GSH-activable heterotrimeric nano-prodrug for precise synergistic therapy of TNBC.

Combination chemotherapy is an effective approach for triple-negative breast cancer (TNBC) therapy, especially when drugs are administered at specific optimal ratios. However, at present, strategies involving precise and controllable ratios based on effective loading and release of drugs are unavailable. Herein, we designed and synthesized a glutathione (GSH)--responsive heterotrimeric prodrug and formulated it with an amphiphilic polymer to obtain nanoparticles (DSSC2 NPs) for precise synergistic chemotherapy of TNBC. The heterotrimeric prodrug was prepared using docetaxel (DTX) and curcumin (CUR) at the optimal synergistic ratio of 1: 2. DTX and CUR were covalently conjugated by disulfide linkers. Compared with control NPs, DSSC2 NPs had quantitative/ratiometric drug loading, high drug co-loading capacity, better colloidal stability, and less premature drug leakage. After systemic administration, DSSC2 NPs selectively accumulated in tumor tissues and released the encapsulated drugs triggered by high levels of GSH in cancer cells. In vitro and in vivo experiments validated that DSSC2 NPs released DTX and CUR at the predefined ratio and had a highly synergistic therapeutic effect on tumor suppression in TNBC, which can be attributed to ratiometric drug delivery and synchronous drug activation. Altogether, the heterotrimeric prodrug delivery system developed in this study represents an effective and novel approach for combination chemotherapy.

Rhinacanthin C Ameliorates Insulin Resistance and Lipid Accumulation in NAFLD Mice via the AMPK/SIRT1 and SREBP-1c/FAS/ACC Signaling Pathways.

Rhinacanthin C (RC) is a naphthoquinone ester with an anti-inflammatory activity extracted from Rhinacanthus nasutus (L.) Kurz (Rn). It has been proven to improve hyperglycemia and hyperlipidemia, but the prevention and mechanism of RC in nonalcoholic fatty liver disease (NAFLD) are not clear. In the current study, we first extracted RC from Rn using ethyl acetate and identified it by HPLC, MS, and NMR. At the same time, molecular docking analysis of RC with AMPK and SREBP-1c was performed using AutoDock software. In addition, the mouse model of NAFLD was induced by a high-fat diet in vivo, and low, medium, and high concentrations of RC were used for intervention. The results showed that RC significantly reduced the body mass and liver body coefficient of NAFLD mice, inhibited liver inflammation and fat accumulation, and improved insulin resistance. Further studies showed that RC significantly reduced the levels of serum leptin and resistin, upregulated the expression levels of adiponectin and adiponectin receptor in the liver, and inhibited the expression levels of MCP-1, TNF-α, and IL-6. In terms of mechanism, RC upregulates the expression of p-AMPK and SIRT1 and downregulates the expression of p-p65, SREBP-1c, Fas, Acc-α, PPAR-γ, and SCD1. These studies suggest that RC improves insulin resistance and lipid accumulation in NAFLD by activating the AMPK/SIRT1 and SREBP-1c/Fas/ACC pathways, respectively.

Volatiles released by Chinese liquorice roots mediate host location behaviour by neonate Porphyrophora sophorae (Hemiptera: Margarodidae).

BACKGROUND: The cochineal scale, Porphyrophora sophorae (Hemiptera: Coccoidea, Margarodidae), is one of the most serious arthropod pests of Chinese liquorice, Glycyrrhiza uralensis (Fabaceae), an important medicinal herb. The adult females tend to deposit the ovisacs in soil relatively far away from liquorice plants. After hatching, neonates move out of the soil and may use chemical cues to search for new hosts. RESULTS: We collected and analysed the volatiles from soils with and without liquorice roots, and chromatographic profiles revealed hexanal, ß-pinene and hexanol as potential host-finding cues for P. sphorae. The attractiveness of these compounds to neonates was studied in the laboratory using four-arm olfactometer bioassays. The larvae showed a clear preference for ß-pinene over hexanal and hexanol, as well as all possible combinations of the three compounds. In addition, a field experiment confirmed that ß-pinene was significantly more attractive than hexanal and hexanol. CONCLUSION: Newly eclosed larvae of P. sphorae exploit root volatiles as chemical cues to locate their host plant. ß-Pinene proved to be the major chemical cue used by P. sphorae neonates searching for roots of their host plant. © 2016 Society of Chemical Industry.

[Planting area estimation of Chinese Tibetan medicine Herpetospermum pedunculosum based on RS&GIS-by case study of Lengqi and Xinglong town in Luding county].

The herbs used as the material for traditional Chinese medicine are mostly planted at mountain areas where there is appropriate weather condition. Due to the complex terrain condition in mountain area, the planting at such places is always associated with a scattered pattern, which inevitably bring difficulty to the work of accurate measurement for the planting area. Advanced research about monitoring the planting area for medicine-herb under complex environmental condition is so critical and meaningful for developing the medicine-herb planting to a large scale and an industry. Therefore, this research, taking the planting of Herpetospermum pedunculosum in Luding county as an example, utilizes RS&GIS: using the image data from TM and ETM datum as the remote sensing information source, integrating GPS data from quadrat survey on the spots, and analyzing on a GIS platform, to extract the planting area of H. pedunculosum in Luding county. The results indicate that: (1) the method and technology used to estimate the planting area of H. pedunculosum are feasible and can be applied to monitoring the planting area of medicine-herb at mountain area under complex environmental conditions: (2) the planting area of H. pedunculosum in Luding county is estimated to be 857. 246 acres by the methods utilized in this research, which is closed to the value from local statistical data with an error range less than 5%; (3) in consideration of those inevitable errorrs generating from the procedures such as remote sensing data acquisition, data preprocessing, data interpretation, and so on, and the fact that the classification of remote sensing data, which must be implemented by those above procedures, was used directly to extract the herb type, the accuracy of area estimation for the herb is significantly influenced by the accuracy of classification for herb type, and the estimated area is inevitably associated with some error.

Scutellarin isolated from Erigeron multiradiatus inhibits high glucose-mediated vascular inflammation.

Erigeron multiradiatus (Lindl.) Benth is a traditional Tibetan medicine herb long used to treat various diseases related to inflammation. Our previous phytochemical studies on E. multiradiatus resulted in the isolation of scutellarin, which is a known flavone glucuronide with comprehensive pharmacological actions. In present study, we investigated the inhibition action of scutellarin on high glucose-induced vascular inflammation in human endothelial cells (ECV304 cells). Consistent with previous reports, exposure of ECV304 cells to high glucose for 24 h caused an increase of intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein 1 (MCP-1), and promoted cell adhesion between monocyte and ECV304 cells. However, pretreatment with scutellarin (0.1 and 1 microM) reversed these effects in a concentration-dependent manner. Scutellarin was able to inhibit the activation of NF-kappaB induced by high glucose in ECV304 cells. Furthermore, although oral administration of scutellarin (10 and 50 mg/kg) did not produce significant antihyperglycemic action, it lowered the serum MCP-1 levels significantly in alloxan-induced diabetic mice. Therefore, our results suggest that scutellarin has anti-inflammation effect that may afford some protection against hyperglycemia-induced vascular inflammatory both in vitro and in vivo.