Convallatoxin induces HaCaT cell necroptosis and ameliorates skin lesions in psoriasis-like mouse models.

Psoriasis is considered an immune-mediated inflammatory skin disorder that affects the quality of life of nearly four percent of the world population. Considering the side effects of existing therapeutic drugs and the urgent need for new drug development, we screened more than 250 traditional Chinese medicine compounds to identify drugs that significantly reduced the viability of human HaCaT keratinocytes, a psoriasis-related model cell line. Convallatoxin (CNT) was found to be a highly effective inhibitor of HaCaT cell viability. Subsequent mechanistic studies revealed that CNT induced HaCaT cell death by necroptosis rather than by apoptosis. CNT destroyed the membrane integrity of HaCaT cells, as detected by nuclear propidium iodide (PI) staining and lactate dehydrogenase (LDH) release. Additionally, the intercellular levels of adenosine triphosphate (ATP) were lower in HaCaT cells treated with CNT than in control HaCaT cells, and typical necroptosis-associated characteristics were observed by electron microscopy in cells treated with CNT. Furthermore, compared with control HaCaT cells, CNT-treated HaCaT cells produced more reactive oxygen species (ROS), but this effect was inhibited by the antioxidants N-acetyl-cysteine (NAC), diphenyleneiodonium chloride (DPI), and apocynin and the necroptosis inhibitor Nec-1. In addition, antioxidant treatment attenuated necroptotic cell death, suggesting that CNT-induced HaCaT necroptosis is mediated by oxidative stress. More importantly, CNT ameliorated skin lesions and inflammation in imiquimod (IMQ)- and 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced psoriasis-like mouse models. In conclusion, our results demonstrate that CNT is cytotoxic against HaCaT cells in vitro and exerts antipsoriatic activities in two mouse models of psoriasis in vivo, making CNT a potential promising candidate drug for future research.

Chromatogram-Bioactivity Correlation-Based Discovery and Identification of Three Bioactive Compounds Affecting Endothelial Function in Ginkgo Biloba Extract.

Discovery and identification of three bioactive compounds affecting endothelial function in Ginkgo biloba Extract (GBE) based on chromatogram-bioactivity correlation analysis. Three portions were separated from GBE via D101 macroporous resin and then re-combined to prepare nine GBE samples. 21 compounds in GBE samples were identified through UFLC-DAD-Q-TOF-MS/MS. Correlation analysis between compounds differences and endothelin-1 (ET-1) in vivo in nine GBE samples was conducted. The analysis results indicated that three bioactive compounds had close relevance to ET-1: Kaempferol-3-O-α-l-glucoside, 3-O-{2-O-{6-O-[P-OH-trans-cinnamoyl]-ß-d-glucosyl}-α-rhamnosyl} Quercetin isomers, and 3-O-{2-O-{6-O-[P-OH-trans-cinnamoyl]-ß-d-glucosyl}-α-rhamnosyl} Kaempferide. The discovery of bioactive compounds could provide references for the quality control and novel pharmaceuticals development of GRE. The present work proposes a feasible chromatogram-bioactivity correlation based approach to discover the compounds and define their bioactivities for the complex multi-component systems.

Effectiveness of Acupressure in Promoting Sleep Quality: A Systematic Review of Randomized Controlled Trials.

This review aimed to evaluate the effectiveness of acupressure in promoting sleep quality among adults. Study findings included in the review showed that acupressure significantly improved sleep quality compared with the control group, but no superior effect of acupressure was found compared with sham acupressure.

The effects of acupressure on depression, anxiety and stress in patients with hemodialysis: a randomized controlled trial.

BACKGROUND: Patients with end stage renal disease on hemodialysis are affected by physiological and psychological stressors, which contribute to poor quality of life and negative clinical outcomes. Depression, anxiety, and stress are highly prevalent in this population. Effective interventional strategies are required to manage these psychological symptoms. Acupressure has been believed to be one of the complementary therapies that could promote psychological wellbeing. OBJECTIVE: The aim of this study was to evaluate the effects of acupressure on depression, anxiety, stress, and general psychological distress in patients with hemodialysis. DESIGN: Open-label randomized controlled trial. SETTING: Three hemodialysis centers. PARTICIPANTS: A total of 108 patients with hemodialysis were randomly recruited into the acupressure group (n=54) and the control group (n=54). METHOD: The intervention was carried out from January to March 2014. The acupressure group received routine hemodialysis treatment plus 15 min acupressure applied three times a week for four weeks. The control group received only usual care with routine hemodialysis treatment. The outcome measurements were the Depression, Anxiety Stress Scales (DASS-21), and general psychological distress using the General Health Questionnaire (GHQ-28). Statistical analysis was performed using Wilcoxon signed-rank test to compare DASS scales and GHQ-28 scores before and after acupressure intervention. RESULTS: The acupressure group had significantly lower DASS scores and GHQ scores compared to the control group, signifying improvements in depression, anxiety, stress and general psychological distress. The sub-score of the GHQ-28 for social dysfunction, however, were similar in both groups. CONCLUSION: Findings from this study indicates that acupressure therapy delivered three times a week for four weeks was able to significantly reduce depression, anxiety, stress, and general psychological distress in patients with hemodialysis. This positive finding suggests that acupressure may have a role in promoting psychological wellbeing of patients. Promoting psychological wellness will improve patients' quality of life, and reduce negative outcomes associated with psychological illnesses and distress experienced by patients with hemodialysis.