Exploring the Roles of Dispositional Mindfulness and Cognitive Reappraisal in the Relationship Between Neuroticism and Depression Among Postgraduate Students in China.

Objectives: Previous studies revealed a positive association between neuroticism and depression. This study further extended the previous findings by exploring the psychological processes underlying this association among Chinese postgraduates. Guided by theoretical models and empirical research, we proposed a multiple mediation and moderated mediation model to investigate the roles of dispositional mindfulness and cognitive reappraisal in the relationship between neuroticism and depression. Methods: Using the NEO Five-Factor Inventory, Beck Depression Inventory, Mindfulness Attention Awareness Scale, and Emotion Regulation Questionnaire, 1103 first-year postgraduates at a comprehensive university in China were surveyed. Path analysis was adopted to test the models. Results: The results showed that dispositional mindfulness mediated the association between neuroticism and depression. Further, this mediating effect was moderated by cognitive reappraisal, with this effect being stronger in individuals with low engagement in cognitive reappraisal. Conclusion: The results support interrelations among neuroticism, depression, dispositional mindfulness, and cognitive reappraisal as moderated mediation rather than multiple mediation. The results enhance our understanding of psychological mechanisms between neuroticism and depression and provide suggestions for interventions to prevent or reduce depression in highly neurotic postgraduates.

The effects of curcumin on the metabolic parameters of non-alcoholic fatty liver disease: a meta-analysis of randomized controlled trials.

AIMS: Evidence indicates that curcumin seems to improve outcomes in non-alcoholic fatty liver disease (NAFLD). A meta-analysis was performed to evaluate the effects of curcumin inNAFLD. METHODS: We searched PubMed, EMBASE, and the Cochrane Library from inception through March 2018 to identify randomized controlled trials (RCTs) evaluating the role of curcumin inNAFLD. The mean difference (MD) and 95% confidence interval (CI) were calculated. RESULTS: Four RCTs with a total of 229 NAFLD patients were included. Curcumin was more likely to lower LDL-C, triglycerides, FBS, HOMA-IR, weight and AST levels compared with placebo, and the difference was statistically significant [MD = - 27.02, 95% CI (- 52.30, - 1.74); MD = - 33.20, 95% CI (- 42.30, - 24.09); MD = - 5.63, 95% CI (- 10.36, - 0.90); MD = - 0.53, 95% CI (- 1.00, - 0.05); MD = - 2.27, 95% CI (- 3.11, - 1.44); MD = - 7.43, 95% CI (- 11.31, - 3.54), respectively]. However, the beneficial effect of curcumin did not achieve statistical significance in lowering total cholesterol, HDL-C, HbA1c, ALT or insulin levels [MD = - 30.47,95% CI (- 60.89. - 0.06); MD = - 0.98, 95% CI (- 2.88, 0.92); MD = - 0.41, 95% CI (- 1.41, 0.59); MD = - 6.02, 95% CI (- 15.61, 3.57); MD = - 0.92, 95% CI (- 2.33, 0.49)]. CONCLUSIONS: Curcumin is effective in lowering LDL-C, triglycerides, FBS, HOMA-IR, weight, and AST levels in NAFLD patients, and it is well tolerated. Further RCTs are required to confirm our findings.

Antidiabetic Activity of Picris japonica Thunb Aqueous Extract in Diabetic KK-Ay Mice.

OBJECTIVE: To evaluate the hypoglycemic effect of Picris japonica Thunb (Asteraceae) on KK-Ay mice. METHODS: The hypoglycemic effect of Picris japonica aqueous extract (PJE) in a spontaneous type 2 diabetic model (KK-Ay mice) was studied in the present research. PJE was administrated at doses of 700 mg/kg and 350 mg/kg (calculated as crude herb) for 14 days and blood glucose, oral glucose tolerance test, plasma insulin level, and blood lipid were evaluated. Meanwhile, Rosiglitazone was used for the positive control. RESULTS: It was found the PJE treatment significantly reduced blood glucose level and improved oral glucose tolerance ability (p < 0.01 or p < 0.05) in a dose-dependent manner compared to the control diabetic mice. The blood insulin levels were significantly reduced in PJE-treated mice (700 mg/kg) and Rosiglitazone compared with the diabetic control (p < 0.01). Compared with the control diabetic group, the serum total cholesterol, triglyceride, and low density lipoprotein cholesterol were reduced by PJE (700 mg/kg) and Rosiglitazone (p < 0.05), and the serum high density lipoprotein cholesterol was significantly increased only by Rosiglitazone (p < 0.01). CONCLUSIONS: The findings demonstrate that Picris japonica has remarkable antidiabetic effect in diabetic KK-Ay mice, which suggests that Picris japonica may be beneficial to the treatment of type 2 diabetes mellitus.

Optimization of Ultrasound-Assisted Extraction, HPLC and UHPLC-ESI-Q-TOF-MS/MS Analysis of Main Macamides and Macaenes from Maca (Cultivars of Lepidium meyenii Walp).

Ultrasound-assisted extraction (UAE), using petroleum ether as the solvent, was systematically applied to extract main macamides and macaenes from Maca hypocotyls. Extraction yield was related with four variables, including ratio of solution to solid, extraction temperature, extraction time, and extraction power. On the basis of response surface methodology (RSM), the optimal conditions were determined to be the ratio of solution to solid as 10:1 (mL/g), the extraction temperature of 40 °C, the extraction time of 30 min, and the extraction power of 200 W. Based on the optimal extraction method of UAE, the total contents of ten main macamides and two main macaenes of Maca cultivated in twenty different areas of Tibet were analyzed by HPLC and UHPLC-ESI-Q-TOF-MS/MS. This study indicated that UAE was able to effectively extract macamides alkaloids from Maca hypocotyls. Quantitative analysis showed that geographical origins, not ecotypes, played a more important role on the accumulation of active macamides in Maca.

PDTCM: a systems pharmacology platform of traditional Chinese medicine for psoriasis.

INTRODUCTION: Psoriasis is a refractory skin disorder, and usually requires a lifetime control. Traditional Chinese medicine (TCM) is effective and safe for this disease. However, the cellular and molecular mechanisms of TCM remedies for psoriasis are still not fully understood. TCM contains numerous natural products. Natural products have historically been invaluable as a resource of therapeutic agents. Yet, there is no integrated information about active compounds of TCM for psoriasis. METHOD: We use systems pharmacology methods to develop the Psoriasis Database of Traditional Chinese Medicine (PDTCM). The database covered a number of psoriasis-related information (formulas, TCM, compounds, target proteins, diseases and biomarkers). With these data information, an online platform was constructed Results: PDTCM comprises 38 empirical therapeutic formulas, 34373 compounds from 1424 medicinal plants, 44 psoriasis-related proteins and 76 biomarkers from 111 related diseases. On this platform, users can screen active compounds for a psoriasis-related target and explore molecular mechanisms of TCM. Accordingly, users can also download the retrieved structures and data information with a defined value set. In addition, it helps to get a better understanding of Chinese prescriptions in disease treatment. CONCLUSION: With the systems pharmacology-based data, PDTCM would become a valuable resource for TCM in psoriasis-related research. Key messages PDTCM platform comprises a great deal of data on TCM and psoriasis. On this platform, users can retrieve and get needed information with systems pharmacology methods, such as active compounds screening, target prediction and molecular mechanisms exploration. It is a tool for psoriasis-related research on natural drugs systematically.

Multiscale Modeling of Drug-induced Effects of ReDuNing Injection on Human Disease: From Drug Molecules to Clinical Symptoms of Disease.

ReDuNing injection (RDN) is a patented traditional Chinese medicine, and the components of it were proven to have antiviral and important anti-inflammatory activities. Several reports showed that RDN had potential effects in the treatment of influenza and pneumonia. Though there were several experimental reports about RDN, the experimental results were not enough and complete due to that it was difficult to predict and verify the effect of RDN for a large number of human diseases. Here we employed multiscale model by integrating molecular docking, network pharmacology and the clinical symptoms information of diseases and explored the interaction mechanism of RDN on human diseases. Meanwhile, we analyzed the relation among the drug molecules, target proteins, biological pathways, human diseases and the clinical symptoms about it. Then we predicted potential active ingredients of RDN, the potential target proteins, the key pathways and related diseases. These attempts may offer several new insights to understand the pharmacological properties of RDN and provide benefit for its new clinical applications and research.

System-level study on synergism and antagonism of active ingredients in traditional Chinese medicine by using molecular imprinting technology.

In this work, synergism and antagonism among active ingredients of traditional Chinese medicine (TCM) were studied at system-level by using molecular imprinting technology. Reduning Injection (RDNI), a TCM injection, was widely used to relieve fever caused by viral infection diseases in China. Molecularly imprinted polymers (MIPs) synthesized by sol-gel method were used to separate caffeic acid (CA) and analogues from RDNI without affecting other compounds. It can realize the preparative scale separation. The inhibitory effects of separated samples of RDNI and sample combinations in prostaglandin E2 biosynthesis in lipopolysaccharide-induced RAW264.7 cells were studied. The combination index was calculated to evaluate the synergism and antagonism. We found that components which had different scaffolds can produce synergistic anti-inflammatory effect inside and outside the RDNI. Components which had similar scaffolds exhibited the antagonistic effect, and the antagonistic effects among components could be reduced to some extent in RDNI system. The results indicated MIPs with the characteristics of specific adsorption ability and large scale preparation can be an effective approach to study the interaction mechanism among active ingredients of complex system such as TCM at system-level. And this work would provide a new idea to study the interactions among active ingredients of TCM.

Insights into the inhibition and mechanism of compounds against LPS-induced PGE2 production: a pathway network-based approach and molecular dynamics simulations.

In comparison to the current target-based screening approach, it is increasingly evident that active lead compounds based on disease-related phenotypes are more likely to be translated to clinical trials during drug development. That is, because human diseases are in essence the outcome of the abnormal function of multiple genes, especially in complex diseases. Therefore, as a conventional technology in the early phase of active lead compound discovery, computational methods that can connect molecular interactions and disease-related phenotypes to evaluate the efficacy of compounds are in urgently required. In this work, a computational approach that integrates molecular docking and pathway network analysis (network efficiency and network flux) was developed to evaluate the efficacy of a compound against LPS-induced Prostaglandin E2(PGE2) production. The predicted results were then validated in vitro, and a correlation with the experimental results was analyzed using linear regression. In addition, molecular dynamics (MD) simulations were performed to explore the molecular mechanism of the most potent compounds. There were 12 hits out of 28 predicted ingredients separated from Reduning injection (RDN). The predicted results have a good agreement with the experimental inhibitory potency (IC50) (correlation coefficient = 0.80). The most potent compounds could target several proteins to regulate the pathway network. This might partly interpret the molecular mechanism of RDN on fever. Meanwhile, the good correlation of the computational model with the wet experimental results might bridge the gap between molecule-target interactions and phenotypic response, especially for multi-target compounds. Therefore, it would be helpful for active lead compound discovery, the understanding of the multiple targets and synergic essence of traditional Chinese medicine (TCM).

Network pharmacology study on the mechanism of traditional Chinese medicine for upper respiratory tract infection.

Traditional Chinese medicine (TCM) is a multi-component and multi-target agent and could treat complex diseases in a holistic way, especially infection diseases. However, the underlying pharmacology remains unclear. Fortunately, network pharmacology by integrating system biology and polypharmacology provides a strategy to address this issue. In this work, Reduning Injection (RDN), a well-used TCM treatment in the clinic for upper respiratory tract infections (URTIs), was investigated to interpret the molecular mechanism and predict new clinical directions by integrating molecular docking, network analysis and cell-based assays. 32 active ingredients and 38 potential targets were identified. In vitro experiments confirmed the bioactivities of the compounds against lipopolysaccharide (LPS)-stimulated PGE2 and NO production in RAW264.7 cells. Moreover, network analysis showed that RDN could not only inhibit viral replication but also alleviate the sickness symptoms of URTIs through directly targeting the key proteins in the respiratory viral life cycle and indirectly regulating host immune systems. In addition, other clinical applications of RDN such as neoplasms, cardiovascular diseases and immune system diseases were predicted on the basis of the relationships between targets and diseases.

Traditional Chinese herbs as chemical resource library for drug discovery of anti-infective and anti-inflammatory.

ETHNOPHARMACOLOGICAL RELEVANCE: Infection is a major group of diseases which caused significant mortality and morbidity worldwide. Traditional Chinese herbs have been used to treat infective diseases for thousands years. The numerous clinical practices in disease therapy make it a large chemical resource library for drug discovery. MATERIALS AND METHODS: In this study, we collected 1156 kinds of herbs and 22,172 traditional Chinese medicinal compounds (Tcmcs). The chemical informatics and network pharmacology were employed to analyze the anti-infective effects of herbs and Tcmcs. In order to evaluate the drug likeness of Tcmcs, the molecular descriptors of Tcmcs and FDA-approved drugs were calculated and the chemical space was constructed on the basis of principal component analysis in the eight descriptors. On purpose to estimate the effects of Tcmcs to the targets of FDA-approved anti-infective or anti-inflammatory drugs, the molecular docking was employed. After that, docking score weighted predictive models were used to predict the anti-infective or anti-inflammatory efficacy of herbs. RESULTS: The distribution of herbs in the phylogenetic tree showed that most herbs were distributed in family of Asteraceae, Fabaceae and Lamiaceae. Tcmcs were well coincide with drugs in chemical space, which indicated that most Tcmcs had good drug-likeness. The predictive models obtained good specificity and sensitivity with the AUC values above 0.8. At last, 389 kinds of herbs were obtained which were distributed in 100 families, by using the optimal cutoff values in ROC curves. These 389 herbs were widely used in China for treatment of infection and inflammation. CONCLUSION: Traditional Chinese herbs have a considerable number of drug-like natural products and predicted activities to the targets of approved drugs, which would give us an opportunity to use these herbs as a chemical resource library for drug discovery of anti-infective and anti-inflammatory.

CVDHD: a cardiovascular disease herbal database for drug discovery and network pharmacology.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death and associates with multiple risk factors. Herb medicines have been used to treat CVD long ago in china and several natural products or derivatives (e.g., aspirin and reserpine) are most common drugs all over the world. The objective of this work was to construct a systematic database for drug discovery based on natural products separated from CVD-related medicinal herbs and to research on action mechanism of herb medicines. DESCRIPTION: The cardiovascular disease herbal database (CVDHD) was designed to be a comprehensive resource for virtual screening and drug discovery from natural products isolated from medicinal herbs for cardiovascular-related diseases. CVDHD comprises 35230 distinct molecules and their identification information (chemical name, CAS registry number, molecular formula, molecular weight, international chemical identifier (InChI) and SMILES), calculated molecular properties (AlogP, number of hydrogen bond acceptor and donors, etc.), docking results between all molecules and 2395 target proteins, cardiovascular-related diseases, pathways and clinical biomarkers. All 3D structures were optimized in the MMFF94 force field and can be freely accessed. CONCLUSIONS: CVDHD integrated medicinal herbs, natural products, CVD-related target proteins, docking results, diseases and clinical biomarkers. By using the methods of virtual screening and network pharmacology, CVDHD will provide a platform to streamline drug/lead discovery from natural products and explore the action mechanism of medicinal herbs. CVDHD is freely available at http://pkuxxj.pku.edu.cn/CVDHD.

[Effects of acupuncture-moxibustion intervention on proprioception in athletes with lateral collateral ligament injury of ankle joint].

OBJECTIVE: To compare the efficacy differences between acupuncture-moxibustion and physiotherapy interventions in improving proprioception of athletes with lateral collateral ligament injury of the ankle joint. METHODS: Thirty patients with injured lateral collateral ligament of ankle joint were randomly divided into acupuncture group (n = 15) and physiotherapy group (n = 15). Patients of the acupuncture group were treated by acupuncture and moxibustion stimulation of Qiuxu (GB40), Kunlun (BL 60), Shenmai (BL 62), Jiexi (ST 41), and Ashi-points, etc., and those of the physiotherapy group treated with TDP irradiation of the regional lateral malleolus. The treatment of the two groups was conducted once the other day, 3 times each week, continuously for 8 weeks. Before and after the treatment, the ankle-joint's active and passive repositioning error angles were measured by using a joint angle ruler. RESULTS: The average error angle values of active and passive reposition tests of the injured ankle-joint were 4.98 +/- 1.11 and 4.78 +/- 1.3 before the treatment, and 3.67 +/- 0.58 and 3.51 +/- 0.64 after the treatment, respectively in the acupuncture group, being reduced significantly after the treatment (both P < 0.01). No significant changes of the average error angle values of both active and passive reposition tests of the ankle-joint were found after the treatment in the physiotherapy group (P > 0.05). Comparison between two groups showed that the average error angle, average active and passive reposition angles of the injured ankle in the acupuncture group were evidently lower than those in the physiotherapy group (P < 0.01). CONCLUSION: Acupuncture and moxibustion can effectively improve the proprioception of the injured lateral collateral ligament of the ankle joint in athletes, which is superior to conventional physiotherapy in the therapeutic effect.

A Drug-Target Network-Based Approach to Evaluate the Efficacy of Medicinal Plants for Type II Diabetes Mellitus.

The use of plants as natural medicines in the treatment of type II diabetes mellitus (T2DM) has long been of special interest. In this work, we developed a docking score-weighted prediction model based on drug-target network to evaluate the efficacy of medicinal plants for T2DM. High throughput virtual screening from chemical library of natural products was adopted to calculate the binding affinity between natural products contained in medicinal plants and 33 T2DM-related proteins. The drug-target network was constructed according to the strength of the binding affinity if the molecular docking score satisfied the threshold. By linking the medicinal plant with T2DM through drug-target network, the model can predict the efficacy of natural products and medicinal plant for T2DM. Eighteen thousand nine hundred ninety-nine natural products and 1669 medicinal plants were predicted to be potentially bioactive.

Platelet aggregation pathway network-based approach for evaluating compounds efficacy.

Traditional Chinese medicines (TCMs) contain a large quantity of compounds with multiple biological activities. By using multitargets docking and network analysis in the context of pathway network of platelet aggregation, we proposed network efficiency and network flux model to screen molecules which can be used as drugs for antiplatelet aggregation. Compared with traditional single-target screening methods, network efficiency and network flux take into account the influences which compounds exert on the whole pathway network. The activities of antiplatelet aggregation of 19 active ingredients separated from TCM and 14 nonglycoside compounds predicated from network efficiency and network flux model show good agreement with experimental results (correlation coefficient = 0.73 and 0.90, resp.). This model can be used to evaluate the potential bioactive compounds and thus bridges the gap between computation and clinical indicator.

Drug-target network and polypharmacology studies of a Traditional Chinese Medicine for type II diabetes mellitus.

Many Traditional Chinese Medicines (TCMs) are effective to relieve complicated diseases such as type II diabetes mellitus (T2DM). In this work, molecular docking and network analysis were employed to elucidate the action mechanism of a medical composition which had clinical efficacy for T2DM. We found that multiple active compounds contained in this medical composition would target multiple proteins related to T2DM and the biological network would be shifted. We predicted the key players in the medical composition and some of them have been reported in literature. Meanwhile, several compounds such as Rheidin A, Rheidin C, Sennoside C, procyanidin C1 and Dihydrobaicalin were notable although no one have reported their pharmacological activity against T2DM. The association between active compounds, target proteins and other diseases was also discussed.

Surface-initiated molecularly imprinted polymeric column: In situ synthesis and application for semi-preparative separation by high performance liquid chromatography.

In this work, we prepared a monolithic and surface initiated molecularly imprinted polymeric (MIP) column for HPLC and explored its application for template separation from plant extract. The silica beads (40-60 µm) were coupled with initiator on the surface and then packed in to a stainless steel HPLC column. The pre-polymerization mixture (the template, functional monomer and crosslinker were emodin, acrylamide and divinylbenzene, respectively) was injected into the column and polymerized by thermal initiation. The prepared MIP column exhibited excellent retention capability and large imprinted factor for template (the retention time and imprinted factor for emodin on MIP column were 16.26 min and 7.21, respectively). Moreover, the emodin-molecularly imprinted polymeric column could be applied to separate emodin from alcohol extract of Rheum palmatum L. at semi-preparative scale and 1.2 mg of emodin was obtained in 4 h.

[Effects of sinomenine on synovial fluid and serum content of interleukin-1beta in rabbits with osteoarthritis].

OBJECTIVE: To investigate the effects of intra-articular injection of sinomenine on interleukin-1beta (IL-1beta) content in synovial fluid and serum in rabbits with osteoarthritis (OA). METHODS: Degenerative osteoarthritis in the knee joint of left posterior limb was induced in 36 rabbits by full extension using plaster cast for 6 weeks. Then the rabbits were randomly divided into untreated group, hyaluronic acid group and sinomenine group. Another 4 normal rabbits were selected as normal control group. Rabbits in the sinomenine group and the hyaluronic acid group received intraarticular injections of sinomenine and hyaluronic acid once a week for 5 weeks, respectively. The content of IL-1beta in synovial fluid and serum were measured before and after treatment by enzyme-linked immunosorbent assay. The pathological changes of cartilaginous tissue were analyzed by using Mankin's score. RESULTS: Compared with those in the untreated group, synovial fluid and serum IL-1beta contents in the sinomenine group and the hyaluronic acid group were significantly decreased (P<0.01). And the synovial fluid and serum IL-1beta contents in the sinomenine group were lower than those in the hyaluronic acid group (P<0.05). The mean Mankin's score of cartilage in the sinomenine group was significantly lower than that in hyaluronic acid group (P<0.05). CONCLUSION: Sinomenine may reduce the degree of articular degeneration in rabbit with OA through decreasing the content of IL-1beta in synovial fluid and serum.

Can the aggregation be a new approach for understanding the mechanism of Traditional Chinese Medicine?

"Frequent hitter" phenomenon emerged in the high-throughput screening; one of the most common mechanisms behind artifactual inhibition is that some organic molecules formed large colloid-like aggregates which are able to sequester and thereby inhibit enzymes. To investigate the situation in Traditional Chinese Medicine (TCM), 60 medicinal herbs and 24 Chinese herbal formulae were detected by dynamic light scattering (DLS), and aggregates were observed in all the 84 solution mixtures. The aggregates of two Chinese herbal formulae, 'Xue-Fu-Zhu-Yu Tang' (XF) and 'Jing-Guan Tang' (JG), were not only able to survive in the gastro-intestinal environment, but also had the ability to pass through the monolayer of the Caco-2 cell. The activities of XF and JG against three cardiovascular targets were also aggregates-related. Based on these findings, a new possible mechanism of the action of Chinese medicine was proposed.

Activity of compounds from Chinese herbal medicine Rhodiola kirilowii (Regel) Maxim against HCV NS3 serine protease.

Treatment of the chronic hepatitis C virus (HCV) infection is an unmet medical need, and the HCV NS3 serine protease (NS3-SP) has been used as an attractive target of antiviral screening against HCV. To find naturally chemical entities as lead compounds from which novel anti-HCV agents could be developed, bioassay-guided fractionation and isolation were performed on a crude ethanol extract from rhizomes of the Chinese medicinal herb Rhodiola kirilowii (Regel) Maxim using column chromatography (CC) techniques and in vitro inhibitory activity against HCV NS3-SP. The partition of the extract between water and different organic solvents led to the isolation and identification of 12 compounds in the ethyl acetate part which proved to be the most active. These compounds were tested for in vitro activity against HCV NS3-SP, among which four (-)-Epicatechin derivatives: 3,3'-Digalloylproprodelphinidin B2 (Rhodisin, 1); 3,3'-Digalloylprocyanidin B2 (2); (-)-Epigallocatechin-3-O-gallate (EGCG, 3); and (-)-Epicatechin-3-O-gallate (4, ECG) represented the most potent ones with IC(50) of 0.77, 0.91, 8.51, and 18.55 microM, respectively. Salidroside, the commonly known compounds, together with the other compounds showed no activity up to 100.0 microM. Methylation and acylation of the hydroxyl groups of 1-4 caused a decrease of activity. Cell viability and secreted alkaline phosphatase (SEAP) activity assays with 1-4 revealed little if any toxicity. These nonpeptide inhibitors of HCV NS3-SP might serve as potential candidate anti-HCV agents.