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Graphical abstract Abstract The anti-tumor efficacy of curcumin can be markedly improved by nano-drug self-delivery systems with high drug loading capacity and smart stimulus-triggered drug release in tumor cells. Herein, a type of novel, glutathione (GSH)-responsive, PEGylated prodrug nano-micelles (PPNMs) was prepared by self-assembly of curcumin-s-s-vitamin E/mPEG2k-DSPE mixture. The PPNMs (entrapment efficiency: 96.7%) was acceptably stable in water with a mean particle size of 29.84 nm. Compared with curcumin-loaded mPEG2k-DSPE nano-micelles (CUR-NMs), PPNMs showed a higher drug loading (1.68% vs 27.3%) and remarkably improved the chemical stability of curcumin in phosphate buffer saline (PBS) (pH = 7.4), 10% FBS culture medium, and rat plasma. In vitro release study showed that PPNMs could redox responsively control the release of curcumin from the prodrug. Moreover, PPNMs showed a cytotoxicity in HepG2 cells similar to that of the free curcumin; however, when the HepG2 cells were pretreated with 1 mM GSH, PPNMs displayed a markedly enhanced cytotoxicity and cellular uptake than the free curcumin. After intravenous injection, PPNMs showed an increased half-life in blood circulation (10.6-fold) and bioavailability (107-fold) compared with the free curcumin injection. Altogether, the prodrug nano-micelles represent a promising preparation for sustained and controlled delivery of curcumin with enhanced antitumor activity. [ABSTRACT FROM AUTHOR]

Introduction The quest for novel cancer drugs is one of the most significant studies in natural products, and Chinese herbs with its promising antitumor properties cannot be exempted from this chemotherapeutic bracket. This study was therefore aimed at piloting the use of receptor-rich lipid raft biomaterial as a mass screening tool for rapid isolation of effective antitumor components from some Chinese herbs used in the treatment of diseases consistent with cancer symptoms. Method Aqueous crude extracts from 10 different Chinese herbs (Paeonia suffruticosa, Vaccaria segetalis, Terminalia chebula, Trichosanthes kirilowii, Arisaema erubescens, Morus australis, Centella asiatica, Rhematoxylon campechianum, Trachelospermum jasminoides and Taraxacum officinale) were screened using lipid raft silica beads. The identified bioactive products were separated into various fractions (petroleum ether, ethyl acetate, n-butanol and raffinate extracts) with another affinity screening analysis. Conventional MTT bioassay was employed to authenticate the susceptibility of liver cancer cells to the final bioactive isolates. Results The results showed that only Vaccaria segetalis and Arisaema erubescens significantly interacted with the system. The MTT bioassay further confirmed the cytotoxicity of these plants and the data correlated very well with its reported cancer-related activities. Conclusion These findings support the reliable application of the lipid raft biomaterial as a prospective mass screening technique for antitumor natural products. [ABSTRACT FROM AUTHOR]

Two heterometallic tetranuclear {Dy 2 Zn 2 } clusters were hydrothermally prepared by the reactions of same mixed-ligands with different dysprosium sources. Substituting two carboxylate-groups of the former complex with a couple of hydroxide-bridges generated a smaller shortest Dy−O bond and the larger bond length difference, leading to more uniaxial anisotropy of DyIII spins resulting from the strong coordination ability of OH– groups, thus exhibiting better dynamics behaviour. [Display omitted] • A novel m-COO− and µ-OH−-linked linear {Dy 2 Zn 2 } cluster was obtained by tuning the dysprosium source. • Substituting carboxylate-groups with hydroxide-bridges significantly change the Dy-O bonds. • A smaller shortest Dy-O bond and the larger bond length difference lead to better dynamics behaviour. Two heterometallic tetranuclear clusters [Dy 2 Zn 2 (bipy) 2 (nb) 10 ] (1) and [Dy 2 Zn 2 (bipy) 2 (μ−OH) 2 (nb) 8 ] (2) (bipy = 2,2′-bipyridine, Hnb = m -nitrobenzoic acid) were hydrothermally prepared by the reactions of same mixed-ligands with different dysprosium sources. Structurally, the coordination environment, configuration, and the binding modes of the mixed ligands are almost similar to each other. Only a slight difference is a pair of μ -COO− moieties connecting DyIII and ZnII cations in 1 replaced by a couple of scarcely µ -OH– bridges in 2. Magnetically, complex 1 displays no slow magnetic relaxation behavior, while the complex 2 behaves as a single molecule magnet with the effective energy barrier of 78.69 K due to the large uniaxial anisotropy of DyIII ions, which is mainly originating from the strong coordination ability of hydroxide-bridges. [ABSTRACT FROM AUTHOR]

Abstract Fine particulate matter (PM 2.5) exposure could cause many acute and chronic respiratory diseases. In this study the protective effects of polysaccharide from Morchella esculenta (FMP-1) and its derivatives against PM 2.5 -induced inflammation were evaluated. By flow cytometry and ELISA analysis, sulfated polysaccharide SFMP-1 showed the best protective effect in reducing PM 2.5 -induced cell death, cell apoptosis and production of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β), which was accompanied by a diminished level in reactive oxygen species (ROS) formation caused by PM 2.5 in rat alveolar macrophage NR8383 cells. Furthermore, the mechanism was studied by immunofluorescence, qRT-PCR and western blotting. SFMP-1 could down-regulate the expression of inducible NO synthesis (iNOS) and cyclooxygenase-2 (COX-2) at both mRNA and protein levels in PM 2.5 -treated cells. The PM 2.5 -induced phosphorylation of nuclear factor-kappa B (NF-κB) was also reduced through suppressing nuclear translation of the NF-κB and inhibiting the degradation and phosphorylation of IκBα. These results indicated that SFMP-1 could protect NR8383 cells from PM 2.5 -induced inflammation by inhibiting NF-κB activation. Highlights • Polysaccharide from Morchella esculenta (FMP-1) was chemically modified to obtain sulfated and carboxymethylated derivatives. • Protection of FMP-1 and its derivatives against PM 2.5 -induced inflammation were comparatively investigated. • Sulfated polysaccharide SFMP-1 showed the best protective effect in PM 2.5 -treated alveolar macrophage NR8383 cells. • SFMP-1 could protect NR8383 cells from PM 2.5 -induced inflammation by inhibiting NF-κB activation. [ABSTRACT FROM AUTHOR]

Abstract: Selective serotonin reuptake inhibitors (SSRIs), one of popular antidepressants as “one-compound-one-target” paradigm, cannot but discontinue because of inhibiting gut movement. Traditional Chinese medicine (TCM) Chaihu–Sugan–San (CSS) can simultaneously exert anti-depression and prokinetics. From this thread, we aimed to find a new antidepressant with polypharmacological mechanisms. In vivo antidepressive and prokinetic comparisons between CSS and its absorbed compound ferulic acid (FA) were made. And FA''s action mechanisms involved in monoaminergic systems, HPA axis and gastrointestinal peptide ghrelin was then studied in forced swimming test (FST) of rat. Lastly, the jejunal contraction activity evoked by FA was measured in vitro. Compared with vehicle, FA reduced immobility time, increased locomotor activity, accelerated gastric emptying and intestinal transit similar to CSS whose absorbable component FA was identified in hippocampus and jejunum. FA''s prokinetics in vivo was further supported by its jejunal contraction in vitro. FA-induced anti-immobility was prevented by pretreated with PCPA, WAY-100635, ketanserin, sulpiride, SCH233390, haloperidol and yohimbine, respectively. CRH, ACTH and 5-HT were significantly decreased, but ghrelin was apparently increased compared with vehicle. In summary, FA induced anti-depression and prokinetics similar to CSS via inhibiting serotonin, norepinephrine and dopamine reuptakes, regulating HPA axis, increasing ghrelin and stimulating jejunal contraction simultaneously. [Copyright &y& Elsevier]