Pharmacokinetics of costunolide and dehydrocostuslactone after oral administration of Radix aucklandiae extract in normal and gastric ulcer rats.

Costunolide and dehydrocostuslactone are the main active ingredients of Radix Aucklandiae (RA). An accurate and sensitive LC-MS/MS method was established to simultaneously determine contents of costunolide and dehydrocostuslactone in plasma. There were significant differences in pharmacokinetic parameters (AUC0-t, Cmax,1, Cmax,2, Tmax,1, Vd, and CL) of costunolide and dehydrocostuslactone between RA group and costunolide group or dehydrocostuslactone group. The relative bioavailability of costunolide or dehydrocostuslactone of RA extract was improved. As compared to normal group, the Tmax,2 values of dehydrocostuslactone of RA in gastric ulcer group were prolonged, while the Cmax,1, Cmax,2, and AUC0-t values decreased.

[Effect of inhibiting the expression of hSMG-1 on chemosensitivity of human non-small cell lung cancer H1299 cells].

OBJECTIVE: To investigate the effect of inhibiting the expression of human suppressor of morphogenesis in genitalia-1 (hSMG-1) on chemosensitivity in human lung cancer H1299 cells. METHODS: Specialized small interference RNAs (siRNAs) of hSMG-1 were transfected into H1299 cells. The knockdown effect was evaluated by quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) and immunofluorescence. After the administration of anti-cancer drugs, the cell viable rate was determined by cell counting kit (CCK-8) and apoptotic rate was measured by Annexin V-FITC PI double staining on flow cytometry. The apoptotic related activated caspase 3 and caspase 9 were determined by colorimetric assay. RESULTS: The expression of hSMG-1 mRNA was significantly inhibited by hSMG-1 siRNA. And the inhibition rate of (73.8 ± 10.3)% was obtained (P < 0.01). The knockdown effect was further confirmed by immunofluorescence. The inhibition of hSMG-1 enhanced the sensitivity of H1299 cells to gemcitabine and cisplatin. The survival rates significantly decreased when the hSMG-1 siRNA transfected cells were treated with 10.0 mg/L gemcitabine and 10.0 mg/L cisplatin for 48 h respectively (0.51 ± 0.02 vs 0.69 ± 0.01, P < 0.01 and 0.34 ± 0.03 vs 0.48 ± 0.01, P < 0.01;all compared with control siRNA group). Annexin V-FITC PI double staining showed that, under the treatment of anti-cancer drugs, the apoptotic rate of H1299 cells was significantly increased by hSMG-1 knockdown [gemcitabine, (20.9 ± 3.4)% vs (12.0 ± 2.7)%, P < 0.05; cisplatin, (10.2 ± 1.8)% vs (4.5 ± 2.0)%, P < 0.05; all compared with control siRNA group]. Further study showed the inhibition of hSMG-1 up-regulated the activated caspase 3 and caspase 9 in the treated H1299 cells (gemcitabine, 0.1 mg/L, 48 h, caspase 3: 14.4 ± 3.8 vs 2.3 ± 0.4, P < 0.01; caspase 9: 15.5 ± 2.4 vs 4.2 ± 0.9, P < 0.01; cisplatin, 1.0 mg/L, 48 h, caspase 3: 18.8 ± 3.0 vs 6.5 ± 1.5, P < 0.01; caspase 9: 20.3 ± 4.2 vs 8.1 ± 2.0, P < 0.05; all compared with control siRNA group). CONCLUSION: The inhibition of hSMG-1 significantly enhances the sensitivity of human lung cancer H1299 cells to gemcitabine and cisplatin through an induction of more apoptotic cells. And the activation of mitochondrial apoptotic pathway is involved.

Norcyperone, a novel skeleton norsesquiterpene from Cyperus rotundus L.

A novel norsesquiterpene, named norcyperone (1), and three known compounds: (-)-clovane-2,9-diol (2), rosenonolactone (3), and 5 alpha,8 alpha-epidioxy-(20S,22E,24R)-ergosta-6,22-dien-3beta-ol (4) were isolated from the rhizomes of Cyperus rotundus L. The structure of 1 was elucidated as 8,11,11-trimethylbicyclo[5.3.1]undecane-5 alpha, 8 alpha-epoxy-3-one on the basis of extensive spectroscopic analyses, including 1D- and 2D-NMR, MS experiments, and single-crystal X-ray diffraction. This is the first report of a 8,11,11-trimethyl- bicyclo[5.3.1]undecane-3-one type norsesquiterpene with a tetrahydrofuran ring at C-5 and C-8.

[Comparative study on two methods of back propagation network test in TCM syndrome typing of depression].

OBJECTIVE: To compare the effect of the two methods of back propagation network (BPN) test on TCM syndrome typing of depression. METHODS: Test was carried out by two methods as following: (1) Cross train-test method: 1731 patients with depression typed to 5 syndrome types were randomly divided into 2 groups, and they were trained and tested in turn; (2) Round-Robin method: Test was conducted in an altered cycle mode, that is, in a cycle, one out of the 1731 patients were selected to be tested, while the others were trained, the next cycle started when the test on the selected patient was finished and another one for test was selected. In this way, one cycle after the other, until all patients had been tested. RESULT: The total training sensitivity of the two methods was 97.9% and 98.2% respectively, and the total testing sensitivity was 72.7% and 74.2% respectively. CONCLUSION: (1) The five TCM syndrome types of depression could be well differentiated by BPN, which is valuable for TCM syndrome typing in certain extent; (2) The sensitivity of Round-Robin method is slightly higher than that of Cross train-test method, but in comparison between them no remarkable significance was shown.

A new naphthalenone isolated from the green walnut husks of Juglans mandshurica Maxim.

Phytochemical study of green walnut husks of Juglans mandshurica Maxim. led to the isolation of a new naphthalenone, (4R)-3,4-dihydro-4-butoxy-5-hydroxy-naphthalen-1(2H)-one (1), together with 16 known compounds. Compounds 4-6, 13, 14 and 17 were isolated from the genus Juglans for the first time, and their chemotaxonomic significance was also evaluated.

Chinese herbs and their active ingredients for activating xue (blood) promote the proliferation and differentiation of neural stem cells and mesenchymal stem cells.

Some Chinese herbs are anti-thrombolysis, and anti-inflammatory, improves brain RNA content, promotes brain protein synthesis, enhances dopamine function, regulates brain hormones, and improves microcirculation in central nervous system that might improve, repair and rehabilitation from the stroke and brain injury. Specific Chinese herbs and their components, such as Acanthopanax, Angelica, could maintain the survival of neural stem cells, and Rhodiola, Ganoderma spore Polygala, Tetramethylpyrazine, Gardenia, Astragaloside and Ginsenoside Rg1 promoted proliferation of neural stem cells, and Rhodiola, Astragaloside promoted differentiation of neural stem cell into neuron and glia in vivo. Astragalus, Safflower, Musk, Baicalin, Geniposide, Ginkgolide B, Cili polysaccharide, Salidroside, Astragaloside, Antler polypeptides, Ginsenoside Rg1, Panax notoginseng saponins promoted proliferation and differentiation of neural stem cells in vitro. Salvia, Astragalus, Ginsenoside Rg1, P. notoginseng saponins, Musk polypeptide, Muscone and Ginkgolide B promoted neural-directed differentiation of MSCs into nerve cells. These findings are encouraging further research into the Chinese herbs for developing drugs in treating patients of stroke and brain injury.

UPLC-Q/TOF MS standardized Chinese formula Xin-Ke-Shu for the treatment of atherosclerosis in a rabbit model.

Xin-Ke-Shu (XKS), a patent traditional Chinese medicine (TCM) preparation, has been commonly used for the treatment of coronary heart disease in China. In order to understand its mechanism of action, a metabonomic approach based on ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF MS) was utilized to profile the plasma metabolic fingerprints of atherosclerosis (AS) rabbits with and without XKS treatment. The metabolic profile of model group clearly separated from normal, and that of XKS group was closer to the control group. Metabolites with significant changes during atherosclerosis were characterized as potential biomarkers related to the development of atherosclerosis by using orthogonal partial least-squares-discriminate analysis (OPLS-DA). Twenty potential biomarkers, including l-acetylcarnitine (1), propionylcarnitine (2), unknown (3), phytosphingosine (4), glycoursodeoxycholic acid (5), LPC(14:0) (6), sphinganine (7), LPC(20:5) (8), LPC(16:1) (9), LPC(18:2) (10), LPC(18:3) (11), LPC(22:5) (12), LPC(16:0) (13), LPC(18:1) (14), LPC(22:4) (15), LPC(17:0) (16), LPC(20:2) (17), elaidic carnitine (18), LPC(18:0) (19) and LPC(20:1) (20), were identified by their accurate mass and MS(E) spectra. The derivations of those biomarkers can be regulated by administration of XKS, which suggested that the intervention effect of XKS against AS may involve in regulating the lipid perturbation including fatty acid ß-oxidation pathway, sphingolipid metabolism, glycerophospholipid metabolism and bile acid biosynthesis. This study indicated that the UPLC-Q/TOF MS-based metabonomics not only gave a systematic view of the pathomechanism of AS, but also provided a powerful tool to study the efficacy and mechanism of complex TCM prescriptions.

A new phenylethanoid glucoside from Plantago depressa Willd.

Chemical research of Plantago depressa Willd. led to one new phenylethanoid glucoside with α-L-rhamnosyl (1 → 2)-ß-D-glucose structure, together with four known compounds. These five compounds (1-5) were isolated from the family Plantaginaceae for the first time; the chemotaxonomic significance of cerebrosides was also discussed.

Comparative pharmacokinetics of naringin in rat after oral administration of chaihu-shu-gan-san aqueous extract and naringin alone.

Chaihu-Shu-Gan-San (CSGS), a traditional Chinese medicine (TCM) formula containing seven herbal medicines, has been used in the clinical treatment of gastritis, peptic ulcer, irritable bowel syndrome and depression in China. In order to explore the interaction between naringin and other constituents in CSGS, the pharmacokinetic difference of naringin in rats after oral administration of CSGS aqueous extract and naringin alone was investigated. The pharmacokinetic parameters of naringin in rats were achieved by quantification of its aglycone, naringenin by LC-MS/MS method. The double peaks phenomenon was observed in both serum profiles of rats after orally administered CSGS aqueous extract and naringin alone. However, the T1/2b was significantly decreased in rats given CSGS aqueous extract compared with naringin alone, and the mean residence time (MRT) and the area under the serum concentration-time curve (AUC0-τ) were higher than those of naringin, which indicated that naringin in CSGS had higher bioavailability, longer term efficacy and somewhat faster metabolism and excretion than those of naringin. The results suggested that certain ingredients co-exist in CSGS could influence pharmacokinetic behavior of naringin. This also provides a reference for human studies.

Urinary metabonomics study of anti-depressive effect of Chaihu-Shu-Gan-San on an experimental model of depression induced by chronic variable stress in rats.

Chaihu-Shu-Gan-San (CSGS), a traditional Chinese medicine (TCM) formula, has been effectively used for the treatment of depression in clinic. However, studies of its anti-depressive mechanism are challenging, accounted for the complex pathophysiology of depression, and complexity of CSGS with multiple constituents acting on different metabolic pathways. The variations of endogenous metabolites in rat model of depression after administration of CSGS may offer deeper insights into the anti-depressive effect and mechanism of CSGS. In this study, metabonomics based on ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) was used to profile the metabolic fingerprints of urine obtained from chronic variable stress (CVS)-induced depression model in rats with and without CSGS treatment. Through partial least squares-discriminate analysis, it was observed that metabolic perturbations induced by chronic variable stress were restored in a time-dependent pattern after treatment with CSGS. Metabolites with significant changes induced by CVS, including 3-O-methyldopa (1), pantothenic acid (2), kynurenic acid (3), xanthurenic acid (4), 2,8-dihydroxyquinoline glucuronide (5), 5-hydroxy-6-methoxyindole glucurnoide (8), l-phenylalanyl-l-hydroxyproline (9), indole-3-carboxylic acid (10), proline (11), and the unidentified metabolites (6, 2.11min_m/z 217.0940; 7, 2.11min_m/z 144.0799), were characterized as potential biomarkers involved in the pathogenesis of depression. The derivations of all those biomarkers can be regulated by CSGS treatment except indole-3-carboxylic acid (10), which suggested that the therapeutic effect of CSGS on depression may involve in regulating the dysfunctions of energy metabolism, tryptophan metabolism, bone loss and liver detoxification. This study indicated that the rapid and noninvasive urinary metabonomics approach may be a powerful tool to study the efficacy and mechanism of complex TCM prescriptions.