ABSTRACT
Sophorae Flavescentis Radix,derived from the root of Sophora flavescens in the Leguminosae family,has been widely used in the medicine,agriculture,animal husbandry,and daily chemical industry. A pharmacophore model-based method for rapid discovery of tyrosinase inhibitors( TIs) from S. flavescens was established by molecular docking under Lipinski rules,and verified by enzyme assays. Briefly,the chemical constituent database of S. flavescens( CDSF) was established based on the previous papers. Theoptimal pharmacophore model( OPM) was constructed by DS 2019 on the basis of known active TIs. Eighty-three hits predominated by flavonoids having higher fitting scores with OPM than the positive control were screened out,and subjected to molecular docking based on the three-dimensional structure of tyrosinase crystal protein. The potential TIs such as kurarinone and nor-kurarinone were rapidly discovered from the compounds with higher docking scores than the positive control under the Lipinski rules. The results were verified by the in vitro enzyme assays. The inhibition activities of tyrosinase from non-medicinal parts of S. flavescens were also tested to explore the relationship between the inhibition activity and chemical compositions. This study is expected to provide data support for the comprehensive application and development of S. flavescens and also a new method for the rapid discovery of active substances or functional constituents in the complex systems.
Subject(s)
Animals , Flavonoids , Molecular Docking Simulation , Monophenol Monooxygenase , Plant Extracts/pharmacology , Plant Roots , SophoraABSTRACT
Objective:To systematically evaluate the efficacy and safety of modified Buyang Huanwu Tang in the treatment of chronic heart failure. Method:CNKI database，Wanfang database，VIP database，Pubmed，MEDLINE，EMBASE and Cochrane database were retrieved systematically. The literature retrieval period is from no limit to December 2019，with "Buyang Huanwu Tang" and "chronic heart failure" "heart failure" as the key words for full-text retrieval of Chinese and English databases. Literatures of randomized controlled trials（RCTs） for chronic heart failure were included， and the data were extracted. Cochrane system evaluation method was used to score the quality of literature. Stata 14.0 was applied in Meta-analysis on the retrieval results. TSA0.9 was applied in test sequential analysis. Sensitivity analysis was made to explain heterogeneity，and funnel chart was used to evaluate publication bias. Result:A total of 2 037 patients were included in 21 RCT studies. The article quality risk assessment was generally unclear risk of bias. The results of meta-analysis showed that the left ventricular ejection fraction （LVEF） in the experimental group was significantly higher than that in the control group，with statistically significant differences ［MD=0.901，95% CI （0.772，1.029），P<0.01］，the left ventricular end diastolic diameter （LVEDd） in the experimental group was significantly lower than that in the control group，with statistically significant differences ［OR=-0.650，95% CI=（-0.854，-0.446），P<0.01］，BNP in the experimental group was significantly lower than that in the control group，with statistically significant differences ［MD=-1.212，95% CI=（-1.359，-1.066），P<0.01］，6-minute walk test （6MWT） in the experimental group was significantly higher than that in the control group，with statistically significant differences ［MD=0.797， 95% CI=（0.447，1.146），P<0.01］，and the effective rate in the experimental group was significantly improved，with statistically significant differences ［OR=1.840，95% CI=（1.680，2.016），P<0.01］. Conclusion:Modified Buyang Huanwu Tang combined with conventional western medicine treatment of chronic heart failure is more effective than single administration of western medicine treatment，and can improve clinical efficacy， effectively improve the LVEF of patients with chronic heart failure，reduce the LVEDd reduces plasma BNP levels，prolong the 6-minute walking distance，and reduce the incidence of adverse reactions.
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BACKGROUND:In recent years, the application of stem cel s to treat autoimmune diseases has become a hot spot. But, studies on umbilical cord blood mesenchymal stem cel s transplantation for the treatment of polymyositis/dermatomyositis are rarely reported. OBJECTIVE:To explore the immunologic mechanism of Th cytokines on the occurrence and development of polymyositis/dermatomyositis by observing the changes in serum interferon-γ, interleukin-4 and interleukin-17 in patients after umbilical cord blood mesenchymal stem cel s transplantation. METHODS:Eighty-one polymyositis/dermatomyositis patients were selected and divided into conventional therapy group (n=44) undergoing glucocorticoid and immunosuppressants therapy and cel transplantation group (n=37) undergoing intravenous infusion of umbilical cord blood mesenchymal stem cel s at a density of (3.5-5.2 )×107 . Dosing regimen was same in the two groups. After fol ow-up of 1, 3, 6 months, the changes of creatine kinase and myodynamia were evaluated;after fol ow-up of 3 and 6 months, lung imaging was evaluated;in the cel transplantation group, interferon-γ, interleukin-4 and interleukin-17 levels were detected before treatment and at 3 and 6 months after treatment. RESULTS AND CONCLUSION:At 1, 3, 6 months after treatment, the creatine kinase level was significantly decreased, and the muscle force grade was significantly increased in both groups (both P0.05). These findings indicate umbilical cord blood mesenchymal stem cel s transplantation combined with glucocorticoid and immunosuppressants therapy can adjust immune network effects and improve the immune tolerance in polymyositis/dermatomyositis patients, which is safe and effective.
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Objective To investigate the roles of hemopoietic stem cells (HSCs) in the pathogenesis of psoriasis. Methods HSCs were isolated from the bone marrow of a patient with psoriasis vulgaris and a normal human control. Forward- and reverse-subtracted cDNA libraries were constructed by using suppression subtractive hybridization (SSH) technique between HSCs from the patient and control. Bacterial PCR and dot hybridization were performed to screen for positive clones followed by gene sequencing, identification and functional analysis. Real time quantitative PCR was carried out to measure the mRNA expression of interferon-γ and thymosin 10 (TMSB10). Results Nine genes were screened from the forward-subtracted cDNA library which encoded interferon-γ, tyrosine phosphatase, SUMO1 activase, etc, and 8 genes including the TMSB10-encoding gene were screened from the reverse-subtracted cDNA library. The relative expression level of interferon-γ in HSCs from the patient was 47.5 times that in HSCs from the control, while the level of TMSB10 from the control was 22.6 times that from the patient. Conclusion The abnormal expression of 17 genes which encode interferon-γ, thyrosin, and so on, may be involved in the development of psoriasis.
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Objective To observe the growth and biological features of bone mesenchymal stem cells (BMSC) from psoriatic patients. Methods Peripheral blood mononuclear cells were isolated from 5 patients with active psoriasis vulgaris and 5 normal human controls, and BMSC were obtained and purified using plastic adherence method followed by primary culture and passage in vitro. The cell morphology, density and growth were observed with microscopy. Cell growth pattern was evaluated by MTT assay. Flow cytometry was applied to identify surface antigens, including CD29, CD34, CD45 and CD106, on these cells. Results No significant difference was observed in the morphology of primary or descendant BMSC between the patients and controls.The primary BMSC from psoriatic patients tended to adhere to the plastic wall later, confluence and grow more slowly compared with those from the controls. The BMSCs from both psoriatic patients anti healthy donors were positive for CD29, but negative for CD34 or CD45. On the 4th day of culture, the BMSC from psoriatic patients exhibited a decrease in proliferation, with the absorbence at 470 nm (A470) being 0.081±0.0066 and 0.095±0.0130, respectively for BMSC from the patients and controls (t=2.358, P<0.05). Conclusion There is a decrease in the proliferation of BMSC from psoriatic patients which show a morphological similarity to those from healthy controls.