UPLC-MS-based serum metabolomics reveals protective effect of Ganoderma lucidum polysaccharide on ionizing radiation injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Ganoderma lucidum Polysaccharide (GLP),traditional Chinese medicine (TCM) active ingredient, has a long history and has good curative effects on radiation injury. However, the mechanism of GLP treating radiation injury has not been clearly elucidated. THE AIM OF THE STUDY: This study was aimed to investigate the preventive effects of GLP on mice with radiation injury and to explore its mechanisms by serum metabolomics. MATERIALS AND METHODS: Thirty mice were randomly divided into three groups,and namely 10 per group. The normal control group and the radiation model with normal saline and GLP group with GLP treatment (96 mg·kg-1) for 14 days. 2 h after 7th day after the intragastric administration, the model group and GLP group were subjected to whole body irradiation by X-rays except the normal control group. The peripheral blood WBC, RBC, HGB, PLT indicators.UPLC-Q-TOF-MS technique was used to analyze the serum of normal group, model group and GLP group, and to explore its potential key biomarkers and corresponding related metabolic pathways. RESULTS: The number of peripheral blood leukocytes (WBC) in the radiation model group was lower than that in the GLP group and the number of platelets (PLT) in the GLP group was significantly higher than that in the model group.Combined with the methods of principal component analysis (PCA), projection to latent structure-discrimination analysis (PLS-DA), three group were clearly distinguished from each other and 18 metabolites were identified as the potential biomarkers in the GLP treated mice. The identified biomarkers indicated that there were perturbations of the taurine and hypotaurine metabolism and glycerophospholipid metabolism. CONCLUSION: GLP can play a role in radiation protection by improving the expression of related potential biomarkers and related metabolic pathways in serum of radiation-induced mice.

The dietary freeze-dried fruit powder of Actinidia arguta ameliorates dextran sulphate sodium-induced ulcerative colitis in mice by inhibiting the activation of MAPKs.

In this study, we aimed at investigating the antiinflammatory activity of the freeze-dried fruit powder of Actinidia arguta (FAA) on dextran sulphate sodium (DSS)-induced ulcerative colitis (UC) in mice and the effect of its extract on lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. For pharmacodynamic studies, the oral administration of FAA (300 or 600 mg kg-1) could decrease the disease activity index (DAI), reduce the incidence of colon and spleen edemas (caused by inflammation), and alleviate the pathological changes in UC. For research involving biochemical indicators, FAA could decrease the expression of inflammatory markers (such as myeloperoxidase (MPO)) and attenuate the oxidative stress levels. ELISA results revealed that the expressions of proinflammatory cytokines (IL-1ß, IL-6, and TNF-α) were downregulated by FAA. Furthermore, the expression levels of the inflammation-induced activation of p38, JNK, and ERK were decreased by FAA. Hence, it was concluded that FAA could alleviate the UC symptoms in mice and the inflammatory response of macrophages via the MAPK signal pathway. Overall, FAA might have the potential to treat UC when used as a dietary supplement.

Screening and Verification of Compatibility Proportion of Effective Components from Traditional Chinese Medicine of Diabetes / 中国实验方剂学杂志

Objective: To screen the best compatibility proportion of total alkaloids of Coptidis Rhizoma and Notoginseng Radix et Rhizoma total saponins (HS composition)by uniform design and pharmacological model and to observe the effect on diabetic complications. Method: The total alkaloids of Coptidis Rhizoma and Notoginseng Radix et Rhizoma total saponins were used as the research objects, U6(62) table was choosed for grouping design.The content of triglyceride fasting blood-glucose (FBG), prothrombin time (PT) and active partial thromboplastin time (APTT) was chosen as index. The best dose ratio was obtained by multipleregression analysis. Rats with type 2 diabetes mellitus induced by high-fat diet combined streptozotocin were divided into blank group, model group, metformin group (150 mg·kg-1), HS composition group (total alkaloids of Coptidis Rhizoma 360 mg·kg-1+ Notoginseng Radix et Rhizoma total saponins 40 mg·kg-1). Rats were administered orally for 10 weeks.By observing the blood glucose, glucose tolerance,area under the curve (AUC), triglyceride (TG), high-density lipoprotein (HDL-C)and low-density lipoprotein (LDL-C), hemorheological indexes and pathological changes of pancreas, heart, kidney and retina in rats of each group, the effect of this composition on diabetic complications was verified. Result: Combination of 625 mg·kg-1 total alkaloids of Coptidis Rhizoma and 60 mg·kg-1 Notoginseng Radix et Rhizoma total saponins was the optimal dosage ratio of HS composition.The validation test showed that compared with blank group, the fasting blood glucose and lipid levels in the model group were significantly increased (PPPPPPPPPPPConclusion: The optimum compatibility dose of HS composition have a good therapeutic effect on diabetic complication rats induced by high-fat diet and streptozotocin.

Two new diterpenes from the seeds of Caesalpinia minax Hance.

Molecules with diterpene skeletons often possess valuable medicinal properties. Two new diterpenes 1α,6α,7ß-triacetoxy-5α-hydroxy-14ß-ethyl-O-vouacapane (1) and 2α-acetoxy-14,15-cyclopimara-7ß,16-diol (2) were isolated from the seeds of Caesalpinia minax Hance. Their structures were established on the basis of extensive spectroscopic analyses, including HR-ESI-MS, UV, IR, 1D, and 2D NMR (HSQC, HMBC, NOESY) methods. The stereochemical structure of 1 was confirmed via the circular dichroism spectrum and calculated ECD experiment. The inhibitory activity of nitric oxide production of RAW264.7 macrophages stimulated by lipopolysaccharide of compounds 1 and 2 was evaluated, and compound 1 was found to show significant inhibitory effect.

Cantharidin and norcantharidin inhibit the ability of MCF-7 cells to adhere to platelets via protein kinase C pathway-dependent downregulation of α2 integrin.

Cancer metastasis is a highly coordinated and dynamic multistep process in which cancer cells interact with a variety of host cells. Morphological studies have documented the association of circulating tumor cells with host platelets, where a surface coating of platelets protects tumor cells from mechanical trauma and the immune system. Cantharidin is an active constituent of mylabris, a traditional Chinese medicine. Cantharidin and norcantharidin are potent protein phosphatase 2A (PP2A) inhibitors that exhibit in vitro and in vivo antitumor activity against several types of cancer, including breast cancer. We investigated whether cantharidin and norcantharidin could repress the ability of MCF-7 breast cancer cells to adhere to platelets. Using MTT, clone formation, apoptosis, adhesion and wound-healing assays, we found that cantharidin and norcantharidin induced apoptosis and repressed MCF-7 cell growth, adhesion and migration. Moreover, we developed a flow cytometry-based analysis of tumor cell adhesion to platelets. We proved that cantharidin and norcantharidin repressed MCF-7 cell adhesion to platelets through downregulation of α2 integrin, an adhesion molecule present on the surface of cancer cells. The repression of α2 integrin expression was found to be executed through the protein kinase C pathway, the activation of which could have been due to PP2A inhibition.

Two new compounds from the fruits of Trichosanthes kirilowii Maxim.

Two new compounds 1,3-O-[5-(hydroxymethyl)-furan-2-yl]methenyl-2-n-butyl-α-fructofuranoside and n-butyl-3,4-dihydroxyl-5-hydroxymethyl-4-O-[5-(hydroxymethyl)-furan-2-yl]-tetrahydrofuran-2-carboxylate were isolated from the fruits of Trichosanthes kirilowii Maxim, and their structures were established on the basis of spectroscopic methods.

[Eeffects of Coptis Chinensis on vasoconstrictive activity of isolated thoracic aorta of normoxic and chronic intermittent hypobaric hypoxic rats].

OBJECTIVE: To observe the effects of Coptis Chinensis on vasoconstrictive activity of isolated thoracic aorta rings of normoxic and chronic intermittent hypobaric hypoxic (CIHH) rats, and to investigate the underlying mechanisms. METHODS: Young male Sprague-Dawley rats were randomly divided into normoxic group and CIHH group: the fonnrmer were not given any special treatment; the latter were exposed to hypoxia in a hypobaric chamber simulating 5000 m altitude (PB = 404 mmHg, PO2 = 84 mmHg, 11.1% O2), 6 hours daily for 28 days. The isolated thoracic aorta rings of rats were prepared and perfused in thermostat, and the effects of Coptis on vasoconstrictive activity of aorta rings were recorded, the mechanisms were investigated simultaneouly. RESULTS: Coptis Chinensis significantly decreased NE and KC-induced vasoconstriction of normoxic and CIHH rats' isolated aortic rings, but the inhibitive effects had no obvious discrepancy between the two groups. The contractive amplitude had no marked change after the removal of endothelium. When calculated by Logit Loglinear analysis, IC50 of NE and KCl-induced contractive amplitude in normoxic group were respectively 2.99 g/L and 6.14 g/L, while they were 3.45 g/L and 5.81 g/L in CIHH group. The inhibitive effect of Coptis on vasoconstrictive activity of both groups could be partly decreased by Glibenclamide and nitro-L-arginine methyl ester; Indomethacin suppressed the effect on normoxic group as well. Also Coptis significantly inhibited NE-induced both intracellular and extracellular calciumion-depended vasoconstriction. CONCLUSION: Coptis Chinensis obviously relaxes isolated thoracic aorta rings of normoxic and CIHH rats, but the effects are endothelium-independent and have no marked discrepancy between the two groups. The mechanisms of the effects may be related to the opening of ATP-sensitive K+ channel, raise of nitric oxide concentration in both groups, and the increasing of PGI2 in normoxic group. Besides, Coptis may inhibit sarcoplasmic reticulum releasing Ca2+ and decrease the inflow of extracellular Ca2+ via cell membrane.

Eeffects of Coptis Chinensis on vasoconstrictive activity of isolated thoracic aorta of normoxic and chronic intermittent hypobaric hypoxic rats / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To observe the effects of Coptis Chinensis on vasoconstrictive activity of isolated thoracic aorta rings of normoxic and chronic intermittent hypobaric hypoxic (CIHH) rats, and to investigate the underlying mechanisms.</p><p><b>METHODS</b>Young male Sprague-Dawley rats were randomly divided into normoxic group and CIHH group: the fonnrmer were not given any special treatment; the latter were exposed to hypoxia in a hypobaric chamber simulating 5000 m altitude (PB = 404 mmHg, PO2 = 84 mmHg, 11.1% O2), 6 hours daily for 28 days. The isolated thoracic aorta rings of rats were prepared and perfused in thermostat, and the effects of Coptis on vasoconstrictive activity of aorta rings were recorded, the mechanisms were investigated simultaneouly.</p><p><b>RESULTS</b>Coptis Chinensis significantly decreased NE and KC-induced vasoconstriction of normoxic and CIHH rats' isolated aortic rings, but the inhibitive effects had no obvious discrepancy between the two groups. The contractive amplitude had no marked change after the removal of endothelium. When calculated by Logit Loglinear analysis, IC50 of NE and KCl-induced contractive amplitude in normoxic group were respectively 2.99 g/L and 6.14 g/L, while they were 3.45 g/L and 5.81 g/L in CIHH group. The inhibitive effect of Coptis on vasoconstrictive activity of both groups could be partly decreased by Glibenclamide and nitro-L-arginine methyl ester; Indomethacin suppressed the effect on normoxic group as well. Also Coptis significantly inhibited NE-induced both intracellular and extracellular calciumion-depended vasoconstriction.</p><p><b>CONCLUSION</b>Coptis Chinensis obviously relaxes isolated thoracic aorta rings of normoxic and CIHH rats, but the effects are endothelium-independent and have no marked discrepancy between the two groups. The mechanisms of the effects may be related to the opening of ATP-sensitive K+ channel, raise of nitric oxide concentration in both groups, and the increasing of PGI2 in normoxic group. Besides, Coptis may inhibit sarcoplasmic reticulum releasing Ca2+ and decrease the inflow of extracellular Ca2+ via cell membrane.</p>