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The application of nanotechnology for antimicrobial delivery has capacity to improve antibacterial efficacy. Currently, the usage of various inorganic and organic carriers, such as metal ions, nano-silicon and surfactants, might increase the potential toxicity of nanoparticles and make their clinical transformation more difficult. Herein, a nano-delivery system was constructed by direct self-assembly of antibacterial phytochemicals (berberine and rhein) originated from traditional Chinese medicine Coptis chinensis Franch. and Rheum palmatum L., respectively. Combining X-ray single crystal diffraction, nuclear magnetic resonance and other spectra characterizations, the stacked structure of nanoparticles was profoundly demonstrated. Briefly, rhein acted as the layered backbone and berberine embedded in it. In vitro bacteriostasis experiment showed the minimum bactericidal concentration of nanoparticles was 0.1 μmol/mL, which was lower than that of berberine and rhein. The results of confocal laser scanning microscope, biofilm quantitive assay and scanning electron microscopy indicated that nanoparticles had strong inhibitory effects on Staphylococcus aureus biofilm. More importantly, transmission electron microscopy and mass spectra indicated the further bacteriostatic mechanism of nanoparticles. Meanwhile, the nanoparticles had well biocompatibility and safety. Current study will open up new prospect that the design of self-assemblies between active phytochemicals can be originated from traditional Chinese medicine combination. Ber-Rhe nanoparticles (NPs) were formed by direct self-assembly of Ber and Rhe. Combining X-ray single crystal diffraction and spectral analyses, the self-assembly mechanism of NPs had been demonstrated. Meanwhile, Ber–Rhe NPs demonstrated the inhibitory effect against Staphylococcus aureus by destroying the cell wall & membrane and cleaning the biofilm. Image 1 [ABSTRACT FROM AUTHOR]

The effect of Zanthoxylum bungeanum Maxim. (ZBM) on anti-obesity, lipid-lowering and liver protection has been identified, but the effect on the development of NAFLD induced by high-fat diet remains unclear. To evaluate the alleviation effect of ZBM on NAFLD in vivo and explore the mechanisms by analyzing the liver transcriptome, microbiota and fecal metabolites. NAFLD model was induced in C57BL/6J mice by feeding with high-fat diet (HFD). The potential mechanism of ZBM in improving NAFLD was studied by liver transcriptome analysis, real-time PCR, immunofluorescence, 16s rRNA sequencing and non-targeted metabonomics. ZBM has alleviation effects on HFD-induced NAFLD. The liver transcriptome, real-time PCR and immunofluorescence analysis showed that ZBM could efficiently regulate fatty acid and cholesterol metabolism. The 16S rRNA sequencing and LC-MS based metabonomic demonstrated that ZBM could rebalance gut microbiota dysbiosis and regulate metabolic profiles in HFD-induced NAFLD mice. Spearman correlation analysis revealed a strong correlation between gut microbiota and biochemical, pathological indexes and differential metabolic biomarkers. ZBM ameliorates HFD-induced NAFLD by regulating fatty acid and cholesterol metabolism, gut microbiota and metabolic profile. [Display omitted] [ABSTRACT FROM AUTHOR]

• Zedoray oil confronts hepatic oxidative stress via PI3K/Akt/FoxO1 pathway. Zedoray oil (ZO) is the main component of Curcuma zedoaria , one traditional herb used for dispersing stasis clinically in China. Previously, the potential of ZO was discovered against lethal and acute liver injury (ALI) mice with little impact on the immune, which deserved further study. An approach combined systems pharmacology with GC-MS metabolomics was applied for predicting pathways affected by ZO. Subsequently, H 2 O 2 and tertbutyl hydroperoxide (t-BHP) were respectively applied to induce the ALI model in vitro for validation. First, systems pharmacology and intracellular metabolites suggested that ZO might regulate oxidative stress via PI3K/Akt/FoxO1 pathway, TCA cycle, pantothenate, and CoA biosynthesis, beta-alanine metabolism, and propanoate metabolism. Further, levels of ALT, AST, ROS, T-AOC, MDA, GR, ΔΨm, and related proteins affected by ZO had been detected to validate the above mechanisms using dual cell models. ZO could protect the L02 cells against ALI by regulating the PI3K/Akt/FoxO1 pathway, as well as restore the function of mitochondria and redox imbalance damaged by toxicants. This work has uncovered the nonimmune mechanisms of ZO against ALI to provide the basis for relevant research and disease treatment. [ABSTRACT FROM AUTHOR]

Abstract: A comprehensive phytochemical investigation of the rhizomes of Dryopteris crassirhizoma Nakai resulted in the isolation and identification of one new trimeric phloroglucinol, trisflavaspidic acid ABB (1) together with 12 known compounds including phloroglucinol, flavan, terpene, phenolic and acyclic analogs. Their structures were established by spectroscopic methods including IR, UV, MS and 1D and 2D NMR. [Copyright &y& Elsevier]

Multidrug-resistance (MDR) Pseudomonas aeruginosa (P. aeruginosa) is a lethal gram-negative pathogen causing hospital-acquired and ventilator-associated pneumonia, which is difficult to treat. Our previous studies confirmed that baicalin, an essential bioactive component in Scutellaria baicalensis Georgi, exhibited anti-inflammatory effects in an acute pneumonia rat model induced by MDR P. aeruginosa. However, this effect of baicalin in constrast its low bioavailability, and its mechanism of action is still unknown. Thus, this study investigated whether the therapeutic effects of baicalin against MDR P. aeruginosa acute pneumonia are owing to the regulation of gut microbiota and their metabolites using pyrosequencing of the 16S rRNA genes in rat feces and metabolomics. As a result, baicalin attenuated the inflammation by acting directly on neutrophils and regulated the production of the inflammatory cytokines TNF-α, IL-1β, IL-6, and IL-10. The mechanisms were through down-regulation of TLR4 and inhibition of NF-κB. Furthermore, pyrosequencing of the 16S rRNA genes in rat feces revealed that baicalin regulated the composition of gut microbial communities. At the genus level, baicalin efficiently increased the abundance of Ligilactobacillus , Lactobacillus and Bacteroides , but decreased the abundance of Muribaculaceae and Alistipes. Further, arginine biosynthesis was analyzed as the core pathway regulated by baicalin via combination with predicting gut microbiota function and targeted metabolomics. In conclusion, this study has demonstrated that baicalin relieved inflammatory injury in acute pneumonia rat induced by MDR P. aeruginosa via arginine biosynthesis associated with gut microbiota. Baicalin could be a promising and effective adjunctive therapy for lung inflammation caused by MDR P. aeruginosa infection. [Display omitted] • Baicalin relieves pseudomonas aeruginosa lung inflammation via arginine biosynthesis. • Baicalin regulate the composition of gut microbiota in pseudomonas aeruginosa pneumonia to anti-inflammatory. • Baicalin targets arginaseⅠ, arginaseⅡ, ASS1, BUN, NO in arginine biosynthesis. [ABSTRACT FROM AUTHOR]

[Display omitted] • The natural small molecule self-assembled hydrogel of GK-GA was designed in a one-step "green" approach for breast cancer treatments. • The inhibition rate of tumor growth (IRG) of GK-GA was over 90 % at 6.25 mg·kg−1 without any obvious toxicity. • GK-GA hydrogel inhibited breast cancer growth and metastasis via dual pathways of BCL2-CASP3 and CXCL1/2-S100A8/9. It is crucial to inhibit tumor growth and distant metastasis for breast cancer (BC) therapy. However, the treatment primarily dependent on surgery, chemotherapy, and radiotherapy is far from satisfactory. It had been demonstrated that the CXCL1/2-S100A8/9 axis played an essential role in BC therapy. Therefore, we constructed a natural product hydrogel for BC therapy by blocking CXCL1 signaling. The GK-GA (phytochemicals of Genkwa Flos -glycyrrhizic acid) hydrogel was designed in a one-step "green" approach. The pharmacodynamics study showed GK-GA exhibited significant anti-tumor and anti-lung metastasis activities, resulting in the inhibition rate of tumor growth (IRG) over 90 % at 6.25 mg·kg−1, and did not display any obvious toxicity. In addition, the potent antitumor efficiency was also attributed to aggregation/assembly-induced retention (AIR) property. RNA sequencing analysis revealed the gene expression was significantly down-regulated in the GK-GA group, which were BCL2, CASP3, CXCL1, CXCL2, CXCR2, S100A8, S100A9, and confirmed further by western blot (WB). Our findings indicated natural product GK-GA hydrogel inhibited tumor growth and lung metastasis via the BCL2-CASP3 mitochondrial apoptosis pathway as well as the CXCL1/2-S100A8/9 pathway. This study provides inspiration for the fabrication of new excipients-free nano-dispersion in a one-step, no‐carrier‐added, organic solvent-free, "green" approach, particularly for small molecular antitumor agents. [ABSTRACT FROM AUTHOR]

Oxyntomodulin (OXM) was identified as a glucagon (GCG) receptor (GCGR) and glucagon-like peptide 1 (GLP-1) receptor (GLP-1R) dual agonist to suppress appetite, increase energy expenditure, and induce body weight loss in obese humans. However, the activities of native OXM to activate GCGR and GLP-1R in vitro were much weaker than the natural ligands. To address this gap, structural modifications were adopted and novel OXM analogues were obtained through chimeric peptide sequence design. One specific analogue with enhanced and balanced GCGR/GLP-1R activations was chemically conjugated with polyethylene glycol (PEG) to achieve sustained release in vivo. This PEGylated analogue was further explored pharmacologically in db/db and diet-induced obese (DIO) mice models. Chronic weekly administration significantly induced hypoglycemic effects and body weight loss with dose dependency, along with normalized adiposity, lipid metabolism, and liver steatosis. Based on its profiles in vitro and in vivo , the analogue has the great potential to develop as a novel anti-diabetic and/or anti-obese candidate. As observed more insulin stimulation and improved insulin resistance, it may be also explored for the treatment of nonalcoholic steatohepatitis (NASH) in the future. Image 1 • A novel OXM analogue with enhanced and balanced GCGR/GLP-1R activations was obtained through chimeric peptide structural modifications. • The specific analogue was then conjugated with PEG to achieve sustained release in vivo. • Based on its profiles in vitro and in vivo , the PEGylated analogue has the great potential to develop as a novel anti-diabetic and/or anti-obese candidate. [ABSTRACT FROM AUTHOR]