Gambogic acid, a caged xanthone compound derived from Garcinia, has been proven to be an important substance basis for the pharmacological effects of the plant. In recent years, it has received continuous attention due to its broad and significant pharmacological activities. Modern pharmacological investigations have demonstrated that gambogic acid endows various therapeutic effects such as anti-inflammatory, antioxidant, and anti-tumor activities, as well as benefits in retinopathy, organ protection, anti-microbial infection, bone protection, and neuropathic pain relief. Nevertheless, there is currently a lack of systematic summary and integration of the pharmacological effects and mechanisms of gambogic acid, which is critical for advancing the clinical application of this natural product. In addition, current research has raised concerns about potential safety risks associated with gambogic acid, such as organ toxicity, developmental toxicity, and hemolysis. Given this, this paper systematically reviewed and summarized the pharmacological effects, mechanisms, and toxicological profiles of gambogic acid, aiming to provide reference and data support for its clinical translation.
Xanthones/toxicity* ; Humans ; Animals ; Drugs, Chinese Herbal/toxicity* ; Garcinia/chemistry*

Male ; Humans ; Urinary Bladder/diagnostic imaging* ; Prostate/diagnostic imaging* ; Multiparametric Magnetic Resonance Imaging ; Cystitis/diagnostic imaging* ; Hemorrhage/etiology* ; Urinary Bladder Neoplasms/complications*

OBJECTIVE: To investigate the antidepressant-like effects of Chaihu Shugan Powder (CSP, ) and to explore its underlying mechanisms. METHODS: Thirty-two Sprague-Dawley rats were randomly divided into control (CON), chronic unpredictable mild stress (CUMS), fluoxetine (FLU), and CSP groups, 8 rats in each group. All of the rats except for those in the control group were subjected to 3 consecutive weeks of CUMS to establish the depression model. The open field test (OFT), forced swimming test (FST), and sucrose preference test were used to assess the anti-anxiety and antidepressant effects of CSP. Terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling was used to determine the apoptosis rate in the hippocampal tissues. The mRNA and protein levels of glucose-regulated protein (GRP) 78, spliced X-box-binding protein (XBP)-1, CCAAT/enhancer-binding protein homologous protein (CHOP), caspase-12, and c-Jun N-terminal kinase (JNK) in the hippocampus of rats were evaluated by real-time PCR and Western blot analysis, respectively. RESULTS: Administration of CSP alleviated anxiety and depression-like behavior in CUMS rats, as revealed by enhanced time and distance in the center of the OFT (P<0.05), an increased preference for sucrose, and longer swimming time and shorter immobility time during the FST (all P<0.05). In addition, CSP treatment significantly reduced the rate of apoptosis in rat hippocampal neurons (P<0.05). The mRNA and protein expression levels of GRP78, spliced XBP-1, and CHOP were down-regulated along with the expression of caspase-12 and cleaved caspase-12 proteins (all P<0.05), whereas total and phosphorylated JNK1 protein levels did not differ significantly between control and CSP-treated rats. CONCLUSION CSP can improve depression-like behavior in rats exposed to CUMS, possibly by suppressing CHOP and caspase-12 mediated apoptosis in the rat hippocampus.

OBJECTIVE: To develop the visual uroflow scale (VUS), analyze the relationship of VUS score and index of free uroflowmetry, assess urination function preliminarily and improve the work efficiency in the clinic. METHODS: Male lower urinary tract symptoms (LUTS) patients, who attended the Department of Urology in Peking University People's Hospital from March 2016 to March 2017, were assessed for their urination function according to the Visual Uroflow Scale without help from clinicians before undertaking a free uroflowmetry test. And afterwards, a free uroflowmetry was undertaken, and variables including maximal flow rate (Qmax), the average flow rate (Qave) and voiding volume (VV) was obtained. During the study, 124 cases were collected and 53 cases met the inclusion and exclusion criteria and were included in the study cohort. The Spearman correlation analysis was used for analyzing the correlation of VUS scores with free uroflowmetry variables and age. The validity of VUS was evaluated. RESULTS: Most of the patients could choose the very figure matched with self-condition by first instinct without any help from the clinician. The data were analyzed by Spearman correlation analysis. In the present study, voiding time was positively correlated with the VUS score (correlation coefficient, 0.62, P < 0.05). In the present cohort, the patients chose the third and fourth figures to take longer time to urinate, implying worse LUTS situation. Flow time and VUS scores were positively correlated (correlation coefficient, 0.61, P < 0.05). The patients with higher VUS scores would spend more time on urinate, no matter how long urinary hesitation was. Both Qmax and Qave were negatively correlated with the VUS score (correlation coefficient －0.54, －0.62, P < 0.05). The study illustrated that the VUS score suggested that the Qmax basically and further reflected the urination function. And its relationship to age revealed the decreased urination function of aging male, which had reached a consensus. CONCLUSION Development of VUS has helped the clinician assess the urination function preliminarily at the first time. Patients are assessed for a VUS score before getting surgery or receiving the drug for treatment, and can be re-assessed after. The VUS score can provide an objective quantitative basis to evaluate the treatment efficacy. In addition, considering that it is convenient, timesaving and easy to understand, the VUS is available for follow-up.
Cohort Studies ; Humans ; Lower Urinary Tract Symptoms ; Male ; Urination ; Urodynamics

Objective: To investigate the relationship between the erythrocyte membrane protein gene mutations and the clinical severity of hereditary spherocytosis (HS). Methods: Targeted sequencings were performed on 25 HS patients, correlation between HS mutations and patients' clinical characteristics were evaluated. Results: A total of 25 HS patients were enrolled, including 13 males and 12 females with median age of 20 (4-55) years, including 9 compensatory hemolysis patients, 9 patients with mild anemia, 3 patients with moderate anemia and 4 patients with severe anemia. Of them, 18 patients (72%) harbored HS-related mutations, including ANK1 mutation in 6 cases, SLC4A1 mutation in 6 cases, SPTB mutation in 5 cases and 1 case with EPB41 mutation. Seven patients (28%) didn't carry common HS mutations. SPTB and SLC4A1 mutations mainly affected male patients. There was no significant difference between the age of diagnosis (P=0.130) and HGB level (P=0.585) in patients with HS mutation and those without mutation, however, the EMA binding fluorescence intensity (P=0.015), AGLT50 (P=0.032) and EOF minimal hemolytic concentration (P=0.027) were significantly different in these two groups of HS patients. Conclusion: To screen erythrocyte membrane protein coding gene mutations could favor the diagnosis of HS, and patients without mutations have mild clinical phenotype.
Adolescent ; Adult ; Child ; Child, Preschool ; Erythrocyte Membrane ; Female ; Hemolysis ; Humans ; Male ; Middle Aged ; Mutation ; Spherocytosis, Hereditary ; Young Adult

Objective:To compare the feasibility and prognosis of different surgical methods used for vesicovaginal fistulas and to explore the value of electrocoagulation treating small ones.Methods:The medical data of 19 patients who had undertaken transvaginal VVF repairs in Peking University People's Hospital between October 2008 and November 2016 were retrospectively collected.The follow-ups were performed.The patients' age ranged from 31 to 55 years with the median age of 48 years and the history length ranged from 1 month to 24 months with the median length of 3 months.Their fistula situation,surgical methods and prognosis were analyzed and the differences and similarities were compared.Results:Three patients (15.79％) was performed by electrocoagulation,4 (21.05％) by transvaginal repair,5 (21.32％) by laparoscopic repair and 7(36.84％) by open operation.Except one patient who rejected urinary catheter and D-J catheters,the rest of the patients discharged with catheters.Twelve patients (63.2％) got full satisfaction with one operation.One of the 3 patients who undertook electrocoagulation repeated the operation for twice and got completely cured within 1 month while the other two undertook the operation once and got dry within 1 month.Three patients who undertook transvaginal repair got dry within 1 month.Two of the 5 patients who undertook laparoscopic repair had readmission for a second operation and the other 3 got dry after operation.Five of the 7 open repair patients got dry while the other 2 attempted other center for treatment.Conclusion:Transvaginal repair has been the main surgery procedure for VVF,but it is limited by the location of fistula and the condition of vaginal.For patients not suitable for transvaginal repair,laparoscopic repair and open surgery are feasible.However both laparoscopic repair and open surgery are more invasive.Based on that,electrocoagnlation becomes a better choice.In our research,patients with small and high location fistula treated by electrocoagulation got a higher cure rate and bear less surgical trauma.Electrocoagulation used in the treatment of VVF showed advantages of less trauma,less bleeding and better satisfaction.Fistulas with low location were more suitable for transvaginal repair.Complex VVF,especially with narrow ureteral open and ureteral fistulas,were more suitable for open and laparoscopic repair.As for single and small fistula,the electrocoagulation can be the first choice.

Objective: To develop a micro-neutralization test for determination of neutralizing antibody against ZIKA virus (ZIKV) in human sera and to verify the acute and convalescent serum samples of 10 ZIKA virus-infected cases diagnosed by nucleic acid detection and/or virus isolation. Methods: ZIKV isolated from ZIKA cases was used to determine micro-neutralization antibody. The virus solution was prepared by infecting BHK21, VERO and VERO-E6 cell lines and viral titer was tested; 100 TCID₅₀ viral solution and 4 times diluted sera which were inactivated at 56 ℃ for 30 min were neutralized, then added the cell suspension and incubated in 5% CO₂ incubator at 37 ℃ for 7 d. The CPE was observed every day. Results: The sensitivity of BHK21, VERO and VERO-E6 was different after infection with ZIKA virus. VERO cell line was the most sensitive and showed typical CPE. VERO cell line was used to establish a micro-neutralization test for determination of neutralizing antibody against ZIKA virus in sera. Conclusions The neutralizing antibody test for zika virus in sera is a special and usefulmethod to diagnose human infection of ZIKV and to conduct population based epidemiological investigation.

Objective To establish a method for the isolation of Zika virus and to gather experi-ences for viral isolation. Methods Suckling mice at age 1-3 days were inoculated with serum samples posi-tive for Zika virus through intracranial injection. All mice were sacrificed 6 days after the injection. Viral nu-cleic acids were extracted from brain, heart, liver, spleen, lung, kidney, muscle, skin and intestine tissue samples and analyzed by real-time RT-PCR. The supernatants of brain tissues positive for Zika virus were used for subculturing. Nested PCR was performed to amplify the NS5 gene of the isolated virus. The se-quences of NS5 gene were analyzed by using MEGA6. 0 software. Results All of the tissue samples were positive for Zika virus. Higher viral loads were detected in heart and brain tissue samples with cycle thresh-old (Ct) values of 24. 4 and 25. 3, respectively. The second generation of Zika virus was identified in suck-ling mice brain tissues 2 days after infection by using real-time RT-PCR. The amplified product of nested PCR was 972 bp in length. Sequencing analysis showed that the isolated Zika virus ( GDZ16002 strain) be-longed to the Asian lineage. Conclusion A strain of Zika virus was successfully isolated in China by using intracranial injection via a suckling mouse model. The isolated Zika virus belonged to the Asian lineage.

OBJECTIVETo study the effect of Tiantai No. 1 [symbol in text] on gene expression profile in hippocampus of Alzheimer's disease (AD) rat, molecular genetic target points of the effect of this drug were defined, its molecular genetic pharmacodynamic mechanism of anti-AD was further explored at molecular gene level, and a scientific basis was provided for its clinical availability and promotion.

METHODSThirty male Sprague-Dawley rats were divided into three groups with 10 rats per group: sham-operation group, model group and Tiantai No. 1 group. Sterile surgical procedure was applied, the model group with bilateral hippocampal injection of Aβ1-40 was established, and normal saline was used instead of Aβ1-40 in the sham-operation group. One week after the models was made, rats were administered by gastric lavage once every day for three consecutive weeks. The rats of the sham-operation group and the model group were daily fed with purified water by lavage; the rats of the Tiantai No.1 group treated group were administered with Tiantai No.1 by lavage. Total RNAs of hippocampus tissues were extracted with Trizol, the changes of hippocampus gene expression profiles in the above three groups were analyzed by using Affymetrix rat whole genome expression profile microarray.

RESULTSMicroarray analysis showed that, compared with the sham-operation group, the hippocampus of the model group had 50 up-regulated genes with significant difference (fold change >2), and 21 down-regulated genes with significant difference (fold change <0.5); compared with the hippocampus of the model group, the hippocampus of the Tiantai No. 1 group was found to have 5 up-regulated genes with significant difference (fold change >2) and 20 down-regulated genes with significant difference (fold change <0.5). The functions of differentially expressed genes of the groups were involved in nervous system's development, neuronic differentiation and function-regulation, cellular growth and differentiation and apoptosis, synaptic occurrence and plasticity, inflammation and immune response, ion channels/transporters, cellular signal transduction, cellular material/energy metabolism and so on.

CONCLUSIONTiantai No. 1 can regulate hippocampal function, and further regulate the brain function of animals in multiple gene target points by a number of ways.

Alzheimer Disease ; genetics ; pathology ; Animals ; Body Weight ; drug effects ; Computational Biology ; methods ; Drugs, Chinese Herbal ; pharmacology ; Electrophoresis, Agar Gel ; Gene Expression Profiling ; Gene Expression Regulation ; drug effects ; Hippocampus ; drug effects ; metabolism ; pathology ; Male ; Nucleic Acid Denaturation ; Organ Size ; drug effects ; RNA ; isolation & purification ; metabolism ; Rats, Sprague-Dawley

OBJECTIVETo investigate the chemical constituents in leaves of Ilex centrochinensis and their antitumor bioactivity.

METHODVarious chromatography techniques such as column chromatography on silica gel, Sephadex LH-20 and preparative HPLC were used to isolate and purify the compounds and their structures were identified by spectral data and physicochemical properties. Their antitumor effect was tested by MTT method.

RESULTTen compounds were isolated and identified as 1,4-benzenediol (1), (2S)-5,4'-dihydroxy-7,3'-dimethoxyflavan(2), (2S)-5,4'-dihydroxy-7-methoxyflavan (3), kaempferol (4), quercetin (5), naringenin (6), ursolic acid (7), uvaol (8), oleanolic acid (9) and beta-sitosterols (10).

CONCLUSIONCompounds 1-5, 7, 8 were isolated from the species for the first time, among which compounds 1-3 were isolated from the Ilex genus for the first time. Compounds 2 and 3 showed strong cytotoxic activity against Huh7 cell lines with IC50 values of 8.98, 13.04 mg x L(-1), respectively. Compounds 7-9 exhibited weak cytotoxic activity against Caco-2 cell lines with IC50 values of 28.52, 38.28, 33.04 mg x L(-1), respectively.

Antineoplastic Agents ; chemistry ; pharmacology ; Caco-2 Cells ; Cell Line, Tumor ; Cell Survival ; drug effects ; Dose-Response Relationship, Drug ; Humans ; Ilex ; chemistry ; Inhibitory Concentration 50 ; Plant Extracts ; chemistry ; pharmacology ; Plant Leaves ; chemistry ; Plants, Medicinal ; chemistry