[Research progress on liposome and nanomicelle targeted drug delivery system across blood-brain barrier].

The blood-brain barrier(BBB), a protective barrier between brain tissues and brain capillaries, can prevent drugs from entering the brain tissues to exert the effect, which greatly increases the difficulty in treating brain diseases. The drug delivery system across the BBB can allow efficient drug delivery across the BBB by virtue of carriers and formulations, thereby enhancing the therapeutic effect of drugs on brain tissue diseases. Liposomes and micelles have been extensively studied with advances in the targeted therapy across the BBB for the brain due to their unique structures and drug delivery advantages. This study summarized the research status of liposome and micelle drug delivery systems across the BBB based on the literature in recent years and analyzed their application advantages and mechanism in terms of trans-BBB capability, targeting, and safety. Moreover, the problems and possible countermeasures in the research on trans-BBB liposomes and micelles were discussed according to the current clinical translation, which may provide refe-rences and ideas for the development of trans-BBB targeted nano-drugs.

The Active Ingredients Identification and Antidiarrheal Mechanism Analysis of Plantago asiatica L. Superfine Powder.

Plantago asiatica L. is a natural medicinal plant that has been widely used for its various pharmacological effects such as antidiarrheal, anti-inflammatory, and wound healing. This study aims to explore the antidiarrheal active ingredients of Plantago asiatica L. that can be used as quality markers to evaluate P. asiatica L. superfine powder (PSP). Molecular docking experiment was performed to identify the effective components of P. asiatica L., which were further evaluated by an established mouse diarrhea model. Na+/K+-ATPase and creatine kinase (CK) activities and the Na+/K+ concentrations were determined. The gene expression of ckb and Atp1b3 was detected. PSP was prepared and evaluated in terms of the tap density and the angle of repose. The structures of PSPs of different sizes were measured by infrared spectra. The active ingredient contents of PSPs were determined by HPLC. The results indicated that the main antidiarrheal components of P. asiatica L. were luteolin and scutellarein that could increase the concentration of Na+ and K+ by upregulating the activity and gene level of CK and Na+/K+-ATPase. In addition, luteolin and scutellarein could also decrease the volume and weight of small intestinal contents to exert antidiarrheal activity. Moreover, as the PSP size decreased from 6.66 to 3.55 µm, the powder tended to be amorphous and homogenized and of good fluidity, the content of active compounds gradually increased, and the main structure of the molecule remained steady. The optimum particle size of PSP with the highest content of active components was 3.55 µm, and the lowest effective dose for antidiarrhea was 2,000 mg/kg. Therefore, the antidiarrheal active ingredients of PSP were identified as luteolin and scutellarein that exert antidiarrheal activity by binding with Na+/K+-ATPase. PSP was successfully prepared and could be used as a new dosage form for the diarrhea treatment.

Transcriptomic analysis reveals flavonoid biosynthesis of Syringa oblata Lindl. in response to different light intensity.

BACKGROUND: Hazy weather significantly increase air pollution and affect light intensity which may also affect medicinal plants growth. Syringa oblata Lindl. (S. oblata), an effective anti-biofilm medicinal plants, is also vulnerable to changes in plant photoperiods and other abiotic stress responses. Rutin, one of the flavonoids, is the main bioactive ingredient in S. oblata that inhibits Streptococcus suis biofilm formation. Thus, the present study aims to explore the biosynthesis and molecular basis of flavonoids in S. oblata in response to different light intensity. RESULTS: In this study, it was shown that compared with natural (Z0) and 25% ~ 35% (Z2) light intensities, the rutin content of S. oblata under 50% ~ 60% (Z1) light intensity increased significantly. In addition, an integrated analysis of metabolome and transcriptome was performed using light intensity stress conditions from two kinds of light intensities which S. oblata was subjected to: Z0 and Z1. The results revealed that differential metabolites and genes were mainly related to the flavonoid biosynthetic pathway. We found out that 13 putative structural genes and a transcription factor bHLH were significantly up-regulated in Z1. Among them, integration analysis showed that 3 putative structural genes including 4CL1, CYP73A and CYP75B1 significantly up-regulated the rutin biosynthesis, suggesting that these putative genes may be involved in regulating the flavonoid biosynthetic pathway, thereby making them key target genes in the whole metabolic process. CONCLUSIONS: The present study provided helpful information to search for the novel putative genes that are potential targets for S. oblata in response to light intensity.

Process optimization of Syringa oblata Lindl. by response surface methodology and its effect on Staphylococcus xylosus biofilm.

Syringa oblata Lindl. (S. oblata) is a medicinal plant with effective broad-spectrum antibacterial activity, which can also inhibit Streptococcus suis biofilm formation. The processing of herbal medicine can purify medicinal materials, provide acceptable taste, reduce toxicity, enhance efficacy, influence performance and facilitate preparation. Thus, the aim of this study was to enhance the biofilm inhibition activity of S. oblata toward Staphylococcus xylosus (S. xylosus) using the best processing method. The content of rutin and flavonoids and the ability to inhibit the biofilm formation by S. oblata were examined using four processing methods. One of the best methods, the process of stir-frying S. oblata with vinegar, was optimized based on the best rutin content by response surface methodology. The histidine content and hisB gene expression of S. xylosus biofilm in vitro, resulting from stir-frying S. oblata with vinegar, were evaluated and were found to be significantly decreased and down-regulated, respectively. The results show that S. oblata stir-fried with vinegar can be used to effectively treat diseases resulting from S. xylosus infection. This is because it significantly inhibited S. xylosus biofilm formation by interfering with the biosynthesis of histidine; thus, its mechanism of action is decreasing histidine synthesis.

Inhibition of Streptococcus suis Adhesion and Biofilm Formation in Vitro by Water Extracts of Rhizoma Coptidis.

Streptococcus suis is difficult to treat and responsible for various infections in humans and pigs. It can also form biofilms and induce persistent infections. Rhizoma Coptidis is a medicinal plant widely used in Traditional Chinese Medicine. Although the inhibitory effects of Rhizoma Coptidis on biofilm formation have been investigated in several studies, the ability of Rhizoma Coptidis to inhibit S. suis biofilm formation and the underlying mechanisms have not yet been reported. In this study, we showed that sub-minimal inhibitory concentrations (25 and 50 µg mL-1) of water extracts of Rhizoma Coptidis (Coptis deltoidea C.Y.Cheng & P.K.Hsiao, obtained from Sichuan Province) were sufficient to inhibit biofilm formation, as shown in the tissue culture plate (TCP) method and scanning electron microscopy. Real-time PCR and iTRAQ were used to measure gene and protein expression in S. suis. Sub-minimum inhibitory concentrations (25 and 50 µg mL-1) of Rhizoma Coptidis water extracts inhibited S. suis adhesion significantly in an anti-adherence assay. Some genes, such as gapdh, sly, and mrp, and proteins, such as antigen-like protein, CPS16V, and methyltransferase H, involved in adhesion were significantly modulated in cells treated with 50 µg mL-1 of Rhizoma Coptidis water extracts compared to untreated cells. The results from this study suggest that compounds in Rhizoma Coptidis water extracts play an important role in inhibiting adhesion of S. suis cells and, therefore, biofilm formation.