BackgroundSelenium (Se) is an indispensable trace element required for animals and humans, and extra Se-supplement is necessary, especially for those having Se deficiency. Recently, selenium nanoparticles (SeNPs), as a special form of Se supplement, have attracted worldwide attention due to their distinguished properties and excellent bioactivities. In this present study, an eco-friendly and economic way to prepare stable SeNPs was introduced. SeNPs were synthesized in the presence of chitosan (CTS) and then embedded into chitosan/citrate gel, generating selenium nanoparticles-loaded chitosan/citrate complex (SeNPs-C/C). Additionally, the clinical potential of SeNPs-C/C was evaluated by using d-galactose (d-gal)-induced aging mice model.ResultsSeNPs in high uniform with an average diameter of around 50 nm were synthesized in the presence of chitosan, and reversible ionic gelation between chitosan and citrate was utilized to load SeNPs. Subsphaeroidal SeNPs-C/C microspheres of 1–30 μm were obtained by spay-drying. Single SeNPs were physically separated and embedded inside SeNPs-C/C microparticles, with excellent stability and acceptable release. Acute fetal test showed SeNPs-C/C was safer than selenite, with a median lethal dose (LD50) of approximately 4-fold to 11-fold of that of selenite. Oral administration of SeNPs-C/C remarkably retarded the oxidative stress of d-gal in Kunming mice by enhancing the activity of antioxidase, as evidenced by its significant protection of the growth, liver, Se retention and antioxidant bio-markers of mice against d-gal.ConclusionsThe design of SeNPs-C/C opens a new path for oral delivery of SeNPs with excellent stability, energy-conservation and environment-friendliness. SeNPs-C/C, as a novel supplement of Se, could be further developed to defend the aging process induced by d-gal.

Obesity is associated with enhanced colonic inflammation, which is a major risk factor for colorectal cancer. Considering the obesity epidemic in Western countries, it is important to identify novel therapeutic targets for obesity-induced colonic inflammation, to develop targeted strategies for prevention. Eicosanoids are endogenous lipid signaling molecules involved in regulating inflammation and immune responses. Using an LC-MS/MS-based lipidomics approach, we find that obesity-induced colonic inflammation is associated with increased expression of soluble epoxide hydrolase (sEH) and its eicosanoid metabolites, termed fatty acid diols, in colon tissue. Furthermore, we find that pharmacological inhibition or genetic ablation of sEH reduces colonic concentrations of fatty acid diols, attenuates obesity-induced colonic inflammation, and decreases obesity-induced activation of Wnt signaling in mice. Together, these results support that sEH could be a novel therapeutic target for obesity-induced colonic inflammation and associated diseases.

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The C-10–C-4a bond cleavage of anthraquinone is believed to be a crucial step in fungal seco-anthraquinone biosynthesis and has long been proposed as a classic Baeyer–Villiger oxidation. Nonetheless, genetic, enzymatic, and chemical information on ring opening remains elusive. Here, a revised questin ring-opening mechanism was elucidated by in vivo gene disruption, in vitro enzymatic analysis, and 18O chasing experiments. It has been confirmed that the reductase GedF is responsible for the reduction of the keto group at C-10 in questin to a hydroxyl group with the aid of NADPH. The C-10–C-4a bond of the resultant questin hydroquinone is subsequently cleaved by the atypical cofactor-free dioxygenase GedK, giving rise to desmethylsulochrin. This proposed bienzyme-catalytic and dioxygenation-mediated anthraquinone ring-opening reaction shows universality.

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SCAP has a protective effect on ethanol-induced liver injury in mice and cells, and the mechanism underlying may be via inhibiting the expression of CYP2E1 protein and then alleviating oxidative stress injury induced by ethanol.

Astragaloside IV is an important constituent of Radix Astragali, a herbal remedy widely used in traditional Chinese medicine. Radix Astragali is administered orally but little is known about the transport properties and bioavailability of astragaloside IV. In this paper we report studies of the absorption of astragaloside IV in the perfused rat intestinal model, transport and uptake in Caco-2 cell monolayers and in vivo bioavailability in rat after an oral dose. In the perfused rat intestinal model, absorption of astragaloside IV was low from an aqueous solution but was significantly higher from a solution of Radix Astragali. Absorption was not affected by bile duct ligation. Transport through Caco-2 cells gave a very low permeability value (mean P app of 6.7∫1.0¿10ª8 cm/sec.) and uptake was unaffected by P-glycoprotein inhibitors. The absolute bioavailability of astragaloside IV in rat was 2.2%. The correlation between low permeability in vitro and poor bioavailability in vivo indicates in vitro absorption studies are useful in the evaluation of traditional Chinese medicines.Radix Astragali had been widely used as an effective herbal remedy in traditional Chinese medicine for its antiinflammatory, antimicrobial and immune stimulating activities (Rios & Waterman 1997; Pharmacopoeia of P.R. China 2000). Astragaloside IV ( fig. 1), a cycloartane-type triterpene glycoside, is regarded as a characteristic and active constituent of Radix Astragali and the content of astragaloside IV is the main criterion of its quality assurance and control. Although astragaloside IV has relatively high lipophilicity (ClogP of 2.0), the high molecular weight (785) and low solubility predict it would be poorly absorbed and have low bioavailability. We were interested to confirm this and establish whether in vitro methods of drug absorption would correctly predict bioavailability in vivo. Accordingly, we examined transport properties of astragaloside IV in the in situ perfused rat intestinal model, uptake and transport in monolayers of the human colon carcinoma cell line Caco-2 and absolute bioavailability in rat. Materials and MethodsCompounds and animals. Astragaloside IV, cyclosporin A and verapamil were purchased from the National Institute for the Control of Pharmaceutical and Biological Products (Beijing, China). Radix Astragali Oral Solution (containing 0.5 mg/ml astragaloside IV) was obtained from the Jiangsu Provincial Hospital (Nanjing, China). All other reagents were analytical grade. Unless otherwise indicated, astragaloside IV was dissolved in dimethyl sulfoxide (DMSO) and diluted to the desired concentration with water (final concentration of DMSOϽ0.1%). Sprague-Dawley rats (male, 190-210 g) were purchased from Sino-British Sippr/BK Lab Animal Ltd (Shanghai, Author for correspondence: J. Paul Fawcett, School of Pharmacy, University of Otago, P.O. Box 913, Dunedin, New Zealand (fax 64 3 4797034, e-mail njguyc/hotmail.com). China) and housed six to a plastic walled cage with unlimited access to food and water exce...

To examine the anti-fatigue function of anwulignan from Schisandra and its underlying mechanism.