Antimalarial activity and sensitization of chrysosplenetin against artemisinin-resistant genotype Plasmodium berghei K173 potentially via dual-mechanism of maintaining host P-glycoprotein homeostasis mediated by NF-κB p52 or PXR/CAR signaling pathways and regulating heme/haemozoin metabolism.

This study investigated antimalarial efficacy and sensitization of chrysosplenetin against artemisinin-resistant Plasmodium berghei K173 and potential molecular mechanism. Our data indicated a risk of artemisinin resistance because a higher parasitaemia% and lower inhibition% under artemisinin treatment against resistant parasites than those in the sensitive groups were observed. Two non-antimalarial components, verapamil and chrysosplentin, being P-gp inhibitors, possessed a strong efficacy against resistant parasites but it was not the case for Bcrp inhibitor novobiocin. Artemisinin-chrysosplenetin combination improved artemisinin susceptibility of resistant P. berghei. Artemisinin activated intestinal P-gp and Abcb1/Abcg2 expressions and suppressed Bcrp whereas chrysosplenetin reversed them. Resistant parasite infection led to a decreased haemozoin in organs or an increased heme in peripheral bloods compared with the sensitives; however, that in Abcb1-deficient knockout (KO)-resistant mice reversely got increased or decreased versus wild type (WT)-resistant animals. Chrysosplenetin as well as rifampin (nuclear receptor agonist) increased the transcription levels of PXR/CAR while showed a versatile regulation on hepatic and enternal PXR/CAR in WT- or KO-sensitive or -resistant parasites. Oppositely, hepatic and enteric NF-κB p52 mRNA decreased conformably in WT but increased in KO-resistant mice. NF-κB pathway potentially involved in the mechanism of chrysosplenetin on inhibiting P-gp expressions while PXR/CAR play a more complicated role in this mechanism.

Ferruginol prevents degeneration of dopaminergic neurons by enhancing clearance of α-synuclein in neuronal cells.

Lewy bodies are characteristic spherical inclusions in Parkinson's disease (PD) that are formed by α-synuclein fibrils. Ferruginol (Fer) is an amonomeric compound isolated from a traditional Chinese herb. Here, we show that Fer exerted potent neuroprotective effects in both in vitro and in vivo PD models. Neuronal cells transfected with A53T mutant (A53T) α-synuclein plasmids and treated with Fer exhibited attenuated the cytotoxicity induced by pathogenic A53T α-synuclein overexpression. Further, when we transfected neuronal cells with siRNA-SNCA (alpha-synuclein) plasmids and incubated them with Fer, the protective role of Fer decreased. We also found that Fer was a potent α-synuclein inhibitor in neuronal cells, which promotes the clearance of αsynuclein in dopaminergic neurons exposed to 1-Methyl-4-phenylpyridinium (MPP +). Fer could inhibit abnormal α-synuclein aggregation and dopaminergic neuron depletion in A53T-Tg mice, suggesting that a role for Fer in α-synuclein accumulation and nigrostriatal pathway injury. Our study revealed that Fer strongly alleviated neurodegeneration by promoting α-synuclein clearance, indicating a neuroprotective role against α-synuclein oligomer-induced neurodegeneration, which makes it a promising candidate for the treatment of PD and other neurodegenerative diseases.

Abnormalcortical thickness in relapsing-remitting multiple sclerosis, correlations with cognition impairment, and effect of modified Bushenyisui decoction on cognitive function of multiple sclerosis.

OBJECTIVE: To investigate the changes of subcortical gray matter volume and cortical thickness, andexplorethe correlations between regional abnormalities of cortical thickness and cognitive impairment and the effect of modified Bushenyisui decoction ( BSYSD) on the cognitive function of multiple sclerosis (MS). METHODS: This prospective study was approved by the institutional review board. 92 subjects were recruited, including 46 relapsing-remitting multiple sclerosis (RRMS) patients and 46 healthy controls (HC). Of the 46 patients, 22 patients experienced the treatment of BSYSD for half a year. A conventional three-dimensional T1-weighted sequence were acquired for all participants on a 3.0 tesla magnetic resonance system. Basic information, detailed cognitive scales Montreal Cognitive Assessment (MoCA), symbol digit modalities test (SDMT), immediate memory, delayed recall, and long-term recognition were evaluated. Subcortical gray matter volume and cortical thickness weremeasured by FreeSurfer. The correlations between cortical thickness which MS patients showed reduced with respect to HC and cognitive scales wereanalyzed by Pearson correlation in RRMS patients. The influence of modified BSYSD on MS patients' cognition was analyzed by paired T Test. RESULTS: MoCA, immediate memory, delayed recall, and long-term delayed recognition in RRMS were significantly decreased than those of HC. Gray matter atrophy measured by FreeSurfer showed mainly in thalamus and hippocampus of RRMS patients. Compared with HC, the cortical thickness of several regions in frontal lobe, parietal lobe, temporal lobe, hippocampal, cingulate gyrus, and fusiform gyrus of RRMS patients were decreased with significant difference. The regions of cortical thickness thinning related to MoCA, immediate memory, delayed recall, and long-term delayed recognition were temporal lobe and fusiform gyrus. Modified BSYSD could improve MoCA, SDMT, immediate memory, delayed recall, and long-term delayed recognition of MS patients, and it could promote the recovery of cognitive function in MS patients. CONCLUSIONS: Gray matter atrophy and cortical thickness thinning were validated in RRMS. Cortical thickness thinning of temporal lobe and fusiform gyrus strongly related to cognitive deficits in RRMS. The modified BSYSD could promote the recovery of cognitive function in MS.

Facile construction of reduced graphene oxide supported three-dimensional polyaniline/WO2.72 nanobelt-flower as a full solar spectrum light response catalyst for efficient photocatalytic conversion of bromate.

As a carcinogenic byproduct in drinking water treatment, bromate has raised global concerns on environmental and health hazard, calling for effective treatments. In the current work, a novel reduced graphene oxide supported polyaniline/WO2.72 nanobelt-flower (RGO/PANI/WO2.72) ternary composite was prepared through a solvent volatilization method for photocatalytic reduction of bromate. The prepared sample was characterized, and the influence of aqueous pH, ions and dissolved oxygen on the bromate reduction was explored. As expected, the introduction of RGO and PANI on the WO2.72 exhibited great synergistic effects on the separation of photogenerated carriers. The calculated reduction rate constant of RGO/PANI/WO2.72 was about six times as high as that of pure WO2.72. Specially, the prepared photocatalyst possessed strong optical absorption in a broad range of 250-2500 nm, and thus displaying excellent catalytic performance in utilization of all solar spectrum energy. Moreover, the RGO/PANI/WO2.72 exhibited stable photocatalytic activity in cycling test. Considered holistically, the present study offered a valuable approach for rational construction of heterogeneous structure in the development of bromate-catalyzed reduction.

Ginsenosides and ginsenosidases in the pathobiology of ginseng-Cylindrocarpon destructans (Zinss) Scholten.

To investigate the role that ginsenosides (and some of their metabolites) play in interactions between plants and phytopathogenic fungi (e.g. Cylindrocarpon destructans (Zinss) Scholten), we systematically determined the anti-fungal activities of six major ginsenosides (Rb1, Rb2, Rc, Rd, Re and Rg1), along with the metabolites of ginsenoside Rb1 (Gypenoside XVII (G-XVII) and F2), against the ginseng root pathogen C. destructans (Zinss) Scholten and non-ginseng pathogens Fusarium graminearum Schw., Exserohilum turcicum (Pass.) Leonard et Suggs, Phytophthora megasperma Drech. and Pyricularia oryzae Cav. Our results showed that the growth of both ginseng pathogens and non-pathogens could be inhibited by using the proto-panaxatriol (PPT) ginsenosides Re and Rg1. In addition, the growth of the non-pathogens could also be inhibited by using proto-panaxadiol (PPD) ginsenosides Rb1, Rb2, Rc and Rd, whereas the growth of ginseng pathogen C. destructans (Zinss) Scholten was enhanced by ginsenosides Rb1 and Rb2. In contrast, ginsenoside G-XVII and F2 strongly inhibited the hyphal growth of both C. destructans (Zinss) Scholten and the non-pathogens tested. Furthermore, addition of sucrose to the media increased the growth of C. destructans (Zinss) Scholten, whereas glucose did not affect the growth. Moreover, C. destructans (Zinss) Scholten and all four non-pathogens were able to deglycosylate PPD ginsenosides using a similar transformation pathway, albeit with different sensitivities. We also discussed the anti-fungal structure-activity relationships of the ginsenosides. Our results suggest that the pathogenicity of C. destructans (Zinss) Scholten against ginseng root is independent of its ability to deglycosylate ginsenosides.

Fungal sensitivity to and enzymatic deglycosylation of ginsenosides.

A ginseng pathogen, Cylindrocarpon destructans, and five nonpathogens were tested for their sensitivity to a total ginsenoside fraction (T-GF), a protopanaxadiol-type ginsenoside fraction (PPD-GF) and a protopanaxatriol-type ginsenoside fraction (PPT-GF) from the roots of Panax ginseng C.A. Meyer. The results showed that T-GF inhibited growth of the five ginseng nonpathogens, while it promoted growth of the ginseng pathogen C. destructans. PPT-GF and PPD-GF both inhibited the growth of the five ginseng nonpathogens, although the activity of PPT-GF was higher than that of PPD-GF. PPT-GF and PPD-GF exhibited different activities on C. destructans: PPT-GF inhibited its growth, whereas PPD-GF significantly enhanced its growth. The subsequent analysis of enzymatic degradation of ginsenosides by the test fungi showed that C. destructans can consecutively hydrolyze the terminal monosaccharide units from the sugar chains attached at C3 and C20 in PPD-type ginsenosides by extracellular glycosidase activity to yield four major products, gypenoside XVII (G-XVII), compound O, compound Mb and the ginsenoside F(2). By contrast, the ginseng nonpathogens Aspergillus nidulans and Cladosporium fulvum have no extracellular glycosidase activity toward sugar chains attached to C3 in PPD-type ginsenosides. These results indicated that ginsenosides might act as host chemical defenses, while the ginseng root pathogenic fungi might counter their toxicity by converting PPD-type ginsenosides into growth or host recognition factors. The ability of ginseng root pathogens to deglycosylate PPD-type ginsenosides may be a pathogenicity factor.