Steroidal constituents in the whole plants of Helleborus niger and their cytotoxic activity in vitro.

Phytochemical investigation of the whole plants of Helleborus niger L. (Ranunculaceae) resulted in the isolation of five undescribed compounds, including one bufadienolide (1), two bufadienolide rhamnosides (2 and 3), and two ecdysteroids (12 and 13), along with eight known compounds (4-11). The chemical structures of 1-3, 12, and 13 were determined by spectroscopic studies, including 2D NMR, and chromatographic and spectroscopic analyses of the hydrolyzed products. Compounds 1-13 were evaluated for their cytotoxic activity against HL-60 human leukemia cells, A549 human lung adenocarcinoma cells, SBC-3 human small-cell lung cancer cells, and TIG-3 human normal diploid lung cells. Compounds 1-12 showed cytotoxic activity against HL-60, A549, and SBC-3 cells, with IC50 values ranging from 0.0016 to 6.1 µM. Bufadienolide rhamnoside 2 exhibited potent cell proliferation inhibitory activity against SBC-3 cells after 24-48 h of treatment and apoptosis-inducing activity in SBC-3 cells via an intrinsic pathway after 72 h of treatment. The JFCR39 panel screening of 2 suggests that the molecular target of 2 is Na+,K+-ATPase.

Bufadienolides and ecdysteroids from the whole plants of Helleborus niger and their cytotoxicity.

A new bufadienolide (1), two new bufadienolide glycosides (2 and 3), a new ecdysteroid (4), and four known compounds (5-8), were isolated from the whole plants of Helleborus niger L. (Ranunculaceae). The structures of the new compounds (1-4) were determined by spectroscopic analysis, including 2D NMR spectral data, and hydrolytic studies. Compounds 1-6 showed cytotoxicity against HL-60 human leukemia cells, A549 human lung adenocarcinoma cells, and SBC-3 human small-cell lung cancer cells, with IC50 values ranging from 0.0055 to 1.9 µM. HL-60 cells treated with either 3 or 4 showed apoptosis characteristics, such as nuclear chromatin condensation, accumulation of sub-G1 cells, and activation of caspase-3/7.

Motivation factors for suicidal behavior and their clinical relevance in admitted psychiatric patients.

BACKGROUND: Suicidal behavior (SB) is a major, worldwide health concern. To date there is limited understanding of the associated motivational aspects which accompany this self-initiated conduct. AIMS: To develop a method for identifying motivational features associated with SB by studying admitted psychiatric patients, and to examine their clinical relevance. METHODS: By performing a factor analytic study using data obtained from a patient sample exhibiting high suicidality and a variety of SB methods, Motivations for SB Scale (MSBS) was constructed to measure the features. Data included assessments of DSM-IV psychiatric and personality disorders, suicide intent, depressive symptomatology, overt aggression, recent life events (RLEs) and methods of SB, collated from structured interviews. Association of identified features with clinical variables was examined by correlation analyses and MANCOVA. RESULTS: Factor analyses elicited a 4-factor solution composed of Interpersonal-testing (IT), Interpersonal-change (IC), Self-renunciation (SR) and Self-sustenance (SS). These factors were classified according to two distinctions, namely interpersonal vs. intra-personal directedness, and the level of assumed influence by SB or the relationship to prevailing emotions. Analyses revealed meaningful links between patient features and clinical variables. Interpersonal-motivations (IT and IC) were associated with overt aggression, low suicidality and RLE discord or conflict, while SR was associated with depression, high suicidality and RLE separation or death. Borderline personality disorder showed association with IC and SS. When self-strangulation was set as a reference SB method, self-cutting and overdose-taking were linked to IT and SS, respectively. CONCLUSIONS: The factors extracted in this study largely corresponded to factors from previous studies, implying that they may be useful in a wider clinical context. The association of these features with SB-related factors suggests that they constitute an integral part of the process leading to SB. These results provide a base for further research into clinical strategies for patient management and therapy.

Pathways from life-historical events and borderline personality disorder to symptomatic disorders among suicidal psychiatric patients: A study of structural equation modeling.

AIMS: Suicidal behavior (SB) is a major mental health problem. The research has identified many factors related to SB, such as problems in the developmental period and psychiatric and personality disorders. However, the interrelation of these factors has not been clearly delineated. METHODS: The subjects were 155 patients consecutively admitted with SB to a psychiatric center in Tokyo. Structured interviews, including the Structured Clinical Interview for DSM-IV (SCID)-I and SCID-II, were conducted to determine characteristics of the SB-related factors. To illustrate their interrelation, this study applied the technique of structural equation modeling. The latent constructs of life-historical events, borderline personality disorder (BPD) features and three symptomatic disorders (depression, anxiety disorders and substance dependence) were aligned in the chronological order of their manifestation, and connected one another within the model. Indicator variables of life-historical events were maltreatment in the developmental period and early onset of problematic behaviors. Indicators of BPD features and symptomatic disorders included the scales composed of the items in the SCID-I and II. RESULTS: The constructed model with favorable goodness-of-fit indices confirmed that BPD features had a mediating role in which they were influenced by life-historical events, and exerted an influence on the symptomatic disorders. Outside the BPD-mediating paths, the model suggested three clinically interpretable links between life-historical events and symptomatic disorders. CONCLUSIONS: The model of this study demonstrated the pathways from life-historical events and BPD to symptomatic disorders, and indicated a generating process of psychiatric comorbidity among suicidal patients. The wide-range view this study portrayed has important clinical implications, and deserves further substantiation by future studies.

Post-hospitalization course and predictive signs of suicidal behavior of suicidal patients admitted to a psychiatric hospital: a 2-year prospective follow-up study.

BACKGROUND: Suicidal patients admitted to a psychiatric hospital are considered to be at risk of suicidal behavior (SB) and suicide. The present study aimed to seek predictors of SB recurrence of the high-risk patients by examining their post-hospitalization course. METHOD: The design was 2-year prospective follow-up study of patients consecutively admitted with SB to a psychiatric center in Tokyo. The DSM-IV diagnoses and SB-related features of subjects were determined in structured interviews. Subsequently, the subjects underwent a series of follow-up assessments at 6-month intervals. The assessment included inquiries into SB recurrence, its accompanying suicidal intent (SI) and SF-8 health survey. Analyses of serial change over time in the follow-up data and Cox proportional hazards regression analyses of SB recurrence were performed. RESULTS: 106 patients participated in this study. The dropout rate during the follow-up was 9%. Within 2 years, incidences of SB as a whole, SB with certain SI (suicide attempt) and suicide were 67% (95% CI 58 - 75%), 38% (95% CI 29 - 47%) and 6% (95% CI 3 - 12%), respectively. Younger age, number of lifetime SBs and maltreatment in the developmental period were predictive of SB as a whole, and younger age and hopelessness prior to index admission were predictive of suicide attempt. Regarding diagnostic variables, anxiety disorders and personality disorders appeared to have predictive value for SB. Additionally, poor physical health assessed during the follow-up was indicated as a possible short-term predictor of SB recurrence. CONCLUSIONS: This study demonstrated a high incidence of SB and suicide and possible predictors of SB recurrence in the post-hospitalization period of psychiatric suicidal patients. Specialized interventions should be developed to reduce the suicide risk of this patient population.