Identification of chemical components and rat serum metabolites in Danggui Buxue decoction based on UPLC-Q-TOF-MS, the UNIFI platform and molecular networks.

Danggui Buxue Decoction (DBD), consisting of Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao (Huangqi, HQ) and Angelica sinensis (Oliv.) Diels (Danggui, DG), is a traditional Chinese medicine (TCM) formula with the function of tonifying Qi and promoting blood. In this study, ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was used to comprehensively identify the chemical constituents in DBD and those entering into the rat serum after gastric perfusion. A combination of the UNIFI platform and Global Natural Product Social molecular networking (GNPS) was used to analyze the chemical composition of DBD. As a result, 207 compounds were unambiguously or tentatively identified including 60 flavonoids, 38 saponins, 35 organic acids, 26 phthalides, 12 phenylpropanoids, 11 amino acids and 25 others. Furthermore, a total of 80 compounds, including 29 prototype components and 51 exogenous metabolites, were detected in the serum of rats. Phase I reactions (oxidation, reduction, and hydration), phase II reactions (methylation, sulfation, and glucuronidation), and their combinations were the main metabolic pathways of DBD. The results provided fundamental information for further studying the pharmacological mechanisms of DBD, as well as its quality control research.

Age and sex-specific differences of mindfulness traits with measurement invariance controlled in Chinese adult population: A pilot study.

Objectives: To examine the relationships of age and sex with mindfulness traits among Chinese adults with controlling for measurement invariance. Methods: A total of 1777 participants completing the Five-Facet Mindfulness Questionnaire were included for analysis. Their age and sex information were also collected. Descriptive analysis, Pearson's Chi-Square test and analysis of variance were performed to test the age- and sex-specific differences, measurement invariance was examined by confirmatory factor analysis. Results: Excellent data fit to the model indicated configural, metric, and scalar invariance across age and sex. Participants aged 60 or above scored significantly higher in dimensions of acting with awareness, nonjudging of inner experience, nonreactivity to inner experience, and the total scores than younger individuals, who had higher scores in the observing domain. In addition, females scored higher in describing and observing than males, while the latter had higher score in nonreactivity to inner experience. Conclusions: The Five-Facet Mindfulness Questionnaire Mindfulness showed acceptable measurement invariance across age and sex in Chinese adult population. The old and the young differs in the traits of awareness, observing, nonjudging of inner experience, nonreactivity to inner experience and the total mindfulness level, while males and females varied in describing, observing and nonreactivity to inner experience. Individual differences should be considered and well addressed in future studies on mindfulness.

Integrated transcriptomic and metabolomic profiles reveal the protective mechanism of modified Danggui Buxue decoction on radiation-induced leukopenia in mice.

Leukopenia caused by radiation hinders the continuous treatment of cancers. Danggui Buxue Decoction (DBD) has been widely used in clinical owing to low toxicity and definite therapeutic effects to increase leukocytes. Meanwhile, icaritin (ICT) has also been proved to have the effect of boosting peripheral blood cells proliferation. However, there is no study to prove the efficacy of MDBD (Modified Danggui Buxue Decoction), a derivative herbal formula composed of DBD and ICT, in the treatment of radiation-induced leukopenia. In this study, we performed a model of 3.5 Gy whole-body radiation to induce leukopenia in mice. The results of pharmacodynamic studies demonstrated that MDBD could significantly increase the white blood cells in peripheral blood by improving the activity of bone marrow nuclear cells, reducing bone marrow damage, modulating spleen index, and regulating hematopoietic factors to alleviate leukopenia. We also analyzed the integrated results of metabolomics and transcriptomics and found that MDBD could relieve leukopenia and alleviate bone marrow damage by targeting steroid biosynthesis and IL-17 signaling pathway, in which the key genes are Jun, Cxcl2 and Egr1. Therefore, our study provides a basis for the effectiveness and compatibility in the combination of traditional Chinese medicine formula and small molecule drugs.

Cryptotanshinone alleviates radiation-induced lung fibrosis via modulation of gut microbiota and bile acid metabolism.

Cryptotanshinone (CPT), a major biological active ingredient extracted from root of Salvia miltiorrhiza (Danshen), has shown several pharmacological activities. However, the effect of CPT on radiation-induced lung fibrosis (RILF) is unknown. In this study, we explored the protective effects of CPT on RILF from gut-lung axis angle, specifically focusing on the bile acid (BA)-gut microbiota axis. We found that CPT could inhibit the process of epithelial mesenchymal transformation (EMT) and suppress inflammation to reduce the deposition of extracellular matrix in lung fibrosis in mice induced by radiation. In addition, 16S rDNA gene sequencing and BAs-targeted metabolomics analysis demonstrated that CPT could improve the dysbiosis of gut microbiota and BA metabolites in RILF mice. CPT significantly enriched the proportion of the beneficial genera Enterorhabdus and Akkermansia, and depleted that of Erysipelatoclostridium, which were correlated with increased intestinal levels of several farnesoid X receptor (FXR) natural agonists, such as deoxycholic acid and lithocholic acid, activating the FXR pathway. Taken together, these results suggested that CPT can regulate radiation-induced disruption of gut microbiota and BAs metabolism of mice, and reduce the radiation-induced lung inflammation and fibrosis. Thus, CPT may be a promising drug candidate for treating RILF.

Astragalus polysaccharide ameliorated complex factor-induced chronic fatigue syndrome by modulating the gut microbiota and metabolites in mice.

Chronic fatigue syndrome (CFS) is a debilitating disease with no symptomatic treatment. Astragalus polysaccharide (APS), a component derived from the traditional Chinese medicine A. membranaceus, has significant anti-fatigue activity. However, the mechanisms underlying the potential beneficial effects of APS on CFS remain poorly understood. A CFS model of 6-week-old C57BL/6 male mice was established using the multiple-factor method. These mice underwent examinations for behavior, oxidative stress and inflammatory indicators in brain and intestinal tissues, and ileum histomorphology. 16 S rDNA sequencing analysis indicated that APS regulated the abundance of gut microbiota and increased production of short chain fatty acids (SCFAs) and anti-inflammatory bacteria. In addition, APS reversed the abnormal expression of Nrf2, NF-κB, and their downstream factors in the brain-gut axis and alleviated the reduction in SCFAs in the cecal content caused by CFS. Further, APS modulated the changes in serum metabolic pathways induced by CFS. Finally, it was verified that butyrate exerted antioxidant and anti-inflammatory effects in neuronal cells. In conclusion, APS could increase the SCFAs content by regulating the gut microbiota, and SCFAs (especially butyrate) can further regulate the oxidative stress and inflammation in the brain, thus alleviating CFS. This study explored the efficacy and mechanism of APS for CFS from the perspective of gut-brain axis and provides a reference to further explore the efficacy of APS and the role of SCFAs in the central nervous system.

[Chemical constituents in Dolomiaea plants and their pharmacological activities: a review].

Dolomiaea plants are perennial herbs in the Asteraceae family with a long medicinal history. They are rich in chemical constituents, mainly including sesquiterpenes, phenylpropanoids, triterpenes, and steroids. The extracts and chemical constituents of Dolomiaea plants have various pharmacological effects, such as anti-inflammatory, antibacterial, antitumor, anti-gastric ulcer, hepatoprotective and choleretic effects. However, there are few reports on Dolomiaea plants. This study systematically reviewed the research progress on the chemical constituents and pharmacological effects of Dolomiaea plants to provide references for the further development and research of Dolomiaea plants.

[Metabonomics and its application in Chinese medicine processing].

Chinese medicine processing is a procedure to process medicinal materials under the guidance of traditional Chinese medicine(TCM) theories by using unique methods in China. The medicinal materials can only be used clinically after proper processing. With the development of the modernization of TCM, it is difficult to solve the problems in the inheritance, development, and internationalization of Chinese medicine processing. Metabonomics, a new omics technology developed at the end of the last century, is used to infer the physiological or pathological conditions of the organism with the methods such as NMR and LC-MS via investigating the changes in endogenous small molecule metabolic network after the organism is stimulated by external environment. Metabonomics coincides with the holistic view of TCM because it displays the characteristics of integrity, comprehensiveness, and dynamics, and it has been widely applied in the field of Chinese medicine processing in recent years. This study summarized the application of metabonomics in the processing mechanism and quality control of Chinese medicine processing and prospected the development of this technology in the field of Chinese medicine processing.

[Application of metabonomics in study of traditional Chinese medicine syndrome:a review].

Syndrome is a nonlinear "internal-excess external-deficiency", "dynamic spatial-temporal" and "multi-dimensional" complex system and thus only by using a versatile method can the connotation be expounded. Metabonomics, which is dynamic, holistic, and systematic, is consistent with the overall mode of traditional Chinese medicine(TCM)(holistic view and syndrome differentiation and treatment). Therefore, metabonomics is very important for the research on the differentiation, material basis, and metabolic pathways of syndromes, and efficacy on syndromes. This study reviewed the application of metabonomics in the study of TCM syndromes in recent years, which is expected to objectify the research on TCM syndromes.

Mutation of CESA1 phosphorylation site influences pectin synthesis and methylesterification with a role in seed development.

Cell wall biogenesis is required for the production of seeds of higher plants. However, little is known about regulatory mechanisms underlying cell wall biogenesis during seed formation. Here we show a role for the phosphorylation of Arabidopsis cellulose synthase 1 (AtCESA1) in modulating pectin synthesis and methylesterification in seed coat mucilage. A phosphor-null mutant of AtCESA1 on T166 (AtCESA1T166A) was constructed and introduced into a null mutant of AtCESA1 (Atcesa1-1). The resulting transgenic lines showed a slight but significant decrease in cellulose contents in mature seeds. Defects in cellulosic ray architecture along with reduced levels of non-adherent and adherent mucilage were observed on the seeds of the AtCESA1T166A mutant. Reduced mucilage pectin synthesis was also reflected by a decrease in the level of uronic acid. Meanwhile, an increase in the degree of pectin methylesterification was also observed in the seed coat mucilage of AtCESA1T166A mutant. Change in seed development was further reflected by a delayed germination and about 50% increase in the accumulation of proanthocyanidins, which is known to bind pectin and inhibit seed germination as revealed by previous studies. Taken together, the results suggest a role of AtCESA1 phosphorylation on T166 in modulating mucilage pectin synthesis and methylesterification as well as cellulose synthesis with a role in seed development.

The Effectiveness of Music Therapy for Terminally Ill Patients: A Meta-Analysis and Systematic Review.

CONTEXT: The quality of death has increasingly raised concern because of the physical and psychological suffering of patients with advanced disease. Music therapy has been widely used in palliative care; however, its physical and mental effectiveness remains unclear. OBJECTIVE: To assess the effectiveness of music therapy during palliative care in improving physiology and psychology outcomes. METHODS: Randomized controlled trials evaluating music therapy for terminally ill patients were searched and included from inception up to April 25, 2018. The quality of the studies was assessed using the risk of bias tool recommended by the Cochrane Handbook V.5.1.0. RESULTS: In this study, 11 randomized controlled trials (inter-rater agreement, κ = 0.86) involving 969 participants were included. The quality of the included studies ranged from moderate to high. Compared with general palliative care, music therapy can reduce pain (standardized mean difference: -0.44, 95% confidence interval: -0.60 to -0.27, P < 0.00001) and improve the quality of life (standardized mean difference: 0.61, 95% confidence interval: 0.41 to 0.82, P < 0.00001) in terminally ill patients. In addition, anxiety, depression, and emotional function are improved as well. However, no significant differences were found in the patient's physical status, fatigue, and social function. CONCLUSION: This meta-analysis study demonstrated that music therapy served as an effective intervention to alleviate pain and psychological symptoms of terminally ill patients. However, considering the limitation of the quantity of the studies included, these results would need to be further confirmed.

[Effect of modified zhenzhu tiaozhi capsule on lipid peroxidation and endothelial functions in atherosclerotic rabbits].

OBJECTIVE: To observe the anti-atherosclerotic effect and its possible mechanisms of Modified Zhenzhu Tiaozhi Capsule (MZTC) in rabbits. METHODS: 50 rabbits were divided into five groups, i.e., the normal group, the model group, the simvastatin group (3 mg/kg), the high dose MZTC group (1.6 g crude drug/kg), and the low dose MZTC group (1.6 g crude drug/kg), respectively, ten in each group. The atherosclerosis (AS) model was established by feeding rabbits with high fat diet. Corresponding medicines were administrated on the basis of high fat diet for twelve successive weeks. Levels of blood lipids, serum superoxide dismutase (SOD), malondialdehyde (MDA), and nitric oxide (NO) were detected. The area of the aortic tunica intima plaque was determined. The pathological changes of the aorta were observed. RESULTS: Compared with the model group, serum levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), MDA, and atherosclerotic index (AI) were significantly lowered in the MZTC groups (P<0.05, P<0.01), while serum levels of high-density lipoprotein cholesterol (HDL-C), SOD, and NO obviously increased (P<0.05, P<0.01). Serum levels of TC, TG, LDL-C, and in the MZTC groups were obviously higher than those of the simvastatin group (P<0.01), and there was insignificant difference in other indices. The ratio of the aortic tunica intima plaque percentage to the total tunica intima area was also markedly lower than that of the model group (P<0.05, P<0.01). Results under light microscope indicated the pathological changes of the aorta was obviously attenuated. CONCLUSIONS: MZTC could inhibit the formation and development of AS plaque. Its mechanism might be associated with regulating lipids metabolism, antioxidation, and improving endothelial functions.

[The effect of fufang zhenzhu tiaozhi capsule on lipid metabolism in atherosclerotic rabbits].

OBJECTIVE: To observe the effect of fufang zhenzhu tiaozhi capsule (FTZ) on lipid metabolism in atherosclerotic rabbits. METHODS: 50 rabbits were divided into five groups: normal control group, model group, simvastatin group, the high-dose group and low-dose group of FTZ. The atherosclerotic model was established by feeding the rabbits with high fat diet. The medicine interfered groups were administrated with homologous medicine on the base of high fat diet. All the rabbits were fed for 12 weeks. The blood lipids levels were determined just before the experiment and at the forth, the eighth and the twelfth weekend of the experiment. At the end of the experiment, serum apolipoprotein levels, liver lipid contents and the area of atherosclerotic plaque were determined respectively. RESULTS: Compared with model group, TC, TG, LDL-C and ApoB levels were significantly decreased in FTZ groups (P < 0.05 or P < 0.01). The level of HDL-C and the ratio of ApoA I /ApoB were raised significantly (P < 0.05). The contents of TC,TG in liver tissue and the area percentage of atherosclerotic plaque were also markedly reduced (P < 0.05 or P < 0.01) in the FTZ groups. CONCLUSION: FTZ could efficiently regulate the abnormality of lipid metabolism in experimental atherosclerotic rabbits, and this maybe one mamechanisms of its antiatherogenic effect.

[Establishment and initial application of a medicine screening technique based on human promoter of CCR5].

This research ws carried out to construct a medicine screening system targeting at human promoter of CCR5. The gene Human promoter of CCR5 was inserted into the rebuilt vector pGL3-neo. The pGL3-neo-CCR5 plasmids were transfected into Jurkat cells (the cell line of acute T lymphocyte leukemia). The lasting transfected cells were screened by G418. After seven kinds of traditional Chinese medicine had acted separately on the lasting transfected cells for 16h, the expression levels of CCR5 promoter in the cells were detected. The results showed that the level of luciferase activity of Shuanghuanglian-injectio group was remarkably lower than that of control (P < 0.05), and the levels of luciferase activity of Chuanhuning group, Baical skullcap root group, and Milkvetch root group were remarkably higher than that of control (P < 0.01). Shuanghuanglian-injectio depressed the activity of the transfected CCR5 promoter in cells cultivated in vitro; Chuanhuning, Baical skullcap root and Milkvetch root boosted the activity of the transfected CCR5 promoter in cells cultivated in vitro. Thus a medicine screening system based on Human promoter of CCR5 was initially constructed.

[Effects of Huoxue Tongmai Lishui method on fundus fluorescein angiography of non-ischemic retinal vein occlusion: a randomized controlled trial].

BACKGROUND: Huoxue Tongmai Lishui method, a traditional Chinese medicine treatment for eliminating water, activating and promoting blood circulation, could inhibit fundus hemorrhage on experimental retinal vein occlusion (RVO) with high obvious effective rate, and improve symptoms in traditional Chinese medicine. The action mechanism may be related to reducing plasma viscosity and non-perfusion area, and the formation of collateral circulation. OBJECTIVE: To explore the therapeutic effects of Huoxue Tongmai Lishui method (Sanxue Mingmu Tablet) on fundus fluorescent angiograph of non-ischemic retinal vein occlusion (RVO). DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: Thirty-four patients with non-ischemic RVO in Department of Ophthalmology, the First Affiliated Hospital, Hunan University of Traditional Chinese Medicine from April 2005 to April 2009 were included. All the patients were diagnosed as qi stagnation and blood stasis syndrome or hyperactivity of liver yang syndrome, and they were randomly divided into two groups, with 17 eyes of 17 patients in treatment group treated by Sanxue Mingmu Tablet combined with conventional treatment, and 18 eyes of 17 patients in control group treated by Xueshuantong Tablet combined with conventional treatment. The patients were treated for two months. MAIN OUTCOME MEASURES: Fundus colour photography, and fundus fluorescent angiograph were detected in two groups before and after the treatment. RESULTS: The curative effect of Sanxue Mingmu Tablet was better than that of Xueshuantong Tablet. Huoxue Tongmai Lishui method could significantly shorten the retinal circulation time, reduce the non-perfusion area, decrease the formation of angiogenesis and promote the formation of collateral circulation. CONCLUSION: Huoxue Tongmai Lishui method is an effective traditional Chinese medicine treatment with high obvious effective rate in reducing non-perfusion area and avoiding venous occlusion and formation of collateral circulation.