Bear bile powder attenuates senecionine-induced hepatic sinusoidal obstruction syndrome in mice / 中国天然药物

Hepatic sinusoidal obstruction syndrome (HSOS) via exposure to pyrrolizidine alkaloids (PAs) is with high mortality and there is no effective treatment in clinics. Bear bile powder (BBP) is a famous traditional animal drug for curing a variety of hepatobiliary diseases such as cholestasis, inflammation, and fibrosis. Here, we aim to evaluate the protective effect of BBP against HSOS induced by senecionine, a highly hepatotoxic PA compound. Our results showed that BBP treatment protected mice from senecionine-induced HSOS dose-dependently, which was evident by improved liver histology including reduced infiltration of inflammatory cells and collagen positive cells, alleviated intrahepatic hemorrhage and hepatic sinusoidal endothelial cells, as well as decreased conventional serum liver function indicators. In addition, BBP treatment lowered matrix metalloproteinase 9 and pyrrole-protein adducts, two well-known markers positively associated with the severity of PA-induced HSOS. Further investigation showed that BBP treatment prevents the development of liver fibrosis by decreasing transforming growth factor beta and downstream fibrotic molecules. BBP treatment also alleviated senecionine-induced liver inflammation and lowered the pro-inflammatory cytokines, in which tauroursodeoxycholic acid played an important role. What's more, BBP treatment also decreased the accumulation of hydrophobic bile acids, such as cholic acid, taurocholic acid, glycocholic acid, as well. We concluded that BBP attenuates senecionine-induced HSOS in mice by repairing the bile acids homeostasis, preventing liver fibrosis, and alleviating liver inflammation. Our present study helps to pave the way to therapeutic approaches of the treatment of PA-induced liver injury in clinics.

Origin traceability of main root of spring Panax notoginseng based on stable isotope fingerprint / 中国中药杂志

This paper established the identification technology of the main root origin of three-year-old spring Panax notoginseng aiming at providing theoretical basis for the protection and traceability of geographical indication products of P. notoginseng. Forty-four samples of three-year-old spring P. notoginseng from Guangxi Baise, Yunnan Wenshan, Yunnan new cultivating regions. The stable isotopic ratios of carbon, nitrogen, hydrogen and oxygen were determined by elemental analysis and stable isotope mass spectrometer. Combined with Duncan multiple comparative analysis, fisher discriminant analysis and sequential discriminant analysis, a origin discriminant model for the main root of three-year-old spring P. notoginseng was established for 3 production areas of P. notoginseng. The geographical climate and environment of three production areas of P. notoginseng are obviously different. From Guangxi Baise-Yunnan Wenshan-Yunnan new cultivating regions, the longitude, average annual temperature and annual precipitation gradually decrease, and the elevation and latitude are increasing. The results of multiple comparative analysis showed that there were significant or very signi-ficant differences in the δ~(13)C,δ~(15)N,δ~2H,δ~(18)O of the main roots of P. notoginseng in three regions. The results of fisher's discriminant analysis and sequential discriminant analysis showed that the correct discriminant rates of the main roots of P. notoginseng for three regions were 80.05%,76.47% and 90.91%, respectively, based on four stable isotope ratios, with an average of 84.09%. Using stable isotope fingerprint and chemometrics method, we can distinguish the origin of the main raw materials and products of P. notoginseng.

The protective effects and mechanism of Alismatis Rhizoma extracts against senecionine-induced acute liver injury in mice / 药学学报

Drug-induced liver injury and herbal preparations containing pyrrolizidine alkaloid (PA) have gained global attention. The purpose of this research was to investigate the effects and mechanisms of Alismatis Rhizoma, a traditional Chinese medicine, to protect against acute liver injury in mice induced by senecionine (SEN), a representative toxic PA compound. 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 intragastric administration of SEN (50 mg·kg-1). Mice in the protection groups received intragastric administration of Alismatis Rhizoma water extract (WE, 18 g·kg-1 per day) or ethanol extract (EE, 18 g·kg-1 per day) 5 days before SEN treatment. The results show that Alismatis Rhizoma extracts can significantly attenuate acute liver injury in mice. Mice in the protection groups showed decreased serum activities of alanine aminotransferase and aspartate aminotransferase, as well as decreased total bile acids. In addition, the infiltration of inflammatory cells, sinusoidal hemorrhage, and hepatic necrosis in SEN-treatment mice was clearly attenuated in the protection groups. Interestingly, EE showed a better effect than WE. The content of principal bile acids in serum and the mRNA and protein expression of key factors related to bile acid metabolism were also measured. Alismatis Rhizoma up-regulated the bile acid transporters and drug metabolism enzymes, consistent with the observed bile acid homeostasis and alleviation of SEN-induced injury to hepatocytes. The present study points to the possibility of utilizing Alismatis Rhizoma for protection against liver injury caused by drugs and preparations containing PA.

Prediction of Q-markers of Citri Reticulatae Pericarpium volatile oil and GC-MS based quantitative analysis / 中国中药杂志

This study was designed to predict the Q-markers of Citri Reticulatae Pericarpium volatile oil and conduct quantitative analysis by GC-MS. The common components of Citri Reticulatae Pericarpium volatile oil were detected by GC-MS. The network pharmacology approaches were utilized for constructing the component-target network and protein-protein interaction(PPI) network, followed by the GO and KEGG pathway enrichment analysis to clarify the pharmacological effects of common components. Molecular docking was conducted to observe the biological activities of common components, thus identifying the Q-markers of Citri Reticulatae Pericarpium volatile oil. The obtained Q-markers were subjected to quantitative analysis by GC-MS. The GC-MS analysis of 19 batches of Citri Reticulatae Pericarpium volatile oil revealed three common components, namely, D-limonene, γ-terpinene, and myrcene. The common components were analyzed based on network pharmacology, and the results showed that Citri Reticulatae Pericarpium volatile oil mainly acted on the core targets GABRA1, GABRA6, GABRA5, GABRA3, and GABRA2 through D-limonene and γ-terpinene, with five important pathways such as nicotine addiction and GABAergic synapse involved. The core targets were mainly distributed in olfactory region, cerebral cortex, cerebellum, basal ganglia, hippocampus, and amygdala to exert the pharmacological effects. As revealed by molecular docking, D-limonene and γ-terpinene exhibited good biological activities, so they were identified as the Q-markers of Citri Reticulatae Pericarpium volatile oil. The results of quantitative analysis showed that the volume fraction of D-limonene was within the range of 0.77-1.03 μL·mL~(-1), and that of γ-terpinene within the range of 0.04-0.13 μL·mL~(-1). The prediction of D-limonene and γ-terpinene as the Q-markers of Citri Reticulatae Pericarpium volatile oil has laid an experimental foundation for the establishment of the quality evaluation standard for Citri Reticulatae Pericarpium volatile oil.

Research Progress on Processing of Polygalae Radix / 中国实验方剂学杂志

Polygalae Radix， a traditional Chinese medicine， has the functions of improving intelligence， calming nerves， relieving cough and eliminating phlegm. Its processing methods are various， but the purpose of processing is to reduce toxicity and increase efficiency. In this paper， the methods of ancient processing， such as cleansing， cutting， processing with excipient and processing without excipient， were summarized， the processing methods of Polygalae Radix in the different versions of Chinese Pharmacopoeia and the local processing specifications were summarized， in order to compare the differences and research progress of different processing methods. On this basis， taking the modern research of processed products of Polygalae Radix as the breakthrough point， this paper reviewed the modern research on processed products of Polygalae Radix from the aspects of processing technology， chemical composition changes and pharmacodynamics changes before and after processing， and the mechanism of reducing toxicity and increasing efficiency. Based on the research status of processing of Polygalae Radix， some existing problems were analyzed in this paper， including not many ancient processing methods used in modern times， lack of standardized research on processing technology， few studies on the ingredients introduced by excipients， etc. The author thinks that it is necessary to strengthen the research on the ancient processing of Polygalae Radix combined with processing methods with local characteristics. While discussing the processing technology， combining with the composition and efficacy， we should carry out in-depth research on the processing mechanism of different processing products of Polygalae Radix， so as to provide scientific basis for the rationality of processing of Polygalae Radix and ensure the clinical safety of medication.

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 Changji'an Prescription on Intestinal Permeability of IBS-D Rats / 中国实验方剂学杂志

Objective:To observe the effect of Changji'an prescription on intestinal permeability in diarrhea-predominant irritable bowel syndrome (IBS-D) rats and explore its mechanism for treatment of IBS-D. Method:Male SD neonatal rats were randomly divided into five groups:normal group, model group, pinaverium bromide group(0.018 g·kg-1), high-dose(33.48 g·kg-1) and low-dose (16.74 g·kg-1)Changji'an prescription groups. Except for the normal group, the IBS-D model was established by the combination of maternal and infant separation+acetic acid stimulation+restraint stress. After drug treatment, the ultrastructure of rat intestinal mucosa was observed by using transmission electron microscopy and the plasma D-lactate level was detected by enzyme-linked immunosorbent assay (ELISA). The expression levels of tight junction proteins Occludin and Claudin-1 were detected by Western blot. The mRNA expression levels of Occludin,Claudin-1 and zonula occluden(ZO)-1 were detected by real time polymerase chain reaction (Real-time PCR). Result:As compared with the normal group, the intestinal mucosal epithelial cells were damaged in IBS-D model group, and the microvilli arrangement was sparse and tight junction was widened, and some were not obvious,and the plasma D-lactate level in IBS-D rats was increased significantly (PPD-lactate level in pinaverium bromide group and high-dose Changji'an prescription group was significantly decreased (PD-lactate level in the low-dose group Changji'an prescription group had a tendency to decrease with no statistical difference. The mRNA and protein expression levels of Occludin and Claudin-1 and the mRNA expression of ZO-1 in the colon of rats in each administration group were higher than those in the model group (PConclusion:The therapeutic effect of Changji'an prescription on IBS-D may be achieved by improving the intestinal permeability.

Analysis of TSC gene mutations in five patients with tuberous sclerosis complex / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To identify pathogenic mutations of TSC1 and TSC2 genes in two familial and one sporadic cases with tuberous sclerosis complex (TSC).</p><p><b>METHODS</b>For five patients and their family members, potential mutations of the TSC1 and TSC2 genes were detected by direct sequencing.</p><p><b>RESULTS</b>For one family, a novel missense mutation c.1964C>T (p.S655F) was detected in the exon 19 of the TSC2 gene. For the sporadic patient, a repeat substitution with deletion mutation c.5238-5255delCATCAAGCGGCTCCGCCA (p.His1746GlnfsX56) was detected in the exon 40 of the TSC2 gene, which led to a stop codon TGA after the 56th amino acids. No mutation was found in another family.</p><p><b>CONCLUSION</b>The missense mutation c.1964C>T(P.S655F) and the substitution with deletion mutation 5238-5255delCATCAAGCGGCTCCGCCA(p.His1746GlnfsX56) of the TSC2 gene probably underlie the disease in the first family and the sporadic case.</p>

Cost-effectiveness Analysis of Xiyanping Injection and Ribavirin Injection for Common Type Hand-foot-mouth Disease in Children / 中国药房

OBJECTIVE:To compare cost-effectiveness of Xiyanping injection and Ribavirin injection in the treatment of com-mon type hand-foot-mouth disease (HFMD) in children,and to provide evidence for rational drug use in the clinic. METHODS:The literatures about Xiyanping injection in the treatment of common type HFMD in children using Ribavirin injection as control were retrieved from CNKI,VIP,Wanfang,PubMed,Cochrane library and other databases. The decision tree was established with TreeAge Pro 2011 software to conduct cost-effectiveness analysis. Tornado diagram was used to analyze sensitive factors;single fac-tor and double factors sensitivity analysis were also conducted. RESULTS & CONCLUSIONS:The total cost of Xiyanping injection and Ribavirin injection were 2 887.53 and 3 058.72 yuan,respectively. The total effective rates were 92.49% and 78.12%. Xiyan-ping injection shows cost-effectiveness advantage. The results of cost-effectiveness analysis were supported by sensitivity analysis.

Two novel mutations of the ADAR1 gene associated with dyschromatosis symmetrica hereditaria / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To identify potential mutation of the ADAR1 gene in a Chinese family and a sporadic case affected with dyschromatosis symmetrica hereditaria(DSH).</p><p><b>METHODS</b>Clinical data and peripheral blood samples from the pedigree and the sporadic patient were collected. Following extraction of genomic DNA, all 15 exons and exon-intron flanking sequences of the ADAR1 gene were amplified by polymerase chain reaction and subjected to direct sequencing.</p><p><b>RESULTS</b>A novel frame-shift mutation c.2638delG (p.Asp880ThrfsX15) from the patients of the pedigree was detected in exon 8 of the ADAR1 gene. And a novel nonsense mutation c.2867C>A (p.Ser956X) was detected in exon 10 of the ADAR1 gene from the sporadic case. Neither mutation was identified among the unaffected family members nor 100 unrelated healthy controls.</p><p><b>CONCLUSION</b>The frame-shift mutation c.2638delG (p.Asp880ThrfsX15) and the nonsense mutation c.2867C>A (p.Ser956X) in the ADAR1 gene probably underlie the DSH in our patients.</p>

Comparison Analysis of Drug Instructions between Hospital Directory and OTC Standard Model Instruc-tions in 2014 / 中国药房

OBJECTIVE:To analyze the differences of drug instructions between hospital directory and OTC standard model in-structions,and to provide reference for enhancing instruction management and reducing the safety risk of clinical drug use. METH-ODS:1 324 drugs of hospital directory in a hospital in 2014 were compared with OTC directory from CFDA websites. The instruc-tion of drug types included in OTC directory were compared OTC model instruction. According to the degree of risks which the dif-ferences may bring,differences were divided into four levels for analysis as negligible,general,important and severe. RESULTS:244 drugs belonged to OTC,of which 32.38%were different from standard model instructions. The four risk levels rates of negligi-ble,general,important and severe accounted for 29.11%,34.18%,7.59% and 29.11%,respectively. Among important risk,the difference of“indication limit”occupied the highest proportion,being 50.00%. Among severe risk,the difference of“forbidden for special disease”and“forbidden for pregnant women”accounted for 43.48% and 39.13%. CONCLUSIONS:There are problems, such as the absence of important medication information,statement conflicts. The hospital and administration departments should en-hance the standard management of drug instruction to guarantee safe and rational drug use in the clinic.

Resistant effect of water decoction of root of Crataegus cuneata on male infertility induced by GTW in rats / 中国中药杂志

<p><b>OBJECTIVE</b>To observe the effects of water decoction of the root of Crataegus cuneata on infertility induced by multi-glucoside of Tripterygium wilfordii (GTW) in rats.</p><p><b>METHOD</b>Male adult rats were randomly divided into five groups, which were treated via gastric gavage of distilled water (1 mL x kg(-1)) , solution of GTW (10 mg x kg(-1)) and three doses of water decoction of root of C. cuneata (1.8, 5.4, 18 g x kg(-1)) + GTW (10 mg x kg(-1)), respectively. 8 weeks later, GTW was stopped and the decoction and water continued for another 4 weeks. And then, all the male rats were copulated with adult female rats. The rates of pregnancy, average numbers of embryos and luteum of female rats, relative weights of reproductive organs, sperm counts, sperm motility and viability were compared among all the groups. The histology and ultrastructure of testis and epididymis were observed, while the concentrations of follicle stimulating hormone (FSH), luteinizing hormone (LH) and testostorone (T) in serum and T in testicular homogenate were detected by radioimmunoassay.</p><p><b>RESULT</b>Compared with those in GTW model group, the embryo numbers, the relative weight of testis and epididymis and sperm counts and motility in C. cuneata groups were increased obviously (P < 0.05). After treatment, the morphological damages of seminiferous tubules and sperms were recovered, while concentrations of T in testicular homogenate were also significantly increased (P < 0.01).</p><p><b>CONCLUSION</b>C. cuneata could relieve the reproductive lesions induced by GTW, and hence improve the uberty of the male infertile model rats.</p>

Urokinase-type plasminogen activator improves the reproductive function of male rats / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the effects of urokinase-type plasminogen activator (uPA) on the reproductive function of the male rats with ornidazole-induced infertility.</p><p><b>METHODS</b>Fifty 10-12 weeks old adult male Sprague-Dawley rats were randomly divided into five groups: low-dosage uPA (330 IU/[kg x d]), mid-dosage uPA (1000 IU/[kg x d]), high-dosage uPA (3000 IU/[kg x d]), ornidazole (400 mg/[kg x d]) and control (0.5% Carboxymethylcellulose solution). The ornidazole group was treated by gastric gavage, and the rats in the uPA groups given both ornidazole by gastric gavage and uPA by intraperitoneal injection at the same time. All the rats were treated for 20 days consecutively, followed by copulation experiment. The rats were sacrificed and the reproductive system explored.</p><p><b>RESULTS</b>The percentage of motile sperm and the number of embryos in the high-dosage uPA group increased significantly (P < 0.01) compared with the ornidazole group.</p><p><b>CONCLUSION</b>uPA can antagonize ornidazole-induced infertility in male rats. The effect might be attributed to the improvement of sperm motile function by uPA.</p>

Expression of Cyclin D3 and PCNA in Cutaneous Malignant Melanoma / 中华皮肤科杂志

Objective To investigate the expression of cyclin D3 and proliferating cell nuclear antigen (PCNA) and their clinical significance in mal ignant melanoma. Methods The expression of cyclin D3 and PCNA was measured by streptavidin-peroxidase complex immunohistochemical technique in 57 cases of pri mary cutaneous malignant melanoma (CMM), 37 cases of metastatic melanoma and 20 cases of benign nevi. Results The positive expression rate of cyclin D3 in CM M and metastatic melanoma were 35.1% and 59.5% respectively, while the high expr ession rate of PCNA were 57.9% and 78.6% respectively. Compared with that in ben ign nevi, the expression of cyclin D3 and PCNA was significantly increased. The expression of cyclin D3 and PCNA in CMM was positively related to Clark′s grade and the metastasis to lymph nodes. The 3-year survival rate in patients with ne gative expression of cyclin D3 was significantly higher than that with positive expression in superficial melanomas. The 3-year survival rate of patients with l ow expression of PCNA was significantly higher than that with high expression in CMM. The expression of cyclin D3 was positively correlated with the high expres sion of PCNA in superficial and metastatic melanomas. Conclusions The expressi on of cyclin D3 and PCNA may be involved in the carcinogenesis process and progr ession of CMM and have important implications in the selection of therapeutic re gimens and prognostic assessment. The expression level of cyclin D3 may be regar ded as a prognostic factor for superficial melanoma.

Expression of Fragile Histidine Triad Gene and its Association with Proliferation and Apoptosis of Tumor Cells in Cutaneous Malignant Melanoma / 中华皮肤科杂志

Objective To investigate the expression of fragile histid ine triad (FHIT)gene and its relationship with the proliferation and apoptosis of tumor cells in cutaneous malignant melanoma (CMM).Methods The expression o f FHIT gene and PCNA were detected by streptavidin peroxidase method with skin s pecimens taken from 57 primary cutaneous melanoma and 20 normal controls.Apopto sis of tumor cells was detected by terminal deoxynuclneotidyl transferase mediat ed dUTP nick end labeling (TUNEL).Results The expression level of FHIT protei n was significantly lower in CMM than that in the normal skin tissue (P