Network Pharmacology and Molecular Docking Analyses Unveil the Mechanisms of Yiguanjian Decoction against Parkinson's Disease from Inner/Outer Brain Perspective.

Objective: This study aims to explore the pharmacodynamic mechanism of Yiguanjian (YGJ) decoction against Parkinson's disease (PD) through integrating the central nervous (inner brain) and peripheral system (outer brain) relationship spectrum. Methods: The active components of YGJ were achieved from the TCMSP, TCMID, and TCM@Taiwan databases. The blood-brain barrier (BBB) permeability of the active components along with their corresponding targets was evaluated utilizing the existing website, namely, SwissADME and SwissTargetPrediction. The targets of PD were determined through database retrieval. The interaction network was constructed upon the STRING database, followed by the visualization using Cytoscape software. Then, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses on potential targets. Finally, the molecular docking approach was employed to assess the binding affinity between key components and key targets. Results: Overall, we identified 79 active components, 128 potential targets of YGJ, and 97 potential targets of YGJ-BBB potentially suitable for the treatment of PD. GO and KEGG analyses showed that the YGJ treatment of PD mainly relied on PI3K-Akt pathway while the YGJ-BBB was mostly involved in endocrine resistance. The molecular docking results displayed high affinity between multiple compounds and targets in accordance with previous observations. Conclusions: Our study unveiled the potential mechanisms of YGJ against PD from a systemic perspective: (1) for the YGJ, they have potential exerting effects on the peripheral system and inhibiting neuronal apoptosis through regulating the PI3K-Akt pathway; (2) for the YGJ-BBB, they can directly modulate endocrine resistance of the central nervous and holistically enhance body resistance to PD along with YGJ on PI3K-Akt pathway.

Experimental study on the effect of the split-type air-conditioner on the transmission of smoking pollutants in a room.

Environmental tobacco smoke (ETS) has become one of the most important sources of indoor air pollution. The study aimed to obtain the variation characteristics of typical air pollutant concentrations when people smoke in a closed room and explore the effect of the air-conditioner. A closed and air-conditioned room of 21 m2 was taken as the research object. Fine particulate matter (PM2.5) and total volatile organic compound (TVOC) were measured while 10 cigarettes were burnt in smoldering or smoking mode, with the air-conditioner on or off. The contents of nicotine in condensate samples were obtained by liquid chromatography. The impact of ETS on indoor air quality lasted for hours, causing typical pollutant concentrations to far exceed the Chinese standard. The PM2.5 produced by smoking was 11 times higher than by smoldering, but the TVOC produced by smoldering was more than by smoking. After one hour of the cigarette burning off, the PM2.5 concentration would be decreased by 96.1% with the air-conditioner on, in contrast to 67.9% with the air-conditioner off. Nicotine was detected in all samples of condensate from the air-conditioner. It is concluded that smoking cigarettes cannot be replaced by smoldering to evaluate the pollution of ETS. The air-conditioner has a positive effect on reducing the concentration of air pollutants produced by cigarette burning. More than 10% of the indoor nicotine may be taken away by condensate discharge, and its possible pollution should be paid attention to.Implications: This study provides new evidence of the effect of the split-type air-conditioner on ETS. The TVOC concentrations, which were less considered previously, were measured. PM2.5 concentration in human breathing zone can be reduced more quickly with the air-conditioner on. This study shows that there is a big difference in the concentrations of typical pollutants between smoking and smoldering. And it could be a guide for the formulation of relevant research methods. This study also demonstrates that the air conditioning condensate from the smoking room may contain nicotine. Attention should be paid to the recovery and utilization of such condensate.

Environmental level of the antidepressant venlafaxine induces behavioral disorders through cortisol in zebrafish larvae (Danio rerio).

Psychoactive drugs discharged into the environment have different effects on the behavior of vertebrates. The objective of this study was to evaluate the effect of venlafaxine on the behavior of zebrafish, and whether melatonin could reverse the induction of venlafaxine. In this study, a series of venlafaxine concentrations (1 µg/L, 10 µg/L, 100 µg/L) was used to treat zebrafish embryos from 2 hours post-fertilization (hpf) to 5dpf. We found that venlafaxine (1 µg/L) can stimulate the growth of the head area, eye area, and body length of zebrafish. The light-dark test showed that venlafaxine (1 µg/L) could increase the activity of zebrafish larvae. What's more, venlafaxine (1 µg/L) upregulated the expression of steroid regulatory factors including steroidogenic acute regulatory protein (star), cytochrome P450 family member 11A1 (cyp11a1) and 11 ß hydroxylase (cyp11b1) by cAMP-pCREB pathway, affecting the function of the steroidogenic cells, which might be involved in the increased cortisol levels in zebrafish larvae. Whereas, melatonin (230 µg/L) restored the altered locomotion behavior induced by venlafaxine and recovered the altered gene expression. Our results demonstrate that venlafaxine at levels detected in the aquatic environment impacts behavior and may compromise the adaptive responses to the environment in zebrafish larvae.

Polydatin alleviates parkinsonism in MPTP-model mice by enhancing glycolysis in dopaminergic neurons.

Parkinson's disease (PD) is a common neurodegenerative disease. Damage to energy metabolism and reduced adenosine triphosphate (ATP) levels in dopaminergic neurons are common features of PD. Previous studies suggested that the occurrence of PD often affects glucose metabolism and ATP production in the brain, and increased glycolysis or ATP production protects dopaminergic neuronal degeneration in the brain of PD patients. These systems may provide new potential therapeutic targets for the prevention of PD. The present study investigated the inhibitory action of polydatin (PLD) on early dopaminergic neuronal degeneration induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The results showed that PLD protected against MPTP-induced early dopaminergic neuronal degeneration. PLD reduced the MPTP-induced loss of dopaminergic neurons in substantia nigra and striatum, inhibited the occurrence of neural apoptosis, and restored motor function in mice. PLD also increased the continuous activity duration and rhythm amplitude in mice during the circadian activity test. PLD improved glucose metabolism in the brain and restored ATP production levels. These observations suggest that PLD attenuates MPTP-induced early PD-like symptoms, and its mechanism of action may be associated with the promotion of glucose metabolism in neurons.

The effects of fluorene-9-bisphenol on female zebrafish (Danio rerio) reproductive and exploratory behaviors.

Endocrine disruptor chemicals induce adverse effects to animals' development, reproduction and behavior in environment. We investigated the effects of fluorene-9-bisphenol (BHPF), one substitute of bisphenol A, on courtship behavior and exploratory behavior of adult zebrafish. Customized apparatus was used to evaluate courtship behavior. The result showed that the male spent less time with BHPF and anti-oestrogenic fulvestrant (FULV) treated female in region of approaching (ROA). Courtship index between BHPF-exposed female and male decreased. The body orientation of BHPF- and FULV-exposed female to male decreased. Furthermore, BHPF exposure downregulated the expression of genes related to estrogen receptor, steroidogenesis and upregulated oxidative stress related genes. It indicated that BHPF exposure interfered the preference of male and female in courtship, and induced detrimental effects on reproduction. BHPF treatment decreased locomotor activity and time spent in top, increased freezing bouts, and induced anxiety/depression-like behavior. The tyrosine hydroxylase in brain decreased under BHPF exposure. Here we showed the potential adverse effects of BHPF on reproduction and exploratory behaviors.

Resveratrol synergizes with low doses of L-DOPA to improve MPTP-induced Parkinson disease in mice.

L-DOPA (L-3,4-dihydroxyphenylalanine) relieves symptoms of Parkinson disease (PD), but long-term use can cause serious side effects. Resveratrol (3,5,4'-trihydroxy-trans-stilbene, RV), a polyphenolic compound derived from grapes and red wine that has antioxidant activity, has been shown to have neuroprotective effects. RV was investigated to enhance the therapeutic effect of L-DOPA in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mouse model of Parkinson disease. Mice received a saline or RV injection (10 mg/kg/day), then 2 h later, saline or MPTP (15 mg/kg/day) was administered for 7 consecutive days. Saline or L-DOPA (5 or 8 mg/kg/day) was injected post-administration of MPTP for the last 2 consecutive days. Our results indicated that RV alleviated MPTP-induced loss of dopaminergic neurons and attenuated astroglial activation in the nigrostriatal pathway. In parallel, RV reduced the expression of α-synuclein in the striatum. In addition, RV also increased levels of the anti-apoptotic signalling molecule Bcl-2, reduced levels of the pro-apoptotic signalling molecule Bax, and reduced activation of caspase-3 in the striatum. Specifically, RV significantly reduced motor dysfunction in MPTP-treated mice. Furthermore, the RV-treated group showed less IL-1ß and an enhanced pAkt/Akt ratio, which promoted dopamine neuron survival in the striatum. We found that the effects of co-administration of RV with L-DOPA (5 mg/kg) were equivalent to those of administration of 8 mg/kg L-DOPA in MPTP-induced PD mice. Therefore, with fewer side effects, L-DOPA can be effectively used in the treatment of PD over a long period of time.

Enhanced antitumor activity in A431 cells via encapsulation of 20(R)-ginsenoside Rg3 in PLGA nanoparticles.

OBJECTIVE: The objective of this study is to investigate the encapsulation of 20(R)-ginsenoside Rg3 (20(R)-Rg3) using polylactic-co-glycolic acid (PLGA) and promotion for its antitumor activity. SIGNIFICANCE: Preparation and evaluation of the antitumor efficacy of 20(R)-Rg3-loaded PLGA nanoparticles were the first reported. The data will be helpful to apply 20(R)-Rg3 efficiently and broadly in new drug form development and clinical cancer treatment. METHODS: The nanoparticles were prepared using emulsion and solvent evaporation methods. The uniform particle size and good dispersion were further confirmed by scanning electron microscopy. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was applied to detect cell proliferation after 20(R)-Rg3-loaded PLGA nanoparticles treatment. Western blotting and immunofluorescent staining were used for observation of key proteins related with proliferation and apoptosis. Cell cycle and apoptosis were analyzed by flow cytometer technology. RESULTS AND DISCUSSION: The results showed that the size of 20(R)-Rg3-loaded PLGA was 97.5 nm in diameter, and zeta potential was -28 mV detected by Malvern particle size analyzer. The encapsulation efficiency was 97.5%, and drug loading was 70.2% measured by high-performance liquid chromatography. The in vitro study showed that the encapsulated 20(R)-Rg3 was consecutively released and the release ratio reached to the highest value (19.36%) at the time point of 96 h. The encapsulated 20(R)-Rg3 significantly inhibited the proliferation and induced apoptosis in A431 cancer cells compared with the unencapsulated 20(R)-Rg3, control and PLGA alone. CONCLUSION: 20(R)-Rg3-loaded PLGA nanoparticles was well prepared and characterized. The antitumor activity was increased after PLGA encapsulation. The data will be beneficial to the development of new dosage forms of 20(R)-Rg3 and extensive application.

Enhanced isopropanol and n-butanol production by supplying exogenous acetic acid via co-culturing two clostridium strains from cassava bagasse hydrolysate.

The focus of this study was to produce isopropanol and butanol (IB) from dilute sulfuric acid treated cassava bagasse hydrolysate (SACBH), and improve IB production by co-culturing Clostridium beijerinckii (C. beijerinckii) with Clostridium tyrobutyricum (C. tyrobutyricum) in an immobilized-cell fermentation system. Concentrated SACBH could be converted to solvents efficiently by immobilized pure culture of C. beijerinckii. Considerable solvent concentrations of 6.19 g/L isopropanol and 12.32 g/L butanol were obtained from batch fermentation, and the total solvent yield and volumetric productivity were 0.42 g/g and 0.30 g/L/h, respectively. Furthermore, the concentrations of isopropanol and butanol increased to 7.63 and 13.26 g/L, respectively, under the immobilized co-culture conditions when concentrated SACBH was used as the carbon source. The concentrations of isopropanol and butanol from the immobilized co-culture fermentation were, respectively, 42.62 and 25.45 % higher than the production resulting from pure culture fermentation. The total solvent yield and volumetric productivity increased to 0.51 g/g and 0.44 g/L/h when co-culture conditions were utilized. Our results indicated that SACBH could be used as an economically favorable carbon source or substrate for IB production using immobilized fermentation. Additionally, IB production could be significantly improved by co-culture immobilization, which provides extracellular acetic acid to C. beijerinckii from C. tyrobutyricum. This study provided a technically feasible and cost-efficient way for IB production using cassava bagasse, which may be suitable for industrial solvent production.

Preliminary study on the freeze-drying of human bone marrow-derived mesenchymal stem cells.

Long-term preservation and easy transportation of human bone marrow-derived mesenchymal stem cells (hBM-MSCs) will facilitate their application in medical treatment and bioengineering. A pilot study on the freeze-drying of hBM-MSCs was carried out. hBM-MSCs were loaded with trehalose. The glass transition temperature of the freeze-drying suspension was measured to provide information for the cooling and primary drying experiment. After freeze-drying, various rehydration processes were tested. The highest recovery rate of hBM-MSCs was (69.33±13.08)%. Possible methods to improve freeze-drying outcomes are discussed. In conclusion, the present study has laid a foundation for the freeze-drying hBM-MSCs.