX group (p < 0.05) and did not have a significant difference when compared with the sham group. Notably, the YGY + RLX group had a dramatically increased trabecular number (Tb.N) compared with that of the YGY group (p < 0.05). Moreover, the BV/TV (bone volume/total volume) and Tb.N in the YGY + RLX group were higher than that in the RLX group (p < 0.05), and the Tb.Sp (trabecular separation) was lower than that in the RLX group (p < 0.05). Moreover, the serum level of P1NP from the YGY + RLX group dramatically increased when compared with that from the YGY and RLX groups (YGY group: p < 0.05; RLX groups: p < 0.01). Notably, there was no significant difference between the YGY and YGY + RLX groups. In addition, cell proliferation from the co-administration of YGY and RLX was clearly higher than a single use of YGY and RLX (p < 0.01, respectively). The ALP/BCA (alkaline phosphatase/bicinchoninic acid) in the YGY + RLX group was higher than that in the RLX group (p < 0.01). CONCLUSION: Overall, co-administered YGY and RLX could partially attenuate bone loss and were more effective than individually using either one; this outcome might be associated with the proliferation and osteogenic differentiation of BMSCs.

Folate-targeting annonaceous acetogenins nanosuspensions: significantly enhanced antitumor efficacy in HeLa tumor-bearing mice.

Annonaceous acetogenins (ACGs) are one of the most active constituents isolated from Annona species with potent antitumor activity. However, the poor solubility and severe side effect greatly limit their use in clinic. In this study, folic acid (FA) modified annonaceous acetogenins nanosuspensions (FA-PEG-ACGs-NSps) had been successfully prepared using DSPE-PEG-FA and soybean lecithin (SPC) as stabilizers. The resultant FA-PEG-ACGs-NSps had a mean particle size of 119.7 nm, a zeta potential of -23.0 mV and a high drug payload of 49.68%. The obtained ACGs-NSps had a good stability in various physiological media, and showed sustained drug release. Compared to common ACGs nanoparticles (PEG-ACGs-NSps), FA-PEG-ACGs-NSps showed significantly enhanced in vitro cytotoxicity against folate receptor-positive HeLa cell lines (IC50, 0.483 µg/mL vs. 0.915 µg/mL, p < .05), which could be effectively reversed simply by pretreatment of free FA. In vivo experiments demonstrated that FA-PEG-ACGs-NSps brought more drug molecules into tumors and greatly improved the antitumor efficacy (TIR, 76.45% vs. 25.29%, p < .001). Therefore, DSPE-PEG-FA is considered as a proper stabilizer with active targeting effect for ACGs-NSps to reduce toxicity, enlarge the safe dosage range and apply in clinic for the treatment of folate-positive tumors. Therefore, FA-PEG-ACGs-NSps may be a prospective drug delivery system for ACGs to improve their therapeutic window and find application in clinic to treat FR over-expressed tumors.

Phytochemistry, Bioactivity and Potential Impact on Health of Juglans: the Original Plant of Walnut.

Walnuts are seeds with a hard shell from the genus Juglans (J. mandshurica, J. regia, J. sinensis, J. cathayensis, J. nigra and J. sigillata). Walnuts can nourish brain cells to improve human memory. Other parts of the plant are also employed as traditional Chinese medicines. Modern research on Juglans species has been mostly focused on the above-mentioned species, the seeds of which are all called walnuts. Juglans species have diverse chemical constituents, including diarylheptanoids, quinones, polyphenols, flavones and terpenes. The diarylheptanoids and quinones have notable antitumor activity, supplying new lead compounds for preparing antitumor drugs. The potent pain-relieving, antioxidant, antibacterial and antitumor activities of these plants are significant. In the review, comprehensive information on the nutritional characteristics, traditional functions, chemical constituents, and biological activities of the Juglans species, together with the seeds used as walnuts is provided to explore their potential and to advance research.