Heme peroxidases are responsible for the dehydrogenation and oxidation metabolism of harmaline into harmine / 中国天然药物

Harmaline and harmine are β-carboline alkaloids with effective pharmacological effects. Harmaline can be transformed into harmine after oral administration. However, enzymes involved in the metabolic pathway remain unclear. In this study, harmaline was incubated with rat liver microsomes (RLM), rat brain microsomes (RBM), blood, plasma, broken blood cells, and heme peroxidases including horseradish peroxidase (HRP), lactoperoxidase (LPO), and myeloperoxidase (MPO). The production of harmine was determined by a validated UPLC-ESI-MS/MS method. Results showed that heme peroxidases catalyzed the oxidative dehydrogenation of harmaline. All the reactions were in accordance with the Hill equation. The reaction was inhibited by ascorbic acid and excess H2O2. The transformation of harmaline to harmine was confirmed after incubation with blood, plasma, and broken blood cells, rather than RLM and RBM. Harmaline was incubated with blood, plasma, and broken cells liquid for 3 h, and the formation of harmine became stable. Results indicated an integrated metabolic pathway of harmaline, which will lay foundation for the oxidation reaction of dihydro-β-carboline. Moreover, the metabolic stability of harmaline in blood should not be ignored when the pharmacokinetics study of harmaline is carried out.

The protective effect of ritonavir against Gynura japonica-induced liver injury in rats / 药学学报

Numerous in vitro studies have shown that most pyrrolizidine alkaloids (PAs) are hepatotoxic after being metabolically activated by cytochrome P450 (CYP) 3A4. However, the key role of CYP3A4 has not been confirmed in vivo. Therefore, the CYP3A4 chemical inhibitor ritonavir was employed in this work and the effect of ritonavir on Gynura japonica-induced liver injury in rats was investigated. All experiments were approved by the Animal Research Committee of Shanghai University of Traditional Chinese Medicine. Animal welfare and the animal experimental protocols were strictly consistent with related ethics regulations of Shanghai University of Traditional Chinese Medicine. Acute liver injury was induced by a single gavage of Gynura japonica extracts (GJE, 8 g·kg-1); rats in the protection group were gavaged with ritonavir (RIT, 30 mg·kg-1) 1 h before GJE treatment. The results show that RIT could significantly attenuate GJE-induced liver injury in rats. Rats in the protection group showed decreased serum activities for alanine aminotransferase and aspartate aminotransferase, as well as lower total bile acids. In addition, the infiltration of inflammatory cells, sinusoidal hemorrhage, and hepatic necrosis in GJE-treated rats were markedly attenuated in the protection group. The content of pyrrole-protein adducts (PPAs), a recommended biomarker for PA-induced hepatotoxicity in clinics, was determined at 10 min to 24 h after GJE treatment. The content of 13 bile acids was also quantified. RIT treatment reduced the content of PPAs in serum dramatically and restored the impaired bile acid homeostasis caused by GJE. These studies indicate that RIT attenuated Gynura japonica-induced liver injury in rats, which was closely related to the inhibition of the metabolic activation of PAs and the regulation of bile acid metabolism. These results provide a better understanding of the relationship between CYP3A4 and PA-induced toxicity. This work will also be helpful in developing effective treatments for PA-induced liver injury and making a reasonable evaluation of the safety of drugs containing PAs in clinic.

The protective effect of schisandrol A against senecionine-induced hepatotoxicity in mice / 药学学报

Hepatotoxicity induced by herbal medicines such as Gynura japonica, which contains large amount of pyrrolizidine alkaloids (PAs) such as senecionine (SEN), is among the most serious problems of herbal drug-induced liver injury, yet there is no effective treatment in clinic. We have previously reported that ritonavir (the well-known CYP3A4 inhibitor) protected rats against Gynura japonica-induced liver injury in rats, which was closely related to the inhibition of the metabolic activation of PAs. A large number of lignans have been identified in Schisandrae Chinensis Fructis and are reported to attenuate drug-induced liver injuries by modulating the drug metabolism enzymes. Therefore, the present study investigated the protective effect and potential mechanism of schisandrol A (SoA, a representative lignan identified in Schisandrae Chinensis Fructis) against SEN-induced hepatotoxicity in mice. All experiments were approved by the Animal Research Committee of Shanghai University of Traditional Chinese Medicine (PZSHUTCM210604002). Animal welfare and the animal experimental protocols were strictly consistent with related ethics regulations of Shanghai University of Traditional Chinese Medicine. Liver injury was induced by a single gavage of SEN (150 μmol·kg-1); mice in the protection group were gavaged with SoA (116 μmol·kg-1) 7 days before SEN treatment. The results show that SoA dramatically alleviated SEN-induced liver injury in mice. Mice in the protection group showed decreased serum activities for alanine aminotransferase and aspartate aminotransferase; in addition, the hepatic necrosis and sinusoidal hemorrhage in SEN-treated mice were markedly attenuated in the protection group. The serum contents of SEN metabolites in mice were decreased. In vitro studies were performed by using human liver microsomes and proved that SoA inhibits CYP3A4 to decrease the metabolism of SEN. These studies indicate that SoA attenuated SEN-induced liver injury in mice, which was closely related to the inhibition of the metabolic activation of SEN. These results provide a better understanding of the relationship between CYP3A4 and PA-induced toxicity. This work also will be helpful in developing effective treatments for SEN-induced liver injury based on inhibition of its metabolic activation, and in making reasonable evaluations of the safety of herbal medicines containing PAs such as G. japonica.

Prescription Research and Clinical Application of Yiguanjian / 中国实验方剂学杂志

By systematically sorting out the ancient medical books and modern clinical literature of Yiguanjian， the historical evolution of this formula， including its source， composition， origin， processing， dosage， preparation and usage， functions and indications， evolution of prescription meaning， is textual so as to clarify the historical evolution and clinical application of Yiguanjian. On the basis of fully considering the actual demand of development of famous classical formula preparation and the usage habit of modern clinical practice， the feasible development suggestions were put forward. Yiguanjian is composed of six herbs， which is derived from Yifang Jiedu (《医方絜度》) . It is an ancient book of traditional Chinese medicine edited by QIAN Min-jie in Qing dynasty. The original medicinal plants and medicinal parts of the formula were basically the same as those recorded in the 2020 edition of Chinese Pharmacopoeia. The raw products should be selected for decoction pieces and processed according to the methods recorded in the 2020 edition of Chinese Pharmacopoeia. The reference dose of the medicine in this formula is set out in Yifang Jiedu. According to dosage of one Qian（钱）=3.73 g， the dosages of Glehniae Radix， Ophiopogonis Radix and Angelicae Sinensis Radix were 5.60 g， the dosages of Lycii Fructus and Rehmanniae Radix were 11.19 g， the dosage of Toosendan Fructus was 7.46 g. These decoction pieces were boiled and warm decoction was taken. According to ancient medical records， the formula always has the effect of nourishing Yin and relieving Qi of liver. It is used to treat syndrome of stagnation of liver-Qi and deficiency of liver-Yin and kidney-Yin， which can be seen with pain in chest， stomach and flank， acerbity and vomiting， dry throat and mouth， red tongue， weak pulse or deficiency of string and hernia. Here， the source， processing and others of Yiguanjian were clarified， providing a literature reference for the development and application of this famous classical formula.

Strictosidine synthase, an indispensable enzyme involved in the biosynthesis of terpenoid indole and β-carboline alkaloids / 中国天然药物

Terpenoid indole (TIAs) and β-carboline alkaloids (BCAs), such as suppressant reserpine, vasodilatory yohimbine, and antimalarial quinine, are natural compounds derived from strictosidine. These compounds can exert powerful pharmacological effects but be obtained from limited source in nature. the whole biosynthetic pathway of TIAs and BCAs, The Pictet-Spengler reaction catalyzed by strictosidine synthase (STR; EC: 4.3.3.2) is the rate-limiting step. Therefore, it is necessary to investigate their biosynthesis pathways, especially the role of STR, and related findings will support the biosynthetic generation of natural and unnatural compounds. This review summarizes the latest studies concerning the function of STR in TIA and BCA biosynthesis, and illustrates the compounds derived from strictosidine. The substrate specificity of STR based on its structure is also summarized. Proteins that contain six-bladed four-stranded β-propeller folds in many organisms, other than plants, are listed. The presence of these folds may lead to similar functions among organisms. The expression of STR gene can greatly influence the production of many compounds. STR is mainly applied to product various valuable drugs in plant cell suspension culture and biosynthesis in other carriers.

Kinetic study of pyrrolizidine alkaloid-derived pyrrole-protein adducts in rats after intragastric administration of Gynura japonica / 药学学报

Recently, hepatic sinusoidal obstruction syndrome (HSOS) induced by misuse of Gynura japonica has increased and gained global attention. Large amounts of pyrrolizidine alkaloids (PAs) are present in G. japonica; these PAs are metabolically activated to generate pyrrole-protein adducts (PPAs). In this study, male SD rats were treated orally with a single dose of G. japonica extract (GJE) at 0.062 5, 0.25, 0.5, 1, and 2 g·kg-1. Blood was collected from the orbital venous plexus at 2, 12, 24 and 48 h, and at 48 h after treatment the rats were anesthetized with isoflurane and livers were collected for hematoxylin & eosin staining. The kinetics of PPAs at different doses were studied at 10, 20, 30 min, 1, 2, 4, 6, 12, 24 h, and 48 h, after a single gavage of GJE. The experimental scheme was approved by the ethics committee of animal experiments of Shanghai University of Traditional Chinese Medicine (PZSHUTCM190912019). The concentration of PPAs in serum was determined by liquid chromatography-mass spectrometry (LC-MS). Kinetic data were processed by using the non-compartmental pharmacokinetics data analysis software program PK solutions 2™. The results demonstrate that the concentration of PPAs increased with the dose of GJE and positively correlated with the severity of liver injury. The elimination rate of PPAs in rats was significantly prolonged at higher doses. The level of PPAs and their clearance rate may serve as useful references for the detoxification of PAs-induced injuries.

Effect of fluoxetine on the depression-like behavior and mitogen-activated protein kinase-p38 signaling pathway in depression rats / 新乡医学院学报

Objective To investigate the effect of fluoxetine on the depression-like behavior and the expression of mitogen-activated protein kinase phosphatase-1 (MKP-1),phosphorylated p38 and p38 in hippocampus of rats with depression,in order to provide clues for the molecular pathological mechanism of depression.Methods Forty Sprague Dawley rats were randomly divided into normal group,depression group,normal saline group and fluoxetine group,with ten rats in each group.The rats in the depression group,normal saline group and fluoxetine group were treated with chronic unpredictable mild stress (CUMS) for eight weeks to prepare the depression models.The rats in the normal saline group and fluoxetine group were treated with normal saline and fluoxetine by intragastric administration respectively from the fifth to eighth week,but the rats in the normal group did not give CUMS and any intervention.The behavior changes of rats in the four groups were evaluated at the time points of before modeling,after modeling and postintervention.The hippocampal tissues of rats were taken after the last the last behavioral evaluations.The expression of MKP-1,p-p38 and p38 protein in hippocampus was detected by Western blot;and the ratio of the expression of p-p38 to p38 protein (p-p38/p38) was calculated.Results There was no significant difference in the behavioral indexes of rats among the four groups (P ＞ 0.05).Compared with pre-modeling,the sucrose preference index decreased,the horizontal movement distance and vertical frequency decreased in the open field test,and the inactivity time of rats in forced swimming test increased in the depression group,normal saline group and fluoxetine group,the differences were statistically significant (P ＜ 0.05).There was no significant difference in the behavioral indexes of rats among the depression group,normal saline group and fluoxetine group (P ＞ 0.05).Compared with the normal group,the sucrose preference index decreased,the horizontal movement distance and vertical frequency of rats in open field test decreased,and the inactivity time of rats in forced swimming test increased in the depression group,normal saline group and fluoxetine group after modeling,the differences were statistically significant(P ＜0.05).Compared with the depression group and normal saline group,the sucrose preference index of rats increased,the horizontal movement distance and vertical frequency of rats in open field test increased,and the inactivity time of rats in forced swimming test shortened in fluoxetine group,the differences were statistically significant (P ＜ 0.05).The expression of MKP-1 in the hippocampus of rats in the depression group and the normal saline group was significantly higher than that in the normal group (P ＜ 0.05).The expression of MKP-1 in the hippocampus of rats in the fluoxetine group was significantly lower than that in the depression group and normal saline group (P ＜ 0.05).There was no significant difference in the expression of MKP-1 in the hippocampus of rats between the depression group and the normal saline group (P ＞ 0.05).There was no significant difference in the expression of MKP-1 in the hippocampus of rats between the fluoxetine group and normal group(P ＞ 0.05).There was no significant difference in the expression of p-p38 and p38 protein and p-p38/p38 in the hippocampus of rats among the four groups (P ＞ 0.05).Conclusions MKP-1 may be associated with the pathogenesis of depression,and p38 may not be the signaling pathway for MKP-1 to take part in the pathogenesis of depression.Fluoxetine may play a role in the treatment of depression by down-regulating MKP-1 expression.MKP-1 may play a key role in the pathogenesis of depression.Fluoxetine may play a role in the treatment of depression by down-regulating.

Simultaneous determination of four constituents in Yangxin Dingji Capsules by HPLC / 中成药

AIM To establish an HPLC method for the simultaneous content determination of four constituents in Yangxin Dingji Capsules (a cardiac tonic for palpitation,containing Glycyrrhizae Radix et Rhizoma Praeparata cum Melle,Cinnamomi Ramulus,Rehmanniae Radix,etc.).METHODS The analysis of 50％ methanol extract of Yangxin Dingji Capsules was performed on a 40 ℃ thermostatic Diamonsil C1s column (250 mm × 4.6 mm,5 μm),with the mobile phase comprising of 0.1％ formic acid-acetonitrile flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelength was set at 265 nm.RESULTS Liquiritin,glycyrrhizic acid,cinnamic acid and cinnamic aldehyde showed good linear relationships within the ranges of 1.00-80.24 μg/mL (r=0.999 0),2.52-100.70 μg/mL (r--0.999 7),0.50-40.40 μg/mL (r =1.000 0) and 0.66-52.96 μg/mL (r =1.000 0),whose average recoveries were 97.74％,100.97％,101.48％ and 99.49％ with the RSDs of 0.45％,1.11％,1.27％ and 1.66％,respectively.CONCLUSION This simple,accurate and reproducible method can be used for the quality control of Yangxin Dingji Capsules.

Separation and authentication of tilianin and quality standards of semen of Dracocephalum moldavia / 中国中药杂志

Tilianin was separated and authenticated from the seeds of Dracocephalum moldavia, a Uygur medicine, by chromatographic technique and spectroscopic method. The purity of tilianin is more than 98% determined by HPLC area normalization method. Thin layer chromatography (TLC) method was used to separate tilianin from D. moldavia by mixture of chloroform-methanol (5: 1) as a developing solvent on high performance silicagel precoated plate (SGF254) and using aluminium trichloride as a chromogenic agent for qualitative identification of D. moldavia. To establish a HPLC method for quantitative analysis of D. moldavia, tilianin was used as a Quantitative marker and separated on a C18 (4.6 mm x 250 mm, 5 μm) column with acetonitrile-01% formic acid (25: 75) as the mobile phase and detected at 330 nm. The calibration curve of tilianin displayed ideal linearity over the range of 0.617 2-123.44 μg x mL(-1) with a regression equation of Y = 33.773X - 0.824 8 (r = 1). The average recovery of tilianin was 101.0% with RSD of 3.7%. The RSD values of intra-day and inter-day precision were less than 2%. The content of tilianin in 4 batches of the authenticated semen of D. Moldavia was between 0.016 and 0.187 mg x g(-1). The qualitative and quantitative method established is suitable for the quality evaluation and assessment of semen of D. Moldavia.

Effect of Fuzheng Huayu recipe on CYP450 isozymes in normal and liver fibrosis rats / 中国中药杂志

To study the effect of Fuzheng Huayu recipe (FZHY) on five types of isozymes of cytochrome P450 (CYP450) of normal and liver fibrosis rats by using the cocktail probe method. Dimethylnitrosamine ( DMN) was injected to induce the liver fibrosis model. After the tail vein injection with Cocktail probe solutions prepared with five CYP450s probe substrates (phenacetin-CYP1A2, omeprazole-CYP2C9, tolbutamide-CYP2C19, dextromethorphan-CYP2D6, midazolam-CYP3A4), the plasma concentrations of the five probe substrates were determined by LC-MS/MS, and the pharmacokinetic parameters were calculated by PK solutions 2. After the oral administration with FZHY, normal rats given phenacetin, omeprazole, tolbutamide and dextromethorphan showed increase in AUC(0-t) and decrease in CL to varying degrees, indicating that FZHY obviously inhibited the activities of CYP1A2, CYP2C9, CYP2C19 and CYP2D6 in normal rats, but with no obvious effect on the activity of CYP3A4. After the oral administration with FZHY, liver fibrosis rats treated with CYP2C9 showed the significant increase in AUC(0-t) and significant decrease in Vd, hut with no obvious changes in the pharmacokinetic parameters of other four types of prove substances, suggesting that FZHY could significantly inhibit the activity of CYP2C9 in rats but had no effect on the activities of CYP1A2, CYP2C19, CYP2D6 and CYP3A4. The changes in the activity of CYP450 isozymes in liver fibrosis rats may be the reason for FZHY's different effects on CYP450 isozymes in normal and liver fibrosis rats.

Research on quality standards of herbs of Peganum harmala / 中国中药杂志

<p><b>OBJECTIVE</b>To establish the quality standards of the herbs of Peganum harmala.</p><p><b>METHOD</b>According to the Chinese Pharmacopoeia (2010 version, volume 1) and its appendix method, the water, total ash, acid insoluble ash, water-soluble extractives, and heavy metal were analyzed for herbs of P. harmala. TLC method was used to separate harmaline, harmine and vasicine from the herb samples by mixture of ethyl acetate-methanol-ammonia (10: 1.5: 0.5) as a developing solvent on high performance silica gel precoated plate (HSGF254) and to identify them inspected under UV 366 nm, visualized by spraying with both Dragendorff reagent, and by bioautographic assay. In the HPLC method, vasicine was separated on a C18 (4.6 mm x 250 mm, 5 microm) column with metnanol-0.1% trifluoroacetic acid (15:85) as the mobile phase and detected at at 280 nm.</p><p><b>RESULT</b>In the TLC procedures, 254 nm fluorescent and bioautographic assay for the detection of acetylcholinesterase inhibitor can be used for the qualitative identification of the active ingredients. For the HPLC quantitation method, the calibration curve of vasicine displayed ideal linearity over the range of 0.7923-792.3 mg x L(-1) with the regression equation of Y = 18,227X - 24.879 (r = 0.9999). The average recovery of vasicine was 101.6% with a RSD of 1.9%. The RSD values of intra-day and inter-day precision were less than 2%. The content of vasicine in 10 batches of herbs of P. harmala fluctuates between 0.23% and 1.47%.</p><p><b>CONCLUSION</b>The results indicated that the limit of vasicine was not lower than 0.6%, and the water, total ash, acid insoluble ash, and water-soluble extractives were not more than 10.0%, 20.0%, 1.7%, and 30.0%, respectively. The heavy metal of plumbum, cadmium, arsenic, mercury, and copper were not more than 5, 3, 2, 2, and 20 mg x kg(-1), respectively. The qualitative and quantitative method established was suitable for the quality evaluation and assessment of herbs of P. harmala.</p>

Identification of metabolites of nobiletin in rats using ultra-performance liquid chromatography coupled with triple-quadrupole mass spectrometry / 药学学报

In this study, metabolism of nobiletin in rats was studied using ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS). As a result, seven major metabolites were found in bile, urine and serum of rats. Three phase I products were assigned to be demethyl and di-demethyl products, and other four phase II products were assigned to be glucuronic and sulfonic conjugates. The four phase II metabolites were reported for the first time. Among the metabolites found in the present study, the glucuronic conjugates of demethyl-nobiletin played a predominant role in the metabolic pathway, indicating that its potential role for glucuronidation-related factors, such as gene polymorphism, drug-drug interaction, etc., in changing the active and toxic effect of nobiletin and that it should be paid more attention in further development.

Effect of jianpi tiaogan wenshen recipe in treating diarrhea-predominant irritable bowel syndrome / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To verify the efficacy of Jianpi Tiaogan Wenshen Recipe (JTWR) in treating diarrhea-predominant irritable bowel syndrome (IBS-D) and to analyze its therapeutic mechanism through observing the effect of JTWR on clinical symptoms and rectal sensibility in patients.</p><p><b>METHODS</b>With a prospective, randomized controlled trial adopted, 80 patients with IBS-D were assigned randomly equally and to two groups. The treatment group was treated with JTWR, and the control group was treated with pinaverium bromide tablet (PVB), all for four weeks. Patients' symptoms, such as abdominal discomfort, pain, and distension; frequency of defecation; appearance of stool; and occurrence of tenesmus were recorded before and after treatment by scoring, and the rectal sensitivity was detected as well. Patients with therapeutic effect of cured and markly effective were followed up four weeks after withdrawal of medication.</p><p><b>RESULTS</b>Three cases in the treatment group and four cases in the control group were dropped. Except the appearing of mucus stool, no statistically significant difference was shown between the two group in all other symptoms, either at before or after treatment; but the end point scores of individual symptoms between pre- and post-treatment were different statistically in both groups (P<0.05). Per-protocol population set (PPS) analysis on comprehensive effect showed that the total effective rate and the cure rate in the treatment group was 81.1% (30/37) and 24.3% (9/37), and those in the control group, 80.6% (29/36) and 19.4% (7/36) respectively; while the full analysis set (FAS) showed a result of 80.0% (32/40) and 22.5% (9/40) vs 77.5% (31/40) and 17.5% (7/40) respectively, all with insignificant difference between groups (P>0.05). Follow-up study showed that relapse or aggravation of disease occurred in four cases in the treatment group and 12 in the control group respectively, showing significant difference between groups (P<0.01). Rectal sensitivity examination showed that the rectal thresholds of sensation, defecation, and maximum tolerable volume were improved in both groups after treatment (P<0.05), but showed no significant difference between groups (P>0.05).</p><p><b>CONCLUSIONS</b>JTWR is effective in treating IBS-D, with the effect better than PVB in improving mucus stool, also in the remote effect. Its therapeutic mechanism is possibly by way of adjusting the sensitivity of rectum.</p>

Advances on investigation of chemical constituents, pharmacological activities and clinical applications of Capparis spinosa / 中国中药杂志

In this paper, the chemical constituents, pharmacological activities and clinical applications of Capparis spinosa had been reviewed. The constituents of C. spinosa include the saccharides and glycosides, flavonoids, alkaloids, terpenoids and volatile oils, fatty acids and steroides and so on. C. spinosa had many extensive pharmacological effects such as anti-inflammatory, odynolysis, antifungus, hepatoprotective effect, hypoglycemic activity, antioxidation, anti-hyperlipemia, anticoagulated blood, smooth muscle stimulation, anti-stress reaction, improve memory. It was used to treat arthrolithiasis, rheumarthritis and dermatosis in clinic in domestic, and it would have a broad application prospects.

A new compound from Senecio cannabifolius var integrilifolius / 药学学报

Senecio cannabifolius var integrilifolius (Compositae), locally known as "Fanhuncao" in China, is a folk herb used for the treatment of pneumonia, virus influenza and bronchitis. To investigate the chemical constituents of this herb, water extract of the aerial parts was subjected to various chromatography on normal/reversed phase silica gel and Sephadex LH-20 column. Eleven compounds were obtained and identified on the basis of their physicochemical properties and spectroscopic analysis as senecine (1), p-hydroxy-benzeneacetic acid (2), protocatechuic acid (3), 2,5-dihydroxy-benzeneacetic acid (4), 3,4-dihydroxy-benzeneacetic acid (5), vanillic acid (6), caffic acid (7), succinic acid (8), 2-furoic acid (9), 1, 2, 4, 5-tetrahydro-jacaranone (10), and 4-(pyrrolidin-2-one)-phenylacetic acid (11). Compound 1 was structurally identified to be a new compound; the other compounds were isolated from this plant for the first time.

Lead expelling effect of carboxymethyl chitosan calcium in lead poisoned mice / 中华预防医学杂志

<p><b>OBJECTIVE</b>To observe the effects of carboxymethyl chitosan calcium (CCC) on concentration of lead, calcium and zinc, and the liver antioxidative capacity in lead poisoned mice.</p><p><b>METHODS</b>Mice were randomly divided into 7 groups, including normal group, calcium carbonate group, lead-model group, and three experimental groups treated with CCC in three different doses, and the CaNa2EDTA positive control group. The lead poisoned mice model was established by giving water contained with lead acetate. CCC was administrated to mice i.g. once a day. Thirty days later, mice were killed and the concentrations of lead, calcium and zinc in blood, liver, brain and femur were determined by atomic absorption spectrophotometer. Maleic dialdehyde (MDA), total antioxidative capacity (T-AOC), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) activities in liver were measured by using assay kit.</p><p><b>RESULTS</b>CCC significantly reduced the concentration of lead in blood, brain, liver and femur from about 1.56 microg/g, 13.38 microg/g, 16.15 microg/g, 1011.62 microg/g to about 0.50 microg/g, 5.57microg/g, 5.64 microg/g, 457.86 microg/g, and markedly increased the concentration of calcium in femur in lead poisoned mice. CCC had no significant side-effects on concentration of zinc in lead poisoned mice. The antioxidative profile was favorably changed as manifested by decreasing the level of MDA, increasing the activities of SOD, GSH-Px and T-AOC in livers of the in lead poisoned mice.</p><p><b>CONCLUSION</b>CCC might significantly advance the excretion of lead, increase the concentration of calcium in femur and the antioxidative capacity in lead-loaded mice.</p>

Association of Gonadal Receptor Genes′ Microsatellites and Dysfunctional Attitudes in Adolescent with Major Depressive Disorder / 实用儿科临床杂志

Objective To explore the associations between microsatellites in gonadal receptor genes and dysfunctional attitudes in adolescent with major depressive disorder(MDD).Methods Polymerase chain reaction(PCR),capillary electrophoresis and genetic scanning were performed in testing the length of microsatellites in first-onset adolescent depressive patients.Dysfunctional attitudes scale(DAS) was used in rating the dysfunctional cognition of adolescent depressive sample.These results were tested by correlative analysis and comparison analysis.Results 1.There existed significantly negative correlation between microsatellite′s length in estrogen receptor ?(ER?) gene and total score of DAS in female adolescent patients with first-onset depressive disorder.2.DAS′ total score of shorter alleles′ group was significantly higher than that of longer alleles′ group on female′ estrogen receptor ?(ER?) Gene.Conclusion The microsatellite′s length of ER? and ER? gene may have associations with dysfunctional attitudes of female adolescent with MDD.

Cognitive Function and P300 Potentials in First-Episode Schizophrenia Treated with Quetiapine and Risperidone / 中国心理卫生杂志

Objective:To compare the effects of quetiapine and risperidone on cognitive function of first-episode schizophrenic patients.Methods:A randomized comparative clinical design was applied to compare the cognitive function of 67 patients with first-episode schizophrenia treated with quetiapine(n=35,25-750mg/d)and risperidone(n=32,1-7rag/d)before and after 12-week treatment.PANSS,WMS and P300 were used to evaluate adverse effects of drags and cognitive function.Results:The Long-term memory,Short-term memory,Immediate memory,Memory Quotient of first-episode schizophrenia were damaged obviously.Latency periods of P_2、N_2 and P_3 of P_(300) potentials with first-episode schizophrenia group were longer than the control group,The amplitudes of P_2 and P_3 of P_(300) potentials with first-episode schizophrenia group were lower than the control group(P