Effects of Ganoderma lucidum polysaccharide peptide ameliorating cyclophosphamide-induced immune dysfunctions based on metabolomics analysis.

Ganoderma lucidum polysaccharide peptide (GLPP) is one of the most abundant constituents of Ganoderma lucidum (G. lucidum), with a wide range of functional activities. The present study investigated the immunomodulatory effects of GLPP in cyclophosphamide (CTX)-induced immunosuppressive mice. The results showed that 100 mg/kg/day of GLPP administration significantly alleviated CTX-induced immune damage by improving immune organ indexes, earlap swelling rate, the index of carbon phagocytosis and clearance value, secretion of cytokines (TNF-α, IFN-γ, and IL-2), and immunoglobulin A(IgA) in the mice. Furthermore, ultra-performance liquid chromatography with mass/mass spectrometry (UPLC-MS/MS) was conducted to identify the metabolites, followed by biomarker and pathway analysis. The results showed that GLPP treatment alleviated CTX-induced alterations in the fecal metabolome profile, including arachidonic acid (AA), leukotriene D4 (LTD4), indole-3-ethanol, and formyltetrahydrofolate (CF), by reversing citric acid, malic acid, cortisol, and oleic acid. These results support the concept that GLPP exhibits immunomodulatory activity via the folate cycle, methionine cycle, TCA cycle, fatty acid biosynthesis and metabolism, glycerophospholipid metabolism, AA metabolism, and cAMP pathways. In conclusion, the results could be helpful to understand the use of GLPP to clarify the immunomodulatory mechanism and be used as immunostimulants to prevent CTX-induced side effects in the immune system.

Turning On the Near-Infrared Photoluminescence of Erbium Metallofullerenes by Covalent Modification.

The photoluminescence of lanthanide ions inside fullerenes is usually very weak due to the quenching effect of the fullerene cage. In the case of Er@C82, the near-infrared emission from the Er3+ ion is completely quenched by the C82 fullerene cage. It remains challenging to turn on the photoluminescence of Er@C82 and other monometallofullerenes. In this work, we adopt a covalent modification strategy to alter the electronic structure of the fullerene cage for sensitizing the near-infrared emission of Er3+ ions in metallofullerenes Er@C2n (2n = 72, 76, and 82). After covalent modification with trifluoromethyl, phenyl, or dichlorophenyl groups, the erbium metallofullerenes exhibit photoluminescence at 1.5 µm, which is the characteristic emission of the Er3+ ion. Particularly, the otherwise nonfluorescent metallofullerene Er@C82 is transformed into fluorescent derivatives by using this strategy. The photoluminescence from the Er3+ ion is ascribed to energy transfer from the fullerene cage to the Er3+ ion. According to theoretical calculations, the sensitization of the Er3+ ion by the fullerene cage is associated with the large HOMO-LUMO gap and the closed-shell electronic structure of the metallofullerene derivatives. This work provides useful guidance for the design and synthesis of new fluorescent metallofullerenes.

Luminescence enhancement in Eu3+, Sm3+ co-doped liy(MoO4)2 nano-phosphors by sol-gel process.

A series of LiY(0.95-x)Eu(0.05)Sm(x)(MoO4)2 red light emitting phosphors were synthesized by sol-gel technique. The phase impurity and spectroscopic properties were characterized by X-ray Diffraction (XRD), Photo-Luminescence (PL) and Photo-Luminescence Excitation (PLE) spectra, respectively. It is found that the PLE spectra of the Eu3+, Sm3+ co-doped nanoparticles are enhanced and broadened as compared with the solely doped samples, which will make the co-doped phosphors match better with blue and/or UV GaN based LED chips. The red emission intensity of Eu3+ is largely enhanced by the energy transfer from Sm3+. The mechanism of the enhancement is clearly proven to be the increase in the quantum efficiency of 5D0 state of Eu3+ rather than the increase in the absorption of Eu3+. Meanwhile, the characteristic f-f transitions of Sm3+ are greatly reduced, resulting in little influence in the color purity of the co-doped phosphors. The present material is an amendatory promising red light emitting phosphor for white LEDs.

Simultaneous determination of seven flavonoids in dog plasma by ultra-performance liquid chromatography-tandem mass spectrometry and its application to a bioequivalence study of bioactive components in Herba Epimedii and Er-Xian Decoction.

In this study, a sensitive and specific ultra-performance liquid chromatography-tandem mass method has been developed and validated for the identification and determination of 7 flavonoids in dog plasma for the first time: epimedin A, epimedin B, epimedin C, icariin, sagittatoside B, 2″-O-rhamnosyl icariside II, and baohuoside I. Chromatographic separation was accomplished on an Agilent Zorbax-SB C(18) column (50 mm × 2.1mm, 1.8 µm) with a gradient elution system composed of 0.3% acetic acid and 0.3% acetic acid in acetonitrile at a flow rate of 0.4 mL/min. Detection was based on a triple quadrupole mass spectrometer using a multiple reaction monitoring mode with an electrospray ionization source. All of the calibration curves showed good linearity (r>0.99) within the tested concentration ranges. The lower limits of quantification of the seven analytes were all lower than 0.0654 ng/mL. The relative standard deviations for intra- and inter-batches of the seven analytes were less than 13.7% and 14.9%, respectively, at four concentration levels of quality control samples, and the recoveries were between 92.8% and 114.5%, respectively. In addition, the seven flavonoids were found to be stable in dog plasma samples under short- and long-term storage and processing conditions. The validated method was successfully applied to a bioequivalence study in dog plasma after the oral administration of extracts of Herba Epimedii and Er-Xian Decoction.

Metabolism of ferulic acid in rats.

Ferulic acid is the major active constituent in many natural Chinese medicinal herbs. The metabolism of ferulic acid has been investigated using solid-phase extraction and HPLC-DAD methods that were established to separate and analyze the metabolites in urine, feces and bile. Three metabolites, identified by enzymatic hydrolysis, HPLC-DAD, HPLC-MS and MS/MS, are all glucuronic acid conjugates of ferulic acid. Ferulic acid conjugated with one glucuronic acid at different positions produces M1 and M3. Ferulic acid conjugated with two glucuronic acids produces M2, which is the main metabolite. A metabolic pathway is proposed.

Study on metabolism of scutellarin in rats by HPLC-MS and HPLC-NMR.

Scutellarin is the major active constituent of Scutellaria barbata D. The metabolism of scutellarin has been investigated in rats. The solid-phase extraction and HPLC-DAD methods were established to separate and analyse metabolites. Five metabolites (M1-M5) were identified by enzymatic hydrolysis, HPLC-DAD, HPLC-MS and HPLC-NMR. M1 and M3 were conjugates of scutellarin with two sulfate groups, which have not been reported in natural plants. M2 was scutellarin; M4 was 6-methyl-scutellarin; and M5 was 6-methyl-scutellarein. The metabolic pathway was proposed.

[The metabolic transformation of (-)-securinine].

AIM: To study the in vitro and in vivo metabolism of (-)-securinine. METHODS: The metabolic transformation of (-)-securinine was studied by using phenobarbital-induced rat liver microsomal incubate containing the NADPH-generating system in vitro and the constitution of the system was optimized. A reversed phase HPLC method was established to analyze the parent drug and its metabolites. The major metabolites were isolated and purified by liquid-liquid extraction, preparative TLC and HPLC, and their structures were elucidated as 6-hydroxyl securinine, 6-carbonyl securinine, 5 beta-hydroxyl securinine and 5 alpha-hydroxyl securinine by 1HNMR, 13CNMR and MS spectral analysis. An HPLC method was developed to analyze securinine and its metabolites in biofluids (bile, urine) of rat. The bile, urine and their enzymatic hydrolyzed samples of the rat i.p. administrated with (-)-securinine were determined by using this method. RESULTS: Four main metabolites of (-)-securinine in rat hepatic microsome incubation were obtained and their structures were elucidated. Metabolites from in vitro study were confirmed in biofluids (bile, urine) which were collected from rats given securinine i.p. It was suggested that 6-hydroxyl securinine was excreted in conjugated form as well by analyzing enzymatic hydrolyzed bile. CONCLUSION: The main metabolic pathway of (-)-securinine in vitro and in vivo is basically elucidated.

[Study on the chiral separation of securinine by high-performance capillary electrophoresis and its stereoselective metabolism in rat].

AIM: To establish a high-performance capillary electrophoresis (HPCE) chiral separation method for d-securinine and l-securinine, and use this method to investigate the stereoselective metabolism process of d- and l-securinine in Wistar rats. METHODS: The electrophoretic condition and parameters were investigated and the optimized conditions were as following: the electrophoretic medium was 40 mmol.L-1 Tris-H3PO4 buffer (pH adjusted to 6.0 with H3PO4) containing 32 mmol.L-1 HP-beta-CD as chiral selector. Determination was carried out with a UV detector at 254 nm. The separations were performed at 16 degrees C with a positive voltage of 15 kV. Samples were injected into the capillary by pressure for 6 s. The biological samples (urine, bile, plasma and feces) of rats were alkalized and extracted with ethyl acetate. RESULTS: The experimental results showed that the concentration of HP-beta-CD, the concentration of the running buffer and the pH value of the buffer were the main important factors which effected the resolution. d-Securinine and l-securinine were separated at baseline level under the determination conditions. The determination was not interfered by endogenous components and metabolites. After i.p. administration, the rats excreted more d-securinine than l-securinine through bile, urine and feces. The metabolism process in rats was stereoselective. CONCLUSION: This method is simple, reliable and suitable for studying the stereoselective metabolism of securinine in rats.