Xianlian Jiedu Decoction alleviates colorectal cancer by regulating metabolic profiles, intestinal microbiota and metabolites.

BACKGROUND: Xianlian Jiedu Decoction (XLJDD) has been used for the treatment of colorectal cancer (CRC) for several decades because of the prominent efficacy of the prescription. Despite the clear clinical efficacy of XLJDD, the anti-CRC mechanism of action is still unclear. PURPOSE: The inhibitory effect and mechanism of XLJDD on CRC were investigated in the azoxymethane/dextran sulfate sodium (AOM/DSS)-induced mice. METHODS: The AOM/DSS-induced mice model was adopted to evaluate the efficacy after administering the different doses of XLJDD. The therapeutic effects of XLJDD in treating AOM/DSS-induced CRC were investigated through histopathology, immunofluorescence and ELISA analysis methods. In addition, metabolomics profile and 16S rRNA analysis were used to explore the effective mechanisms of XLJDD on CRC. RESULTS: The results stated that the XLJDD reduced the number of tumor growth on the inner wall of the colon and the colorectal weight/length ratio, and suppressed the disease activity index (DAI) score, meanwhile XLJDD also increased body weight, colorectal length, and overall survival rate. The treatment of XLJDD also exhibited the ability to lower the level of inflammatory cytokines in serum and reduce the expression levels of ß-catenin, COX-2, and iNOS protein in colorectal tissue. The findings suggested that XLJDD has anti-inflammatory properties and may provide relief for those suffering from inflammation-related conditions. Mechanistically, XLJDD improved gut microbiota dysbiosis and associated metabolic levels of short chain fatty acids (SCFAs), sphingolipid, and glycerophospholipid. This was achieved by reducing the abundance of Turicibacter, Clostridium_sensu_stricto_1, and the levels of sphinganine, LPCs, and PCs. Additionally, XLJDD increased the abundance of Enterorhabdus and Alistipes probiotics, as well as the content of butyric acid and isovaleric acid. CONCLUSION: The data presented in this article demonstrated that XLJDD can effectively inhibit the occurrence of colon inner wall tumors by reducing the level of inflammation and alleviating intestinal microbial flora imbalance and metabolic disorders. It provides a scientific basis for clinical prevention and treatment of CRC.

[Multi-index components of Scutellariae Barbatae Herba according to UHPLC-QTRAP-MS coupled with chemometrics].

The present study developed an ultra-fast liquid chromatography coupled with triple quadrupole-linear ion trap composite mass spectrometry(UHPLC-QTRAP-MS) to simultaneously determine the content of potential active components in Scutellariae Barbatae Herba and also to provide a reference approach for screening out the differential quality control components among different batches of Scutellariae Barbatae Herba. Chromatographic separations were conducted on a Thermo Acclaim~(TM) RSLC 120 C_(18) column(3.0 mm×100 mm, 2.2 µm) in a gradient program. The mobile phase consisted of 0.1% aqueous formic acid and acetonitrile, and the column temperature was maintained at 40 ℃. The flow rate was 0.4 mL·min~(-1) and the injection volume was 2 µL. The targeted compounds were monitored in the multiple reaction monitoring(MRM) mode. The acquired data were processed by hierarchical cluster analysis(HCA) and partial least square discriminant analysis(PLS-DA). Sixteen compounds all showed good linear relationship within the corresponding linear ranges and the R~2 values were all higher than 0.993 2. The RSDs of precision, repeatability, and stability were less than or equal to 3.7%. Mean recovery rates were in the range of 95.67% and 104.8% with RSDs≤3.2%. According to HCA and PLS-DA, all samples were clustered into four categories. Scutellarin, acteoside, scutellarein, and scutebarbatine X(VIP>1) were considered as differential chemical markers in the four categories. In conclusion, the developed method can be used for the simulta-neous determination of the multiple components and quality control of Scutellariae Barbatae Herba.

[Analysis on chemical components from water extract of paeoniae radix alba by high performance liquid chromatography-electrospray ionization-quadrupole-time of flight-mass spectrometry].

This experiment was performed to establish a qualitative analysis on chemical composition in water extract of Paeoniae Radix Alba by HPLC-ESI-Q-TOF-MS. The analysis was conducted on a C18 (Hanbon Lichrospher, 4.6 mm x 250 mm, 5 microm) column with methanol-0.1% formic acid as the mobile phase for gradient elution; ESI ion source was used for mass spectra, and data were collected in both positive and negative modes. The results showed that eleven compounds from water extract of Paeoniae Radix Alba had been identified by analyzing positive and negative ion mass data including element composition and by comparing with data from literatures. Since efficient separation of HPLC and the high sensitive detection of MS was used, this experiment, it will provide evidences for elucidation of the effective substance in the water extract of Paeoniae Radix Alba.

Tanshinone IIA: a new activator of human cardiac KCNQ1/KCNE1 (I(Ks)) potassium channels.

Tanshinone IIA, one of the main active components from Chinese herb Danshen, is widely used to treat cardiovascular diseases including arrhythmia in Asian countries especially in China. However, the mechanisms underlying its anti-arrythmia effects are not clear. In this study we investigate the effects of tanshinone IIA on human KCNQ1/KCNE1 potassium channels (I(Ks)), human ether-a-go-go-related gene potassium channels (hERG), Kv1.5 potassium channels, inward rectifier potassium channels (I(K1)) expressed in HEK 293 cells using patch clamp technique. Tanshinone IIA potently and reversibly enhanced the amplitude of I(Ks) in a concentration dependent manner with an EC(50) of 64.5 microM, accelerated the activation rate of I(Ks) channels, decelerated their deactivation and shifted the voltage dependence of I(Ks) activation to negative direction. Isoproteronol, a stimulator of beta-adrenergic receptor, at 1 microM and sodium nitroprusside (SNP), a NO donor, at 1 mM, had no significant effects on the enhancement of I(Ks) by 30 microM tanshinone IIA. N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H89), a selective protein kinase A inhibitor, at 0.1 microM and 1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one (ODQ), a selective nitric oxide-sensitive guanylyl cyclase inhibitor, at 10 microM, also had no significant effects on the enhancement of I(Ks) by 30 microM tanshinone IIA. Tanshinone IIA did not affect expressed hERG channels, Kv1.5 channels and I(K1) channels. These results indicate that tanshinone IIA directly and specifically activate human cardiac KCNQ1/KCNE1 potassium channels (I(Ks)) in HEK 293 cell through affecting the channels' kinetics.

New sphingolipids from the root of Isatis indigotica and their cytotoxic activity.

Two new sphingolipids were isolated from the 95% EtOH extract of traditional Chinese medicinal plant Isatis indigotica. Their structures were elucidated as (2S,3R)-3-hydroxymethyl-N-(2'-hydroxynonacosanoyl)-trideca-9E-sphingenine(1) and 1-O-beta-D-glucopyranosyl-(2S,3R)-3-hydroxymethyl-N-(2'-hydroxynonacosanoyl)-trideca-9E-sphingenine(2) on the basis of spectroscopic data. Their cytotoxic effects were evaluated by using MTT method.

[Chemical constituents from water extract of Radix isatidis].

AIM: To study the chemical constituents from water extract of Radix isatidis. (Isatis indigotica Fort. ). METHODS: The water extract was underwent absorption by D101 macroporous resin, the portion eluted by ethanol of different concentrations was isolated and purified on silica gel column repeatedly. The obtained compounds were identified and structurally elucidated by their physico-chemical properties and spectral analysis. RESULTS: Five compounds were isolated from water extract of Radix isatidis, and were partly identified separately: 3-[2'-(5'-hydroxymethyl) furyl] -1 (2H) -isoquinolinone-7-O-beta-D-glucoside (I), lariciresinol-4,4'-di-O-beta-D-glucopyranoside (II), lariciresinol-4-O-beta-D-glucopyranoside (III), 2-hydroxy-1, 4-benzenedicarboxylic acid (IV), mannitol (V). CONCLUSION: Compound I is a new compound and compounds IV and V were isolated from the plant for the first time.