Publications by authors named "Jingze Zhang"

47 Publications

Pectolinarigenin flavonoid exhibits selective anti-proliferative activity in cisplatin-resistant hepatocellular carcinoma, autophagy activation, inhibiting cell migration and invasion, G2/M phase cell cycle arrest and targeting ERK1/2 MAP kinases.

J BUON 2020 Jan-Feb;25(1):415-420

Department of Blood Purification, Qingdao No.6 People's Hospital, Qingdao, Shandong, 266033, China.

Purpose: The main purpose of the present research article was to investigate the anticancer properties of pectolinarigenin flavonoid in cisplatin-resistant hepatocellular carcinoma cells (SK-HEP-1) and normal liver cells (AML-12), along with examining its effects on autophagy, cell migration and invasion, cell cycle arrest and ERK1/2 MAP signalling pathways.

Methods: Antiproliferative effects in cancer and normal cells were assessed by MTT cell viability assay. Cell autophagy effects were studied by electron microscopy as well as western blot. Effects on cell cycle were evaluated by flow cytometry using Annexin V/propidium iodide (PI) staining. Transwell migration assay and in vitro wound healing assay were performed to study the effects on cell migration and invasion, respectively.

Results: The results indicated that pectolinarigenin inhibited significantly the growth of the SK-HEP-1 liver cancer cells and exhibited an IC50 of 10 µM, while against normal cells the cytotoxic effects were much less pronounced. Further, it was observed that the anticancer effects of pectolinarigenin were due to induction of autophagy which was also associated with upregulation of the expression of Beclin-1, LC3-I and LC3-II. Transmission electron microscopy showed the formation of autophagosomes and vesicles. Pectolinarigenin also caused arrest of the SK-HEP-1 cells at the G2/M-phase of the cell cycle. Wound healing and transwell assays showed pectolinarigenin suppressed the migration and invasive potential of the SK-HEP-1 cells.

Conclusions: The present study revealed that pectolinarigenin exhibits antitumor activity in SK-HEP-1 liver cancer cells via multiple mechanisms and may prove promising in the development of systemic therapy for liver cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
December 2020

Intermedin attenuates cardiomyocytes hypoxia-injury through upregulating long noncoding RNA MALAT1.

J Cell Biochem 2020 Jan 6. Epub 2020 Jan 6.

Department of Cardiovascular Medicine, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China.

Myocardial infarction (MI) is a life-threatening cardiovascular disease, and the prognosis is far from satisfied. It is reported that the protective role of intermedin (IMD), a bioactive peptide, in cardiomyocytes. Nevertheless, its mechanism remains unclear. In vitro hypoxia cell model was established according to the alteration of cell survival. Cell counting kit-8, Western blot, and flow cytometry assay were used to test cell viability, proliferation and apoptosis. Then, the toxicity of IMD was analyzed, the functions of IMD on hypoxia-injury were explored. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was utilized for measurements of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) expression in cells under hypoxia with or without IMD pretreatment. Whether IMD affected H9c2 cells through regulating MALAT1 was studied, and the possible involved signaling pathways were investigated. We found that hypoxia-caused decline of proliferation and the rise of apoptosis were remitted by IMD pretreatment. Hypoxia enhanced MALAT1 expression. MALAT1 expression was upregulated by IMD pretreatment. It was proved that functions of IMD pretreatment in hypoxia-induced H9c2 cells could be reversed by MALAT1 inhibition. Western blot analysis investigated IMD pretreatment elevated phosphorylated levels of phosphatidylinositol-3-kinase (PI3K) and AKT as well as β-catenin levels through upregulating MALAT1. It was the first time found that IMD pretreatment could effectively remit H9c2 cell hypoxia-caused injury via the upregulation of MALAT1and PI3K/AKT and β-catenin pathways.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcb.29642DOI Listing
January 2020

The expression of p-p62 and nuclear Nrf2 in esophageal squamous cell carcinoma and association with radioresistance.

Thorac Cancer 2020 01 21;11(1):130-139. Epub 2019 Nov 21.

Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.

Background: The roles of p62-Keap1-Nrf2 pathway in the radioresistance of esophageal squamous cell carcinoma (ESCC) have not yet been revealed. This study aimed to clarify the expression and correlation of p-p62 and nuclear Nrf2 and their association with radioresistance in ESCC.

Methods: This study included 164 cases of inoperable locally advanced ESCC. All patients received concurrent chemoradiotherapy (CCRT). Immunohistochemical staining was used to detect the expression of p-p62 and nuclear Nrf2. The results were analyzed independently by two pathologists.

Results: There was no significant relationship between p-p62 or nuclear Nrf2 and patients' clinical characteristics. Compared to patients with low expression of p-p62, patients with high expression of p-p62 showed lower objective response rate (ORR). Similarly, patients with high expression of nuclear Nrf2 exhibited lower ORR compared to those with low expression of nuclear Nrf2. The expression of p-p62 was positively correlated with that of nuclear Nrf2. Moreover, the correlation coefficient between them was higher among patients showing no response to CCRT. Univariate analysis revealed that higher expression of p-p62 or nuclear Nrf2 was significantly associated with poorer PFS and OS. Multivariate analysis indicated that the expression of nuclear Nrf2 and treatment response were independent prognostic factors for PFS. Sex, treatment response, expression of p-p62 and nuclear Nrf2 were independent prognostic factors for OS.

Conclusion: Higher expression of p-p62 and nuclear Nrf2 are associated with lower ORR as well as poorer prognosis, which indicates that p62-Keap1-Nrf2 pathway might play an essential role in the radioresistance of ESCC.

Key Points: The expression of p-p62 and nuclear Nrf2 in ESCC show a significant relationship with patients' responses to CCRT and influence the prognosis of ESCC. p62-Keap1-Nrf2 pathway might be a new target for radiosensitization in ESCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1759-7714.13252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6938765PMC
January 2020

MicroRNA-132 protects H9c2 cells against oxygen and glucose deprivation-evoked injury by targeting FOXO3A.

J Cell Physiol 2020 01 18;235(1):176-184. Epub 2019 Jun 18.

Department of Cardiology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China.

Myocardial ischemia/reperfusion injury (MIRI) is a clinically familiar disease, which possesses a great negative impact on human health. But, the effective treatment is still absent. MicroRNAs (miRNAs) have been testified to play a momentous role in MIRI. The purpose of the study aimed to probe the functions of miR-132 in oxygen and glucose deprivation (OGD)-evoked injury in H9c2 cells. miR-132 expression in H9c2 cells accompanied by OGD disposition was evaluated via real-time quantitative polymerase chain reaction. After miR-132 mimic and inhibitor transfections, the impacts of miR-132 on OGD-affected H9c2 cell viability, apoptosis, cell cycle, and the interrelated factors were appraised by exploiting cell counting kit-8, flow cytometry, and western blot analysis. FOXO3A expression was estimated in above-transfected cells, meanwhile, the correlation between miR-132 and FOXO3A was probed by dual-luciferase report assay. Ultimately, above mentioned cell processes were reassessed in H9c2 cells after preprocessing OGD administration and transfection with si-FOXO3A and si-NC plasmids. We got that OGD disposition obviously enhanced miR-132 expression in H9c2 cells. Overexpressed miR-132 evidently reversed OGD-evoked cell viability repression and apoptosis induction in H9c2 cells. In addition, overexpressed miR-132 mitigated OGD-evoked G0/G1 cell arrest by mediating p21, p27, and cyclin D1 expression. Repression of FOXO3A was observed in miR-132 mimic-transfected cells, which was also predicated as a direct gene of miR-132. We discovered that silenced FOXO3A alleviated OGD-evoked cell injury in H9c2 cells via facilitating cell viability, hindering apoptosis and restraining cell arrest at G0/G1 phase. In conclusion, these investigations corroborated that miR-132 exhibited the protective impacts on H9c2 cells against OGD-evoked injury via targeting FOXO3A.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcp.28956DOI Listing
January 2020

Spasmolytic activity of Aquilariae Lignum Resinatum extract on gastrointestinal motility involves muscarinic receptors, calcium channels and NO release.

Pharm Biol 2018 Dec;56(1):559-566

b School of Pharmaceutical Science and Technology , Tianjin University , Tianjin , China.

Context: Aquilariae Lignum Resinatum (ALR), the dry rhizome of Aquilaria agallocha R. (Thymelaeaeeae), has been widely used to treat emesis, stomachache and gastrointestinal dysfunction.

Objective: This study evaluates the effects of ALR methanol extract on gastrointestinal motility (GIM) and possible mechanisms of the action involved.

Materials And Methods: In vivo, the study evaluated the effects of ALR (200-800 mg/kg) on gastric emptying and small intestinal motility in normal and neostigmine-induced adult KM mice. The in vitro effects of ALR (0.2-1.6 mg/mL) on GIM were performed on isolated jejunum of Wistar rats, pretreated with acetylcholine (ACh), KCl, CaCl, and pre-incubation with l-NAME (a selective inhibitor of the nitric oxide synthase).

Results: In vivo, ALR (800 mg/kg) decreased gastric emptying (70.82 ± 9.81%, p < 0.01, compared with neostigmine group 91.40 ± 7.81%), small intestinal transit (42.82 ± 3.82%, p < 0.01, compared with neostigmine group 85.53 ± 5.57%). In vitro, ALR concentration dependently decreased the contractions induced by ACh (10 M) and KCl (60 mM) with respective EC values of 0.35 and 0.32 mg/mL. The Ca concentration-response curves were shifted by ALR to the right, similar to that caused by verapamil (the positive). The spasmolytic activity of ALR was inhibited by pre-incubation with l-NAME.

Discussion And Conclusions: ALR played a spasmolytic role in GIM, which is probably mediated through inhibition of muscarinic receptors, blockade of Ca influx and NO release. This is the first study presenting a comprehensive description of the effects of ALR on GIM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/13880209.2018.1492000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6292371PMC
December 2018

Protective effect of magnolol on oxaliplatin-induced intestinal injury in mice.

Phytother Res 2019 Apr 13;33(4):1161-1172. Epub 2019 Mar 13.

Tianjin Key Laboratory for Modern Drug Delivery and High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, China.

Oxaliplatin (OXL) is the first line treatment therapy for gastrointestinal (GI) cancers and often combines with other chemotherapy. However, few reports have studied on its GI toxicity. Magnolol (MG), one of the mainly active constituents in Magnolia, has been reported to treat digestive diseases. Therefore, the purpose of this study is to evaluate the intestinal protective effect of MG in OXL treatment group. OXL administration mice showed body weight loss, diarrhea, and intestinal damage characterized by the shortening of villi and destruction of intestinal crypts, as well as the colon length change. MG significantly reduced body weight loss, alleviated diarrhea, reversed histopathological changes, and prevented colon length reduction. Oxidative stress and inflammation were activated after OXL, and these responses were repressed by MG through increasing the activities of superoxide dismutase, glutathione peroxidase, and glutathione, decreasing level of nuclear factor of kappa b and downregulating the following pro-inflammatory cytokines. Although the expression of tight junction protein occludin and numbers of proliferative crypt cells were reduced on ileum and colon after OXL, MG administration promoted these expressions. The fecal gut microbiota composition disturbed by OXL was significantly reversed by MG. Thus, MG could prevent the development and progression of mucositis induced by oxaliplatin through multipathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ptr.6311DOI Listing
April 2019

The protective effects of Aquilariae Lignum Resinatum extract on 5-Fuorouracil-induced intestinal mucositis in mice.

Phytomedicine 2019 Feb 20;54:308-317. Epub 2018 Jul 20.

School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China. Electronic address:

Background: Aquilariae Lignum Resinatum as a traditional Chinese medicine is used in prescription for treatment of gastrointestinal diseases. Phytochemical investigations show that there are many anti-ulcer and anti-inflammatory ingredients in A. agallocha methanol extract (AEE). However, scarce data is available about the constituents absorbed into the blood, activity and mechanisms of AEE on intestinal mucositis.

Hypothesis/purpose: To analyze the bioactive constituents of AEE absorbed in the blood, and further explore the potential mechanisms of the protection against chemotherapy-induced intestinal mucositis.

Methods: The serum pharmacochemistry using UHPLC-Q-TOF/MS was performed to screen the bioactive compounds of AEE absorbed in serum. The intestinal mucositis was induced by 5-Fuorouracil (5-Fu) and treated with AEE. The severity of intestinal mucositis was evaluated based on body weight, food-intake and diarrhea. Furthermore, the mechanism of AEE was investigated involved in the pathogenesis of mucositis on repairing injury of intestinal mucosa, immune functions, and inflammatory response.

Results: Altogether, 11 components were identified or tentatively characterized in dosed plasma. In pharmacodynamics study, intestinal mucositis caused by 5-Fu was effectively attenuated after AEE treatment. AEE treatment improved food-intake and injury of the intestinal mucosa, relieved body weight loss and severe diarrhea through up-regulating expression of proliferating cell nuclear antigen (PCNA) and inhibiting the levels of cyclooxygenase-2 (COX-2) and tumor necrosis factor-α (TNF-α) in ileum segments.

Conclusions: AEE protected against 5-Fu-induced intestinal mucositis (IM) in mice through mechanisms that involved in promoting the enterocyte proliferative activity, maintaining the integrity of tight junction proteins, inhibiting oxidative stress and ameliorating the inflammatory disturbances. Accordingly, A. agallocha may be a promising therapeutic candidate used for the prevention of IM during cancer chemotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.phymed.2018.07.006DOI Listing
February 2019

Astragaloside IV Protects Rat Cardiomyocytes from Hypoxia-Induced Injury by Down-Regulation of miR-23a and miR-92a.

Cell Physiol Biochem 2018 26;49(6):2240-2253. Epub 2018 Sep 26.

Department of Cardiovascular Internal Medicine, China-Japan Union Hospital of Jilin University, Changchun, China.

Background/aims: Astragaloside IV (AS-IV), a traditional Chinese medicine isolated from Astragalus membranaceus, has been shown to exert cardioprotective effect previously. This study aimed to reveal the effects of AS-IV on hypoxia-injured cardiomyocyte.

Methods: H9c2 cells were treated with various doses of AS-IV for 24 h upon hypoxia. CCK-8 assay, flow cytometry/Western blot, and qRT-PCR were respectively conducted to measure the changes in cell viability, apoptosis, and the expression of miR-23a and miR-92a. Sprague-Dawley rats were received coronary ligation, and were administrated by various doses of AS-IV for 14 days. The infarct volume and outcome of rats followed by ligation were tested by ultrasound, arteriopuncture and nitrotetrazolium blue chloride (NBT) staining.

Results: We found that 10 μg/ml of AS-IV exerted myocardioprotective effects against hypoxia-induced cell damage, as AS-IV significantly increased H9c2 cells viability and decreased apoptosis. Interestingly, the myocardioprotective effects of AS-IV were alleviated by miR-23a and/or miR-92a overexpression. Knockdown of miR-23a and miR-92a activated PI3K/AKT and MAPK/ ERK signaling pathways. Bcl-2 was a target gene for miR-23a, and BCL2L2 was a target gene for miR-92a. In the animal model of myocardial infarction (MI), AS-IV significantly reduced the infarct volume, ejection fraction (EF), shortening fraction (FS) and LV systolic pressure (LVSP), and significantly increased left ventricular end-diastolic internal diameter (LVEDd). And also, the elevated expression of miR-23a and miR-92a in MI rat was reduced by AS-IV.

Conclusion: AS-IV protected cardiomyocytes against hypoxia-induced injury possibly via down-regulation of miR-23a and miR-92a, and via activation of PI3K/AKT and MAPK/ERK signaling pathways.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000493827DOI Listing
October 2018

Nrf2 and Keap1 abnormalities in esophageal squamous cell carcinoma and association with the effect of chemoradiotherapy.

Thorac Cancer 2018 06 19;9(6):726-735. Epub 2018 Apr 19.

Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, China.

Background: The Keap1-Nrf2 pathway is a key antioxidant and redox signaling cascade. Pathway abnormalities enhance the reactive oxygen species scavenging ability of cancer cells; thus the pathway is involved in carcinogenesis and resistance to chemoradiotherapy (CRT). This retrospective study was conducted to examine the status of the Keap1-Nrf2 pathway in locally advanced esophageal squamous cell carcinoma (ESCC) and to analyze its prognostic value in patients receiving CRT.

Methods: Nrf2 and Keap1 expression were immunohistochemically examined in 152 ESCC and 31 normal esophageal mucosae. All ESCC specimens were obtained from patients with locally advanced ESCC who underwent CRT.

Results: Strong staining of nuclear and cytoplasmic Nrf2 and limited or absent Keap1 expression was uncommon in normal tissues, but frequently observed in ESCC. Interaction between Nrf2 and Keap1 in normal mucosae is negatively correlated, while in tumors there is no negative correlation, indicating that there is little to no interaction between Nrf2 and Keap1 in ESCC. Positive Nrf2 expression in the nucleus was of diagnostic value for predicting ESCC from normal esophageal mucosae, and was significantly associated with poorer clinical response and poor progression-free survival after CRT. The value of Keap1 expression for diagnosis and predicting CRT outcomes was marginal. These different influences of Keap1 and Nrf2 on ESCC indicated that the signaling of this pathway was disturbed and displayed a Keap1-independent pattern.

Conclusion: Aberrant signaling via the Keap1-Nrf2 pathway was common in ESCC and was associated with response and survival after CRT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1759-7714.12640DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5983206PMC
June 2018

Stereotactic ablative radiotherapy in treatment of early-stage non-small cell lung cancer: Unsolved questions and frontiers ahead.

Cancer Lett 2017 08 16;401:46-52. Epub 2017 May 16.

Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan 250117, Shandong Province, PR China. Electronic address:

Stereotactic ablative radiotherapy (SABR) has been recognized as a standard alternative treatment to surgery for inoperable early stage non-small cell lung cancer (NSCLC). Guaranteed local control rates over 90% makes oncologists wonder whether SABR is qualified enough to challenge surgery in operable patients. The role of SABR for centrally located lesions would be another question because of the increased risk of severe toxic effect. Plenty of studies suggest that optimization of dose regimen and appropriate case selection would be helpful. Additionally, the effect of adjuvant therapy following SABR in selected patients is worth looking forward, given that it significantly reduced risk of recurrence after complete resection. A consensus about salvage treatment after SABR also needs, given the current diversity of options. Finally, witnessing the emergence of proton therapy and immunotherapy, we believe that the future of SABR lay behind these novel forms of treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.canlet.2017.04.039DOI Listing
August 2017

Better cancer specific survival in young small cell lung cancer patients especially with AJCC stage III.

Oncotarget 2017 May;8(21):34923-34934

Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan 250117, China.

It has been reported that younger patients with non-small cell lung cancer (NSCLC) tend to have a better prognosis. Yet, few studies have focused on the clinicopathological characteristics and prognosis of young small cell lung cancer (SCLC), especially for patients with age < 50. In our study, we used Surveillance, Epidemiology, and End Results (SEER) population-based data and identified 16503 patients with SCLC including 711 patients aged < 50, 3338 patients aged 50-59, 5937 patients aged 60-69, 4649 patients aged 70-79 and 1868 patients aged ≥ 80 between 2010 and 2013. The Kaplan-Meier methods was used to develop the survival curve, and the results showed that the SCLC patients with aged < 50 tended to a better over survival (OS) and cancer specific survival (CSS) (all, P < 0.001). In addition, Cox regression model was used to analyze survival prognosis factors and perform subgroup analysis. The results showed that age was an independent prognostic factor for CSS (P < 0.001). Importantly, we found that for the patients with AJCC stage III subgroup, the age < 50 had apparent CSS benefit compared with any other age group (all, P < 0.01). Interestingly, for the patients with no surgery, radiation and no radiation subgroup, the age < 50 had no apparent CSS benefit only compared with age 50-59 (all, P > 0.05). In conclusion, our study demonstrated that the SCLC patients with aged < 50 tended had a better survival benefit, especially for patients with AJCC stage III.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.16823DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5471022PMC
May 2017

Significant efficacy and well safety of apatinib in an advanced liver cancer patient: a case report and literature review.

Oncotarget 2017 Mar;8(12):20510-20515

Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Jinan, China.

Apatinib is a novel and highly selective tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2. Previous studies have suggested that apatinib is safe and effective in some solid tumors. We report one case with advanced hepatocellular carcinoma (HCC), who received apatinib combined with transhepatic arterial chemotherapy and embolization (TACE), and chemotherapy respectively. TACE was administered three times once a month, using lipiodol 10ml, oxaliplatin 150mg, and tegafur 1g. The dose of apatinib was 500 mg/d from day 4 to 24. After TACE, the patient received chemotherapy of regimen FOLFOX4, oxaliplatin intravenously at 85 mg/m2 on day 1, calcium levofolinate 200 mg/m2 on day 1 and 2, 5-fluorouracil 400 mg/m2 intravenously and 5-fluorouracil 600 mg/m2 intravenously pumped for 22h on day 1 and 2, cycled every two weeks for seven cycles. He took concurrently apatinib with a dose of 500mg daily from 1 to 10 days per cycle. He was confirmed as partial response (PR) by the Response Evaluation Criteria in Solid Tumors (RECIST). The level of serum alpha-fetoprotein (AFP) decreased from 60500 ng/ml to 12.7 ng/ml, and the progression free survival (PFS) time was more than eight months. It indicated that apatinib may be a superior choice for HCC patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.14724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5386780PMC
March 2017

The prognosis analysis of different metastasis pattern in patients with different breast cancer subtypes: a SEER based study.

Oncotarget 2017 Apr;8(16):26368-26379

Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Shandong 250117, China.

Studies on prognosis of different metastasis patterns in patients with different breast cancer subtypes (BCS) are limited. Therefore, we identified 7862 breast cancer patients with distant metastasis from 2010 to 2013 using Surveillance, Epidemiology, wand End Results (SEER) population-based data. The results showed that bone was the most common metastatic site and brain was the least common metastatic site, and the patients with HR+/HER2- occupied the highest metastasis proportion, the lowest metastasis proportion were found in HR-/HER2+ patients. Univariate and multivariate logistic regression analysis were used to analyze the association, and it was found that there were significant differences of distant metastasis patterns in patients with different BCS(different P value). Importantly, univariate and multivariate Cox regression analysis were used to analyze the prognosis. It was proven that only bone metastasis was not a prognostic factor in the HR+/HER2-, HR+/HER2+ and HR-/HER2+ subgroup (all, P > 0.05), and patients with brain metastasis had the worst cancer specific survival (CSS) in all the subgroups of BCS (all, P<0.01). Interestingly, for patients with two metastatic sites, those with bone and lung metastasis had best CSS in the HR+/HER2- (P<0.001) and HR+/HER2+ subgroups (P=0.009) However, for patients with three and four metastatic sites, there was no statistical difference in their CSS (all, P>0.05).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.14300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5432264PMC
April 2017

Prunella vulgaris L., an Edible and Medicinal Plant, Attenuates Scopolamine-Induced Memory Impairment in Rats.

J Agric Food Chem 2017 Jan 3;65(2):291-300. Epub 2017 Jan 3.

Tianjin Key Laboratory for Modern Drug Delivery and High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University , Tianjin 300072, China.

Prunella vulgaris L. is as a major plant in the Chinese traditional functional beverage Guangdong herbal tea for the treatment of fevers, diarrhea, and sore mouth. In this study, ethyl acetate parts of aqueous extracts from P. vulgaris L. (EtOAc-APV) were found to demonstrate potent acetylcholinesterase (AChE) inhibition in vitro. Therefore, this study was designed to further investigate the effects of EtOAc-APV on scopolamine (SCOP)-induced aging rats. Male Wistar rats were randomly divided into four groups (n = 12) and given orally by gavage EtOAc-APV (100 mg/kg) for 3 weeks. SCOP (1 mg/kg, ip) was administered to rats 30 min before starting behavioral tests consecutively for 3 days. EtOAc-APV could attenuate SCOP-induced brain senescence in rats by improving behavioral performance and decreasing brain cell damage, which was associated with a notable reduction in AChE activity and MDA level, as well as an increase in SOD and GPx activities. Additionally, EtOAc-APV administration could reduce the expression of NF-κB and GFAP, which showed an anti-neuroinflammatory effect on the SCOP-treated rat. Overall, the current study highlights P. vulgaris L. as an antidementia dietary supplement.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jafc.6b04597DOI Listing
January 2017

Transcriptome-Based Discovery of Fusarium graminearum Stress Responses to FgHV1 Infection.

Int J Mol Sci 2016 Nov 17;17(11). Epub 2016 Nov 17.

State Key Laboratory for Biology of Plant Disease and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Science, Beijing 100081, China.

Fusarium graminearum hypovirus 1 (FgHV1), which is phylogenetically related to Cryphonectria hypovirus 1 (CHV1), is a virus in the family that infects the plant pathogenic fungus . Although hypovirus FgHV1 infection does not attenuate the virulence of the host (hypovirulence), it results in defects in mycelial growth and spore production. We now report that the vertical transmission rate of FgHV1 through asexual spores reached 100%. Using RNA deep sequencing, we performed genome-wide expression analysis to reveal phenotype-related genes with expression changes in response to FgHV1 infection. A total of 378 genes were differentially expressed, suggesting that hypovirus infection causes a significant alteration of fungal gene expression. Nearly two times as many genes were up-regulated as were down-regulated. A differentially expressed gene enrichment analysis identified a number of important pathways. Metabolic processes, the ubiquitination system, and especially cellular redox regulation were the most affected categories in challenged with FgHV1. The p20, encoded by FgHV1 could induce H₂O₂ accumulation and hypersensitive response in leaves. Moreover, hypovirus FgHV1 may regulate transcription factors and trigger the RNA silencing pathway in .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms17111922DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5133918PMC
November 2016

Ferulic acid ameliorates memory impairment in d-galactose-induced aging mouse model.

Int J Food Sci Nutr 2016 Nov 26;67(7):806-17. Epub 2016 Jun 26.

a School of Pharmaceutical Science and Technology , Tianjin University , Tianjin , China ;

Ferulic acid (FA) acts as a powerful antioxidant against various age-related diseases. To investigate the effect and underlying mechanism of FA against d-galactose(d-gal)-induced memory deficit, mice were injected with d-gal to induce memory impairment and simultaneously treated with FA and donepezil. The behavioral results revealed that chronic FA treatment reversed d-gal-induced memory impairment. Further, FA treatment inhibited d-gal-induced AChE activity and oxidative stress via increase of superoxide dismutase activity and reduced glutathione content, as well as decrease of malondialdehyde and nitric oxide levels. We also observed that FA significantly inhibits inflammation in the brain through reduction of NF-κB and IL-1β by enzyme-linked immunosorbent assay. Additionally, FA treatment significantly reduces the caspase-3 level in the hippocampus of d-gal-treated mice. Hematoxylin and eosin and Nissl staining showed that FA prevents neurodegeneration induced by d-gal. These findings showed that FA inhibits d-gal-induced AChE activity, oxidative stress, neuroinflammation and neurodegeneration, and consequently ameliorates memory impairment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/09637486.2016.1198890DOI Listing
November 2016

Study on the mechanisms of the bronchodilator effects of Folium Eriobotryae and the selected active ingredient on isolated guinea pig tracheal strips.

Pharm Biol 2016 Nov 1;54(11):2742-2752. Epub 2016 Jun 1.

a Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology , Tianjin University , Tianjin , China.

Context: Folium Eriobotryae (FE), the dry leaf of Eriobotrya japonica (Thunb.) Lindl. (Rosaceae), has been widely used to treat respiratory disorders.

Objective: To examine the bronchodilatory activity of FE and the potential mechanisms involved.

Materials And Methods: The effects of ethyl acetate fraction of FE (EFE) (0.05-0.3 mg/mL) on the isolated tracheal strips, and ursolic acid (UA) (5-30 μg/mL) that was the main constituent of EFE, were tested in vitro. Meanwhile, acetylcholine (Ach) and histamine (His)-induced bronchospasm were conducted in vivo in guinea pig. Furthermore, mechanisms of relaxant effects of EFE and UA were evaluated in the absence and presence of specific inhibitors.

Results: With in vitro studies, the contractile response evoked by Ach or His (EC=0.21 and 0.16 mg/mL) was decreased by EFE, and UA caused a concentration-dependent relaxation precontracted by His (EC=23.2 μg/mL). With in vivo studies, EFE strongly prolonged preconvulsive time similar to isoprenalin. The bronchodilator effects of EFE could be blocked by propranolol (1 μM), N-nitro-l-arginine methyl ester (l-NAME) (100 μM) and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one (ODQ) (1 μM). EFE also inhibited the contraction in Ca-free medium and produced rightward parallel displacement of CaCl curves. In addition, the relaxant effects of UA could only be blocked by l-NAME and ODQ.

Discussion And Conclusion: These results suggest that bronchodilator activities of EFE were related to activation of β-adrenoceptor and NO/cGMP pathway. Blockage of Cachannels and inhibition of IPR-mediated internal Carelease were also involved. Additionally, UA produced relaxant effects by the NO/cGMP pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/13880209.2016.1183134DOI Listing
November 2016

Protective effect and potential mechanisms of Wei-Chang-An pill on high-dose 5-fluorouracil-induced intestinal mucositis in mice.

J Ethnopharmacol 2016 Aug 27;190:200-11. Epub 2016 May 27.

School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China. Electronic address:

Ethnopharmacological Relevance: Wei-Chang-An pill (WCA pill), a traditional Chinese pharmaceutical preparation, possessed potential anti-inflammatory advantages and noteworthy gastrointestinal regulations in digestive diseases, which might represent a promising candidate for the treatment of intestinal mucositis (IM) induced by 5-fluorouracil (5-FU).

Aim Of The Study: To analyze the bioactive constituents and investigate the effect of methanol extraction from WCA pill (WCA ext) on 5-FU induced IM with underlying mechanisms.

Materials And Methods: The analysis of serum bioactive constituents after WCA ext administration in rats was carried out by UHPLC-Quadrupole-Time of Flight-Mass Spectrometry. In mice, IM was induced by 5-FU and physical manifestations were measured during the period of drug delivery. Half of mice were assessed with histology, expression of inflammatory cytokines in ileum and plasma via hematoxylin and eosin staining, immunohistochemical staining as well as cytokine enzyme-linked immunosorbent assay test, respectively. Besides, gastric emptying (GE) and gastrointestinal transit (GIT) were further tested in the other half of 5-FU induced mice.

Results: Twenty-two compounds were identified or tentatively characterized. IM induced by 5-FU was improved significantly after treatment with WCA ext through reducing the body weight loss, relieving the severe diarrhea, and inhibiting the GE as well as GIT. Further assessments validated that WCA ext promoted the recovery of intestinal mucosa, evaluated the activity of enterocyte proliferation, maintained the integrity of tight junction, and ameliorated the inflammatory disturbances.

Conclusions: These results suggested that WCA ext promoted the restoration of intestinal function in 5-FU-induced IM via regulating multiple sites of actions in intestinal homeostasis. Accordingly, WCA pill might be a promising therapeutic candidate for the prevention of IM during cancer chemotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jep.2016.05.057DOI Listing
August 2016

Generation of a high resolution map of sRNAs from Fusarium graminearum and analysis of responses to viral infection.

Sci Rep 2016 05 18;6:26151. Epub 2016 May 18.

State Key Laboratory for Biology of Plant Disease and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing, 100193, China.

Previously, we characterized F. graminearum hypovirus 1 (FgHV1) and F. graminearum hypovirus 2 (FgHV2), which are the only two hypoviruses in F. graminearum that are closely related to Cryphonectria hypovirus 1 (CHV1) and Cryphonectria hypovirus 2 (CHV2) in the Hypoviridae family. In this study, we preliminarily elucidated the RNA silencing mechanism of the F. graminearum/hypovirus system from a small RNA (sRNA) perspective by using HiSeq deep sequencing. The length distributions of F. graminearum sRNA were altered by hypoviral infection. Potential microRNA-like (milRNA) candidates were differentially expressed between the hypovirus-free and hypovirus-infected library types. Extensive virus-derived small interfering RNAs (vsiRNAs) were also principally defined. The 1,831,081 and 3,254,758 total reads generated from the FgHV1 and FgHV2 genomes in F. graminearum yielded the first high-resolution sRNA maps of fungal viruses. In addition, extensive bioinformatics searches identified a large number of transcripts that are potentially targeted by vsiRNAs, several of which were effectively down-regulated. In particular, the RNA silencing-related genes FgDicer1 and FgRdRp5 were predicted targets of FgHV1- and FgHV2-derived siRNAs, possibly revealing a novel anti-RNA silencing strategy employed by mycoviruses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/srep26151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4870495PMC
May 2016

Cerebralcare Granule(®), a Chinese Herb Compound Preparation, Attenuates D-Galactose Induced Memory Impairment in Mice.

Neurochem Res 2016 Sep 9;41(9):2199-214. Epub 2016 May 9.

Tianjin Key Laboratory for Modern Drug Delivery and High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Weijin Road, Tianjin, 300072, China.

Cerebralcare granule(®) (CG) is a preparation of Traditional Chinese Medicine that widely used in China. It was approved by the China State Food and Drug Administration for treatment of headache and dizziness associated with cerebrovascular diseases. In the present study, we aimed to investigate whether CG had protective effect against D-galactose (gal)-induced memory impairment and to explore the mechanism of its action. D-gal was administered (100 mg/kg, subcutaneously) once daily for 8 weeks to induced memory deficit and neurotoxicity in the brain of aging mouse and CG (7.5, 15, and 30 g/kg) were simultaneously administered orally. The present study demonstrates that CG can alleviate aging in the mouse brain induced by D-gal through improving behavioral performance and reducing brain cell damage in the hippocampus. CG prevents aging mainly via suppression of oxidative stress response, such as decreasing NO and MDA levels, renewing activities of SOD, CAT, and GPx, as well as decreasing AChE activity in the brain of D-gal-treated mice. In addition, CG prevents aging through inhibiting NF-κB-mediated inflammatory response and caspase-3-medicated neurodegeneration in the brain of D-gal treated mice. Taken together, these data clearly demonstrates that subcutaneous injection of D-gal produced memory deficit, meanwhile CG can protect neuron from D-gal insults and improve memory ability.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11064-016-1934-9DOI Listing
September 2016

Two Novel Relative Double-Stranded RNA Mycoviruses Infecting Fusarium poae Strain SX63.

Int J Mol Sci 2016 Apr 30;17(5). Epub 2016 Apr 30.

State Key Laboratory for Biology of Plant Disease and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing 100193, China.

Two novel double-stranded RNA (dsRNA) mycoviruses, termed Fusarium poae dsRNA virus 2 (FpV2) and Fusarium poae dsRNA virus 3 (FpV3), were isolated from the plant pathogenic fungus, Fusarium poae strain SX63, and molecularly characterized. FpV2 and FpV3, with respective genome sequences of 9518 and 9419 base pairs (bps), are both predicted to contain two discontinuous open reading frames (ORFs), ORF1 and ORF2. A hypothetical polypeptide (P1) and a RNA-dependent RNA polymerase (RdRp) are encoded by ORF1 and ORF2, respectively. Phytoreo_S7 domain (pfam07236) homologs were detected downstream of the RdRp domain (RdRp_4; pfam02123) of the ORF2-coded proteins of both FpV2 and FpV3. The same shifty heptamers (GGAAAAC) were both found immediately before the stop codon UAG of ORF1 in FpV2 and FpV3, which could mediate programmed -1 ribosomal frameshifting (-1 PRF). Phylogenetic analysis based on RdRp sequences clearly place FpV2 and FpV3 in a taxonomically unassigned dsRNA mycovirus group. Together, with a comparison of genome organization, a new taxonomic family termed Fusagraviridae is proposed to be created to include FpV2- and FpV3-related dsRNA mycoviruses, within which FpV2 and FpV3 would represent two distinct virus species.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms17050641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4881467PMC
April 2016

Evaluation of protective effects of costunolide and dehydrocostuslactone on ethanol-induced gastric ulcer in mice based on multi-pathway regulation.

Chem Biol Interact 2016 Apr 10;250:68-77. Epub 2016 Mar 10.

School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China. Electronic address:

The aim of the present study was to evaluate the anti-ulcerogenic activity of costunolide (Co) and dehydrocostuslactone (De) on ethanol-induced gastric ulcer in mice and to elucidate the potential mechanisms of the action involved. Mice were pretreated orally with Co (5 or 20 mg/kg), De (5 or 20 mg/kg) and omeprazole (OME, 20 mg/kg) for 7 consecutive days, followed by ulcer induction using absolute ethanol (0.2 mL/20 g body weight). Treatment with Co had a remarkable gastroprotection compared to the ethanol-ulcerated mice that significantly reduced the ulcerative lesion index (ULI) and histopathological damage. Daily intragastric administration of Co exerted a powerful anti-inflammatory activity as evidenced by the suppression of nuclear factor (NF)-κB, tumor necrosis factor (TNF)-α, nitric oxide (NO), inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, as well as increased interleukin (IL)-10. Also, pretreatment with Co effectively inhibited ethanol-induced malondialdehyde (MDA) overproduction, increased the depleted superoxide dismutase (SOD) and promoted gastric mucosa epithelial cell proliferation by up-regulating proliferating cell nuclear antigen (PCNA) expression. Similarly, De had a protective effect on ethanol-induced ulcer, which was dependent on the inhibition of inflammatory cytokines and MDA generation, but independent of IL-10, SOD and PCNA improvement. Conclusively, the results have clearly demonstrated the anti-ulcerogenic potential of Co and De on ethanol-induced gastric ulcer; nevertheless, the gastroprotective activity of Co was superior to De due to more multi-pathway regulation than De. These findings suggested that Co or De could be a new useful natural gastroprotective tool against gastric ulcer, which provided a scientific basis for the gastroprotection of sesquiterpene lactones.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cbi.2016.03.003DOI Listing
April 2016

Inhibitory effect and enzymatic analysis of E-cinnamaldehyde against sclerotinia carrot rot.

Pestic Biochem Physiol 2016 Feb 4;127:8-14. Epub 2015 Sep 4.

State Key Laboratory of Rice Biology, Institute of Biotechnology, Zhejiang University, Hangzhou 310058, PR China.

This study was conducted to determine the inhibitory effect of E-cinnamaldehyde (EC) against causal agent of storage carrot rot, Sclerotinia sclerotiorum, under in vivo and in vitro conditions. Based on the results, EC was able to completely inhibit mycelial growth of three isolates (P>0.05) in both volatile and contact phases after 6days at the concentrations 200μl and 1μl/ml, respectively. In addition, EC at concentrations 1 and 10μl/ml completely inhibited carpogenic germination of three isolates. The results of in vivo trials showed that EC at the concentration of 10μl/ml was able to control the disease caused by isolates 1 and 3. However the disease caused by isolate 2 was inhibited with the concentration of 20μl/ml. In enzyme analyses, the activity of polyphenoloxidase and peroxidase did not change in the inoculated carrots after application of EC. Furthermore, the level of phenylalanine ammonia lyase decreased. These results indicated that EC does not have any potential to be considered as resistance inducers against sclerotinia carrot rot.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pestbp.2015.08.005DOI Listing
February 2016

Antihypertensive and cardioprotective effects of Cerebralcare granule® on spontaneously hypertensive rats from the perspective of the gaseous triumvirate NO-CO-H2S system.

Environ Toxicol Pharmacol 2016 Jan 22;41:22-31. Epub 2015 Nov 22.

School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China.

Cerebralcare granule(®) (CG) has been reported to have hypotensive effect. However, several pathways involved in the mechanism of hypotension are still unclear. This study was designed to verify the antihypertensive effect of CG and to characterize its mechanism of action, especially from the perspective of gasotrasmmiter NO/cGMP, CO/HO and H2S/CSE systems. By using the widely used in vitro model of rat isolated thoracic aortic rings, the vasorelaxant effect of CG were studied. Furthermore, we assessed the chronic hypotensive effect of CG on spontaneously hypertensive rats (SHRs) and further to explore the potential mechanisms of its antihypertensive activity. Data in the present study demonstrated that oral treatment with CG could induce a potent antihypertensive effect. CG could reduce the intima-media thickness (IMT) of thoracic aorta significantly and increase the serum NO and H2S levels. In addition, the present results indicated that CG played a critical protective role against pressure overload-induced cardiac hypertrophy. CG not only inhibited the development of cardiac hypertrophy but also improved ventricular function. In vitro, the results showed that CG induced relaxation in rat aortic rings through an endothelium-dependent pathway mediated by NO/cGMP, CO/HO and H2S/CSE systems. Taken together, the present study demonstrated that CG could induce a potent antihypertensive effect that was partly due to the improvement of endothelial function. Also CG played a critical protective role against pressure overload-induced cardiac hypertrophy. In addition, CG could induce relaxation in rat aortic rings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.etap.2015.11.010DOI Listing
January 2016

Protective effect of tetrahydropalmatine against d-galactose induced memory impairment in rat.

Physiol Behav 2016 Feb 22;154:114-25. Epub 2015 Nov 22.

Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China. Electronic address:

Aging is associated with Alzheimer's disease (AD), cardiovascular disease and cancer. Oxidative stress is considered as a major factor that accelerates the aging process. d-galactose (d-gal), a reducing sugar, induces oxidative stress resulting in alteration in mitochondrial dynamics and apoptosis of neurons. To understand the ability of tetrahydropalmatine (THP) to ameliorate memory impairment caused by aging, we investigated the effect of THP on d-gal induced memory impairment in rats. Subcutaneous injection of d-gal (100mg/kg/d) for 8weeks caused memory loss as detected by the Morris water maze and morphologic abnormalities of neurons in the hippocampus regions and cortex of rat brain. THP treatment ameliorated d-gal induced memory impairment associated with the decrease of malondialdehyde (MDA) and nitric oxide (NO) contents, as well as the increase of glutathione (GSH) levels, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities. THP treatment was also found to reverse the abnormality of acetylcholine (ACh) levels and acetylcholinesterase (AChE) activities. In addition, treatment with THP could decrease the expression of nuclear factor κ (NF-κB) and glial fibrillary acidic protein (GFAP) which prevented the neuroinflammation and memory impairment in the d-gal treated rats. Taken together, these results clearly demonstrated that subcutaneous injection of d-gal produced memory deficits, meanwhile THP could protect neuron from d-gal insults and improve cognition. This study provided an experimental basis for clinical application of THP in AD therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.physbeh.2015.11.016DOI Listing
February 2016

Vasorelaxant effects of Shunaoxin pill are mediated by NO/cGMP pathway, HO/CO pathway and calcium channel blockade in isolated rat thoracic aorta.

J Ethnopharmacol 2015 Sep 31;173:352-60. Epub 2015 Jul 31.

School of Pharmaceutical Science and Technology, Tianjin University, Weijin Road, Tianjin 300072, China. Electronic address:

Ethnopharmacological Relevance: Shunaoxin pill (SNX), one of the famous classical recipes in traditional Chinese medicine, is developed from the "Decoction of Xionggui". It has been used for treatment of cerebrovascular related diseases. It is well known that vasodilatation plays a very important role in cerebrovascular diseases. The effect of SNX on vasorelaxant activity has not yet been explored. Therefore, we aimed to investigate the vasorelaxant effects of SNX on isolated rat thoracic aorta so as to assess some of the possible mechanisms. We also investigate the gasotransmitter signaling pathway involved which has been rarely reported in isolated rat thoracic aorta before.

Aim Of The Study: The present study was performed to examine the vasodilative activity of SNX and its mechanisms in isolated rat thoracic aorta.

Materials And Methods: SNX was studied on isolated rat thoracic aorta in vitro, including endothelium-intact and endothelium-denuded aortic rings. In present study, specific inhibitors including soluble guanylate cyclase (sGC) inhibitor 1 H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one (ODQ), cyclooxygenase (COX) inhibitor indomethacin (INDO), NO synthase inhibitor NG-nitro-l-arginine methyl ester (L-NAME), heme oxygenase-1 (HO-1) inhibitor zinc-protoporphyrin (ZnPP), cystathionine γ-lyase (CSE) inhibitor DL-Propargylglycine (PAG), non-selective K(+) channel inhibitor tetraethylammonium chloride (TEA), KV channel inhibitor 4-Aminopyridine (4-AP), and KATP channel inhibitor Glibenclamide (Gli) were used, they were added 20min before NE contraction and then added SNX to induce vasodilation.

Results: Removal of endothelium or pretreatment of aortic rings (intact endothelium) with L-NAME, ODQ or ZnPP significantly blocked SNX-induced relaxation. Pretreatment with the non-selective K(+) channel inhibitor TEA, KV channel inhibitor 4-AP or the KATP channel inhibitor Gli, none of them had influences on the SNX-induced response (p>0.05). Besides, SNX inhibited the contraction triggered by NE in endothelium-denuded rings in Ca(2+)-free medium. SNX also produced rightward parallel displacement of CaCl2 curves.

Conclusions: These results suggest that SNX can induce less endothelium-dependent and more endothelium-independent vascular relaxation. The NO/cGMP and HO/CO pathways, blockade of Ca(2+) channels are inhibition of IP3R mediated Ca(2+) mobilization from intracellular stores, are likely involved in this relaxation. Furthermore, the underlying mechanisms of combined compositions in SNX await further investigations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jep.2015.07.048DOI Listing
September 2015

The influence of compatibility of processed radix Aconiti Kusnezoffii on the pharmacokinetic of four components in Glycyrrhiza uralensis Fisch.

J Ethnopharmacol 2015 Jul 16;169:1-7. Epub 2015 Apr 16.

Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China.

Ethnopharmacological Relevance: Glycyrrhiza uralensis Fisch. and processed radix Aconiti kusnezoffii are the main components in many Chinese traditional patent medicines with the ratio of 1:1, which are used for treatment of rheumatoid arthritis, heart failure and so on. Glycyrrhizic acid, glycyrrhetic acid, liquiritigenin and isoliquiritigenin are the essential bioactive triterpenes and flavones in the extract of G. uralensis, which were analysis by a simple but accurate method.

Materials And Methods: In the present study, a specific HPLC method was developed and validated for simultaneous determination of pharmacokinetic parameters of glycyrrhizic acid, glycyrrhetic acid, liquiritigenin and isoliquiritigenin in G. uralensis after oral administration of single herb extract and a combination of two herbs extracts respectively.

Results: The calibration curves of the four components had good linearity higher than 0.9991 in the measured range. The intra-day and inter-day precisions (RSD) at different levels were both within 9.73%, and the accuracies (RE) were in the range of -7.9-8.0%. Compared with pharmacokinetic parameters of G. uralensis administered orally, values of AUC and Cmax of liquiritigenin and isoliquiritigenin decreased significantly (p<0.05), plasma concentrations of glycyrrhizic acid rose slightly and bimodal phenomenon of concentration-time of isoliquiritigenin and glycyrrhetinic acid disappeared after combined administration.

Discussion And Conclusions: Some components in the extract of processed radix A. kusnezoffii showed different effects on the pharmacokinetics of the four ingredients in G. uralensis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jep.2015.03.059DOI Listing
July 2015

Identification of Chemical Constituents in the Extract and Rat Serum from Ziziphus Jujuba Mill by HPLC-PDA-ESI-MSn.

Iran J Pharm Res 2014 ;13(3):1055-63

The State Key Laboratories of Pharmacodynamics and Pharmacokinetics, Tianjin, 300193, China.

Chinese jujube (Ziziphus jujuba Mill.) has long been widely used for human consumption and medicinal purposes in China. It has been reported to possess several vital biological activities. However, the systematic study on the chemical constituents absorbed into plasma and their metabolites is still insufficient.A high-performance liquid chromatography-photodiode array detector-electrospray ionization ion-mass spectrometry (HPLC-PDA-ESI-MS(n)) method was established to analyze the ethanol extract in Ziziphus jujuba Mill and the constituents absorbed into rat serum. In the present study, a dose of 10 mL/Kg of ethanol extract of jujube, which is equivalent to 12.5 g crude dried herb/Kg, was orally administrated to rats. The main components were analyzed in the ethanol extract of Ziziphus jujuba Mill and the parent constituents and metabolites were studied in rat plasma samples after oral administration of the ethanol extract of jujube.D101 macroporous polystyrene resin was a good pretreatment method to obtain better separation and impurity removal effect. Twenty-two compounds were identified in the ethanol extract of Ziziphus jujuba Mill. Four parent compounds and four metabolites were detected in rat serum. Among them, seventeen compounds were reported for the first time.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4177628PMC
October 2014

Systematic Analysis of Main Constituents in Rat Biological Samples after Oral Administration of the Methanol Extract of Fructus Aurantii by HPLC-ESI-MS/MS.

Iran J Pharm Res 2014 ;13(2):493-503

The State Key Laboratories of Pharmacodynamics and Pharmacokinetics, Tianjin, 300193, China.

High performance liquid chromatography (HPLC) with diode array detection (DAD) and electrospray ionization tandem mass spectrometry (ESI/MS/MS) was used to analyze the main components in the methanol extract of Fructus Aurantii (FA) and the metabolites in rat biological samples after oral administration of the methanol extract of FA. There were 31 constituents identified in the extract of FA including 2 alkaloids, 1 coumarin, 10 flavonoid glycosides and 18 ploymethoxylated flavones. According to the UV spectrum and MS fragment character of main components in the methanol extract of FA, 18 parent constituents and 11 metabolites were tentatively identified in rat biological samples. Three groups of components in biological samples detected included flavonoid glycosides, their glucuronides and ploymethoxylated flavones. It was interested that flavonoid glycosides, their glucuronides and ploymethoxylated flavones can be investigated in rat plasma and urine, while in rat feces samples only flavonoid glycosides were detected. Triglycosyl, naringenin, neoeriocitrin, neoeriocitrin narirutin and hesperidin were the main components in rat feces which were found either in the plasma or in urine samples. However, naringin and neohesperidin were the main flavonoid glycosides which absorbed after oral administration. Except flavonoid glycosides and their glucuronides, ploymethoxylated flavones also the constituents absorbed because it was investigated mainly in rat plasma and urine but not in feces samples. The identification and elucidation of parent and metabolism components analyzed in biological samples provided the data for further pharmacological and clinical research on FA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4157024PMC
September 2014

Bidirectional effects of methanol extract of Wei-Chang-An pill on gastrointestinal transit and the spasmolytic activity on isolated rat jejunum.

J Ethnopharmacol 2014 Aug 11;155(1):203-12. Epub 2014 Jun 11.

The State Key Laboratories of Pharmacodynamics and Pharmacokinetics, Tianjin, China.

Ethnopharmacological Relevance: Wei-Chang-An pill (WCA pill), a traditional Chinese medicine, has been used for treating various gastrointestinal diseases for several decades. Despite the popular medicinal use of WCA pill, less data was available to its activity and mechanism in gastrointestinal disorders. To examine the effects of the methanol extract of WCA pill (ME) on gastrointestinal tract so as to assess some of the possible mechanisms involved in the clinical treatment.

Materials And Methods: ME was studied on gastrointestinal transit in vivo including gastric emptying and small intestinal motility in normal and neostigmine-induced mice, as well as on the isolated tissue preparations of rat jejunum in vitro.

Results: In vivo, the gastric emptying decreased and intestinal transit increased after administration of ME in normal mice. However, administration of ME accelerated the intestinal transit ranging from 0.01 to 0.8 mg/mL and reduced it at the concentration of 1.6 and 3.2 mg/mL, while the gastric emptying was inhibited throughout the concentrations in neostigmine-induced mice. in vitro, ME caused inhibitory effect on the spontaneous contraction of rat-isolated jejunum in dose-dependent manner ranging from 0.01 to 6 mg/mL and also relaxed the acetylcholine chloride (Ach, 10(-6) M)-induced and K+ (60 mM)-induced contractions. ME shifted the Ca2+ concentration-response curves to right, similar to that caused by verapamil (0.025 mM).

Conclusions: These results indicated that ME might play a bidirectional role in gastrointestinal transit modulation and the effects on isolated tissue are probably mediated through calcium influx and muscarinic receptors, which provides pharmacological basis for the clinical use of WCA pill in gastrointestinal tract disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jep.2014.05.017DOI Listing
August 2014