Bacillus spp. are probiotics and can secrete a variety of natural antimicrobiol active substances, of which lipopeptides are an important class. Up to now, about 90 lipopeptides have been identified, and most of them are cyclic lipopeptides. surfactin, iturin, fengycin, bacillomycin and polymyxins are widely studied, and the first three have huge potential for application due to their properties of surfactants and anti-fungal, anti-bacterial, anti-viral, anti-tumor and anti-inflammatory functions. In this paper, the research progress in the structure, function, synthesis regulation, separation, purification and production of surfactin, iturin and fengycin was reviewed. Synthetic biology is a vital means to increase the yield of lipopeptides, and in the future, lipopeptides can be used in crop cultivation, animal farming, food, medicine and petroleum industries as well as environmental protection. Future research should be strengthened on the discovery of new lipopeptides, synthesis of high-activity lipopeptides, economical production of lipopeptides on a large scale and their safety evaluation.
Anti-Bacterial Agents ; Anti-Infective Agents/pharmacology* ; Bacillus ; Bacillus subtilis ; Lipopeptides/pharmacology* ; Peptides, Cyclic/pharmacology*

Four cyclic peptides were isolated from the 75% ethanol extract of the fibrous roots of Pseudostellaria heterophylla by silica gel, Sephadex LH-20 column chromatography, and semi-preparative HPLC. Through mass spectrometry, NMR and other methods, they were identified as pseudostellarin L(1), heterophyllin B(2), pseudostellarin B(3), and pseudostellarin C(4). Among them, compound 1 was a new cyclic peptide, and compounds 2-4 were isolated from the fibrous roots of P. heterophylla for the first time. None of these compounds displayed cytotoxic activities against MCF-7, A549, HCT-116, and SGC-7901 cells.
Caryophyllaceae/chemistry* ; Chromatography, High Pressure Liquid ; Magnetic Resonance Spectroscopy ; Peptides, Cyclic/pharmacology* ; Plant Roots/chemistry*

One new cyclopeptide was isolated from the ethyl acetate fraction of the 75% EtOH extract of Selaginella tamariscina by various column chromatography methods(HP-20, polyamide and semi-preparative HPLC). Its structure was identified as selapeptin A(1) by extensive spectroscopic analysis(HR-ESI-MS, 1 D and 2 D NMR). Compound 1 was evaluated for cytotoxic activities by MTT assay. It showed potent cytotoxic activity against B16 F10 with the inhibition rate of 51.57%±4.34% at 40 μmol·L~(-1) while had no impacts on MDA-MB-231 and MDA-MB-468 at 100 μmol·L~(-1).
Chromatography, High Pressure Liquid ; Magnetic Resonance Spectroscopy ; Molecular Structure ; Peptides, Cyclic/pharmacology* ; Selaginellaceae/chemistry*

The aim of this paper was to discuss the protective effect and mechanism of Acanthopanax senticosus polysaccharides( ASPs) on immunological liver injury caused by conanavalin A( Con A). BALB/c mice were randomly divided into seven groups: control group,model group( Con A),low-,medium-,and high-dose( 36. 25,72. 5,145 mg·kg~(-1)) ASPs groups,bifendate( 200 mg·kg~(-1),positive drug) group and pyrrolidinedithiocarbamate( PDTC,NF-κB inhibitor,200 mg·kg~(-1)) group. ASPs groups and bifendate group were given with corresponding drugs by ig administration once daily for 7 d. Control group,model group and PDTC group were given with normal saline by ig administration once daily for 7 d. After the last ig administration,PDTC was given in DTC group by iv administration( 200 mg·kg~(-1)); 0. 5 h after that,Con A( 20 mg·kg~(-1)) was injected via the tail vein to induce immunological liver injury in all the mice except normal control group. The mice were killed 8 h later and their liver tissues were collected for histopathological examination. The contents of nitric oxide( NO),superoxide dismutase( SOD),malondialdehyde( MDA),reduced glutathione( GSHPX),interleukin( IL-1β) and tumor necrosis factor( TNF-α) in liver tissues were detected by kit assay. Western blot method was used to detect TNF-α,intercellular cell adhesion molecule-1( ICAM-1),inducible nitric oxide synthase( i NOS) and nuclear factor( NF-κB) protein expression in liver tissues. As compared with model group,ASPs not only could reduce the activity of MDA,NO,IL-1β and TNF-α,but also increase the content of GSH-PX and SOD; at the same time,the protein expression levels of TNF-α,ICAM-1,i NOS and NF-κB were reduced in liver tissues; in addition,inflammatory cell infiltration was alleviated,hepatocyte cytoplasm was loose and swollen,and nuclear condensation and staining were improved. ASPs has a protective effect on immunological liver injury,and the mechanism may be associated with regulating secretion of inflammatory cytokines and the expression of adhesion factor through NF-κB signaling pathway.
Animals ; Chemical and Drug Induced Liver Injury ; drug therapy ; Cytokines ; metabolism ; Eleutherococcus ; chemistry ; Liver ; drug effects ; Mice ; Mice, Inbred BALB C ; NF-kappa B ; metabolism ; Peptides, Cyclic ; Polysaccharides ; pharmacology ; Random Allocation ; Signal Transduction

Romipeptides A and B (1 and 2), two new romidepsin derivatives, and three known compounds, chromopeptide A (3), romidepsin (4) and valine-leucine dipeptide (5) were isolated from the fermentation broth of Chromobacterium violaceum No. 968. Their structures were elucidated by interpretation of their UV, HR-ESI-MS and NMR spectra. The absolute configuration of compound 1 and 2 were established by single crystal X-ray diffraction analysis. Compounds 1-5 were evaluated for their anti-proliferative activities against three human cancer cell lines, SW620, HL60, and A549. The results showed most of these compounds exhibited antitumor activities in vitro, in which compound 2 displayed potent cytotoxicity to SW620, HL60 and A549 cell lines, with IC of 12.5, 6.7 and 5.7 nmol·L, respectively.
Antineoplastic Agents ; chemistry ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cell Survival ; drug effects ; Chemistry Techniques, Analytical ; Chromobacterium ; metabolism ; Depsipeptides ; chemistry ; pharmacology ; Dipeptides ; chemistry ; Drug Screening Assays, Antitumor ; Fermentation ; Humans ; Molecular Structure ; Peptides, Cyclic ; chemistry

OBJECTIVETo research Angelica tenuissima Nakai (ATN) for use in novel Alzheimer's disease (AD) therapeutics.

METHODSThe effect of a 30% ethanol extract of ATN (KH032) on AD-like cognitive impairment and neuropathological and neuroinflammatory changes induced by bilateral intracerebroventricular injections of β-amyloid (Aβ) peptide (Aβ) was investigated. Male C57Bl/6 mice were randomly divided into 4 groups, 10 in each group. KH032-treated groups were administrated with a low or high dose of KH032 (50 and 200 mg/kg, respectively), intragastrically for 16 days; distilled water was applied in the sham and negative groups. Open fifield test, Y maze and Morris water maze test were used for behavior test and cognitive ability. In addition, the neuroprotective effects of KH032 in Aβ-infused mice on the histopathological markers [neuronspecific nuclear protein (NeuN), Aβ] of neurodegeneration were examined. The levels of glial fibrillary acidic protein (GFAP), NeuN, phosphorylation extracellular signal-regulated kinase (ERK)/ERK, brain-derived neurotrophic factor (BDNF), phosphorylation cAMP response element-binding (CREB)/CREB protein expression were measured by Western blot.

RESULTSKH032 treatment ameliorated cognitive impairments, reduced the overexpression of Aβ, and inhibited neuronal loss and neuroinflammatory response in the Aβ-infused mice. Moreover, KH032 treatment enhanced BDNF expression levels in the hippocampus. Finally, KH032 treatment increased phosphorylation of ERK1/2 and CREB, vital for ERK-CREB signaling.

CONCLUSIONSKH032 attenuated cognitive defificits in the Aβ-infused mice by increasing BDNF expression and ERK1/2 and CREB phosphorylation and inhibiting neuronal loss and neuroinflflammatory response, suggesting that KH032 has therapeutic potential in neurodegenerative disorders such as AD.

Alzheimer Disease ; drug therapy ; pathology ; physiopathology ; Amyloid beta-Peptides ; Angelica ; chemistry ; Animals ; Brain ; pathology ; Brain-Derived Neurotrophic Factor ; metabolism ; Cognitive Dysfunction ; complications ; drug therapy ; physiopathology ; Cyclic AMP Response Element-Binding Protein ; metabolism ; Disease Models, Animal ; Male ; Maze Learning ; drug effects ; Memory, Short-Term ; drug effects ; Mice, Inbred C57BL ; Neurogenesis ; drug effects ; Neuroglia ; drug effects ; metabolism ; pathology ; Neurons ; drug effects ; metabolism ; pathology ; Neuroprotective Agents ; pharmacology ; therapeutic use ; Phosphorylation ; drug effects ; Phytotherapy ; Plant Extracts ; pharmacology ; therapeutic use ; Plaque, Amyloid ; drug therapy ; pathology ; physiopathology ; Signal Transduction ; drug effects

OBJECTIVENew rationally designed i,i+7-hydrocarbon-stapled peptides that target both HIV-1 assembly and entry have been shown to have antiviral activity against HIV-1 subtypes circulating in Europe and North America. Here, we aimed to evaluate the antiviral activity of these peptides against HIV-1 subtypes predominantly circulating in China.

METHODSThe antiviral activity of three i,i+7-hydrocarbon-stapled peptides, NYAD-36, NYAD-67, and NYAD-66, against primary HIV-1 CRF07_BC and CRF01_AE isolates was evaluated in peripheral blood mononuclear cells (PBMCs). The activity against the CRF07_BC and CRF01_AE Env-pseudotyped viruses was analyzed in TZM-bl cells.

RESULTSWe found that all the stapled peptides were effective in inhibiting infection by all the primary HIV-1 isolates tested, with 50% inhibitory concentration toward viral replication (IC50) in the low micromolar range. NYAD-36 and NYAD-67 showed better antiviral activity than NYAD-66 did. We further evaluated the sensitivity of CRF01_AE and CRF07_BC Env-pseudotyped viruses to these stapled peptides in a single-cycle virus infectivity assay. As observed with the primary isolates, the IC50s were in the low micromolar range, and NYAD-66 was less effective than NYAD-36 and NYAD-67.

CONCLUSIONHydrocarbon-stapled peptides appear to have broad antiviral activity against the predominant HIV-1 viruses in China. This finding may provide the impetus to the rational design of peptides for future antiviral therapy.

Amino Acid Sequence ; Anti-HIV Agents ; chemistry ; pharmacology ; China ; epidemiology ; HIV Envelope Protein gp120 ; genetics ; metabolism ; HIV Infections ; epidemiology ; virology ; HIV-1 ; drug effects ; genetics ; Humans ; Peptides, Cyclic ; administration & dosage ; pharmacology ; Phylogeny

BACKGROUNDAdipocytes behave like a rich source of pro-inflammatory cytokines including monocyte chemoattractant protein-1 (MCP-1). Oxidized low-density lipoprotein (oxLDL) participates in the local chronic inflammatory response, and high-density lipoprotein could counterbalance the proinflammatory function of oxLDL, but the underlying mechanism is not completely understood. This study aimed to evaluate the effect of apolipoprotein A-I mimetic peptide L-4F on the secretion and expression of MCP-1 in fully differentiated 3T3-L1 adipocytes induced by oxLDL and to elucidate the possible mechanisms.

METHODSFully differentiated 3T3-L1 adipocytes were incubated in the medium containing various concentration of L-4F (0-50 μg/ml) with oxLDL (50 μg/ml) stimulated, with/without protein kinase A (PKA) inhibitor H-89 (10 μmol/L) preincubated. The concentrations of MCP-1 in the supernatant, the mRNA expression of MCP-1, the levels of CCAAT/enhancer binding protein α (C/EBPα), and CCAAT/enhancer binding protein β (C/EBPβ) were evaluated. The monocyte chemotaxis assay was performed by micropore filter method using a modified Boyden chamber.

RESULTSOxLDL stimulation induced a significant increase of MCP-1 expression and secretion in 3T3-L1 adipocytes, which were inhibited by L-4F preincubation in a dose-dependent manner. PKA inhibitor H-89 markedly reduced the oxLDL-induced MCP-1 expression, but no further decrease was observed when H-89 was used in combination with L-4F (50 μg/ml) (P > 0.05). OxLDL stimulation showed no significant effect on C/EBPα protein level but increased C/EBPβ protein level in a time-dependent manner. H-89 and L-4F both attenuated C/EBPβ protein level in oxLDL-induced 3T3-L1 adipocytes.

CONCLUSIONSOxLDL induces C/EBPβ protein synthesis in a time-dependent manner and enhances MCP-1 secretion and expression in 3T3-L1 adipocytes. L-4F dose-dependently counterbalances the pro-inflammatory effect of oxLDL, and cyclic AMP/PKA-C/EBPβ signaling pathway may participate in it.

3T3-L1 Cells ; Animals ; CCAAT-Enhancer-Binding Protein-beta ; analysis ; physiology ; Chemokine CCL2 ; genetics ; secretion ; Cyclic AMP ; physiology ; Cyclic AMP-Dependent Protein Kinases ; physiology ; Humans ; Lipoproteins, LDL ; antagonists & inhibitors ; pharmacology ; Mice ; Peptides ; pharmacology ; Signal Transduction ; physiology

To simplify the macrocyclic fragment and to modify the zinc binding group of the natural product apicidin, two series of S-hexyl (heptyl) ethanethioate derivatives were designed and synthesized. Twenty-six compounds were synthesized and confirmed with 1H NMR, IR, MS and HR-MS spectrum, which were not reported. Take vorinostat as control, their antiporliferative activities against cancer cell lines, MCF-7 and HL-60, were tested with MTT assay or trypan blue staining method. Generally in both series it was found that, the chiral carbon atom at 7 position is not necessary, compounds II-1, II-3, II-6 and II-13 showed good activity on HL-60 cells in vitro, with the IC50 values less than 10 micromol x L(-1). II-7 and II-8 showed stronger activity against MCF-7 than Vorinostat, with the IC50 of 3.19 and 6.29 micromol x L(-1), respectively.
Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Cell Proliferation ; drug effects ; Drug Screening Assays, Antitumor ; HL-60 Cells ; Histone Deacetylase Inhibitors ; chemical synthesis ; chemistry ; pharmacology ; Humans ; Inhibitory Concentration 50 ; MCF-7 Cells ; Peptides, Cyclic ; chemical synthesis ; chemistry ; pharmacology ; Structure-Activity Relationship

The microstructure of cationic cyclopeptide (TD-34) treated Caco-2 cell membrane was observed, and we discussed the relationship between membrane structure and insulin transmembrane permeability. Atomic force microscope (AFM) was used to observe living cell membrane in air condition and tapping mode. Results showed that the surface of Caco-2 cell membrane treated with TD-34 lost its smoothness and nearly doubled its roughness. Apparent permeability coefficients (P(app)) of insulin in Caco-2 cell monolayers increased 2.5 times. In conclusion, AFM can be used to observe microstructure of cationic cyclopeptide treated cell membrane and cationic cyclopeptide enhanced insulin delivery across Caco-2 cell membrane by increasing membrane fluidity.
Caco-2 Cells ; Cations ; Cell Membrane ; drug effects ; Cell Membrane Permeability ; drug effects ; Humans ; Insulin ; metabolism ; Membrane Fluidity ; drug effects ; Microscopy, Atomic Force ; Peptides, Cyclic ; pharmacology