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Actinomycete strain YIM PH20520, isolated from the rhizosphere soil sample of Panax notoginseng collected in Wenshang, Yunnan Province, China, exhibited antifungal activity against root-rot pathogens of the Panax notoginseng. The structures of bioactive molecules, isolated from the ethyl acetate extract of the fermentation broth of the strain, were identified as echinosporin (1) and 7-deoxyechinosporin (2) based on extensive spectroscopic analyses. 1 exhibited antifungal activity against four tested root-rot pathogens of Panax notoginseng include Fusarium oxysporum, Fusarium solani, Alternaria panax, and Phoma herbarum with the MIC value at 64, 64, 32, and 64 μg/mL, respectively. 2 exhibited antifungal activities against F. oxysporum, F. solani, A. panax, and P. herbarum with the MIC value at 128, 128, 64, and 128 μg/mL, respectively. Based on the phylogenetic analyses, the closest phylogenetic relative of strain YIM PH20520 is Amycolatopsis speibonae JS72T (97.69%), so strain YIM PH20520 was identified as Amycolatopsis strain. To the best of our knowledge, this is the first report of echinosporin antibiotics isolated from Amycolatopsis strain besides Streptomyces strain and their antifungal activity against four tested root-rot pathogens of the Panax notoginseng. The results provide a reliable evidence for the following related biosynthetic investigations on Amycolatopsis strain YIM PH20520 due to echinosporins antibiotics’ unique tricyclic acetal-lactone structures.

Bafilomycin C1, which was isolated from Streptomyces albolongus in our previous work, exhibited strong cytotoxicity against several cancer cell lines. This study aimed to evaluate its antitumor effect on human hepatocellular cancer SMMC7721 cells and the underlying mechanism in vitro and in vivo. MTT assay revealed that bafilomycin C1 retarded SMMC7721 cell growth and proliferation. Western blot and real-time qPCR analysis revealed that bafilomycin C1 caused partial G0/G1 phase cell-cycle arrest, downregulated the expression of cyclin D3, cyclin E1, CDK2, CDK4, and CDK6 and upregulated the expression of p21. Moreover, bafilomycin C1 caused mitochondrial membrane dysfunction through oxidative stress. Furthermore, bafilomycin C1 decreased the expression of Bcl-2; increased the expression of Bax, p53, and P-p53; and increased cleavage of caspase-9 and caspase-3, thereby inducing the intrinsic caspase-dependent apoptotic pathway. In vivo experiments in mice suggested that bafilomycin C1 suppressed tumor growth with few side effects. Cell-cycle arrest and induced apoptosis in tumor tissues in a mouse model treated with bafilomycin C1 were demonstrated by histological analyses, western blot and TUNEL. These findings indicate that bafilomycin C1 may be a promising candidate for hepatic cellular cancer therapy.

The first total synthesis of (±)-(1β,4β,4aβ,8aα)-4,8a-dimethylocta-hydronaphthalene-1,4a(2H)-diol (1), a degraded sesquiterpene isolated from a fermentation broth of Streptomyces albolongus, has been achieved via three different synthetic approaches (13–15 steps) starting from racemic Wieland–Miescher ketone (2). The configuration of hydroxyl groups at C-1 and C-4a in 1 was availably managed using the Mitsunobu reaction and stereo- and regioselective epoxidation. Moreover, the syntheses of configuration isomers 12, 17, 45 and 54 were also described in the present study.

Published data suggest that dietary-derived phenolics exert beneficial effects against hyperglycemia-mediated diseases, such as diabetes, through inhibiting the formation of advanced glycation endproducts (AGEs) and carbohydrate hydrolyzing enzyme activities. In the course of our investigation on the edible berry, Eugenia jambolana (known as Jamun), 21 phenolics (1-21) were isolated and identified from its seeds. Among these, one compound (1) is new and eleven compounds (3, 6, 9-13, 17, and 19-21) are being reported from E. jambolana for the first time. The anti-AGE activities of thirteen pure isolates (2-7, 9-12, 14, 15, and 20) were either comparable or superior to the synthetic anti-glycation agent, aminoguanidine, at three test concentrations (20, 50, and 100 μM) in the BSA-fructose assay. Most of these phenolics with anti-AGE activity exhibited potent free radical scavenging activity in the DPPH assay, and attenuated intracellular levels of LPS-induced reactive oxygen species in RAW264.7 macrophage. In addition, compounds 2-6, and 14 showed superior α-glucosidase inhibitory activity (IC50 = 5.0-21.2 μM) compared to the clinical α-glucosidase inhibitor, acarbose (IC50 = 289.9 μM). This is the first report of the anti-AGE effects of compounds 2-6 and 9-12, and α-glucosidase inhibitory activities of compounds 3-6, 9, 11 and 14. The current study supports the role of phenolics in the antidiabetic properties attributed to this edible berry, and warrants further animal studies to evaluate their potential as dietary agents for the prevention and/or therapy of hyperglycemia-mediated diseases.

Background/Aims: Nephropathy related with renin can be alleviated with ACE-inhibitors or AT1R blockers, whereas they might be ineffective after long-term administration because of a feedback production of enhanced renin. Therefore, it is urgent to develop a new category of anti-nephropathy medicine directly targeting renin. Riligustilide (C20), originally isolated from the Chinese herb Ligusticumporteri, a rhizome, was confirmed effective against many diseases. Methods: The therapeutic effect of C20 on renal injury and its underlying mechanism were investigated in three different nephrotic models, which were spontaneously hypertension rats (SHR) model, diabetic nephropathy in BTBR ob/ob mice model and 5/6-nephrectomized (5/6NX) rats model. Results: The intensity of kidney fibrosis was extensively decreased in the C20-treated rats compared to the vehicle animals. C20 significantly alleviated renal injury much more in 5/6 NX rats than in vehicle group. The rats in 5/6 NX without administrated C20 developed albuminuria earlier with more severe symptoms. Additionally, our findings showed that C20 down-regulated the renin expression and relocation of CREB-CBP complex in vivo and in vitro. Conclusion: C20 plays importantly reno-protective roles most likely through the relocation of CREB-CBP complex.

Six new polyene macrolactams, heronamides G–L (1–6), one new polyenoic acid derivative, niveamide B (10), together with four known compounds, BE-14106-6 (7), BE-14106 (8), GT32-B (9), and niveamide (11), were isolated from the fermentation broth of Streptomyces niveus. Their planar structures were elucidated by detailed analysis of spectroscopic data. The absolute configurations of compounds 1–6 were determined by calculated ECD spectra and analysis of the possible biosynthetic pathways. Compounds 1–6 and 8–11 did not exhibit any significant antimicrobial activities, cytotoxicities, or inhibitory effects on lipopolysaccharide-induced NO production in BV2 microglial cells.

A nonribosomal peptide synthetase (NRPS) gene cluster (sfa) was identified in Streptomyces thioluteus to direct the biosynthesis of the diisonitrile antibiotic SF2768. Its biosynthetic pathway was reasonably proposed based on bioinformatics analysis, metabolic profiles of mutants, and the elucidation of the intermediate and shunt product structures. Bioinformatics-based alignment found a putative ATP-binding cassette (ABC) transporter related to iron import within the biosynthetic gene cluster, which implied that the product might be a siderophore. However, characterization of the metal-binding properties by high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), metal-ligand titration, thin-layer chromatography (TLC), and chrome azurol S (CAS) assays revealed that the final product SF2768 and its diisonitrile derivatives specifically bind copper, rather than iron, to form stable complexes. Inductively coupled plasma mass spectrometry (ICP-MS) analysis revealed that the intracellular cupric content of S. thioluteus significantly increased upon incubation with the copper-SF2768 complex, direct evidence for the copper acquisition function of SF2768. Further in vivo functional characterization of the transport elements for the copper-SF2768 complexes not only confirmed the chalkophore identity of the compound but also gave initial clues into the copper uptake mechanism of this nonmethanotrophic microorganism.

Huge numbers of bacteria reside in the digestive tract of host and these microorganisms play a vital role in the host health, especially in the digestion of food and the development of immune system. Host phylogeny and diet, especially long-term diet, both have great influence on the gut bacterial community. Other aspects of host, such as gender, age, and the geography and weather they lived, are also correlated to their gut bacterial community. Feces are usually used for gut bacteria study and fecal bacteria can represent the distal gut bacteria. In order to determine the influence of the host phylogeny and diet on the composition of distal gut bacterial community and to interpret bacterial population and diversity in the intestinal of animals, the distal gut bacterial community of four kinds of primates and five kinds of carnivora (including herbivorous, omnivorous, and carnivorous) were investigated using high-throughput sequencing and the isolation of the Actinobacteria from fresh feces of several primates was processed. The results showed the host phylogeny had a greater influence on the distal gut bacterial community of the primates and carnivora than the host diet. A total of 44 bacteria phyla and two archaea phyla were detected, which indicated that the distal gut bacteria of these animals were abundant. The distal gut bacteria were relatively stable and wildly shared in primates and carnivora. The difference in distal gut bacteria of the two animal orders is mainly determined by relative abundance of most distal gut bacteria rather than by the taxa of these bacteria.

Alzheimer's disease (AD) is characterized by the loss of neurogenesis and excessive induction of apoptosis. The induction of neurogenesis and inhibition of apoptosis may be a promising therapeutic approach to combating the disease. Celecoxib (CB), a cyclooxygenase-2 specific inhibitor, could offer neuroprotection. Specifically, the CB-encapsulated erythrocyte membranes (CB-RBCMs) sustained the release of CB over a period of 72 h in vitro and exhibited high brain biodistribution efficiency following intranasal administration, which resulted in the clearance of aggregated β-amyloid proteins (Aβ) in neurons. The high accumulation of the CB-RBCMs in neurons resulted in a decrease in the neurotoxicity of CB and an increase in the migratory activity of neurons, and alleviated cognitive decline in APP/PS1 transgenic (Tg) mice. Indeed, COX-2 metabolic products including prostaglandin E2 (PGE2) and PGD2, PGE2 induced neurogenesis by enhancing the expression of SOD2 and 14-3-3ζ, and PGD2 stimulated apoptosis by increasing the expression of BIK and decreasing the expression of ARRB1. To this end, the CB-RBCMs achieved better effects on concurrently increasing neurogenesis and decreasing apoptosis than the phospholipid membrane-encapsulated CB liposomes (CB-PSPD-LPs), which are critical for the development and progression of AD. Therefore, CB-RBCMs provide a rational design to treat AD by promoting the self-repairing capacity of the brain.

Six new fusicoccane-type diterpenoids (2–7) were isolated from the fermentation broth of Streptomyces violascens, which was isolated from Ailuropoda melanoleuca (giant panda) feces. The structures of these new compounds were elucidated by a detailed spectroscopic data and X-ray crystallographic analysis. Compounds 5–7 demonstrated cytotoxicity against five human cancer cell lines, with IC50 values ranging from 3.5 ± 0.7 to 14.1 ± 0.8 μM. Cell adhesion, migration, and invasion assays showed that 6 inhibited the migration and invasion of human hepatocellular carcinoma SMMC7721 cells in a dose-dependent manner. Through further investigation, it was revealed that 6 inhibited the enzymatic activity of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), in addition to down-regulating the expressions of MMP-2 and MMP-9 at both the protein and mRNA levels to influence the migration and invasion of cancer cells.

In our investigation of the anti-hyperglycaemic constituents of Eugenia jambolana L. (Jamun), one new triterpenoid, 2-O-cis-p-coumaroyl maslinic acid, along with thirteen known triterpenoids were isolated from the fruit ethyl acetate extract. The structures of compounds 1–14 were elucidated on the basis of mass spectrometry and nuclear magnetic resonance analyses. Animal studies demonstrated that the triterpenoid-enriched Jamun fruit extract (TJFE) decreased blood glucose content in C57BL/6 mice (P

Five new compounds including five iridoids (1-5) and six known compounds were isolated from the rhizomes of Scrophularia ningpoensis. Their structures were determined by extensive NMR and IR, MS spectroscopic data analyses. The anti-inflammatory, antibacterial, antifungal, and cytotoxic activities of the isolated compounds were evaluated. Compound 11 exhibited significant inhibitory effects on lipopolysaccharide-induced nitric oxide production in RAW264.7 macrophage cells.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer with high prevalence and mortality. Borrelidin, produced by several actinomycete bacteria of Streptomycin sp. exhibited diversiform activities including anti-bacterial, anti-viral, anti-angiogenic, and anti-tumor. However, the effect of borrelidin on HCC cells has not been characterized. The present study demonstrated borrelidin exhibited great potential to inhibit the growth of HCC cells, HepG2 and SMMC7721 in vitro. Western blot and real-time qPCR analysis revealed that borrelidin decreased the expressions of cyclin D1, cyclin D3, cyclin E1, CDK2, CDK4, and CDK6 and increased the expression of p21, thereby inducing G0/G1 cell cycle arrest. Moreover, borrelidin down-regulated expression of Bcl-2, up-regulated expression of Bax and increased cleavages of caspase-9 and caspase-3 to activate caspase-dependent apoptosis in HCC cells. Borrelidin inhibited migration and invasion through suppressing the expression of MMP-2 and MMP-9 in HCC cells. Further investigation indicated that the anti-tumor effect of borrelidin was mediated by MAPKs signaling pathway. In addition, an in vivo experiment revealed that borrelidin suppressed tumor growth in SMMC7721 xenograft model mice with few side effects. Cell cycle arrest and induced apoptosis were also observed in tumor tissues of model mice treated with borrelidin.

Four new barringtogenol C-type triterpenoid saponins, namely acerplatanosides A – D (1–4), along with 22 known compounds (5–26), were isolated from the stem bark of Norway maple (Acer platanoides). Their structures were elucidated on the basis of comprehensive spectroscopic analyses and chemical hydrolysis. This is the first report of triterpenoid saponins isolated from Norway maple. Compounds 1, 3, and 4 showed cytotoxicity against 4 human cancer cell lines with IC50 values ranging from 9.4 to 39.5 µM.

Spectinabilin (1), spectinabilin derivative (2), and a new analogue, 2-demethyl-spectinabilin (3) were isolated from the fermentation broth of a soil-borne Streptomyces spectabilis strain. The structure of the new compound was elucidated by a detailed spectroscopic data analysis including data from CD spectra. Spectinabilin (1) demonstrated cytotoxicity against five human cancer cell lines, with IC50 values ranging from 18.7 ± 3.1 to 34.6 ± 4.7 μM, while derivatives 2 and 3 showed weak cytotoxicities. Notably, 1 inhibited the growth and proliferation of the hepatocellular carcinoma cell lines SMMC7721 and HepG2 in a time- and dose-dependent manner. Further study demonstrated that 1 caused G2/M phase cell cycle arrest in SMMC7721 and HepG2 cells through decreasing the protein levels of cyclin B1 and cdc2 as well as increasing that of p21. Compound 1 downregulated the protein expression of Bcl-2, upregulated Bax, and activated the cleavage of caspase-9 and -3 as a result of inducing apoptosis in SMMC7721 and HepG2 cells. Furthermore, the antitumor effect of 1 in SMMC7721 and HepG2 cells was mediated by the PI3K/AKT signaling pathway. In addition, 1 also suppressed tumor growth in vivo though inducing cell cycle arrest and apoptosis.

Alzheimer’s disease (AD) is reportedly associated with the accumulation of calcium ions (Ca2+), and this accumulation is responsible for the phosphorylation of tau. Although several lines of evidence demonstrate the above phenomenon, the inherent mechanisms remain unknown. Using APP/PS1 Tg mice and neuroblastoma (N)2a cells as in vivo and in vitro experimental models, we observed that Ca2+ stimulated the phosphorylation of tau by activating microsomal PGE synthase 1 (mPGES1) in a prostaglandin (PG) E2-dependent EP receptor-activating manner. Specifically, the highly accumulated Ca2+ stimulated the expression of mPGES1 and the synthesis of PGE2. Treatment with the inhibitor of Ca2+ transporter, NMDAR, attenuated the expression of mPGES1 and the production of PGE2 were attenuated in S(+)-ketamine-treated APP/PS1 Tg mice. Elevated levels of PGE2 were responsible for the hyperphosphorylation of tau in an EP-1-, EP-2-, and EP-3-dependent but not EP4-dependent cyclin-dependent kinase (Cdk) 5-activating manner. Reciprocally, the knockdown of the expression of mPGES1 ameliorated the expected cognitive decline by inhibiting the phosphorylation of tau in APP/PS1 Tg mice. Moreover, CDK5 was found to be located downstream of EP1-3 to regulate the phosphorylation of tau though the cleavage of p35 to p25. Finally, the phosphorylation of tau by Ca2+ contributed to the cognitive decline of APP/PS1 Tg mice.

Alzheimer's disease (AD) is reported to be associated with the accumulation of calcium ions (Ca2+), which is responsible for the phosphorylation of tau. Although a series of evidence have demonstrated this phenomenon, the inherent mechanisms remain unknown. Using tauP301S and cyclooxygenase-2 (COX-2) transgenic mice and neuroblastoma (n)2a cells as in vivo and in vitro experimental models, we found that Ca2+ stimulates the phosphorylation of tau by activating COX-2 in a prostaglandin (PG) E2-dependent EP receptor-activating manner. Specifically, Ca2+ incubation stimulated COX-2 and PGE2 synthase activity, microsomal PGE synthase 1 and the synthesis of PGE2 by activating the transcriptional activity of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in n2a cells. Elevated levels of PGE2 were responsible for phosphorylating tau in an EP-1, -2, and -3 but not EP4-dependent glycogen synthase kinase 3-activating manner. These observations were corroborated by results that showed tau was phosphorylated when it colocalized with activated COX-2 in tauP301S and COX-2 transgenic mice or n2a cells. To further validate these observations, treatment of mice with the COX-2 inhibitor rofecoxib decreased the phosphorylation of tau via EP1-3 but not EP4. Collectively, our observations fill the gaps between Ca2+ and the phosphorylation of tau in a COX-2-dependent mechanism, which potentially provides therapeutic targets for combating AD.

The objective of this study was to merge genetic and non-genetic factors of tacrolimus pharmacokinetics to establish a more stable population pharmacokinetic model for individualized dosage regimen in Chinese nephrotic syndrome patients. Nephrotic syndrome patients (>16 years old) treated with tacrolimus were included in the study. The population pharmacokinetic approach was analyzed using NONMEM version 7.3.0 software. Monte Carlo simulations were performed to optimize the dosage according to the population pharmacokinetic parameters of tacrolimus. The mean apparent clearance (CL/F) of tacrolimus was 13.4 L/h, with an inter-individual variability of 22.4%. The CL/F of tacrolimus in Wuzhi tablets co-administration and CYP3A5 non-expresser groups were 19.3% and 19.1% lower than that of the non-Wuzhi tablets and CYP3A5 expresser groups, respectively. The NR1I2 rs2276707 TT variant carriers had 1.17-fold CL/F compared to the CC/CT variant carriers. Monte Carlo simulation showed that the nephrotic syndrome patients that were CYP3A5 non-expressers or co-administered Wuzhi tablets received 50% or 33.3% lower dose of tacrolimus to reach the target concentration. In contrast, the NR1I2 rs227707 TT genotype carriers were administered a 33.3% higher dose of tacrolimus than the NR1I2 rs227707 CC/CT genotype carriers. A new population pharmacokinetic model was established to describe the pharmacokinetics of tacrolimus in nephrotic syndrome patients, which can be used to select rational dosage regimens to achieve a desirable whole-blood concentration.

A novel strain, YIM 100770T, was isolated from Rhinoceros unicornis faeces collected from Yunnan Wild Animal Park, China. The taxonomic status was determined based on the physiological, biochemical and phylogenetic characteristics. Strain YIM 100770T was observed to be rod-shaped, non-motile, Gram-stain negative and aerobic. The G+C content of the genomic DNA was determined to be 68.5 mol%. The cells of strain YIM 100770T contain ubiquinone Q-10 as the respiratory quinone. The major fatty acids (>1%) were identified as Summed feature 8 (C18:1 ω7c and/or C18:1 ω6c; 78.1%), Summed feature 4 (iso-C17:1-I and/or anteiso-C17:1-B; 12.9%), C19:0 cyclo ω8c (2.8%), C16:0 (2.2%) and C18:0 (2.2%). Comparison of 16S rRNA gene sequences revealed the strain show high similarities with the members of the genera Psychroglaciecola (94.5%), Methylobacterium (90.5-94.1%) and Microvirga (92.0-93.3%) in the family Methylobacteriaceae. In addition, the strain also showed high similarities with the members of the genera Chelatococcus (93.7-94.0%) and Pseudochelatococcus (93.1-93.7%) in the family Beijerinckiacea, and the genus Bosea (93.1-93.8%) in the family Bradyrhizobiaceae. The phylogenetic analysis, combined with the chemical characteristics, suggest that the strain represents a novel genus in the order Rhizobiales of the class Alphaproteobacteria, for which the name Enterovirga rhinocerotis gen. nov., sp. nov. is proposed. The type strain of E. rhinocerotis is YIM 100770T (=DSM 25903T = CCTCC AB 2012048T).

A Gram-stain-positive, facultatively anaerobic, short rod-shaped, oxidase-negative and non-motile novel strain, designated YIM 101505T, was isolated from the faeces of a primate, Assamese macaque, and was studied to determine its taxonomic position. The cell wall contained meso-diaminopimelic acid and short-chain mycolic acids. Whole cell sugars were mannose, galactose and arabinose as major components. The major fatty acids (>10 %) were C18 : 1 ω9c, C16 : 0 and C17 : 1 ω8c and the major menaquinone was MK-9(H2). The polar lipids included diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol, phosphatidylinositol mannoside, glycolipid and six unidentified lipids. The new isolate shared most of the typical chemotaxonomic characteristics of members of the genus Corynebacterium . The closest related species was Corynebacterium efficiens based on 16S rRNA gene (98.1 % similarity) and partial rpoB gene (91.4 % similarity) sequences. Similarities with other species of this genus were below 97 % based on the 16S rRNA gene. The DNA–DNA hybridization value between YIM 101505T and C. efficiens DSM 44549T was 47.7±3.6 %. Moreover, the physiological and biochemical characteristics of YIM 101505T and C. efficiens DSM 44549T were different. Thus, strain YIM 101505T is considered to represent a novel member of the genus Corynebacterium , for which the name Corynebacterium faecale sp. nov. is proposed. The type strain is YIM 101505T (=DSM 45971T=CCTCC AB 2013226T).

A novel aerobic, non-motile, Gram-positive, rod-shaped actinobacterium, designated YIM 100951(T), was isolated from the faeces of civets (Viverra zibetha) living in the National Nature Protect Region in Selangor, Malaysia. Strain YIM 100951(T) shows high similarities with Microbacterium barkeri DSM 20145(T) (97.6 %), Microbacterium oryzae MB10(T) (97.3 %), Microbacterium lemovicicum ViU22(T) (97.1 %) and Microbacterium indicum BBH6(T) (97.0 %) based on their 16S rRNA genes. However, phylogenetic analysis showed that strain YIM 100951(T) formed a clade with Microbacterium halotolerans YIM 70130(T) (96.7 %), Microbacterium populi 10-107-8(T) (96.7 %) and Microbacterium sediminis YLB-01(T) (96.9 %). DNA-DNA hybridization was carried out between strains YIM 100951(T) and M. barkeri DSM 20145(T), the result showed a value of 23.2 ± 4.5 %. In addition, some of the physiological, biochemical and chemotaxonomic characteristics of strain YIM 100951(T) are different from the closely related strains. Thus, we suggest that strain YIM 100951(T) represents a novel species of the genus Microbacterium, for which the name Microbacterium gilvum sp. nov. is proposed. The type strain is YIM 100951(T) (=DSM 26235(T) = CCTCC AB 2012971(T)).

From a fermentation broth of Streptomyces albolongus obtained from Elephas maximus feces, nine bafilomycins (1-9) and seven odoriferous sesquiterpenoids (10-16) were isolated. The structures of the new compounds, including three bafilomycins, 19-methoxybafilomycin C1 amide (1), 21-deoxybafilomycin A1 (2), and 21-deoxybafilomycin A2 (3), and two sesquiterpenoid degradation products, (1β,4β,4aβ,8aα)-4,8a-dimethyloctahydronaphthalene-1,4a(2H)-diol (10) and (1β,4β,4aβ,7α,8aα)-4,8a-dimethyloctahydronaphthalene-1,4a,7(2H)-triol (11), were elucidated by comprehensive spectroscopic data analysis. The cytotoxicity activity against four human cancer cell lines and antimicrobial activities against a panel of bacteria and fungi of all compounds isolated were evaluated. Compounds 1, 7, and 8 were cytotoxic, with IC50 values ranging from 0.54 to 5.02 μM. Compounds 2, 7, 8, and 10 showed strong antifungal activity against Candida parapsilosis, with MIC values of 3.13, 1.56, 1.56, and 3.13 μg/mL respectively.

One new macrolactam derivative, nivelactam (1) and one new polyenoic acid derivative, niveamide (2), along with two other known 20-atom macrolactams (3 and 4) were isolated from the fermentation broth of Streptomyces niveus, which obtained from the forest soil in northeastern China. The structures of 1 and 2 were elucidated on the basis of HRESIMS, IR, and NMR spectroscopic data analyses. Compound 1 was proposed as an intramolecular [4+6]-cycloaddition product of 3 by S. niveus, and displayed moderate cytotoxic activity against a panel of human tumor cell lines in vitro, with IC50 values ranging from 3.76 ± 0.58 to 15.02 ± 2.81 μM.

Two new nerolidol-type sesquiterpenes were isolated from the culture broth of Streptomyces scopuliridis, and identified based on 1D and 2D NMR spectroscopic data analyses.

Six new terpenoids (1–6) and two new phloroglucinol glucosides (7 and 8) were isolated from the extract of Syzygium szemaoense leaves. Among the isolates, compounds 1 and 2 (named syzygiumursanolides A and B) were unusual 28-norursane type triterpenoids with 19(18→17)-abeo spirocyclic skeleton. And syzygiumone B (8) was rare ascorbyl-modified phloroglucinol glucoside. Their structures were elucidated on the basis of comprehensive 1D and 2D NMR, HRESIMS spectroscopic data analysis, as well as experimental and calculated ECD spectra and acid hydrolysis. Antimicrobial bioassay revealed that syzygiumursanolide D (4) displayed the most potent antifungal activities with MIC values ranging from 6.25 to 25 μg/mL against a panel of fungi.

Physalis pubescens L. is a medicinal plant widely cultivated in northeast of China. Investigation on the extract of P. pubescens fruit led to the isolation and identification of four new withanolides, namely, physapubescins J-M (1, 2, 4 and 5), together with four known analogues (3, 6-8) and fifteen other compounds. Their structures were elucidated on the basis of comprehensive NMR, MS, and ECD spectroscopic data analysis. Among isolates, physapubescin J (1) contained an unusual sulphide linkage, and four withanolides (3, 5, 7 and 8) showed anti-inflammatory potential in LPS-induced RAW264.7 cells. This study supports P. pubescens fruit could be a valuable source of withanolides. Further studies to investigate anti-inflammatory activities of isolated withanolides using in vivo models are warranted.

Glucitol-core containing gallotannins (GCGs) are characteristic constituents of the red maple (Acer rubrum) species. To pursue the development of red maple for nutraceutical applications, GCGs-enriched red maple leaves extract (MLE) was evaluated for its effects on obesity, gut dysbiosis and short chain fatty acids (SCFAs) production. Our results demonstrated that MLE alleviated high-fat diet-induced obesity, reduced body weight gain and fat mass, improved liver steatosis and insulin resistance, and mitigated adipose hypertrophy and inflammation. Additionally, MLE increased total SCFAs, acetic acid and n-butyric acid content, but exerted no impact on propionic acid production. Moreover, MLE modulated gut microbiota community structure and certain bacteria relative abundance, including Prevotella and Eubacterium. Our work firstly reports a potential association between colon-derived SCFAs production and metabolic improvement due to GCGs-enriched red maple leaves extract administration, and highlights the utilization of red maple gallotannins as a dietary ingredient for preventing obesity and related metabolic diseases.

Three pyrrol-2-aldehyde derivatives, including one new compound, jiangrine G (JG), two known compounds, jiangrine A (JA), and pyrrolezanthine (PZ), were isolated from the fermentation broth of Jiangella alba associated with a traditional Chinese medicinal plant Maytenus austroyunnanensis. The structure of jiangrine G was elucidated by a detailed spectroscopic data analysis including data from CD spectra. The anti-inflammatory activities assay demonstrated that JG and JA suppressed the production of pro-inflammatory cytokines including NO, IL-1β, and IL-6 as well as inhibited the expression of iNOS in LPS-induced RAW 264.7 cells in a dose-dependent manner. While high concentration of PZ dramatically suppressed the protein expression of TNF-α, but stimulated the release of IL-1β and IL-6. Western blot results revealed that JG, JA, and PZ modulated the expression of pro-inflammatory cytokines via MAPK p38 and NF-κB signaling pathways. For the unique structure of PZ, difference from JG and JA, the signaling pathway involved in mediating its effects on regulating the synthesis of IL-1β and IL-6 are probably more complicated than that of JG and JA.

A concise total synthesis of an exceedingly potent anti-inflammatory agent violacin A as well as the preparation of thirty analogues of this lead from commercially available orcinol are described. Highlights of our synthetic efforts involve Friedel-Crafts acylation, the regioselective etherification and esterification of phenolic hydroxyl groups, and Baker-Venkatamaran rearrangement to form basic skeleton of violacin A. The deprotection reaction with Pd-catalytic was involved to avoid the elimination of the hemiacetal hydroxyl at C2. In addition, all synthetic compounds were screened for anti-inflammatory activity against nitric oxide (NO) production using lipopolysaccharide (LPS)-induced Raw264.7 cells. A range of violacin A derivatives 11b, 11d, 11f, 12e, 12g, 13g, 17d-g exhibited stronger anti-inflammatory effect than that of violacin A. Notably, halogeno-benzyloxy substituent at C-7 were favourable for anti-inflammatory activities of violacin A derivatives. Additionally, Western blot results indicated halogeno-benzyloxy derivatives inhibited pro-inflammatory cytokines releases correlated with the suppression of NF-κB signaling pathway.

Two new phenazine metabolites, 6-hydroxyphenazine-1-carboxamide (1) and methyl 6-carbamoylphenazine-1-carboxylate (2), were isolated from a soil-derived Streptomyces diastaticus subsp. ardesiacus strain YIM PH20246, and their structures were elucidated by extensive spectroscopic data analysis. The antimicrobial activities of the isolates were assayed. Compound 1 showed moderate antifungal and antibacterial activities against Fusarium oxysporum (ATCC 7808), Fusarium solani (ATCC 36031) and Plectosphaerella cucumerina (local isolate), Staphylococcus aureus (ATCC 25923) and Staphylococcus albus (ATCC 10231), respectively. Compound 2 exhibited moderate antifungal and antibacterial activities against F. oxysporum, F. solani, and Phoma herbarum, S. aureus, S. albus, and Bacillus subtilis, respectively.

Scope Published data support that gut microbiota play an important role in the pathological process of obesity and related metabolic disorders. In the current study, it is investigated whether a standardized extract from Jamun (Eugenia jambolana), a widely consumed tropical fruit, could alleviate obesity and alter gut microbial community in high-fat diet (HFD)-fed mice. Methods and results C57BL/6 mice are fed either a standard diet (SD) or HFD with or without Jamun fruit extract (JFE; 100 mg kg-1 day-1 ) by oral gavage for 8 weeks. JFE supplementation significantly alleviated diet-induced obesity, insulin resistance, and liver steatosis. JFE supplementation also improved HFD-induced gut dysbiosis by restoring the ratio of Firmicutes to Bacteroidetes as revealed by 16S rDNA analyses. The relative abundance of certain genera, as well as levels and proportion of intestinal-derived short-chain fatty acids are improved in JFE-treated mice in comparison to the HFD-fed control group. Conclusion These promising data show the potential association between gut microbiota modulation and metabolism improvement of the JFE administration, and support the utilization and further investigation of Jamun fruit as a dietary intervention strategy for the prevention of obesity and related metabolic disorders.

Six new metabolites, actinofuranones D-I (compounds 1&ndash, 6), were isolated together with three known compounds&mdash, JBIR-108 (7), E-975 (8), and E-492 (9)&mdash, from a fermentation broth of Streptomyces gramineus derived from the lichen Leptogium trichophorum. The structures of the new compounds 1&ndash, 6 were established using comprehensive NMR spectroscopic data analysis, as well as UV, IR, and MS data. The anti-inflammatory activity of these isolated compounds were evaluated by examining their ability to inhibit nitric oxide (NO) production in LPS-stimulated RAW 264.7 macrophage cells. Compounds 4, 5, 8, and 9 attenuated the production of NO due to the suppression of the expression of nitric oxide synthase (iNOS) in LPS-induced RAW 264.7 cells. Moreover, 4, 5, 8, and 9 also inhibited LPS-induced release of proinflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor &alpha, (TNF-&alpha, ).

Borrelidin, a nitrile containing 18-membered polyketide macrolide, display potent antifungal activity. In this study, a library of borrelidin derivatives were synthesized. Their structures were elucidated by detailed spectroscopic data analysis. The antifungal activity and cytotoxicity of these target compounds were evaluated by broth microdilution and 3-(4,5-dimethylthiazol-2-yl)-3,5-phenytetrazoliumromide (MTT) methods. Among forty-seven prepared analogues, compound 3b had the inhibitory effect on Candida albicans and Candida parapsilosis (MIC: 50 and 12.5 μg/mL, respectively). Furthermore, compounds 4n and 4r presented better antifungal activity against Aspergillus fumigatus with 12.5 μg/mL MIC value, which were insensitive to borrelidin. Preliminary structure-activity relationships (SAR) revealed that the ester analogues containing fragment -OCH2CH2N- had an important effect on the antifungal activity. Meanwhile, the molecular docking study indicated the carboxyl substituents in BN could provide extra interaction with pathogenic fungal threonyl-tRNA synthetase (ThrRS).

Six new polyene macrolactams, heronamides G-L (1-6), one new polyenoic acid derivative, niveamide B (10), together with four known compounds, BE-14106-6 (7), BE-14106 (8), GT32-B (9), and niveamide (11), were isolated from the fermentation broth of

The chemical composition and anti-hyperglycaemic effects of polyphenol-enriched Longan pericarp extracts (LPE) were investigated in the present study. The phenolic profile of LPE was determined by HPLC-DAD/MS analysis. Nine phenolics were identified, and of these, three major components were quantified by LC-MS/MS. Anti-hyperglycaemic assays demonstrate that LPE (polyphenol content ca. 37.8 g gallic acid equivalents/100 g) inhibit α-glucosidase (IC50 = 11.68 ± 0.44 µg/mL) in vitro and decrease blood glucose content in mice (P

Twenty four sesquiterpenoids, 1–24, including 11 new sesquiterpenoids, jambolanins A–K, and two new norsesquiterpenoids, jambolanes A and B, along with six known triterpenoids, were isolated from the seeds of Eugenia jambolana fruit. Their structures were elucidated on the basis of NMR and MS spectrometry data analysis. Among the isolates, compound 13 possessed a rare 6,7-seco-guaiene skeleton, and compounds 14 and 15 were norsesquiterpenoids containing a spiro[4.4]nonane skeleton. Antimicrobial assay evaluation revealed that sesquiterpenoids, 4, 5/6, 17, 19, 21, 23, and 24 inhibited the growth of the Gram-positive bacterium, Staphylococcus aureus. The current study advances scientific knowledge of E. jambolana phytochemicals and suggests that its sesquiterpenoids may contribute, in part, to the anti-infective effects attributed to the edible fruit of this plant.

In a previous study on discovering new antimicrobial agents from microbial sources, nine bafilomycins were isolated from the fermentation broth of Streptomyces albolongus. Among them, bafilomycin C1 (Baf C1) showed strong antifungal activity against Candida albicans, with MIC value of 1.56 μg/mL. The aim of this study was to evaluate the action mechanism of Baf C1 against C. albicans. Quantitative PCR analysis revealed that ergosterol biosynthesis-related genes of C. albicans ACS1, HMG1, IDI1, ERG1, ERG2, ERG6, ERG7, ERG8, ERG9, ERG12, ERG13, ERG20, ERG24, ERG251, ERG252, ERG26, ERG27, and ERG28 were all down-regulated (Log2fold change

A novel actinobacterium, designated YIM 101593T, was isolated from the faeces of a primate (Rhinopithecus roxellanae) living in Yunnan Wild Animal Park in Yunnan province, south-west China. The isolate was Gram-stain-positive, facultatively anaerobic, coccus-shaped, oxidase-negative and motile. The cell wall contained meso-diaminopimelic acid as its diagnostic diamino acid, and mannose, ribose, glucose, galactose and arabinose were detected as the main whole-cell sugars. The predominant menaquinone was MK-8(H2). The polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol, two glycolipids, three unidentified phospholipids and two unidentified lipids. The major fatty acids were C17 : 1ω8c, C15 : 0 and summed feature 4 (anteiso-C17 : 1 B and/or iso-C17 : 1 I). The DNA G+C content was 69.8 mol%. The 16S rRNA gene sequence similarity between strain YIM 101593T and Mobilicoccus pelagius was 97.9 %, and the two strains formed a distinct lineage stably on the basis of phylogenetic analysis. In addition, DNA–DNA relatedness between the two strains was 49.0±5.1 %. On the basis of chemotaxonomical and physiological characteristics and the phylogenetic analysis, strain YIM 101593T should be considered to represent a novel species of the genus Mobilicoccus , for which we propose the name Mobilicoccus caccae sp. nov., with the type strain YIM 101593T (=DSM 27611T=CCTCC AB 2013229T).

Streptomyces albolongus YIM 101047 produces novel bafilomycins and odoriferous sesquiterpenoids with cytotoxic and antimicrobial activities. Here, we report the complete genome sequence of S. albolongus YIM 101047, which consists of an 8,027,788bp linear chromosome. Forty-six putative biosynthetic gene clusters of secondary metabolites were found. The sesquiterpenoid gene cluster was on the left arm (0.09-0.10Mb), and the bafilomycin biosynthetic gene cluster was on the right arm (7.46-7.64Mb) of the chromosome. Twenty-two putative gene clusters with high or moderate similarity to important antibiotic biosynthetic gene clusters were found, including the antitumor agents bafilomycin, epothilone and hedamycin; the antibacterial/antifungal agents clavulanic acid, collismycin A, frontalamides, kanamycin, streptomycin and streptothricin; the protein phosphatase inhibitor RK-682; and the acute iron poisoning medication desferrioxamine B. The genome sequence reported here will enable us to study the biosynthetic mechanism of these important antibiotics and will facilitate the discovery of novel secondary metabolites with potential applications to human health.

Alisol F and 25-anhydroalisol F isolated from Alisma orientale, were proved to exhibit anti-inflammatory potential in our previous work. In the current study, the anti-inflammatory effects and action mechanisms of alisol F and 25-anhydroalisol F were investigated in vitro. Moreover, the pharmacological effects of alisol F in lipopolysaccharide (LPS)/d-galactosamine (d-gal)-induced acute liver-injured mice were evaluated. The results demonstrated that alisol F and 25-anhydroalisol F could suppress LPS-induced production of nitric oxide (NO), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and interleukin-1β (IL-1β), as well as inhibit the mRNA and protein levels of inducible nitric oxide (iNOS) and cyclooxygenase-2 (COX-2). In addition, we investigated the role of alisol F and 25-anhydroalisol F in mediating mitogen-activated protein kinases (MAPKs), signal transducers, and activators of transcription 3 (STAT3) and nuclear factor κB (NF-κB) pathways involved in the inflammation process of LPS-stimulated RAW 264.7 cells. The phosphorylation of ERK, JNK, p38, and STAT3, and the NF-κB signaling pathway, were obviously suppressed in alisol F and 25-anhydroalisol F treated cells. Results obtained from in vitro experiments suggested alisol F obviously improved liver pathological injury by inhibiting the production of TNF-α, IL-1β, and IL-6, and significantly decreasing the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in LPS/d-gal-induced mice. Furthermore, the reduction of phosphorylation of ERK and JNK, as well as suppression of the NF-κB signaling pathway, were also observed in liver tissues of the alisol F-treated mice model. Alisol F and 25-anhydroalisol F may serve as potential leads for development of anti-inflammatory agents for acute liver failure treatment.

Nine monoterpenoids from Radix Paeoniae Alba, including paeoniflorin derivatives, paeoniflorin (PF), 4-O-methylpaeoniflorin (MPF), 4-O-methylbenzoylpaeoniflorin (MBPF); paeonidanin derivatives, paeonidanin (PD), paeonidanin A (PDA), albiflorin derivatives, albiflorin (AF), benzoylalbiflorin (BAF), galloylalbiflorin (GAF), and debenzoylalbiflorin (DAF), were obtained in our previous phytochemistry investigations. Their anti-inflammatory effects were determined in the present study. The expression and production of pro-inflammatory cytokines in lipopolysaccharides (LPS)-stimulated RAW 264.7 cells were measured using an Elisa assay and nitric oxide (NO) release was determined using the Griess method. The results demonstrated that the most of the monoterpenoids suppressed the LPS-induced production of NO, interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α). The anti-inflammatory activities of these monoterpenoids were closely related to their structural characteristics. Paeoniflorins and paeonidanins presented stronger anti-inflammatory activities than those of albiflorin derivatives. Furthermore, the action mechanisms of MBPF, having a strong anti-inflammatory effect, were investigated using quantitative reverse transcription polymerase chain reaction (RT-PCR) and Western blot methods. The results indicated that MBPF could down-regulate the mRNA and protein expression level of inducible nitric oxide synthase (iNOS) in LPS-stimulated RAW 264.7 cells. The mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K)/AKT and nuclear factor κB (NF-κB) signaling pathways are involved in mediating the role of MBPF in suppressing the expression and production of pro-inflammatory cytokines in RAW 264.7 cells.

Three new metabolites (2-4), together with one known compound, GTRI-02, (1) were isolated from a fermentation broth of Streptomyces violaceoruber derived from Equus burchelli feces. The structures of the new compounds 2-4 were established using comprehensive NMR spectroscopic data analysis as well as UV, IR and MS data. The anti-inflammatory activity of compounds 1-4 was tested by examining their ability to inhibit nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. Compound 2 showed a moderate inhibition of NO production with IC50 value of 51.2 μm.

Twelve previously undescribed polyketide derivatives, heterocornols A-L, and seven known analogues were isolated from a culture of the fungus Pestalotiopsis heterocornis associated with sponge. Their structures were elucidated by a comprehensive spectroscopic data analysis and CD Cotton effects. These compounds were evaluated for cytotoxic and antibacterial activities in vitro. Among them, heterocornols A-C, F-H, methyl-(2-formyl-3-hydroxyphenyl)propanoate, agropyrenol, and vaccinol G exhibited cytotoxicities against four human cancer cell lines with IC50 values 15–100 μM, and they also showed antibacterial activities against Gram-positive bacteria Staphylococcus aureus and Bacillus subtilis with MIC values ranging from 25 to 100 μg/mL. Moreover, compounds heterocornol C, heterocornol G, agropyrenol, and vaccinol G showed weak antifungal activities against Candida parapsilosis and Cryptococcus neoformans with MIC values 100 μg/mL.

Fifteen new phloroglucinol derivatives, jamunones A–O (1–8 and 10–16, respectively), along with one known analogue spiralisone C (9), were isolated from Eugenia jambolana seeds. Their structures were elucidated by detailed nuclear magnetic resonance and mass spectrometry spectroscopic data interpretation. Compounds 1–9, 11, 12, and 14–16 inhibited protein tyrosine phosphatase 1B activity with IC50 values ranging from 0.42 to 3.2 μM.

Six new nonactic and homononactic acid derivatives, ethyl homononactate (1), ethyl nonactate (2), homononactyl homononactate (6), ethyl homononactyl nonactate (7), ethyl homononactyl homononactate (8), and ethyl nonactyl nonactate (9), as well as four known compounds, homononactic acid (3), nonactic acid (4), homononactyl nonactate (5), and bishomononactic acid (10), were isolated from culture broth of Bacillus pumilus derived from Breynia fruticosa. The structures of new compounds were elucidated by spectroscopic analysis and chemical methods. The optical purities of 1-6 were determined by HPLC/MS after treatment with L-phenylalanine methyl ester. The dimeric compounds 5-9 showed weak cytotoxic activities against five human cancer cell lines (IC50 19-100 μg/ml).