Systematic elucidation of the bioactive alkaloids and potential mechanism from Sophora flavescens for the treatment of eczema via network pharmacology.

ETHNOPHARMACOLOGY RELEVANCE: Sophora flavescens is a frequently used traditional Chinese medicine (TCM) for the treatment of skin disorders, diarrhea, vaginal itching and inflammatory diseases. In particular, the root of S. flavescens combination with other herbs mainly treat eczema ailment in the clinical applications. However, a holistic network pharmacology approach to understanding the mechanism by which alkaloids in S. flavescens treat eczema has not been pursued. AIM OF THE STUDY: To examine the network pharmacological potential effect of S. flavescens on eczema, we studied the alkaloids, performed protein targets prediction and investigated interacting signal pathways. Furthermore, animal experiment was carried out to evaluate its efficacy and real-time quantitative polymerase chain reactions (RT-qPCR) analysis was explored the mechanism of action. MATERIALS AND METHODS: The detail information on alkaloids from S. flavescens were obtained from a handful of public databases on the basis of oral bioavailability (OB ≥ 30%) and drug-likeness (DL ≥ 0.18). Then, correlations between compounds and protein targets were linked using the STRING database, and targets associated with eczema were gathered by the GeneCards database. Human genes were identified and subjected to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and Gene Ontology (GO) functional enrichment analysis. Particularly, matrine, the crucial alkaloid from S. flavescens, was estimated using a 2,4-dinitrochlorobenzene (DNCB)-induced eczema Kunming (KM) mice model, administered (50 mg/kg and 10 mg/kg) to mice for 22 days. On the last day, the activities of serum tumor necrosis factor α (TNF-α), interleukin-4 (IL-4) and histopathologic examinations were determined. For further to elucidate the mechanisms, the mRNA levels of TNF-α, STAT3, TP53, AKT1, IL-6, JUN and EGFR in dorsal skin tissues were also tested. RESULTS: Network analysis collected and identified 35 alkaloids from S. flavescens. Among them, in total 10 dominating alkaloids, including matrine, oxymatrine, sophoridine, sophocarpine, oxysophocarpine, allomatrine, sophoramine, anagyrine, cytisine and N-methylcytisine. And 71 related targets were provided of alkaloids for the treatment of eczema from S. flavescens. Furthermore, matrine dose-dependently (50 or 10 mg/kg, 22 days, apply to dorsal skin) remarkable decreased the serum levels of TNF-α and IL-4, and significantly alleviated the skin lesions. The effects of 50 mg/kg of matrine were almost identical to those of 200 mg/kg of the positive drug dexamethasone (DXM). The further RT-qPCR analyses could reveal that matrine down-regulate TNF-α, STAT3 and TP53 at transcriptional level in dorsal skin tissues. CONCLUSION: Pharmacological network analysis can utilize to illuminate the pharmacodynamic substances and the potential molecular mechanism of S. flavescens for treating eczema. Matrine, as the crucial alkaloid from S. flavescens, could be a promising drug candidate for the treatment of eczema ailment.

First Discovery of Beta-Sitosterol as a Novel Antiviral Agent against White Spot Syndrome Virus.

The outbreak of white spot syndrome (WSS) is a looming challenge, due to dramatic losses to the crustacean aquaculture industry. However, at present, there are no prophylactic or therapeutic means to control this infectious viral disease. Here, we screened fifteen medicinal plants for their inhibitory activity on the white spot syndrome virus (WSSV), using red swamp crayfish (Procambarus clarkii) as a model species. The results showed that the crude extracts of Pinellia ternata (Thunb.) Breit. had the highest inhibitory effect (91.59%, 100 mg/kg) on WSSV proliferation, and its main component, beta-sitosterol, showed a much higher activity (95.79%, 50 mg/kg). Further, beta-sitosterol potently reduced (p < 0.01) viral loads and viral gene transcription levels in a concentration-dependent fashion, and significantly promoted the survival rate of WSSV-challenged crayfish (57.14%, 50 mg/kg). The co-incubation assay indicated that beta-sitosterol did not influence the infectivity of WSSV particles. Both pre- and post-treatment of beta-sitosterol exerted a significant inhibitory effect (p < 0.01) on the viral load in vivo. Mechanistically, beta-sitosterol not only interfered with the expression of viral genes (immediate early gene 1, ie1; DNA polymerase, DNApol) that are important in initiating WSSV transcription, but it also attenuated the hijacking of innate immune signaling pathways (Toll, IMD, and JAK/STAT pathways) by viral genes to block WSSV replication. Moreover, the expression of several antiviral immune, antioxidant, pro-inflammatory, and apoptosis-related genes changed significantly in beta-sitosterol-treated crayfish. Beta-sitosterol is a potent WSSV inhibitor and has the potential to be developed as an effective anti-WSSV agent against a WSS outbreak in crustacean aquaculture.

Ophiopogon japonicus inhibits white spot syndrome virus proliferation in vivo and enhances immune response in Chinese mitten crab Eriocheir sinensis.

White spot syndrome virus (WSSV) is a fatal pathogen threatening global crustacean industry with no commercially available drugs to control. Herbal medicines have been widely used to treat a number of viral infections, which could offer a rich reserve for antiviral drug discovery. Here, we evaluated the inhibition activities of 30 herbal medicines against WSSV in Chinese mitten crab Eriocheir sinensis. A WSSV infection model in E. sinensis was firstly established in order to determine the antiviral effects of the plant extracts and to explore the potential action mechanisms. Results showed that the highest anti-WSSV activity was obtained by the treatment of Ophiopogon japonicus extract (93.03%, 100 mg/kg). O. japonicus treatment decreased viral loads in a dose-dependent manner and significantly improved the survival of WSSV-challenged crabs. O. japonicus reduced the expression of vital genes in viral life cycle in vivo, particularly for the immediate-early stage gene ie1. Further results indicated that O. japonicus could repress the JAK-STAT signaling pathway to block ie1 transcription. Moreover, O. japonicus could modulate certain immune genes such as the myosin, toll-like receptor, crustin, and prophenoloxidase in the interactions between WSSV and crabs. The up-regulated expression of pro-autophagic factors (Gabarap and Atg7) and elevated levels of antioxidant enzymes (SOD, CAT and GSH) suggested that O. japonicus may induce autophagy and attenuate WSSV-induced oxidative stress. Taken together, O. japonicus could inhibit WSSV proliferation and improve the survival of WSSV-challenged crabs. Thus, O. japonicus may have the potential to be developed as a preventive or therapeutic agent against WSSV, and its effective compounds merit further isolation and identification.

The functional effects of voluntary and involuntary phantom color on conscious awareness.

The constructive nature of vision is perhaps most evident during hallucinations, mental imagery, synesthesia, perceptual filling-in, and many illusions in which conscious visual experience does not overtly correspond to retinal stimulation: phantom vision. However, the relationship between voluntary and involuntary phantom vision remains largely unknown. Here, we investigated 2 forms of visual phantom color, neon phantom color spreading and voluntary color mental imagery, and their effect on subsequent binocular rivalry perception. Passively viewing neon phantom color induced time sensitive, suppressive effects on subsequent binocular rivalry. These effects could be attenuated by rotating the color inducers, or like color imagery, by concurrent uniform luminance stimulation. The degree of neon color induced rivalry suppression predicted the degree of voluntary color imagery facilitation, both on subsequent rivalry perception. Further, there were functional interactions between voluntary imagery and involuntary neon phantom vision when experienced successively. Our results suggest potential sensory mechanistic commonalities between voluntary and involuntary phantom vision. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

The functional effects of prior motion imagery and motion perception.

The functional sensory effects and commonalties between mental imagery of different visual features such as color, form or motion remains largely unknown. Mental imagery of static visual features, including color and orientation, can have a facilitative, priming effect on subsequent perception. However, whether motion imagery can have a similar effect remains unknown. Here we used the binocular rivalry method as a measure of motion mental imagery. After imagining or viewing motion of a particular direction, participants were required to report the dominant motion direction in a brief motion rivalry stimulus. We found that motion imagery can have a facilitative priming effect on subsequent motion rivalry perception, and this effect can be attenuated by concurrent expanding and contracting perceptual motion, but not by static or flickering uniform luminance. Unlike color or orientation imagery, the effect of motion imagery on subsequent rivalry was location independent. We also observed this facilitative priming effect with prior low-contrast perceptual motion, but prior high-contrast motion induced a suppressive effect. Simultaneous imagery and perceptual motion in opposite directions induced priming, while congruent directions did not. Counter to prior findings, these results suggest motion imagery can have a priming effect on perception and that the rivalry method can be used to assess visual motion imagery. These results provide evidence for visual imagery as a multi-feature structure.

Dietary Sodium Butyrate Supplementation Promotes Oxidative Fiber Formation in Mice.

Sodium butyrate (SB), a sodium salt of butyric acid, has been shown to improve the animal production performance. The aim of this work was to test the effect of feeding mice with diets containing different dose of SB (1, 3, and 5%) on oxidative fiber formation. Dietary SB supplementation had no effect on body weights and food intakes. Dietary SB supplementation upregulated the expressions of oxidative fiber-related protein including MyHC I, MyHC IIa, myoglobin, and troponin-I-slow. Dietary SB supplementation also upregulated the expressions of phospho-FoxO1 and MEF2C protein, but did not affect total FoxO1 protein expression. Taken together, these results indicate that dietary SB supplementation promotes oxidative fiber formation in mice, which might be through inactivation of FoxO1 and upregulation of MEF2C expression.

Anticancer effects of ß-elemene in gastric cancer cells and its potential underlying proteins: a proteomic study.

Gastric cancer is a common malignancy with a poor prognosis. ß-elemene is a broad-spectrum anticancer drug extracted from the traditional Chinese medicinal herb Curcuma wenyujin. In the present study, we investigated the anticancer effects of ß-elemene in gastric cancer cells and the potential proteins involved. Human SGC7901 and MKN45 gastric cancer cells were treated with different concentrations of ß-elemene. Cell viability, clonogenic survival and apoptotic cell death were assessed. ß-elemene inhibited viability and decreased clonogenic survival of gastric cancer cells in a dose-dependent manner. Apoptosis induction contributed to the anticancer effects. We then employed a proteomic method, isobaric tags for relative and absolute quantitation (iTRAQ), to detect the proteins altered by ß-elemene. In total, 147 upregulated proteins and 86 downregulated proteins were identified in response to ß-elemene treatment in SGC7901 gastric cancer cells. Among them, expression of p21-activated protein kinase­interacting protein 1 (PAK1IP1), Bcl-2-associated transcription factor 1 (BTF) and topoisomerase 2-α (TOPIIα) were validated by western blot analyses and the trends were consistent with iTRAQ results. Top pathways involved in ß-elemene treatment in SGC7901 gastric cancer cells included ribosome signaling, peroxisome proliferator-activated receptors (PPARs) signaling pathway, regulation of actin cytoskeleton, phagosome, biosynthesis and metabolism of some amino acids. Collectively, our results suggest a promising therapeutic role of ß-elemene in gastric cancer. The differentially expressed proteins provide further insight into the potential mechanisms involved in gastric cancer treatment using ß-elemene.

The functional effects of color perception and color imagery.

Functional imaging research and studies of brain-damaged patients suggest the mechanisms of color perception and color imagery have some degree of overlap. Previous research into color imagery has focused on compound images consisting of both color and form, e.g., whole objects. Little is known regarding the characteristics of pure color imagery-color without form structure. Binocular rivalry has proven to be a successful method for assessing mental imagery indirectly, quantitatively, and reliably. Here, we utilized this technique to access pure color imagery. Experiment 1 consisted of three conditions, in which participants were instructed to either imagine pure colors according to a letter cue, imagine pure colors in the presence of background luminance, or passively view weak perceptual color patches. Subsequently, a brief rivalry display was presented. Results indicated that perceptual dominance during rivalry was significantly biased by the participants' prior color imagery and perception. However, for imagery, the addition of background luminance attenuated this priming effect. In Experiment 2, we tested whether color imagery was location-specific in retinotopic space. Color imagery was only found to prime subsequent rivalry when the imagery and rivalry stimuli occurred at the same retinotopic location. These results demonstrate that imagery of pure colors without form structure can influence subsequent color perception and can be localized in retinotopic space. These results are consistent with previous studies examining mental imagery of compound visual stimuli and demonstrate the potential of investigations into mental imagery of individual visual features.

[Observation and multifactor analysis of refractory medium-severe heart failure by micro-inflammation modification in uremic patients].

OBJECTIVE: To investigate the therapeutic strategies and prognostic factors of refractory medium-severe heart failure in uremic patients. METHODS: A single center, self control clinical research was conducted, and the data consisted of 30 uremic patients with refractory medium-severe heart failure undergoing maintenance hemodialysis (MHD), who received routine combined modality therapy and Xuebijing injection (to modify micro-inflammation). The systolic function of the left ventricle was compared before and after therapy. Multiple linear regression models were established to predict the improvements of systolic function of ventricle. Relationship between the accumulated dose of Xuebijing injection and changes of C-reactive protein (ΔCRP) was observed. RESULTS: The values of left ventricle ejection fraction (LVEF), fractional shortening (FS), and stroke volume (SV) after therapy were improved compared with those before therapy [LVEF: 0.42±0.07 vs. 0.34±0.04, FS: (21.07±3.83)% vs. (16.33±2.43)%, SV: 66.83±7.00 ml vs. 52.20±7.62 ml, all P<0.01]. In terms of cardiac output (CO), there was no statistical difference before and after therapy (4.77±0.65 L/min vs. 4.49±0.68 L/min, P>0.05). In the multiple linear regression models of ΔLVEF, ΔFS and ΔSV, the independent variables that affect dependent variables included age, ΔCRP, changes of hemoglobin (ΔHb), accumulated dose of Xuebijing injection, changes of HCO(3)(-) (Δ HCO(3)(-)), changes of serum creatinine (ΔSCr), Hb and CRP after therapy, the factors and weights of which had slight variation on accordance with different dependent variables. There was significant positive correlation between accumulated dose of Xuebijing injection and ΔCRP (r=0.561, P=0.001). CONCLUSIONS: Xuebijing injection can improve heart function in uremic patients by modifying micro-inflammation, whose accumulated dose and therapeutic effect show positive correlation. In addition the improvement of heart failure has something to do with age, ΔHb, Hb after therapy, the correction of acidosis and dialysis sufficiency.

Palladium electrodes for molecular tunnel junctions.

Gold has been the metal of choice for research on molecular tunneling junctions, but it is incompatible with complementary metal-oxide-semiconductor fabrication because it forms deep level traps in silicon. Palladium electrodes do not contaminate silicon, and also give higher tunnel current signals in the molecular tunnel junctions that we have studied. The result is cleaner signals in a recognition-tunneling junction that recognizes the four natural DNA bases as well as 5-methyl cytosine, with no spurious background signals. More than 75% of all the recorded signal peaks indicate the base correctly.

Xiang-qi-tang increases avian pathogenic Escherichia coli-induced survival rate and regulates serum levels of tumor necrosis factor alpha, interleukin-1 and soluble endothelial protein C receptor in chicken.

Xiang-qi-tang (XQT) is a Chinese herbal formula containing rhizoma Cyperi, Andrographis paniculata and Astragalus membranaceus. The present study investigated the effects of XQT on the mortality and inflammatory mediators in a chicken model challenged with avian pathogenic Escherichia coli (APEC). To detect the effect of XQT, the chickens were pretreated with the formula 12 h before being challenged with 10(8) colony forming unit (CFU) of APEC. The results showed that 0.6 g/kg XQT significantly elevated the survival rate of infected chickens. To further investigate the mechanism of decreasing mortality of XQT, we examined plasma inflammatory mediator levels. The levels of tumor necrosis factor alpha (TNF-α), interleukin-1 (IL-1) and soluble endothelial protein C receptor (sEPCR) were significantly increased in chickens challenged with APEC alone, whereas chickens pretreated with 0.6 g/kg XQT showed marked decrease of these inflammatory mediator levels during the death peak. Taken together, this study demonstrates that XQT has protective effects in APEC-treated chickens. The action mechanisms of XQT involve anti-inflammation and antithrombotic activity. These findings may contribute to future research on the action mechanisms of this formula, as well as prevention of or therapy for avian colibacillosis.