Synthesis of N-CF3 Amidines/Imidates/Thioimidates via N-CF3 Nitrilium Ions.

An efficient methodology for the synthesis of a wide range of N-CF3 imidic acid derivatives is presented. In this reaction, N-CF3 nitrilium ions were generated via N-trifluoromethylation of nitriles using PhICF3Cl under catalysis with DMAP, followed by the capture of N-, O-, or S-centered nucleophiles to give diverse N-CF3 amidines, imidates, and thioimidates. The method provides a platform for preparing N-CF3 compounds with potential applications.

An N-Trifluoromethylation/Cyclization Strategy for Accessing Diverse N-Trifluoromethyl Azoles from Nitriles and 1,3-Dipoles.

N-Trifluoromethyl azoles are valuable targets in medicinal chemistry, but their synthesis is challenging. Classical preparation of N-CF3 azoles relies on the functional group interconversions but suffers from tedious N-pre-functionalization and unfriendly agents. Introduction of the CF3 onto the nitrogen of heterocycles provides a direct route to such motifs, but the N-trifluoromethylation remains underdeveloped. Reported here is an alternative and scalable cyclization strategy based on NCF3 -containing synthons for constructing N-CF3 azoles. The approach involves the N-trifluoromethylation of nitriles followed by a [3+2] cyclization between resulting N-CF3 nitrilium derivatives and 1,3-dipoles. PhICF3 Cl was an effective CF3 source for the transformation. As a result, a generic platform is established to divergently synthesize N-trifluoromethylated tetrazoles, imidazoles, and 1,2,3-triazoles by using sodium azide, activated methylene isocyanides, and diazo compounds as dipoles.

[Effects and HPA Axis Related Mechanism of Kaixin-San and Danggui-Shaoyao-San on Glucose and Lipid Metabolism in Chronic Stress Rats with High-fat Diet].

OBJECTIVE: To study the effects and potential mechanism of Kaixin-San and Danggui-Shaoyao-San on glucose and lipid metabolism in chronic stress rats fed with high-fat diet. METHODS: 50 male Wistar rats were randomly divided into normal control group (distilled water), high-fat diet with chronic stress group (distilled water), melatonin group(20 mg/kg), Kaixin-San group (445 mg/kg) and Danggui-Shaoyao-San group (3360 mg/kg). All drugs were orally administered. In addition to the normal control group, each group of rats were fed with high-fat, diet. Simultaneously, stress were carried out after drugs administration 1 h daily. The duration was lasted for six weeks. The rat body weight daily was recorded, and the 24 h period urine was collected to detect the level of urine corticosterone (CORT) after three weeks. The level of plasma intraperitoneal glucose tolerance (IVGTT) was detected after six weeks. Finally, rats were executed, and serum fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), insulin (INS), adrenocorticotropic hormone releasing hormone (CRH), adrenocorticotropic hormone (ACTH), CORT and melatonin ( MLT) were determined. The weight of adrenal gland, liver glycogen and muscle glycogen levels were detected. The adrenal gland index, Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and insulin sensitivity index( ISI) were calculated. RESULTS: Compared with normal group, model rats body weight, IVGTT (120 min), plasm CORT were decreased significantly. Serum TG, TC, LDL-C and urine CORT after three weeks were increased significantly. Kaixin-San and Danggui- Shaoyao-San could regulate the above indexes. CONCLUSION: Kaixin-San and Danggui-Shaoyao-San may regulate the activity of HPA axis, and improve glucose and lipid metabolism disorder in model rats by increasing melatonin secretion.

[Study on the ultraviolet protective effects of the cream of the total flavonoids from Oxytropis falcata].

OBJECTIVE: To study the protective effects of the cream of the total flavonoids from Oxytropis falcata on the destructed skin of mice induced by moderate-wave ultraviolet (UVB) irradiation. METHODS: Dorsal skin of Wistar mice were treated with the cream of the total flavonoids from Oxytropis falcata and then irradiated with UVB in the dosage of 5 min once a day for one week. The tissue of skin was pathological diagnosed and the activities or contents of superoxide dismutase (SOD), malondialdehyde (MDA), hydroxyproline (Hyp), glutathione peroxidease (GSH-Px), glutathione (GSH), glutathion-s-transferase (GST), catalase (CAT) and hydroxy radical (*OH) were determined with chromatometry. RESULTS: The ultraviolet protective effects of the cream could be observed with appearance and pathology examine. The cream could increase the activities of SOD (P < 0.001), GSH-Px (P < 0.001), GST (P < 0.05) and CAT (P < 0.01), raise the content of Hyp (P < 0.001) significantly. The cream could also decrease the contents of MDA and *OH (P < 0.001), and the activities of GSH significantly (P < 0.001). CONCLUSION: The cream of the total flavonoids from Oxytropis falcata has protective effect on the destructed skin of mice induced by moderate-wave ultraviolet (UVB) irradiation.

Phytochemical and biological studies of plants from the genus Meconopsis.

In this review, the literature data on the phytochemical and biological investigations on the genus of Meconopsis are summarized from 49 references. Up to now, more than 95 compounds were isolated from 19 Meconopsis plant species. The chemical constituents are mostly alkaloids, flavonoids, phenols, steroids, and terpenes, together with minor constituents of essential oil, and others. The crude extracts and metabolites have been found to possess various bioactivities including antitumor activity, central action, cardiovascular system effects, antibiosis, antiviral activity, anti-inflammatory effects, and other biological activities.

[Study on the effect of Part III from Cynomorium songaricum on immunosuppressive mice induced by cyclophosphamide].

OBJECTIVE: To study the immunomodulatory effect of Part III of Cynomorium songaricum Rupr. on the immunosuppressive mice. METHODS: The immunity-deficiency model was induced by intraperitoneal injection of cyclophosphamide (CTX) at the dose of 100 mg/kg in mice; all the animals were divided into normal control group, immunity-deficiency model group, Part III treated group (300 mg/kg) and positive control group (TSPG, 300 mg/kg). The hemogram of peripheral blood, the index of immune organs, the phagocytosis activity of macrophage, the content of serum hemolysin were measured. RESULTS: The index of organs, the phagocytosis activity of macrophage and the content of serum hemolysin in the model group increased after administrated of Part III. CONCLUSION: Part III from Cynomorium songaricum Rupr. has protective effect on the immunosuppressive mice, which may be related to the increasing of humoral immunity and nonspecific immunity.

[Establishing and identifying insulin resistance 3T3-L1 adipocytes cell model].

OBJECTIVE: To establish insulin-resistant 3T3-L1 adipocytes cell model. METHODS: 3T3-L1 preadipocytes were cultured and induced to differentation. We established insulin resistant 3T3-L1 induced by dexamethasone and determined the change of glucose concentration in cell culture. RESULTS: In high glucose DMEM culture media, the glusose concentration significantly decreased. Achieved the peak of insulin-resisitant at the 96th hour induced by dexamethasone, and at this time compared with the blank the mRNA expression of Resistin of the model step up about three times. CONCLUSION: 3T3-L1 adipocyte exposed to 1 micromol/L dexamethasone for 24 hours are able to induce a state of insulin resistance which can be maintained for 216 hours.

[Effects of rat serum containing total flavonoid extract of Epimedium sagittatum on development of osteoblasts].

OBJECTIVE: To investigate the effects of total flavonoid extract of Epimedium sagittatum (TFE) on the proliferation and differentiation of newborn rat calvarial osteoblasts (ROB). METHOD: TFE was supplemented into the culture medium of ROB at 0. 1, 1, 10 and 100 microg x mL(-1) respectively. The serum of rats administered TFES (SRAT) was also added into the medium in a parallel treatment at 2.5%, 5% and 10% respectively. Their effects on cell proliferation and differentiation was studied by MTT and the analysis of osteogenic differentiation marks. RESULT: TFE had no appreciable and on cell proliferation and differentiation at any concentration. However, 2.5% and 5% SRAT stimulated cell proliferation strongly and, 5% SRAT significantly promoted the maturation and function of osteoblast by improving the alkaline phosphatase activity, osteocalcin secretion, calcium deposition and the number of mineralized nodular structures. CONCLUSION: The metabolites of TFE should be the anti-osteoporosis constitutes of Epimedium sagittatum.

[Study on chemical constituents of Delphinium grandiflorum].

OBJECTIVE: To study the chemical constituents isolated from the roots of Delphinium grandiflorum L. var. leiocarpum W. T. Wang. METHODS: The constituents were isolated and purified by various chromatographic methods and their structures were identified by spectral analysis. RESULTS: Five known diterpenoid alkaloids lycoctonine (I), methyllycaconitine (II), delsemine A (III), delavaine A (IV) , delajadine (V) and the other two beta-sitosterol (VI), plamitic acid (VII) were isolated from the roots of Delphinium grandiflorum. CONCLUSION: All these compounds are isolated from this plant for the first time.

Rehmannia glutinosa: review of botany, chemistry and pharmacology.

Rehmannia glutinosa, a widely used traditional Chinese herb, belongs to the family of Scrophulariaceae, and is taken to nourish Yin and invigorate the kidney in traditional Chinese medicine (TCM) and has a very high medicinal value. In recent decades, a great number of chemical and pharmacological studies have been done on Rehmannia glutinosa. More than 70 compounds including iridoids, saccharides, amino acid, inorganic ions, as well as other trace elements have been found in the herb. Studies show that Rehmannia glutinosa and its active principles possess wide pharmacological actions on the blood system, immune system, endocrine system, cardiovascular system and the nervous system. Currently, the effective monomeric compounds or active parts have been screened for the pharmacological activity of Rehmannia glutinosa and the highest quality scientific data is delivered to support the further application and exploitation for new drug development.

[Research on isolation and purification of total iridoid glycosides from herbal Lamiophlomis rotata].

OBJECTIVE: Enriching the hemostatic active part total iridoid glycosides from the aqueous extract of herbal Lamiophlomis rotata. METHOD: First derivative spectrophotometry was used as the detection method and the content of total iridoid glycosides was used as tracking target. The abilities of absorption and anti-absorption of ten different types of macroreticular resin were compared, after being used to absorb the iridoid glycosides from aqueous extract of herbal L. rotata. The best purification process was optimized. RESULT: With the optimized purification process, the content of total iridoid glycosides was 67.53%. CONCLUSION: XDA-1 macroreticular resin has good ability of absorption and anti-absorption for iridoid glycosides and 50% ethanol was the best solvent for anti-absorption. The macroreticular resin could be reused.

[Protective effect of Sankang Capsule on immunity-deficiency mice induced by cyclophosphamide].

OBJECTIVE: To study the immunomodulatory effect of Sankang Capsule( SKC) on the immunity-deficiency mice. METHODS: The immunity-deficiency model was induced by intraperitoneal injection (ip) of cyclophosphamide (CTX) at the dose of 100 mg/ kg in mice which were randomly divided into normal control group, immunity-deficiency model group, SKC treated group (250 mg/kg, 500 mg/kg) and positive control group (500 mg/kg). The number of WBC in peripheral blood, the weight of immune organs, the phagocytosis activity of macrophage, the content of serum hemolysin and the proliferation of T lymphocyte in the spleen were measured. RESULTS: The number of WBC, the weight of immune organs, the phagocytosis activity of macrophage, the content of serum hemolysin and the proliferation of T lymphocyte in the model group were all decreased compared with those of normal control group. After the administration of SKC, the index mentioned above was increased compared with those of model group. CONCLUSION: SKC has a protective effect on the immunity-deficiency mice, which may be related to the increasing of cellular immunity, humoral immunity and nonspecific immunity.

[Effects of Rehmannia glutinosa oligosaccharides on proliferation of HepG2 and insulin resistance].

OBJECTIVE: To investigate the effects of Rehmannia glutinosa oligosaccharides (ROS) on the proliferation of HepG2 and insulin resistance. METHOD: The HepG2 cells were divided into control group, rosiglitazone (3.4 mg x L(-1)) treated group and ROS (0.1-30 mg x L(-1)) treated group. The proliferation of HepG2 was detected by MTT method. Insulin resistant HepG2 cells model was induced by high concentration of insulin, then the effects of ROS on glucose consumption in insulin resistant HepG2 cells were investigated. RESULT: In the middle glucose culture medium, the absorbance at 570 nm of HepG2 was increased by high concentration of ROS, and decreased by low concentration of ROS by using MTT method, a concentration-dependent manner. ROS increased glucose consumption in HepG2 cells, and showed a better effect at the dose of 10 mg x L(-1). ROS promoted the glucose consumption in insulin resistance of HepG2 cells, improved the sensitivity of insulin resistance of HepG2 cells to insulin. CONCLUSION: High concentration of ROS can promote the proliferation of HepG2, and however low concentration of ROS inhibits the proliferation of HepG2. ROS can significantly improve insulin resistance of HepG2 cells induced by high insulin.

[Effects of Rehmannia glutinosa oligosaccharides on proliferation of 3T3-L1 adipocytes and insulin resistance].

OBJECTIVE: To investigate the influence of Rehmannia glutinosa oligosaccharides (ROS) on the proliferation of 3T3-L1 adipocytes and insulin resistance. METHOD: 3T3-L1 preadipocytes were cultured, the proliferation of 3T3-L1 preadipocytes was detected by MTT method. Insulin resistant 3T3-L1 adipocytes cell model was induced by dexamethasone and the change of glucose concentration in cell culture was determined after ROS treatment. RESULT: In the high glucose DMEM culture media, MTT method showed that the absorbance at 570nm of 3T3-L1 preadipocytes was increased and that of 3T3-L1 adipocytes was decreased. ROS significantly increased glucose consumption in 3T3-L1 preadipocytes and adipocytes culture in a concentration-dependent manner. ROS improved the sensitivity of 3T3-L1 adipocytes to insulin. CONCLUSION: ROS can promote the proliferation of 3T3-L1 preadipocytes, inhibite the proliferation of 3T3-L1 adipocytes, and also, significantly improve insulin resistance induced by dexamethasone.

[Effect of Herba Lamiophlomis Rotata extract on rats blood conglomeration parameters by oral administration].

OBJECTIVE: To study the effect of Tibet medicine Herba Lamiophlomis Rotata exect (HLRE) on blood conglomeration parameters by oral administration. METHODS: High dose (3 g/kg), middle dose (1.5 g/kg) and low dose (0.75 g/kg) of HLRE had been given orally in rats for 7, 14, 21 days. Blood samples were collected from common carotid artery and prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (FIB) were tested. RESULTS: After 7 days, as compared to the control, the high, middle doses of HLRE induced significant TT reduction, and all doses of HLRE could induce significant hyperfibrinogenemia. But there was no change in PT and APTL. After 14 days, in all groups treated with HLRE, TT decreased and FIB increased. As compared to the control, only the high dose had significantly changes in TT and FIB. After 21 days, as compared to the control, TT of high and middle groups decreased and FIB of high group increased visibly. PT decurtation could also be seen in all groups. There was a decrease in TT paralleling an increase of fibrinogen in our study. CONCLUSION: The aqueous extract of Herba Lamiophlomis Rotata orally administered in rats can increase the contents of FIB and shorten TT. The shorten of PT is found after treated with high dose for a long time. Hemostatic effect of HLRE has a dose-effect and time-effect relationship.