Untiring Researches for Alternative Resources of Rhizoma Paridis.

Rhizoma Paridis (RP, ), a traditional Chinese medicine, is the rhizoma of Paris polyphylla var. yunnanensis (PPY) or P. polyphylla var. chinensis which are widely used as important raw materials for several Chinese patent drugs. However, the wild resources of these herbs have become less and less due to their slow-growing characteristics and previously excessive excavation. This review covers untiring investigations on alternative resources of RP by our research group over the past decades, including non-medicinal parts of PPY as well as other plants of Liliaceae and Liliflorae families. The arial parts of PPY and the whole plants of Trillium kamtschaticum might be alternative resources for RP based on the fact that they shared the same or similar saponins and bioactivities.

Seeing the light: Shifting from wild rhizomes to extraction of active ingredients from above-ground parts of Paris polyphylla var. yunnanensis.

ETHNOPHARMACOLOGICAL RELEVANCE: The dried rhizomes of Paris polyphylla var. yunnanensis are widely used in traditional Chinese medicine (TCM) as hemostatic, antitumor, and antimicrobial agents. More than 70 Chinese patent medicines are based on P. polyphylla var. yunnanensis rhizomes. Steroidal saponins are considered as the main active ingredients of these rhizomes. However, wild populations of P. polyphylla var. yunnanensis are greatly threatened due to the illegal wild harvest and over-utilization of the rhizomes. In contrast, the renewable above-ground parts (leaves and stems) of P. polyphylla var. yunnanensis are usually thrown away as waste material, whether from wild or cultivated material. AIM OF THE STUDY: The aim of this study was to use HPLC analyses of chemical constituents and bioactive assays to assess whether the above-ground parts could be an alternative source of active ingredients to the rhizomes of P. polyphylla var. yunnanensis. MATERIALS AND METHODS: The saponin components of the rhizomes and above-ground parts of P. polyphylla var. yunnanensis were analyzed by HPLC-UV. The total saponins extracted from the rhizomes and above-ground parts of P. polyphylla var. yunnanensis were evaluated for their hemostatic, cytotoxic, and antimicrobial activities by using the rabbit blood in vitro based on turbidimetric method, MTT assay method, and a dilution antimicrobial susceptibility test method, respectively. RESULTS: Four bioactive spirostanol saponins (paris saponins I, II, VI, and VII) were detected in the total saponins from the rhizomes and above-ground parts of P. polyphylla var. yunnanensis, which indicated they should have similar pharmacological properties. The bioactive assays revealed that both the parts of P. polyphylla var. yunnanensis exhibited the same hemostatic, cytotoxic, and antimicrobial effects. CONCLUSION: Our results revealed that based on saponin content in the above-ground parts of P. polyphylla var. yunnanensis and the requirements stipulated in 2015 of Chinese Pharmacopoeia, the above-ground parts (especially its leaves) can be an alternative and more sustainable source of active ingredients compared to the rhizomes.

Effect on intensity of treadmill running on learning, memory and expressions of cell cycle-related proteins in rats with cerebral ischemia.

OBJECTIVE: We discussed the intensity of treadmill running on learning, memory and expression of cell cycle-related proteins in rats with cerebral ischemia. METHOD: Eighty healthy male SD rats were randomly divided into normal group, model group, intensity I group and intensity II group, with 20 rats in each group. The four-vessel occlusion method of Pulsinelli (4-VO) was used to induce global cerebral ischemia. Brain neuronal morphology was observed by hematoxylin-eosin (HE) staining at 3h, 6h, 24h and 48h after modeling, respectively. Hippocampal expressions of cyclin A and cyclin E were detected by immunohistochemistry. At 48h after modeling, the learning and memory performance of rats was tested by water maze experiment. RESULT: Compared with the normal group, the other three groups had a significant reduction in surviving neurons, prolonging of escape latency and decreased number of passes over the former position of the platform (P<0.05). The number of surviving neurons and the number of passes over the former position of the platform were obviously lower in the model group than in intensity I group (P<0.05), but significantly higher compared with intensity II group (P<0.05). Escape latency of the model group was obviously prolonged as compared with intensity I group (P<0.05), but much shorter than that of intensity II group (P<0.05). Compared with the normal group, the expressions of cyclin A and cyclin E were significantly upregulated at different time points after modeling (P<0.05). The expression of the model group was higher than that of intensity I group, but lower than that of intensity II group (P<0.05). CONCLUSION: Moderate intensity of treadmill running can help protect brain neurons and improve learning and memory performance of rats with global cerebral ischemia. But high intensity of treadmill running has a negative impact, possibly through the regulation of cell cycle-related proteins in ischemia/reperfusion injury.

mTOR/autophagy pathway in the hippocampus of rats suffering intermittent hypoxia preconditioning and global cerebral ischemia-reperfusion.

We explored the role of mTOR/autophagy pathway in the aggravation of cerebral ischemia-reperfusion nerve injury caused by intermittent hypoxia. Eighty male wistar rats were divided into four groups by the random number method: sham operation group (SO group, n=20), cerebral ischemia-reperfusion group (I/R group, n=20), intermittent hypoxia and cerebral ischemia-reperfusion group (IH+I/R group, n=20), intermittent hypoxia and cerebral ischemia-reperfusion group plus mTOR inhibitor group (inhibitor group, n=20).The results showed that compared with the SO group, HE staining showed structural damage of neurons at each time point, the immunohistochemical assay showed an increasing number of mTOR and beclin1 immune-positive cells (P<0.05) and RT-PCR showed enhanced expression of mTOR and beclin1 protein in the I/R group (P<0.05). Compared with the I/R group, HE staining showed exacerbating structural damage of neurons at each time point, the immunohistochemical assay showed an increasing number of mTOR and beclin1 immune-positive cells (P<0.05) and RT-PCR showed enhanced expression of mTOR and beclin1 protein in the IH+I/R group (P<0.05). Compared with the IH+I/R group, HE staining showed remissive structural damage of neurons at each time point, the immunohistochemical assay showed a decreasing number of mTOR immune-positive cells and a rising number of beclin1immune-positive cells (P<0.05) and RT-PCR showed weakened expression of mTOR protein and enhanced expression of beclin1 protein in the inhibitor group (P<0.05). Thence, the present study indicated that intermittent hypoxia preconditioning can aggravate the nerve injury of the global cerebral ischemia-reperfusion model, and the mechanism is associated with the activation of mTOR/autophagy pathway.

The mediating role of emotional intelligence between negative life events and psychological distress among nursing students: A cross-sectional study.

BACKGROUND: Previous studies have highlighted that negative life events and emotional intelligence are significant predictors of mental health. However, whether emotional intelligence mediates the relationship between negative life events and psychological distress among nursing students have not been given adequate attention. OBJECTIVES: To explore the relationship among negative life events, emotional intelligence and psychological distress and to examine the mediating role of emotional intelligence in psychological distress among Chinese nursing students. DESIGN: A cross-sectional survey using convenience sampling. SETTINGS AND PARTICIPANTS: A total of 467 nursing students who were enrolled in a university in mainland of China. METHODS: A structured questionnaire was administered from September-November in 2013 to participants who consented to participate in the study. Independent variables were personal variables, emotional intelligence and negative life events. Outcome variable was psychological health. The means and standard deviations were computed. Student's t-test and one-way analysis of variance (ANOVA) were performed, to test the differences among the demographic characteristics on the psychological distress scores. Pearson correlation analyses and hierarchical regression analyses were performed. RESULTS: Negative life events were positively associated with psychological distress. Emotional intelligence was negatively associated with psychological distress and negative life events. Emotional intelligence mediated the relationship between negative life events and psychological distress. CONCLUSIONS: The findings support the theory of Salovey and his colleagues, and provide evidence for emotional intelligence as a factor that buffers effects of negative life events on psychological distress.

Ypsiyunnosides A-E, Five New Cholestanol Glycosides from Ypsilandra yunnanensis.

Phytochemical investigation on the whole plants of Ypsilandra yunnanensis was carried out for the first time and led to the isolation of five new cholestanol glycosides, ypsiyunnosides A-E (1-5), and one known analogue. Their structures were determined mainly by detailed spectroscopic analysis, including extensive 1D and 2D NMR, MS and UV, as well as chemical methods. Among them, compound 1 possessed a rare 6/6/6/5/5 fused-rings cholestanol sketelon, which was identified as (23R,25R)-3ß,16α,26-triol-16,23-cyclocholest-5,17(20)-dien-22-one. Their induced platelet aggregation activities and cytotoxicities were evaluated. Five new cholestanol glycosides, ypsiyunnosides A-E (1-5), were isolated from the whole plants of Ypsilandra yunnanensis. Compound 1 possessed a rare 6/6/6/5/5 fused-rings cholestanol sketelon. Their structures were elucidated by a combination of 1D and 2D NMR, MS and chemical analysis.

Steroidal saponins from stems and leaves of Paris polyphylla var. yunnanensis.

Phytochemical investigation of the stems and leaves of Paris polyphylla var. yunnanensis led to isolation of 12 steroidal saponins, chonglouosides SL-9-SL-20, which had not been described previously, along with 13 known compounds. Their structures were established on the basis of extensive spectroscopic analysis and chemical methods. Four of the twelve steroidal saponins possessed three steroidal aglycones which have not been reported in nature. Steroidal saponins were also evaluated for their cytotoxicities against two human cancer cell lines (HepG2 and HEK293) and anti-HCV effects. One known steroidal saponin was the most cytotoxic compound overall with IC50 values of 2.9 ± 0.5 µM and 5.0 ± 0.6 µM against HepG2 and HEK293 cell lines, respectively, while none showed anti-HCV activity at a concentration of 20 µM.

Plantagiolides K-N, three new withanolides and one withanolide glucoside from Tacca plantaginea.

Phytochemical investigation of the whole plants of Tacca plantaginea led to the isolation of 3 new withanolides and one new withanolide glucoside, named plantagiolides K-N (1-4), together with one known withanolide, 4 known withanolide glucosides, and 2 known taccalonolides. Their structures were elucidated by extensive spectroscopic analysis. Compound 4 is the first withanolide glycoside which the sugar moiety is attached at C-7. The effects of the some of isolates on TNFα-induced NF-κB transcriptional activity and cytotoxicity were evaluated.

Steroidal saponins with induced platelet aggregation activity from the aerial parts of Paris verticillata.

In order to utilize and protect the resources of Rhizoma Paridis rationally, we carried out a phytochemical investigation on the non-medicinal (aerial) parts of Paris verticillata that led to the isolation of fifteen steroidal saponins. Among them, three are new spirostanol saponins, named parisverticosides A­C (1­3), as well as one new cholestane glycoside, named parisverticoside D (4). Their structures were elucidated by extensive spectroscopic analysis and acid hydrolysis. The aglycone of compound 1 is a new spirostane and identified as (23S,24S,25S)-spirost-5-en-1b,3b,23, 24-tetraol. The selected isolates were evaluated for induced platelet aggregation activity and compound 5 showed 62% maximal platelet aggregation rate at the concentration of 300 lg/mL.

[Association between blood pressure level and incidence of carotid artery plaque in middle-aged and elderly people].

OBJECTIVE: To explore the association between blood pressure level and incidence of carotid arterial plaque in middle-aged and elderly people. METHODS: A total of 5852 individuals were randomly stratified from the 101 510 health examination survey participants in Tangshan Kailuan Company community during 2006-2007. A total of 5440 people (age above 40 years old, free of stroke, TIA and myocardial infarction) were enrolled in the final analysis. A questionnaire survey, blood biochemical analysis and carotid artery ultrasound examination were finished by trained medical staff. Sixteen individuals without carotid artery plaques information and 35 individuals without blood pressure information were excluded. Finally, a total of 5389 participants [3235 male, mean age: (54.7 ± 11.8) years] were analyzed. According to 2010 Chinese guideline to prevention and treatment of hypertension and blood pressure level classification, participants were divided into normotensive group (n = 1377), high normal blood pressure group (n = 1971) and hypertensive group (n = 2041). Multivariate logistic regression analysis was used to determine the risk factors of the carotid artery plaques. RESULTS: Age, male gender, BMI, IMT, TG, FBG, smoking and alcohol drinking rate were significantly higher in high normal blood pressure group than in normotensive group (all P < 0.05), LDL-C, HDL-C, hs-CRP and TC were similar between these two groups. Incidence of carotid artery plaques in normotensive, high normal blood pressure and hypertensive groups was 24.8%, 37.4%, 60.2% respectively. The risk of carotid artery plaques was increased to 38% and 163% in high normal and hypertensive groups compared to normotensive group, the OR ratio was 1.38 (95%CI: 1.15-1.66) and 2.63 (95%CI: 2.18-3.18), respectively. After adjusting gender, age, smoking, alcohol consumption, TG, TC, HDL-C, FBG, hs-CRP and BMI, the risk of developing carotid artery plague was increased in proportion to increasing blood pressure and the OR value was 1.24 (95%CI:1.01-1.52) , 1.69 (95%CI:1.34-2.15) and 2.66 (95%CI:2.20-3.21) in high normal group I [SBP/DBP 121-129/80-84 mm Hg(1 mm Hg = 0.133 kPa)] and high normal group II (SBP/DBP 130-139/85-89 mm Hg) and hypertensive group, respectively. CONCLUSIONS: The cardiovascular risk factors and prevalence of carotid artery plague increase in proportion to blood pressure level in this cohort. The detection rate of carotid artery plague is already significantly increased in individuals with high normal blood pressure.

New 23-spirocholestane derivatives from Ypsilandra thibetica.

Three new unusual 23-spirocholestane derivatives, ypsilanogenin (1), ypsilanogenin 3-O-ß-D-glucopyranoside (2), and 4'-acetylypsilanogenin 3-O-ß-D-glucopyranoside (3), were isolated from the whole plants of Ypsilandra thibetica. The structures of compounds 1-3 were deduced by spectroscopic and chemical methods, and the structure of 1 was further confirmed by a single-crystal diffraction analysis. All isolates were evaluated for their inhibitory activities against HIV-1.

Sesquiterpenoids from Chloranthus multistachys.

An 8,9-seco-lindenane disesquiterpenoid, chloramultiol G, four eudesmane sesquiterpenoids, ent-(3R)-3-hydroxyatractylenolide III and multistalactones A-C, and four guaiane sesquiterpenoids, (1R,4S,5R,8S,10S)-zedoalactone A and multistalactones D-F, along with 14 known compounds, were isolated from whole plant tissues of Chloranthus multistachys. Their structures were established by extensive NMR experiments in conjunction with mass spectrometry. Except for chloramultiol G, the absolute stereochemistries of the other eight were confirmed by single-crystal X-ray crystallography and CD spectra. Nine compounds were tested for cytotoxicity against five human tumor cell lines and for antifungal activity against four microorganisms in vitro, but all were inactive.

C(22)-steroidal lactone glycosides from stems and leaves of Paris polyphylla var. yunnanensis.

Further phytochemical investigation on the stems and leaves of Paris polyphylla var. yunnanensis has led to the isolation of three C(22)-steroidal lactone glycosides. Two of these are new compounds, designated as chonglouoside SL-7 (1) and chonglouoside SL-8 (2). Their structures were elucidated on the basis of extensive spectroscopic analysis, as well as comparison with the reported spectroscopic data. This is the first report of C(22)-steroidal lactone glycosides isolated from the Paris genus. Compounds 1 and 3 showed moderate antimicrobic activity against Propionibacterium acnes with MIC values of 31.3 and 3.9µg/mL, respectively.

Steroidal saponins with antimicrobial activity from stems and leaves of Paris polyphylla var. yunnanensis.

Rhizoma Paridis, the root of Paris polyphylla var. yunnanensis (Trilliaceae), is a Chinese traditional medicine, which resources become less and less. However, the aerial parts of this herb, which can regenerate every year, were discarded. In order to expand the resources, detailed chemical investigation on the stems and leaves of Paris polyphylla var. yunnanensis led to isolation of one sapogenin and 24 steroidal saponins (1-25), including 6 new glycosides, named chonglouosides SL-1-SL-6 (1-6). Their structures were elucidated on the basis of detailed analyses of their 1D and 2D NMR spectra and acid hydrolysis. Among them, compounds 3 and 4 are the first 23,27-dihydroxydiosgenin saponin having a sugar chain attached to C-23 or C-27, while compound 6 is the first 27-hydroxyruscogenin glycoside bearing 1, 27-di-O-sugar chains. The known compounds 10, 12, 14, 19, 20, 22, and 25 were isolated from the genus Paris for the first time. Antimicrobial testing activities of the selected compounds showed that compound 2, 3, 6, 8, 9, 11, 13, 17, 18, 21, and 24 were active against Propionibacterium acnes with MIC values of 62.5, 62.5, 3.9, 16.5, 17.2, 7.8, 39.0, 17.2, 31.3, 62.5, and 31.3 µg/ml, respectively.

[Association between blood pressure level and the development of memory dysfunction in patients with hypertension].

OBJECTIVE: It is known that hypertension may be implicated the development of memory dysfunction. Our study tests the hypothesis that prevalence of memory dysfunction is closely linked with the level of SBP (systolic blood pressure) and DBP (diastolic blood pressure) in hypertension patients. METHODS: Non-stroke hypertension patients aged 18-75 years (n = 196, age 54 ± 10, 101 male) with diagnosed hypertension for more than one year were included. Memory function was measured by the Rivermead Behavioral Memory Test Second Edition (RBMTII, 2003). The general information was obtained through questionnaire. RESULTS: RBMTII total score, the ability of recall name, remember storing article, recall faces, delayed route memory and orientation score were significantly decreased in proportion with increasing blood pressure (P < 0.05: hypertension III vs. II and I). RBMTII total score, the ability of recall name, and recall faces were significantly lower in hypertension II group compared to hypertension I group (P < 0.05). The age, male gender, years of hypertension, level of SBP and BMI were risk factors of memory dysfunction while the years of education was protective factor of memory dysfunction. The morbidity of memory dysfunction in patients with hypertension was higher and more serious with increasing blood pressure level (χ(2) = 10.389, P < 0.01). CONCLUSIONS: Our results suggest that blood pressure is positively related to increased risk of memory dysfunction. The age, male gender, years of hypertension, level of SBP and BMI are risk factors of memory dysfunction while the years of education is protective factor of memory dysfunction.

Lindenane disesquiterpenoids with anti-HIV-1 activity from Chloranthus japonicus.

Five new lindenane disesquiterpenoids, chlorajaponilides A-E (1-5), together with 11 known analogues were isolated from whole plants of Chloranthus japonicus. The structure and absolute configuration of 1 was confirmed by X-ray crystallography. Compounds 1 and 2 represent the first examples of lindenane disesquiterpenoids with a C-5 hydroxy group and a C-4-C-15 double bond. Compounds 8, 9, 11, and 12 showed anti-HIV-1 replication activities in both wild-type HIV-1 and two NNRTIs-resistant strains. Shizukaol B (8) exhibited the best activity against HIV(wt), HIV(RT-K103N), and HIV(RT-K103N) with EC50 values of 0.22, 0.47, and 0.50 µM, respectively. Compounds 8, 9, 11, and 12 had significant cytotoxicities against C8166 cells with CC50 values of 0.020, 0.089, 0.047, and 0.022, respectively, and exhibited inhibitory activities against HIV-1 with EC50 values of 0.0014, 0.016, 0.0043, and 0.0033 µM, respectively.

Tigliane-type diterpenoid glycosides from Euphorbia fischeriana.

Investigation of whole plants of Euphorbia fischeriana afforded three new tigliane-diterpenoid glycosides, fischerosides A-C (1-3), together with 11 known diterpenoids. Fischerosides A-C (1-3) are the first tigliane-type diterpenoid glucosides. Their structures were determined by a combination of 1D and 2D NMR, MS, and acid hydrolysis. Inhibitory activity against HIV-1 was assessed for compounds 1-5. The new compound 3 showed an EC50 value of 0.02 µM and a therapeutic index (TI) of 17.50, while prostratin (4) and 12-deoxyphorbol-13,20-diacetate (5) showed significantly greater anti-HIV-1 activity.

Taccasubosides A-D, four new steroidal glycosides from Tacca subflabellata.

By analyzing the steroidal content of fresh whole plants of Tacca subflabellata (Taccaceae), we isolated one sapogenin and eight glycosides with four kinds of steroidal skeletons including four new glycosides, named taccasubosides A-D (1-4), together with five known compounds. Among them, compound 1 is the first pentacyclic sterol glycoside with 6-6-6-5-6 fused rings. The structures of 1-4 were elucidated on the basis of extensive spectroscopic analysis, including that of 2D NMR data, and the results of acidic hydrolysis. The cytotoxicity of the selected steroidal glycosides (1-4, 8, and 9) was evaluated in vitro against five human cancer cell lines. Compound 9 showed significant inhibitory activity against all five cell lines.

[Effect of sleep deprivation on p38MAPK phosphorylation in the rat hippocampus].

OBJECTIVE: To investigate the effect of sleep deprivation (SD) on the expression of p38Mitogen-activated protein kinase (p38MAPK) phosphorylation in the rat hippocampus. METHODS: Male Sprague-Dawley rats (n=60) were divided randomly into control and sleep deprivation groups. The sleep deprivation models were established with the modified multiple platform methods. At 1 d, 3 d, 5 d, and 7 d after sleep deprivations, changes of neuron morphous in the hippocampal region of the rats were observed by HE staining. The expression of p38MAPK phosphorylation was detected by immunohistochemistry and Western blot. The learning-memory function was tested with Morris water maze and 4-PTT dry path maze. RESULTS: More obvious neuronal morphous damages, increased p38MAPK phosphorylation cells and p38MAPK phosphorylation expression, and decreased learning-memory function were found in the rats subject to sleep deprivation than those in the control. The changes were enhanced with the length of sleep deprivation. CONCLUSION: p38MAPK can be activated by sleep deprivation, which mediates the process of neuronal injury.

Plantagiolide F, a minor withanolide from Tacca plantaginea.

A minor new withanolide, named plantagiolide F, was isolated from the whole plant of Tacca plantaginea (Hance). The structure of plantagiolide F was elucidated on the basis of spectroscopic methods including extensive 1- and 2-D NMR experiments.