A new ester glycoside compound from Cyclocarya paliurus / 中国药科大学学报

@#Chemical constituents of n-butanol part of ethanol extract from the leaves of Cyclocarya paliurus (Batalin) Iljinskaja were studied.Eight glycosides were separated and purified by silica gel, MCI, ODS, Sephadex LH-20 column chromatography and semi-preparative high-performance liquid chromatography.Based on the physicochemical properties and spectral data, these compounds were 3-ethyl-4-methyl-pentyl ester-O-β-D-apiofuranosyl-(1→6)-β-D-glucopyranoside (1), juglanoside E (2), (4S)-α-terpineol-8-O-α-L-arabinofuranosyl-(1→6)-β-D-glucopyranoside (3), (4S)-α-terpineol-8-O-β-D-apiofuranosyl-(1→6)-β-D-glucopyranoside (4), eugenyl-O-β-D-apiofuranosyl-(1→6)-O-β-D-glucopyranoside (5), kaempferol-3-O-β-D-glucuronopyranosyl methylester (6), kaempferol-3-O-β-D-glucuronopyranoside (7), and quercetin-3-O-β-D-glucuronopyranoside (8).Among them, compound 1 was a new compound, and compounds 2-6 were isolated from the genus Cyclocarya for the first time.

Therapeutic effects of gypenosides on hypercholesterolemia and it protective effect on liver injury / 中国药科大学学报

@#In order to explore the therapeutic effects and preliminary mechanism of gypenosides (GP) on hypercholesterolemia, as well as the protective effect on liver injury induced by high-dose simvastatin and high cholesterol diet (HCD), the hypercholesterolemia model of golden hamster was established by high cholesterol diet. The experimental animals were divided into blank group, model group, GP low and high dose groups (60 mg/kg, 120 mg/kg), simvastatin group (10 mg/kg), and GP high dose combined with simvastatin group (120 mg/kg + 10 mg/kg).The efficacy was investigated through dynamic monitoring serum cholesterol and liver function related indexes after drug treatment of 14 and 23 days. The results showed that GP could significantly reduce the levels of serum low density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglyceride (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP), increase the level of serum high density lipoprotein cholesterol (HDL-C), and reduce the secretion of PCSK9. It is suggested that GP has a good therapeutic effect on HCD diet-induced hypercholesterolemia hamsters, which may be related to its inhibition of PCSK9 secretion. In addition, GP can significantly ameliorate liver damage caused by HCD diet and high-dose simvastatin. These findings provide a scientific basis and useful reference for the combination of GP and statins to reduce toxicity and increase efficacy.

A new flavonoid glycoside from Cichorium glandulosum / 中国药科大学学报

@#Chemical constituents from the air dried parts of Cichorium glandulosum were studied. The chemical constituents of C. glandulosum were separated and purified by means of silica gel, Sephadex-LH 20, ODS column chromatography and semi-preparative high performance liquid chromatography. The structure was elucidated by physicochemical characteristics and spectral data. One new flavonoid glycoside was isolated from C. glandulosum, and identified as quercetin-3-O-［6″-O-(3-ethoxy-1, 3-dioxopropyl)］-β-D-glucopyranoside(1).

Gypenoside granules improved lipid metabolism in C57BL/6J mice with hyperlipidemia / 中国药科大学学报

@#To investigate the hypolipidemic effects of gypenosides granules and its combination with lipitor, a model of hyperlipidaemia C57BL/6J mice was established by high-fat diet feeding for 4 weeks. The mice were randomly divided into blank group, model group, lipitor group(10 mg/kg of lipitor), low dose group(90 mg/kg of gypenosides granules), medium dose group(120 mg/kg of gypenosides granules), high dose group(180 mg/kg of gypenosides granules)and the combination group(180 mg/kg of gypenosides granules and 10 mg/kg of lipitor). After 4 weeks of continuous administration, the contents of serum lipid indexes, serum ALT, AST and apolipoprotein B(ApoB)were measured. The liver tissues of mice were observed by H&E staining. The expression levels of key factors involved in hepatic cholesterol metabolism were observed by RT-PCR and Western blot methods, such as adenosine triphosphate combined box transporter A1(ABCA1), liver X receptor(LXRα), cholesterol 7 alpha hydroxylase(CYP7A1)and type BΙ scavenger receptor(SR-BΙ). The results revealed that gypenosides granules significantly decreased the mice body weight, total abdominal fat area and the level of serum total cholesterol(TC). The combination group showed a more significant reduction in TC level than the other administration groups. Moreover, gypenosides granules treatment remarkably increased the protein expression of ABCA1 and up-regulated the mRNA expression of ABCA1, CYP7A1 and SR-BI. The above results suggest that gypenosides granules can significantly reduce blood lipid contents, and the combination therapy with lipitor show better the lipid-lowering effect. Meanwhile, gypenosides granules can decrease the level of serum transaminase. Preliminary exploration suggests the lipid-lowering mechanism of gypenosides granules may be involved in cholesterol reversal to regulate the level of TC.

Effect of scutellarein on acute pharyngitis in rats / 中国药科大学学报

@#In order to investigate the therapeutic effects of scutellarein on acute pharyngitis, 60 rats were randomly divided into five groups: blank group, model group, low-dose scutellarein group, high-dose scutellarein group and positive drug group. HE staining, blood-cell-analyzer, IL-6, IL-1β and TNF-α ELISA kit were used to study the effects of scutellarein on acute pharyngitis in pharyngeal tissue morphology, the counts of white blood cells and neutrophil and the serum concentrations of TNF-α, IL-1β and IL-6. Meanwhile, forty mice were randomly divided into four groups: blank group, low-dose scutellarein group, high-dose scutellarein group and positive drug group. Then, hot plate and writhing test of mice were carried out to study the analgesic effects of scutellarein. Results showed that, compared to the model group, scutellarein improved the physical status of acute pharyngitis rats, reduced the number of white blood cells significantly(P< 0. 05)and decreased the number of neutrophils and the levels of TNF-α, IL-1β and IL-6 in rats serum significantly(P< 0. 01). Meanwhile, scutellarein dramatically improved the pain threshold in hot plate test and decreased the number of writhing mice(P< 0. 01). It can be concluded that scutellarein can be used to treat acute pharyngitis with its anti-inflammatory and analgesic effect.

Synthesis and evaluation of necrosis avidity of MRI contrast agent Gd-DO3A-Ether-Rhein / 中国药科大学学报

@#The aim of this study was to synthesize and evaluate the necrosis avidity of MRI contrast agent based on rhein and linked by ether. The novel ligand 10-{［6-(1, 8-dihydroxyanthraquinone-3-carboxamido)ethoxyethyl］amino}carbonylmethyl-1, 4, 7, 10-tetraazacyclododecan-1, 4, 7-triacetic acid(DO3A-Ether-Rhein, E1)was synthesized by two steps of acylation and deprotection reaction. The paramagnetic gadolinium 10-{［6-(1, 8-dihydroxyanthraquinone-3-carboxamido)ethoxyethyl］amino}carbonylmethyl-1, 4, 7, 10-tetraazacyclododecan-1, 4, 7-triacetic acid(Gd-DO3A-Ether-Rhein, GdE1)was obtained by coordination of Gd3+ with the above ligand. We examined the necrotic avidity of GdE1 in human hepatocellular carcinoma HepG2 cell necrosis induced by hyperthermia in vitro and in rat model with muscular necrosis induced by microwave ablation in vivo by MRI. The MRI was implemented before administration of GdE1 and during 0-9 h after administration of GdE1(0. 1 mmol/kg), and Gd-DOTA(gadolinium 1, 4, 7, 10-tetraacetic acid-1, 4, 7, 10-tetraazacyclo dodecane)was used as control. The signal intensity of necrotic cells(4 369±70)was significantly higher than that of normal cells(2 555±84)(P< 0. 05). Similarly, the contrast ratio between necrotic and normal muscle at 3 h after administration of GdE1(2. 00±0. 12)was remarkblely higher than that at 0 h after administration of GdE1(1. 27±0. 03)(P< 0. 05). Therefore, GdE1 presents good necrosis affinity and has the potential to be used in the diagnosis of necrosis-related diseases.

Paeoniflorin inhibits programmed cell death-1-ligand 1 expression in HepG2 cells by regulating JAK/STAT3 signal pathway / 中国药科大学学报

@#In order to explore the effect and its mechanism of paeoniflorin on PD-L1, a PD-L1 high expression cell model was established in interferon gamma(IFN-γ)-induced HepG2 cells. The cytotoxicity of paeoniflorin was detected by MTT assay. Flow cytometry, ELISA and RT-PCR were performed to detect protein and mRNA levels of PD-L1 regulated by paeoniflorin. In HepG2 cells and Jurkat T cell co-culture system, the expression of IL-2 was detected by ELISA. Besides, T cell proliferation was evaluated by CCK-8 method, and the protein expression levels of PD-L1, JAK and STAT3 after drug treatment were determined by Western blot. These results indicated that paeoniflorin could significantly down-regulate the levels of PD-L1 protein and mRNA. In addition, it increased the number of T cells and the concentration of IL-2 in the co-culture system. Furthermore, paeoniflorin could significantly inhibit the protein expression of JAK and STAT3. Au the above experimental data indicated that paeoniflorin could down-regulate the expression of PD-L1, and its mechanism might be related to the JAK/STAT3 pathway.

Antipyretic effect of Isodon eriocalyx extracts on yeast-induced fever in rats / 中国药科大学学报

@#To investigate the antipyretic effects and potential mechanism of Isodon eriocalyx ethanol extracts, the SD rats was injected by dry yeast subcutaneously to establish the model of fever. Experimental groups were divided into blank, model, positive drug paracetamol(150 mg/kg), low doses(200 mg/kg), high doses(800 mg/kg)of ethanol extracts of I. eriocalyx, rosmarinic acid(150 mg/kg), cirsimaritin(150 mg/kg)and maoecrystal D(150 mg/kg). After 4 hours of model establishment, the drugs were administered orally to each group; the blood and tissue samples were then collected 8 hours affer model establishment. Rectal temperature was detected to evaluate the antipyretic effects. The levels of tumor necrosis factor(TNF-α), arginine vasopressin(AVP), cyclic adenosine monophosphate(cAMP)and prostraglandin E2(PGE2)were measured to explore the potential mechanism. Results showed that the inoreased rectal temperature in rats was ameliorated by ethanol extracts of I. eriocalyx. Moreover, administration of ethanol extracts of I. eriocalyx could reduce the serum TNF-α levels and increase AVP levels in rats, decrease the levels of cAMP and PGE2 in hypothalamus and promote AVP secretion in ventral septal area of rats. However, there were no dramatic changes about rectal temperature and biochemical indicators mentioned above after administration of rosmarinic acid, cirsimaritin and maoecrystal D, respectively. In conclusion, ethanol extracts of I. eriocalyx exerted antipyretic effects on fever rats induced by yeast, which is probably due to the suppression of the secretion of TNF-α, cAMP and PGE2 and promotion of the excretion of AVP. However, the material basis of the antipyretic mechanism of this plant still remains to be further explored.

I-Evans blue: evaluation of necrosis targeting property and preliminary assessment of the mechanism in animal models

Necrosis is a form of cell death, which is related to various serious diseases such as cardiovascular disease, cancer, and neurodegeneration. Necrosis-avid agents (NAAs) selectively accumulated in the necrotic tissues can be used for imaging and/or therapy of related diseases. The aim of this study was to preliminarily investigate necrosis avidity of I-evans blue (I-EB) and its mechanism. The biodistribution of I-EB at 24 h after intravenous administration showed that the radioactivity ratio of necrotic to viable tissue was 3.41 in the liver and 11.82 in the muscle as determined by counting in model rats. Autoradiography and histological staining displayed preferential uptake of I-EB in necrotic tissues. nuclear extracts from necrotic cells exhibited 82.3% of the uptake in nuclei at 15 min, as well as 79.2% of the uptake at 2 h after I-EB incubation. The DNA binding study demonstrated that evans blue (EB) has strong binding affinity with calf-thymus DNA (CT-DNA) (=5.08×10 L/(mol/L)). Furthermore, the accumulation of I-EB in necrotic muscle was efficiently blocked by an excess amount of unlabeled EB. In conclusion, I-EB can not only detect necrosis by binding the DNA released from necrotic cells, but also image necrotic tissues generated from the disease clinically.

lntervention effects of the triterpenoids from Cyclocarya paliurus on free fatty acids-induced steatosis in HepG2 cells / 中国药科大学学报

To investigate the therapeutic effects of triterpenoids from Cyclocarya paliurus on non-alcoholic fatty liver disease (NAFLD),the model of NAFLD in HepG2 cells was induced by free fatty acids (FFAs). Cytotoxicity of the triterpenoids from C. paliurus was determined by MTT method,and the effects of triterpenoids without cytotoxicity on intracellular triglyceride (TG)and superoxide dismutase (SOD)were detected by the kits. Data indicated that compound 4 [2α,3α,23-trihydroxy-12,20 (30)-dien-28-ursolic acid,TUA]had hypolipidemic and antioxidant activities. After being treated with TUA and FFAs for 24 h,the intracellular lipid content was observed using Oil Red O staining,and intracellular TG,malondialdehyde (MDA ),SOD and reactive oxygen species (ROS)levels were determined by the assay kits. The protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2),heme oxygenase-1 (HO-1 )and NAD (P)H quinone oxidoreductase 1 (NQO-1 )were measured by Western blot. The results showed that TUA significantly increased SOD activity,and decreased intracellular TG, ROS and MDA levels in FFAs-induced HepG2 cells. Moreover,TUA dramatically improved Nrf2,NQO-1 ,and HO-1 expression. However,the dramatic increase in TG,ROS,MDA levels and the reduction in SOD,NQO-1 and HO-1 expression following Nrf2 inhibitor brusatol treatment were observed. In conclusion,these results suggest that TUA has the therapeutic effect on NAFLD which may be associated with Nrf2 activation.

Clinical and Prognostic Significance of O⁶-Methylguanine-DNA Methyltransferase Promoter Methylation in Patients with Melanoma: A Systematic Meta-Analysis

Tumor suppressor gene O⁶-methylguanine-DNA methyltransferase (MGMT) promoter methylation has been reported in melanoma. However, the clinical and prognostic significance of MGMT promoter methylation in patients with melanoma remained to be determined. A systematic search was performed to identify eligible papers published. The overall odds ratios (ORs) or hazard ratios and their 95% confidence intervals were calculated. Final 12 eligible publications involving Caucasian population were performed in this study, including 1,071 metastatic melanoma patients, 154 primary melanoma patients, and 211 normal controls. MGMT promoter methylation was significantly higher in primary or metastatic melanoma than in normal controls (p < 0.05). No difference of MGMT promoter methylation was found in primary and metastatic melanoma (p=0.432). When metastatic melanoma was compared to normal controls, subgroup analysis showed the correlation between MGMT promoter methylation and different sample materials (tissue: OR=7.01, p < 0.001 and blood: OR=12.04, p=0.005). MGMT promoter methylation was not associated with response to drug therapy and the prognosis in overall survival and progression-free survival for multivariate analysis. Our results show that MGMT promoter methylation may be correlated with the increased risk of primary or metastatic melanoma. Based on blood samples, MGMT promoter methylation may become a noninvasive biomarker for the detection of metastatic melanoma. Further additional clinical studies are necessary.

Clinicopathological features analysis of common complications in pediatric liver transplantation / 中华器官移植杂志

Objective The purpose of this study was to explore common complications and their clinicopathological features in pediatric liver transplantation.Methods Clinical and pathological data of 240 liver biopsies from 168 children that conducted liver puncture from January 2015 to May 2018 in Tianjin First Central Hospital was retrospectively analyzed.We comprehensively analyzed incidence rate and pathological features of various complications,and correlations between acute rejection and C4d staining result or Banff score.Results A total of 86.67％ (208/240) liver biopsies could be definitely diagnosed with incidence rate of main complications in descending order as follows:T cell mediated rejection (TCMR) 60.57％ (126/208),drug-induced liver injury (DILI) 17.31％ (36/208),biliary complication 8.17％ (17/208),vascular complication 3.37％ (7/208),ischemia/reperfusion injury (IRI) 2.88％ (6/208),antibody mediated acute rejection (AMR) 1.92％ (4/208),HBV infection 1.92％ (4/208),non-alcoholic fatty liver disease (NAFLD) 1.44％ (3/208),chronic rejection (CR) 0.96 ％ (2/208) and HCV infection 0.48 ％ (1/208).TCMR and AMR in acute rejection (AR) accounted for 96.92％ (126/130) and 3.08％ (4/160),and into(portal-based,PB)type TCMR accounted for 96.03％(121/126) with the detectable rate of BP type subtype TCMR of 26.45％(32/121)within 30 d.There were 65.87％ (83/126)、25.40％ (32/126) 和4.76％ (6/126) of BP TCMR samples with "Banff ACR RAI" score within 3-5,6-7 and 8-9,and RAI score was negatively correlated with postoperative time (r =0.127,P =0.084).The incidence rate of central perivenulitis (CP) and portal eosinophils infiltration (PEI) in BP TCMR was 63.63％ (77/121) 和43.80％ (53/ 121),respectively,additionally,the PEI level was positively correlate with RAI score (P＜0.05).CP TCMR and AMR occurred within 30d-365 d and 8 d-180 d,respectively postoperative,while,the two CR occurred at 1095 d and 1335 d postoperative,and significant correlation was strikingly observed between rejection subtype and postoperative time (Z =9.231,P =0.026).C4d positive rate was 10％ (24/240),which was associated with Banff score and postoperative time,besides,C4d score was also correlated with rejection subtype and RAI score.The occurrence of DILI was mainly at time of ＜90 d or ＞180 d postoperative,and the detectable rate of biliary complication within 180 d postoperative was 82.35％ (14/17),IRI Appear in ＜30d.Hepatic artery complication account for nearly 57.14％ (4/7),occurrence time is ≤90 d.Occurrence of HBV infection,CMV infection and NAFLD were mainly at ＞365 d,＜90 d and ＜365 d,respectively.Conclusion There were lots of differences in clinical and pathological features among multi pediatric liver transplantation complications.Liver puncture plays an important role in rejection subtype classification and grading,as well as in non-rejection complications identification.

Antiviral activities of flavonoids and diterpenoids isolated from Isodon eriocalyx(Dunn.)Hara / 中国药科大学学报

@#This study aims to isolate two flavonoids and two diterpenoids from Isodon eriocalyx(Dunn. )Hara and investigate their antiviral activities in vitro. Firstly, four compounds were isolated from the ethanol extract of I. eriocalyx by silica gel, ODS and RP-HPLC chromatography, and then identified by spectral data as isothymusin(1), cirsimaritin(2), coetsoidin A(3), and maoecrystal D(4). Next, in vitro antiviral activities against influenza(H1N1/H3N2)and respiratory syncytial virus(RSV)was investigated for the ethanol extract of I. eriocalyx and four compounds. Results showed that the ethanol extract of I. eriocalyx and four compounds exhibited inhibitory effects against influenza H1N1. Especially, compounds 1 and 2 showed better activities with EC50 of(14. 45±4. 90)and(24. 54±3. 82)μmol/L. However, they showed weak inhibitory effects against influenza H3N2 and RSV. These results demonstrate that the ethanol extract of I. eriocalyx and compounds 1- 4 have antiviral activity, especially against influenza H1N1. The flavonoids may be one kind of the effective antiviral substances. This study provides a scientific basis for the clinical application of I. eriocalyx.

Hypoglycemic effect of medicinal formula composed of Cyclocarya paliurus and Mulberry leaves / 中国药科大学学报

@#The purpose of this study was to investigate the hypoglycemic effect and the safety of medicinal formula composed of Cyclocarya paliurus and Mulberry leaves. An experimental diabetic rat model was established by high energy diet plus small dosage of auoxan(ALX). At the same time, each group rats were given distilled water(blank and model), metformin(Met), Cyclocarya paliurus aqueous extract(CP), Mulberry leaves aqueous extract(ML)and the different proportions of aqueous extract mixtures of Cyclocarya paliurus and Mulberry leaves(CM1, CM2 and CM3), respectively. Fasting blood glucose(FBG), OGTT, TC, TG, LDL-C, HDL-C, insulin and liver and kidney function related index were gauged to evaluate the hypoglycemic effect and the safety of samples. The results showed that FBG level of the rats in CM1, CM2 and CM3 groups decreased 21. 64%, 16% and 12. 55%, respectively, comparing with that of model group. Moreover, FBG, glucose tolerance and pancreatic tissue morphology were remarkably improved in CM1 group. TC and LDL-C levels of rats in ML and CM3 groups decreased significantly compared with the those of Model group(P< 0. 05), which showed ML and CM3 were beneficial to regulate the blood lipid level in diabetic rats. Furthermore, all the administration groups had no adverse effect on liver function index. The down regulation of kidney function index of CP, ML, CM1, CM2 and CM3 groups comparing with model group indicated that Cyclocarya paliurus and Mulberry leaves could alleviate the injury of liver and kidney. Our results demonstrated that the medicinal formula composed of Cyclocarya paliurus and Mulberry leaves were favorable to reduce blood glucose and can regulate lipid metabolism without liver and kidney toxicity.

Effect of triterpenic acid-enriched fraction from Cyclocarya paliurus on high glucose-induced pancreatic α cells insulin resistance / 中国药科大学学报

@#To investigate the effect and possible mechanisms of triterpenic acid-enriched fraction from Cyclocarya paliurus(TAE)on glucagon secretion in insulin-resistance pancreatic α cells, the model of insulin resistance in αTC1-6 cells was induced by long term exposure to high glucose. Experimental groups were divided as follow: control(5. 5 mmol/L glucose), model(25 mmol/L), TAE(1, 5, 10 μg/mL), and TAE(10 μg/mL)plus wortmannin(10 nmol/L)group. The supernatant and lysate of treated cells were collected to determine glucagon secretion by ELISA kit. The mRNA and protein abundance of IRS-1, PI3K and Akt were measured by qPCR and Western blot analysis. Results showed that TAE could not only significantly reduce glucagon secretion induce by high glucose in a dose-dependent manner, but also remarkably increased the mRNA and protein abundance of IRS-1, PI3K and Akt in αTC1-6 cells. However, these effects of TAE were reversed by PI3K inhibitor wortmannin. In conclusion, it suggested that TAE could improve the insulin resistance induced by high glucose in pancreatic α cells which may be related with the activation of IRS-1/PI3K/Akt signaling pathway.

Synthesis and necrosis target of necrosis-avid MRI contrast agent Gd-DO3A-rhein / 中国药科大学学报

The purpose of this study was to synthesize and evaluate the necrosis target of MRI contrast agent based on rhein.The novel ligand 10-{ [6-(1,8-dihydroxyanthraquinone-3-carboxamido) hexyl] amino} acetyl-1,4,7,10-tetraazacyclododecan-1,4,7-triacetic acid (DO3A-rhein) was synthesized by two-step acylation and two-step deprotection.The paramagnetic contrast agent gadolinium 10-{ [6-(1,8-dihydroxyanthraquinone-3-carboxamido) hexyl] amino} acetyl-1,4,7,10-tetraazacyclododecan-1,4,7-triacetate (Gd-DO3A-rhein) was obtained by coordination of Gd3+ with the synthesized ligand.Its necrosis affinity was evaluated by liver infarction and muscular necrosis on rat models.The MRI was performed before administration of Gd-DO3A-rhein and during 0 h to 12 h after administration of Gd-DO3A-rhein (0.1 mmol/kg),respectively,and Gd-DOTA was used as control.After MRI scanning,rats were sacrificed and necrotic tissues were stained using triphenyltetrazolium chloride (TTC) and hematoxylin-eosin (HE).MRI images of liver infarction and muscular necrosis on rat models showed significantly enhanced signal intensity compared with normal tissues.The contrast ratios of necrotic liver/normal liver were 1.61 ±0.14 and 2.36 ±0.20 at 3 h and 12 h postinjection of Gd-DO3A-rhein (0.1 mmol/kg) respectively,demonstrating a significant difference compared with pre-administration of Gd-DO3A-rhein (1.16 ±0.10;P ＜ 0.05).The same results were obtained from necrotic muscles.These findings suggested that Gd-DO3A-rhein possessed the necrosis target and imaging capability of necrotic tissues.

Intervention effects of the extract of Alismatis Rhizoma on streptozotocin-induced type 2 diabetic rats / 中国药科大学学报

To investigate the hypoglycemic effects of ethyl acetate extract of Alismatis Rhizoma (AREEA) on type 2 diabetes mellitus,the model of type 2 diabetic rats was induced by high-fat diet feeding for 4 weeks and then intraperitoneal injection of a low dose of streptozotoin (STZ).Rats without the above-mentioned treatment were selected as the normal control group.The diabetic rats were randomly divided into 5 groups:the model control group,low doses (20 mg/kg),medium doses (50 mg/kg),high doses (100 mg/kg) of AREEA groups and positive control-metformin group (100 mg/kg).After four weeks,oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were performed,respectively.12 hours after the last administration,the levels of serum glucose,glycated hemoglobin(HbA1 c),insulin (Ins),total cholesterol (TC),triglyceride (TG),high density lipoprotein (HDL-C),low density lipoprotein (LDL-C),superoxide dismutase (SOD),malondialdehyde (MDA),glutathione (GSH-Px),tumor necrosis factor-or (TNF-α),interleukin-6 (IL-6),insulin-mediated tyrosine of IRS-1 and Akt phosphorylation in adipose tissue were determined.In addition,the pathological changes of pancreas were examined.After administration for 4 weeks,all doses of AREEA significantly reduced the fasting blood glucose of type 2 diabetic rats (P ＜0.05).In the high doses group of AREEA,the levels of GLU,HbA1c,TC,TG,MDA,TNF-α and IL-6 in serum were decreased significantly,and the levels of SOD and GSH-Px were increased (P ＜ 0.05).These results suggest that AREEA has the therapeutic effect on type 2 diabetes-related symptoms by metabolic regulation of glucose and lipids.

Metabolites of hypericin in rats in vivo / 中国药科大学学报

@#The study aimed to separate and identify the metabolites of hypericin in the bile and necrotic tissues in rats. After intravenous injection of 10 mg/kg hypericin, 0-12 h bile of normal rats and 24 h necrotic liver of rats with reperfused hepatic infarction were collected, and metabolites of rats were analyzed by high performance liquid chromatography coupled with electrospray tandemtime of flight mass spectrometry(HPLC-TOF/MS). The prototype(M0)and three glycosylation metabolites(M1, M2, M3)of hypericin in rat bile and the parent compound in rat necrotic liver were detected and identified. Results indicated that prototype and glycosylation of hypericin were the major metabolic form in rat bile and the parent compound was found only in necrotic tissues.

Research on the necrosis target and imaging of necrotic myocardium of 131I-emodin and 131I-emodic acid / 中国药科大学学报

@#The purpose of this study was to evaluate the necrosis target and imaging potential of necrotic myocardium of 131I-emodin and 131I-emodic acid. The iodogen coating method was used to radioiodinate emodin and emodic acid with iodine-131. Mice model of muscular necrosis and rat model of myocardial infarction(MI)were established to evaluate the necrosis affinity and imaging potential of 131I-emodin and 131I-emodic acid. Mice were sacrificed at 2, 12 and 24 h after injection respectively. The radioactive uptake in major organs and necrotic muscle were calculated by a γ-counter. At 6 h after administration, SPECT/CT imaging of necrotic myocardium in rats, biodistribution detection, histopathological analysis were applied to evaluate their necrosis affinity and imaging potential. The results of biodistribution from mice demonstrated that 131I-emodin and 131I-emodic acid showed peculiar necrosis target and exhibited an obvious clearance of radioactivity from normal organs. On SPECT/CT images, relatively high uptake as a hot spot was shown in the heart of the model rat, while no obvious uptake was observed in the heart of the control rat. The radioactivity ratios of necrotic to normal myocardium of 131I-emodin and 131I-emodic acid amounted up to 9. 72 and 13. 14 by quantitative autoradiography analysis, respectively. These results suggested that 131I-emodin and 131I-emodic acid possess the necrosis target and imaging potential of necrotic myocardium.

Chemical constituents from stems and leaves of Micromelum integerrimum / 药学学报

A new benzene derivative microintegerrin C (1) and a new norsesquiterpenoid microintegerrin D (2), along with six known compounds (3-8), were isolated and identified from stems and leaves of Micromelum integerrimum by various chromatographies such as silica gel, Sephadex LH-20, RP-18 column chromatography and HPLC. Their structures were mainly identified based on the spectral data analysis such as 1D-, 2D-NMR and HR-EI-MS. All known compounds were isolated from this plant for the first time.