Current hormone-based treatments for immune thrombocytopenic purpura (ITP) are associated with potentially serious adverse reactions. Zi Dian Fang (ZDF) is a multi-target Traditional Chinese Medicine (TCM) used to treat both the symptoms and root causes of ITP, with fewer side effects than hormone-based treatments. This study analysis of the therapeutic effects of ZDF on ITP from three aspects: platelet proliferation, immunoregulation, and inflammation. After detection of 52 chemical constituents of ZDF by UPLC-Q-TOF/MS, The main targets and pathways affected by ZDF were screened by network pharmacology and verified by Western blot and ELISA. Meanwhile, metabolomics analysis were applied to a mouse model of ITP to identify and screen endogenous terminal metabolites differentially regulated by ZDF. Integrated network pharmacology and metabolomics analysis of the therapeutic effects of ZDF on ITP may be as follows: ZDF counteracts ITP symptoms mainly by inhibiting Ras/MAPKs (Ras/Mitogen-activated protein kinases) pathway, and the expression of upstream protein (Ras) and downstream protein (p-ERK, p-JNK, p-p38) were inhibited, which affects the content of effect index associated with proliferation (Thrombopoietin, TPO; Granulocyte-macrophage colony stimulating factor, GM-CSF), inflammation (Tumor necrosis factor-α, TNF-α; Interleukin-6, IL-6), immune (Interleukin-2, IL-2; Interferon-gamma, IFN-γ; Interleukin-4, IL-4), so that the body’s arginine, Δ12-prostaglandin j2 (Δ12-PGJ2), 9-cis-Retinoic Acid, sphingosine-1-phosphate (S1P), oleic acid amide and other 12 endogenous metabolites significantly changes. Considering the established safety profile, the present study suggests ZDF may be a useful alternative to hormone-based therapies for the treatment of ITP.
Alzheimer’s disease (AD) is the world’s most common form of dementia, in which aggregation of amyloid-β (Aβ) is the hallmark. Unfortunately, few medicines have succeeded to completely cure AD. Yangxue Qingnao (YXQN) is a Chinese traditional medicine, and its pharmacological effect is improving cerebral blood flow. In this study, we firstly demonstrated that YXQN reduced AD-like pathology and cognitive impairment in APPswePS1dE9 (APP/PS1) mice with 2 months administration. Our data showed that YXQN substantially ameliorated behavioral defects in 10-month old APP/PS1 mice using Morris Water Maze and Y-maze tests, in which the cognitive ability of YXQN high-dose group approaches to wild type mice. Next, we focused on the brain pathological alterations in the YXQN group by three experiments, including thioflavin-S, congo-red, and Aβ-immunohistochemistry staining. The results demonstrated that the high-dose of YXQN dramatically suppressed amyloid plaques in the hippocampus and cortex of APP/PS1 mice, which showed a 47–72% reduction in plaque deposits, relative to the vehicle group. In addition, our data verified that YXQN decreased the cerebral amyloid load by attenuating β-secretase BACE1 and γ-secretase PS1 in the pathological processing of APP, and promoting the level of α-secretase ADAM10 in the physiological processing of APP to generate more sAPPα, which combats amyloidosis formation, and also carries out neurotropic and neuroprotective effect. Taken together, our results strongly suggest that YXQN could be a potential medicine for AD, and provide new evidence for further AD drug research and development.
This study investigated the effects of different anesthesia and analgesia methods on immune function and serum tumor marker levels of critically ill patients undergoing tumor resection surgery. Seventy-six critically ill patients with indications for tumor resection surgery were selected in The Second Affiliated Hospital of Zhengzhou University from September 2015 to August 2016. The patients were randomly divided into a control and an observation group (38 patients each). The patients in the control group were treated with general anesthesia and postoperative intravenous analgesia, while the patients in the observation group were treated with general anesthesia and epidural anesthesia and postoperative epidural analgesia. Venous blood samples were collected at 30 min before anesthesia (T1), 2 h after the beginning of the surgery (T2), immediately after surgery (T3), 24 h after surgery (T4) and 72 h after surgery (T5). The viable cell percentage of T lymphocyte subsets (CD3+, CD4+, CD8+, CD4+/CD8+) and natural killer (NK) cells were measured by flow cytometry. The levels of carcinoembryonic antigen, sugar chain antigen 199, sugar chain antigen 125, neuron specific enolase and cytokeratin 19 were detected by electrochemiluminescence at 24 h before and after operation. Our results showed the levels of CD3+, CD4+ and CD4+/CD8+ in the control group at T3-T5 were significantly lower than those at T1 (p<0.05). The CD3+ level in observation group at T3 was also significantly lower than the level at T1 (p<0.05), but it increased at T4 and T5 and showed no significant difference compared with the initial level (p>0.05). The levels of CD4+ and CD4+/CD8+ in the observation group were significantly higher than those in the control group at T2-T5 (p<0.05). And, the levels of CD3+ and CD4+ were significantly higher than those in the control group at T4 (p<0.05). The level of CD4+/CD8+ was significantly higher than that in the control group at T5 (p<0.05). No significant differences were found in the levels of CD8+ and NK cells between the 2 groups at any of the time-points (p>0.05). No significant differences were found either in any of the tested tumor markers in either group after 24 h. Even without differences on the tumor marker levels, these results suggest that general anesthesia combined with epidural anesthesia and analgesia produces milder deleterious effects on the immune function of perioperative critically ill patients than general anesthesia combined with intravenous analgesia.
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