Stem-leaf saponins from Panax notoginseng (SLSP) comprise numerous PPD-type saponins with diverse pharmacological properties; however, their role in Parkinson's disease (PD), characterized by microglia-mediated neuroinflammation, remains unclear. This study evaluated the effects of SLSP on suppressing microglia-driven neuroinflammation in experimental PD models, including the 1-methyl-4-phenylpyridinium (MPTP)-induced mouse model and lipopolysaccharide (LPS)-stimulated BV-2 microglia. Our findings revealed that SLSP mitigated behavioral impairments and excessive microglial activation in models of PD, including MPTP-treated mice. Additionally, SLSP inhibited the upregulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX2) and attenuated the phosphorylation of PI3K, protein kinase B (AKT), nuclear factor-κB (NFκB), and inhibitor of NFκB protein α (IκBα) both in vivo and in vitro. Moreover, SLSP suppressed the production of inflammatory markers such as interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α) in LPS-stimulated BV-2 cells. Notably, the P2Y2R agonist partially reversed the inhibitory effects of SLSP in LPS-treated BV-2 cells. These results suggest that SLSP inhibit microglia-mediated neuroinflammation in experimental PD models, likely through the P2Y2R/PI3K/AKT/NFκB signaling pathway. These novel findings indicate that SLSP may offer therapeutic potential for PD by attenuating microglia-mediated neuroinflammation.
Animals ; Panax notoginseng/chemistry* ; Saponins/pharmacology* ; Microglia/immunology* ; Mice ; NF-kappa B/immunology* ; Signal Transduction/drug effects* ; Proto-Oncogene Proteins c-akt/immunology* ; Phosphatidylinositol 3-Kinases/genetics* ; Male ; Parkinson Disease/immunology* ; Mice, Inbred C57BL ; Disease Models, Animal ; Plant Leaves/chemistry* ; Neuroinflammatory Diseases/drug therapy* ; Humans

Parkinson's disease (PD) is a common neurodegenerative disease in middle-aged and elderly people. In particular, increasing evidence has showed that astrocyte-mediated neuroinflammation is involved in the pathogenesis of PD. As a precious traditional Chinese medicine, bear bile powder (BBP) has a long history of use in clinical practice. It has numerous activities, such as clearing heat, calming the liver wind and anti-inflammation, and also exhibits good therapeutic effect on convulsive epilepsy. However, whether BBP can prevent the development of PD has not been elucidated. Hence, this study was designed to explore the effect and mechanism of BBP on suppressing astrocyte-mediated neuroinflammation in a mouse model of PD. PD-like behavior was induced in the mice by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (30 mg·kg^-1) for five days, followed by BBP (50, 100, and 200 mg·kg^-1) treatment daily for ten days. LPS stimulated rat C6 astrocytic cells were used as a cell model of neuroinflammation. THe results indicated that BBP treatment significantly ameliorated dyskinesia, increased the levels of tyrosine hydroxylase (TH) and inhibited astrocyte hyperactivation in the substantia nigra (SN) of PD mice. Furthermore, BBP decreased the protein levels of glial fibrillary acidic protein (GFAP), cyclooxygenase 2 (COX2) and inducible nitric oxide synthase (iNOS), and up-regulated the protein levels of takeda G protein-coupled receptor 5 (TGR5) in the SN. Moreover, BBP significantly activated TGR5 in a dose-dependent manner, and decreased the protein levels of GFAP, iNOS and COX2, as well as the mRNA levels of GFAP, iNOS, COX2, interleukin (IL) -1β, IL-6 and tumor necrosis factor-α (TNF-α) in LPS-stimulated C6 cells. Notably, BBP suppressed the phosphorylation of protein kinase B (AKT), inhibitor of NF-κB (IκBα) and nuclear factor-κB (NF-κB) proteins in vivo and in vitro. We also observed that TGR5 inhibitor triamterene attenuated the anti-neuroinflammatory effect of BBP on LPS-stimulated C6 cells. Taken together, BBP alleviates the progression of PD mice by suppressing astrocyte-mediated inflammation via TGR5.
Humans ; Mice ; Rats ; Animals ; Aged ; Middle Aged ; Parkinson Disease/pathology* ; Astrocytes/pathology* ; Powders/therapeutic use* ; Ursidae/metabolism* ; NF-kappa B/metabolism* ; Neuroinflammatory Diseases ; Neurodegenerative Diseases/metabolism* ; Cyclooxygenase 2/metabolism* ; Lipopolysaccharides/pharmacology* ; Bile ; Mice, Inbred C57BL ; Microglia ; Disease Models, Animal

Objective:To explore the association between resting heart rate(RHR) and all-cause mortality among the Chinese oldest-old aged more than 80.Methods:Using a total of seven surveys or follow-ups data (1998, 2000, 2002, 2005, 2008, 2011 and 2014) from the Chinese Longitudinal Healthy Longevity Survey (CLHLS). A total of 17 886 elderly over 80 years old were selected as subjects, their resting heart rate were measured though baseline survey and the survival outcome and death time of the subjects were followed up. The subjects were divided into 6 groups according to their resting heart rate. Cox regression model was used to estimate the effect of resting heart rate on mortality risk. The interaction of age, gender and resting heart rate was also analyzed by likelihood ratio test.Results:The age of subjects M( P25, P75) was 92 (86, 100) years old, including 10 531 females (58.9%) and there were 13 598 participants died, the mortality rate was 195.5 per 1 000 person-years. Multivariate Cox regression analysis showed that compared to the control group (60-69 pbm/min), the hazard ratio of the elderly are 1.06 (95% CI: 1.02, 1.11), 1.09 (95% CI: 1.04, 1.15), 1.23 (95% CI: 1.14, 1.34), 1.25 (95% CI: 1.08, 1.44) in the group of RHR between 70-79, 80-89, 90-99 and ≥100 pbm/min and Pvalues are all less than 0.05. Likelihood ratio test showed that RHR and age had an interaction effect. ( P for interaction=0.011). Conclusion:The risk of all-cause death increased with the increase of resting heart rate and this relationship was stronger between the 80-89 years old people.

Objective:To explore the association between resting heart rate(RHR) and all-cause mortality among the Chinese oldest-old aged more than 80.Methods:Using a total of seven surveys or follow-ups data (1998, 2000, 2002, 2005, 2008, 2011 and 2014) from the Chinese Longitudinal Healthy Longevity Survey (CLHLS). A total of 17 886 elderly over 80 years old were selected as subjects, their resting heart rate were measured though baseline survey and the survival outcome and death time of the subjects were followed up. The subjects were divided into 6 groups according to their resting heart rate. Cox regression model was used to estimate the effect of resting heart rate on mortality risk. The interaction of age, gender and resting heart rate was also analyzed by likelihood ratio test.Results:The age of subjects M( P25, P75) was 92 (86, 100) years old, including 10 531 females (58.9%) and there were 13 598 participants died, the mortality rate was 195.5 per 1 000 person-years. Multivariate Cox regression analysis showed that compared to the control group (60-69 pbm/min), the hazard ratio of the elderly are 1.06 (95% CI: 1.02, 1.11), 1.09 (95% CI: 1.04, 1.15), 1.23 (95% CI: 1.14, 1.34), 1.25 (95% CI: 1.08, 1.44) in the group of RHR between 70-79, 80-89, 90-99 and ≥100 pbm/min and Pvalues are all less than 0.05. Likelihood ratio test showed that RHR and age had an interaction effect. ( P for interaction=0.011). Conclusion:The risk of all-cause death increased with the increase of resting heart rate and this relationship was stronger between the 80-89 years old people.

Objective:To evaluate the effect of astaxanthin on neuropathic pain in rats and the role of spinal heme oxygenase-1 (HO-1).Methods:Seventy-two SPF-grade healthy adult male Sprague-Dawley rats, weighing 200-250 g, in which intrathecal catheters were successfully implanted, were divided into 6 groups ( n=12 each) by a random number table method: blank control group (group C), sham operation group (Sham group), neuropathic pain (NP) group, NP plus dimethyl sulfoxide (DMSO) group (NP + DMSO group), NP plus astaxanthin group (NP + AST group) and NP plus zinc protoporphyrin plus astaxanthin group (NP+ ZnPP+ AST group). NP was induced by chronic constriction injury in anesthetized rats.In Sham group, the sciatic nerve was only isolated without ligation.At 5 days after establishing the model, 0.5% DMSO 10 μl was intrathecally injected in NP+ DMSO group, astaxanthin 1 μg (dissolved in 10 μl DMSO) was intrathecally injected in NP+ AST group, HO-1 inhibitor zinc protoporphyrin 24 μg (dissolved in 10 μl DMSO) was intrathecally injected, and 3 h later astaxanthin 1 μg (dissolved in 10 μl DMSO) was intrathecally injected in NP+ ZnPP+ AST group.Injection was given once a day for 10 consecutive days in the 3 groups mentioned above.The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 1 day before establishing the model and 3, 7 and 14 days after establishing the model.The rats were sacrificed at 14 days after establishing the model, and the L 4-6 lumbar segments of the spinal cord were removed for determination of the contents of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), superoxide dismutase (SOD) and glutathione peroxidase (GHS-PX)(by enzyme-linked immunosorbent assay) and expression of HO-1 (by Western blot). Results:Compared with group C and group Sham, the MWT was significantly decreased and TWL was shortened at each time point after establishing the model, the contents of TNF-α and IL-1β were increased, and the expression of HO-1 was up-regulated in the other four groups, the SOD and GSH-PX contents were significantly decreased in NP group, NP+ DMSO group and NP+ ZnPP+ AST group, and the SOD and GSH-PX contents were significantly increased in NP+ AST group ( P<0.05). Compared with NP group, the MWT was significantly increased and TWL was prolonged at 7 and 14 days after establishing the model, the contents of TNF-α and IL-1β were decreased, and the expression of HO-1 was up-regulated in NP+ AST group, the expression of HO-1 was down-regulated in NP+ ZnPP+ AST group ( P<0.05), and no significant change was found in the parameters mentioned above in NP+ DMSO group ( P>0.05). Compared with NP+ AST group, the MWT was significantly decreased and TWL was shortened at 7 and 14 days after establishing the model, the contents of SOD and GSH-PX were decreased, the contents of TNF-α and IL-1β were increased, and the expression of HO-1 was down-regulated in NP+ ZnPP+ AST group ( P<0.05). Conclusion:Astaxanthin can reduce NP in rats, and the mechanism is related to up-regulating the expression of HO-1 in the spinal cord and inhibiting oxidative stress and inflammatory responses.

Objective:To investigate the optimal time of coronary computed tomography angiography (CCTA) after taking nitroglycerine,and to provide basis for improving the image quantity of CCTA .Methods:43 patients underwent CCTA were scanned with coronary artery calcium score (CACS)after taking nitroglycerin 0,3,5 and 10 min.Then the diameters of the same coronary artery from the same anatomic location and the expanding rates were measured,and the change regular was analyzed with single factor analysis of variance of SPSS 17.0 software. Results:The average coronary artery expanding rate was 8% 3 min after taking nitroglycerin, and the difference was significant compared with 0 min (P<0.05);but there were 5 patients whose coronary artery didn’t expand. The coronary artery expanded obviously 5 and 10 min after taking nitroglycerin compared with 0 and 3 min (P<0.05);the maximum expanding rates at 5 and 10 min were both 38%.There were 13 and 28 patients whose coronary artery reached the maximum expanding rates (17% and 19%)5 and 10 min after taking nitroglycerin, respectively;the coronary artery of 2 patients expanded at a same level at 5 and 10 min.The average expanding rates of coronary artery had no significant differences between 5 and 10 min (P>0.05 ).Conclusion:Taking nitroglycerin can significantly expand the diameter of coronary arteries.It is necessary to perform CCTA during 5-1 0 min after taking nitroglycerine.

Objective To explore the safety and feasibility of blocking blood flow in interstitial tubal pregnancy treated with laparoscopic opening-taking embryo operation.Methods The clinical data of 98 patients with lump interstitial tubal pregnancies (requesting reserve procreate function) from January 2006 to December 2013 were chosen.Among them,56 patients were in study group (January 2010-December 2013) and 42 patients were in control group (January 2006-December 2009).All patients were treated with opening-taking embryo by laparoscopic operation.In study group,we first blocked the uterine artery and ovarian artery blood supply of pregnancy lump,secondly opened pregnancy lump and stripped gestation sac with hydraulic pressure separation during operation.Whereas,in control group,we opened pregnancy lump and taken out pregnancy tissues according to convention method without blocking blood flow.Operation success rate,operation blood volume,operation time,persistent ectopic pregnancy (PEP) happening rate,fallopian tube unobstructed information,and pregnancy information after operation were compared between two groups.Results In study group,operation success rate was 96.4％,which was significantly higher than that in control group (61.9％) (P ＜0.01) ; operation blood volume was[(20.7 ± 10.4)ml],which was significantly less than that in control group [(60.7 ± 18.4) ml] (P ＜ 0.01) ; operation time [(46.6 ±14.2) min] was significantly shorter than that in control group [(66.5 ± 19.4) min] (P ＜ 0.01) ; there was no PEP in study group,while there were 5 PEPs (11.9％) in control group.Fallopian tube unobstructed rate after operation in study group (76.9％) was significantly higher than that in control group (41.7％) (P ＜ 0.05).Conclusions Application of blocking blood flow in opening-taking embryo by laparoscopic operation on lump interstitial tubal pregnancies is safe and effective.

Objective: The main ingredients and the inhibitory effects of essential oil of a compound Chinese herbal medicine Weiqi Decoction (WQD) on AGS cell proliferation were to be investigated. Methods: Chemical compounds of WQD essential oil were detected by gas chromatography and mass spectrometry analysis. Cell viability was measured by methyl thiazolyl tetrazolium method. Cell cycle distribution was detected by flow cytometry. Apoptosis and necrosis of AGS cells were determined by Hoechst 33342/propidium iodine staining. Results: Chemical analysis showed that the main ingredients of WQD essential oil were bornylene and 3-n-butylphthalide. Ligustilide, which is the effective compound of Danggui (Radix Angelicae Sinensis), was not detected in WQD essential oil. The essential oil inhibited cell proliferation in a dose- and time-dependent manner, and blocked cell cycle progression at G(2)/M stage. At the concentrations that resulted in significant inhibition of cell proliferation and cell cycle arrest, essential oil induced both apoptosis and necrosis. Conclusion: The results suggest that WQD essential oil contains some effective ingredients for treating chronic atrophic gastritis and functional dyspepsia, and also has an antiproliferative effect on AGS cells through cell cycle arrest and apoptosis promotion in vitro. Therefore, essential oil should be retained as much as possible during stewing this decoction.

Objective: To investigate the effects of taraxerol and taraxeryl acetate on cell cycle and apoptosis of human gastric epithelial cell line AGS cells. Methods: The inhibitory effects of taraxerol and taraxeryl acetate at different concentrations on AGS cell growth were measured by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) method and the concentrations of taraxerol and taraxeryl acetate to be used in following experiments were decided. Then, cell cycle analysis was performed by FACScan flow cytometry after culture with taraxerol or taraxeryl acetate. Annexin V-fluorescein isothiocyanate/propidium iodide staining was used to measure cell apoptosis. Results: Taraxerol significantly inhibited AGS cell proliferation in a dose- and time-dependent manner. Taraxerol arrested the AGS cells at G(2)/M stage. 110 μmol/L taraxerol elevated the population of AGS cells arrested in G(2)/M phase compared with solvent (P<0.05). Taraxerol also promoted early cell apoptosis in AGS cells. 110 μmol/L taraxerol increased the early cell apoptosis rate from 4.45% to 10.29%, which was 1.31 times higher than that of the untreated cells. However, taraxeryl acetate had a lower inhibitory effect than taraxerol, and it showed a tendency of G(2)/M arrest and apoptosis promotion but with no statistical significance (P>0.05). Conclusion: Taraxerol has inhibitory effects on AGS cell growth through inducing G(2)/M arrest and promotion of cell apoptosis. Taraxeryl acetate has less effect on cell cycle arrest and apoptosis of AGS cells than taraxerol.

OBJECTIVETo study the effects and mechanisms of sinensetin on proliferation and apoptosis of human AGS gastric cancer cells.

METHODMTT assay was used to detect the growth inhibition rates of human AGS gastric cancer cells treated with sinsesectin in different concentrations and times. The cell cycle distribution was measured by flow cytometry. The apoptosis was examined by Annexin-FITC/PI staining and DNA fragment analysis. The apoptosis morphology was observed by inverted fluorescence microscope after Hoechst 33342 staining. The protein expressions of p21 and p53 were detected by western blot.

RESULTMTT assay showed that sinensetin inhibited the growth of AGS gastric cancer cells in a dose- and time-dependent manner. Sinensetin blocked AGS cells in G2/ M and increased the apoptosis rates of AGS cells in a dose-dependent manner. DNA ladder was observed in cells treated with 60 micromol x L(-1) sinensetin for 48 h. The typical apoptotic morphological changes including cell nucleus shrinkage, chromatin condensation and apoptotic bodies were observed when treated with different dose of sinensetin. Western blot showed that sinensetin increased expressions of p53 and p21 in a dose-dependent manner.

CONCLUSIONSinensetin could inhibit human AGS gastric cancer cells proliferation and induce cell cycle block in G2/M phase and apoptosis. The up regulation of p53 and p21 protein might be one of the mechanisms.

Apoptosis ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cyclin-Dependent Kinase Inhibitor p21 ; analysis ; Dose-Response Relationship, Drug ; Flavonoids ; pharmacology ; Humans ; Stomach Neoplasms ; drug therapy ; pathology ; Tumor Suppressor Protein p53 ; analysis