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The total synthesis of antibacterial amycolasporin A, (±) amycolasporins B and C and their analogues (18, 19, 30a and 30d–30f) was introduced; 30d obviously inhibited bacterial biofilm formation and promoted intracellular ROS release.

Riligustilide (RG), one of the dimeric phthalides of Angelica sinensis and Ligusticum chuanxiong, was confirmed effective against many diseases. However, its effects on type 2 diabetes mellitus (T2DM) and the underlying molecular mechanisms have not been clearly elucidated yet. The current study was designed to investigate the hypoglycemic potential by which RG affects the pathogenesis of T2DM. Comprehensive insights into the effects and underlying molecular mechanisms of RG on attenuating aberrant metabolism of glucose were determined in high-fat diet-induced T2DM mice and insulin-resistant (IR) HepG2 cells. In high-fat diet-induced C57BL/6J mice, RG administration significantly reduced hyperglycemia, decreased hyperinsulinemia, and ameliorated glucose intolerance. Mechanistically, RG activated PPARγ and insulin signaling pathway to improve insulin sensitivity, and increase glucose uptake as well as glycogenesis. In addition, RG also upregulated AMPK-TORC2-FoxO1 axis to attenuate gluconeogenesis in vivo and in vitro. According to the findings, RG may be a promising candidate for the treatment of T2DM.

Background Neuroinflammation is thought to be a cause of Alzheimer’s disease (AD), which is partly caused by inadequate mitophagy. As a receptor of mitophagy, we aimed to reveal the regulatory roles of optineurin (OPTN) on neuroinflammation in the pathogenesis of AD. Methods BV2 cells and APP/PS1 transgenic (Tg) mice were used as in vitro and in vivo experimental models to determine the regulatory roles of OPTN in neuroinflammation of AD. Sophisticated molecular technologies including quantitative (q) RT-PCR, western blot, enzyme linked immunosorbent assay (ELISA), co-immunoprecipitation (Co-IP) and immunofluorescence (IF) were employed to reveal the inherent mechanisms. Results As a consequence, key roles of OPTN in regulating neuroinflammation were identified by depressing the activity of absent in melanoma 2 (AIM2) inflammasomes and receptor interacting serine/threonine kinase 1 (RIPK1)-mediated NF-κB inflammatory mechanisms. In detail, we found that expression of OPTN was downregulated, which resulted in activation of AIM2 inflammasomes due to a deficiency in mitophagy in APP/PS1 Tg mice. By ectopic expression, OPTN blocks the effects of Aβ oligomer (Aβo) on activating AIM2 inflammasomes by inhibiting mRNA expression of AIM2 and apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC), leading to a reduction in the active form of caspase-1 and interleukin (IL)-1β in microglial cells. Moreover, RIPK1 was also found to be negatively regulated by OPTN via ubiquitin protease hydrolysis, resulting in the synthesis of IL-1β by activating the transcriptional activity of NF-κB in BV2 cells. As an E3 ligase, the UBAN domain of OPTN binds to the death domain (DD) of RIPK1 to facilitate its ubiquitination. Based on these observations, ectopically expressed OPTN in APP/PS1 Tg mice deactivated microglial cells and astrocytes via the AIM2 inflammasome and RIPK-dependent NF-κB pathways, leading to reduce neuroinflammation. Conclusions These results suggest that OPTN can alleviate neuroinflammation through AIM2 and RIPK1 pathways, suggesting that OPTN deficiency may be a potential factor leading to the occurrence of AD.

Radix Astragali (RA) is an important Traditional Chinese Medicine widely used in the treatment of various diseases, such as pneumonia, atherosclerosis, diabetes, kidney and liver fibrosis. The role of isoflavonoids from RA in the treatment of liver injury remains unclear. The study aimed to explore hepatoprotective and anti-inflammatory effects of isoflavonoids from Astragalus mongholicus. Network pharmacological analysis showed that RA had a multi-target regulating effect on alleviating liver injury and inhibiting inflammation through its active ingredients, among which isoflavones were closely related to its key molecular targets. The anti-inflammatory and liver protection effects of isoflavonoids of RA were investigated using lipopolysaccharide (LPS)-induced RAW 264.7 cells in vitro and LPS/D-galactosamine (D-gal)-induced acute liver injury mice in vivo. The experimental results showed that methylnissolin (ML) and methylnissolin-3-O-β-D-glucoside (MLG) presented more notable anti-inflammatory effects. Both of them suppressed the release of pro-inflammatory cytokines, such as iNOS, COX-2, IL-1β, IL-6, and TNF-α in LPS-stimulated RAW 264.7 cells. In vivo investigation demonstrated that ML markedly meliorated liver injury in LPS/D-gal-induced mice. Western blot results revealed that ML and MLG down-regulated the expression of proinflammatory cytokines via NF-κB signaling pathway. The isoflavonoids, methylnissolin (ML), and methylnissolin-3-O-β-D-glucoside (MLG), play a vital role in the hepatoprotective and anti-inflammatory effects of RA.

ABATRACTNine compounds, five phenolic glycosides (1, 2, 4-6), three phenylpropanoids (7-9), and a furanone glycoside (3), were isolated from aqueous soluble extract of the dried roots of Anemone chinensis Bunge. The structures of new compounds (1-4) were elucidated by comprehensive spectroscopic data analysis as well as chemical evidence. Pulsatillanin A (1) demonstrated significant antioxidant effects through scavenging free radical in DPPH assay, and relieved the oxidative stress in LPS-induced RAW 264.7 cells by reducing ROS production, enhancing antioxidant enzyme SOD activity, replenishing depleted GSH in a dose-dependent manner. Western blot analysis revealed that 1 showed antioxidant activity via activating Nrf2 signaling pathway.

Twenty-three natural jamunone analogues along with a series of jamunone-based derivatives were synthesized and evaluated for their inhibitory effects against breast cancer (BC) MDA-MB-231 and MCF-7 cells. The preliminary structure-activity relationship revealed that the length of aliphatic side chain and free phenolic hydroxyl group at the scaffold played a vital role in anti-BC activities and the methyl group on chromanone affected the selectivity of molecules against MDA-MB-231 and MCF-7 cells. Among them, jamunone M (JM) was screened as the most effective anti-triple-negative breast cancer (anti-TNBC) candidate with a high selectivity against BC cells over normal human cells. Mechanistic investigations indicated that JM could induce mitochondria-mediated apoptosis and cause G0/G1 phase arrest in BC cells. Furthermore, JM significantly restrained tumor growth in MDA-MB-231 xenograft mice without apparent toxicity. Interestingly, JM could downregulate phosphatidylinositide 3-kinase (PI3K)/Akt pathway by suppressing protein-tyrosine phosphatase 1B (PTP1B) expression. These findings revealed the potential of JM as an appealing therapeutic drug candidate for TNBC.

Nutraceutical/pharmaceutical agents capable of maintaining redox and inflammation homeostasis are considered as candidates for the prevention and/or treatment of liver diseases. Psidium guajava (commonly known as guava) leaf is a commercially available functional food that has been reported to possess hepatoprotective property. However, the hepatoprotective constituents in guava leaf are not known. In the current study, a standardized triterpenoid-enriched extract of guava leaves (TGL) was developed. A new ursolic acid derivative, namely 2α,3β,6β,23,30-pentahydroxyurs-11,13(18)-dien-28,20β-olide (1), and 23 known triterpenoids were isolated and identified from TGL. The hepatoprotective effects of TGL were evaluated through a model using acetaminophen (APAP)-exposed C57BL/6 male mice. Pretreatment of TGL (75 and 150 mg/kg) restored the mice hepatic architecture, improved the serum ALT and AST levels, and reduced the hepatic ROS and MDA contents. Further molecular mechanistic study revealed that TGL modulated Nrf2 and MAPK signaling pathways to alleviate APAP-induced oxidative and inflammatory stress in liver. In addition, the new compound 1 from TGL showed protective effects against APAP-induced cytotoxicity via activation of the Nrf2 pathway in HepG2 cells. Overall, this is the first report on the hepatoprotective effects of a standardized triterpenoid-enriched extract of guava leaves, which supports its potential nutraceutical application in liver disease management.

Six oxazolomycins (1–6) were isolated from the fermentation broth of a soil-borne bacterial strain, Streptomyces glaucus.

Eleven metabolites, six echinosporins (1-6), four dibenzoyls (7-10), and an aromatic compound (11), were isolated from the fermentation broth of lichen-associated Amycolatopsis hippodromi. The structures of the new compounds (1-5, 8-11) were elucidated by comprehensive spectroscopic analysis including data from experimental and calculated ECD spectra. Amycolasporins A-C (1-3) demonstrated antibacterial activities against Bacillus subtilis, Staphylococcus aureus, and Escherichia coli with MIC values of 25 or 100 μg/mL. Amycolasporin C (3) and the known dibenzoyl (7) attenuated the production of NO due to the suppression of the expression of nitric oxide synthase (iNOS) in LPS-induced RAW 264.7 cells in a dose-dependent manner.

A novel Gram-stain-positive, aerobic, non-spore-forming, irregular short rod-shaped actinobacterial strain, designated YIM 102482-1T, was isolated from the faeces of Macaca mulatta. Strain YIM 102482-1T grew optimally at 30–37 °C, at pH 8.0 and in the presence of 1.0–3.0% (w/v) NaCl. Similarly, analysis based on 16S rRNA gene sequences showed that strain YIM 102482-1T was a member of the genus Gulosibacter and most closely related to Gulosibacter feacalis NBRC 15706T (97.6 %), Gulosibacter bifidus NBRC 103089T (97.6 %), Gulosibacter chungangensis KCTC 13959T (96.4 %) and Gulosibacter molinativorax DSM 13485T (96.0 %), respectively. Furthermore, phylogenetic trees based on 16S rRNA gene sequences and genomic sequences demonstrated that strain YIM 102482-1T formed a distinct branch with all type strains of the genus Gulosibacter . The major whole-cell sugars and cellular fatty acids (>10.0 %) were ribose and rhamnose, and anteiso-C15 : 0, iso-C16 : 0 and C16 : 0, respectively. The predominant menaquinone was MK-9, and 2,4-diaminobutyric acid and ornithine were the diagnostic diamino acids in the cell-wall peptidoglycan. The dominant polar lipids consisted of diphosphatidylglycerol, phosphatidylglycerol and unidentified glycolipid. The DNA G+C content of YIM 102482-1T was 63.0 mol%. Based on analysis results of physiological, biochemical and chemotaxonomic data, strain YIM 102482-1T represents a novel species of the genus Gulosibacter , for which the name Gulosibacter macacae sp. nov. is proposed. The type strain is YIM 102482-1T(=DSM 102156T=CCTCC AB 2016023T).

Strain YIM 102744-1T was isolated from Rhinopithecus roxellanae fecal sample collected at Yunnan Wild Animal Park, Yunnan province, PR China. Cells were Gram-stain-negative, aerobic, non-motile and irregular rods. Optimal growth occurred in the presence of 0–1.0% (w/v) NaCl, at pH 7.0–8.0, and at 30 °C. The predominant ubiquinone was Q-10. The major cellular fatty acids (> 10.0%) were C18:1ω7c and C16:1ω7c/C16:1ω6c. The dominant polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and phosphatidylcholine. The DNA G + C content was 62.4 mol%. Phylogenetic analysis based on 16S rRNA gene sequences revealed that YIM 102744-1T belonged to the family Rhodobacteraceae and shared the highest similarity with the type strain Gemmobacter intermedius 119/4T (96.6%). In addition, phylogenetic trees indicated that strain YIM 102744-1T formed a distinct clade together with the closest relative G. intermedius 119/4T. Based on the results of polyphasic taxonomic analysis, strain YIM 102744-1T is considered to represent a novel species within a new genus Falsigemmobacter, for which the name Falsigemmobacter faecalis gen. nov., sp. nov. is proposed. The type strain of Falsigemmobacter faecalis is YIM 102744-1T(= KCTC 52106T = CCTCC AB 2016031T). Because Gemmobacter intermedius 119/4T formed a branch with YIM 102744-1 in the phylogenetic trees and was clearly separated from the other members within the genus Gemmobacter, it is also proposed to transfer into the genus Falsigemmobacter as Falsigemmobacter intermedius comb. nov. (type strain 119/4T = CIP 110795T = LMG 28215T = CCM 8510T). The type species of the genus Falsigemmobacter is Falsigemmobacter intermedius gen. nov., comb. nov.

As the global climates change, elevated CO2 and soil contamination by heavy metal co-occur in natural ecosystems, which are anticipated to affect soil organic carbon fractions (SOC) and their relation to soil microbial activities, but this issue has not been extensively examined. We investigated the response of SOC and their relation with soil microorganisms and enzyme activities in rhizosphere soils of Robinia pseudoacacia L. seedlings to elevated CO2 plus cadmium (Cd) contamination. We found that elevated CO2 significantly (p

In the process of investigating the antifungal structure-activity relationships (SAR) of borrelidin and discovering antifungal leads, a semisynthetic borrelidin analogue, BN-3b with antifungal activity against Candida albicans, was achieved. In this study, we found that oxidative damage induced by endogenous reactive oxygen species (ROS) plays an important role in the antifungal activity of BN-3b. Further investigation indicated that BN-3b stimulated ROS accumulation, increased malondialdehyde (MDA) levels, and decreased reduced/oxidized glutathione (GSH/GSSG) ratio. Moreover, BN-3b decreased mitochondrial membrane potential (MMP) and ATP generation. Ultrastructure analysis revealed that BN-3b severely damaged the cell membrane of C. albicans. Quantitative PCR (RT-qPCR) analysis revealed that virulence factors of C. albicans SAPs, PLB1, PLB2, HWP1, ALSs, and LIPs were all down-regulated after BN-3b exposure. We also found that BN-3b markedly inhibited the hyphal formation of C. albicans. In addition, in vivo studies revealed that BN-3b significantly prolonged survival and decreased fungal burden in mouse model of disseminated candidiasis.

Benzophenone glycosides are a major type of polyphenols present in guava. To date, there is still poor understanding of the relationship between benzophenone glycosides and the hepatoprotective effects attributed to this edible fruit. Herein, the protective effects of guavinoside B (GUB), a main benzophenone glycoside present in guava fruit, against acetaminophen (APAP)-induced liver injury were investigated in vitro and in vivo. Fluorescence measurement demonstrated that GUB (at a concentration of 30 μM) significantly reduced the intracellular ROS levels in APAP-treated HepG2 cells. In addition, GUB (100 mg kg-1 d-1) pretreatment markedly alleviated APAP-induced hepatocyte infiltration and necrosis in C57BL/6 mice, and improved serum and hepatic biochemical parameters, such as ALT, AST, SOD, GSH, ROS, MDA, and TNF-α levels. RT-PCR and western blot experiments revealed that GUB up-regulated Nrf2, GCLC and NQO1, while reducing p-JNK gene expression in the liver. The fermentation experiment further revealed that the displayed beneficial effects of GUB in vivo might be related to the gut microbial metabolite gallic acid. These promising data suggested that GUB showed potent hepatoprotective effects through regulating the Nrf2 and JNK signaling pathways. Further investigation of the absorption and metabolism of benzophenones would be warranted to promote the utilization of these phenolics as functional food ingredients against oxidative stress-induced chronic diseases.

A yellow, Gram-stain-negative, aerobic, non-gliding, non-spore-forming, rod-shaped strain, designated YIM 102600T, was isolated from the faeces of Macaca mulatta dwelling in the Yunnan Wild Animal Park, Yunnan Province, South-West PR China. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain YIM 102600T was a member of the genus Flavobacterium , and closely related to Flavobacterium qiangtangense F3T (96.9 % similarity) and Flavobacterium noncentrifugens R-HLS-17T (96.0 % similarity). Phylogenetic trees showed that strain YIM 102600T formed a clade with F. qiangtangense F3T and F. noncentrifugens R-HLS-17T. Growth occurred at 4–30 °C (optimum, 28 °C), pH 7.0–8.0 (pH 7.5) and NaCl concentration 0–2 % (w/v; 0–1 %, w/v). The major fatty acids were iso-C15:0 and summed feature 3 (comprising C16:1 ω7c and/or C16:1 ω6c). The predominant polar lipid was phosphatidylethanolamine and the sole respiratory quinone was menaquinone-6. The DNA G+C content was 36.4 mol%. The calculated digital DNA–DNA hybridization values between strain YIM 102600T and other species of Flavobacterium ranged from 70.0 to 75.0 % and average nucleotide identity values were in a range between 13.7 to 23.5 %. Based above the consensus of phenotypic and phylogenetic analyses as well as whole genome comparisons, strain YIM 102600T (=KCTC 52099T=CCTCC AB 201632T) is proposed to represent type strain of a novel species, Flavobacterium macacae sp. nov.

Germacradienol is a main precursor in the biosynthesis of geosmin-type terpenes by a variety of microbes, but its biological activities are still unknown. In the biosynthetic mechanism study of an antifungal degraded sesquiterpenoid (1β,4β,4aβ,8aα)-4,8a-dimethyloctahydronaphthalene-1,4a(2H)-diol (5) with a geosmin scaffold, the germacradienol synthase B7C62_00490 was identified. To exploit the synthetic potential of the enzyme to create germacradienol, engineered strains were constructed by introducing key synthases of farnesyl diphosphate, germacradienol synthase B7C62_00490 and glycosyltransferase UGT73C5 in Escherichia coli BL21(DE3). Germacradienol (1) and the novel glycosylated derivate germacradienyl-11-O-β-d-glucopyranoside (3) were successfully obtained from engineered strains. The cytotoxic activity against nine human cancer cell lines and antimicrobial activities against a panel of bacteria and fungi of germacradienol analogs derived from engineered strains were evaluated. Germacradienol demonstrated multiple biological activities, including broad antimicrobial activities with MIC values ranging from 12.5 to 25.0 μg/mL and cytotoxic activities with IC

Phenolipids are characteristic phytochemicals of Syzygium genus. However, the antidiabetic potential and underlying molecular mechanism of these components are not fully elucidated. Herein, we studied the anti-diabetic effects of jambone E (JE), a phenolipid from S. cumini, with in vitro and in vivo models. Data from current study showed that JE enhanced glucose consumption and uptake, promoted glycogen synthesis, and suppressed gluconeogenesis in insulin resistant (IR)-HepG2 cells and primary mouse hepatocytes. JE also attenuated streptozotocin-induced hyperglycemia and hyperlipidemia in type 1 diabetic (T1D) mice. Eleven metabolites (e.g. trimethylamine n-oxide, 4-pyridoxic acid, phosphatidylinositol 39:4, phenaceturic acid, and hippuric acid) were identified as potential serum biomarkers for JE's antidiabetic effects by an untargeted metabolomics approach. The further molecular mechanistic study revealed that JE up-regulated phosphorylation levels of protein kinase B (AKT), glycogen synthase kinase 3 beta, and forkhead box O1 (FoxO1), promoted nuclear exclusion of FoxO1 whilst decreased gene expression levels of peroxisome proliferator-activated receptor gamma coactivator-1 alpha, phosphoenolpyruvate carboxykinase and glucose 6-phosphatase in IR-HepG2 cells and T1D mice. Our data suggested that JE might be a potent activator for AKT-mediated insulin signaling pathway, which was confirmed by the usage of AKT inhibitor and AKT-target siRNA interference, as well as the cellular thermal shift assay. Findings from the current study shed light on the anti-diabetic effects of phenolipids in the Syzygium species, which supports the use of medicinal plants in the Syzygium genus for potential pharmaceutical applications.

Guava is a popular fruit consumed worldwide with beneficial effects in regulation of glucose and lipid metabolism. Although polysaccharides are a major phytochemical component of guava, to date, the alleviative effects of polysaccharides from the guava fruit against diet-induced obesity remain unclear. The relationship between the anti-obesity effects of guava polysaccharide (GP) and gut microbiota is unknown. In current study, seven-week-old C57BL/6 mice were fed high-fat diet (HFD) supplemented with GP (100 mg/kg) by oral gavage for 11 weeks. GP supplementation alleviated HFD-induced body weight gain and visceral obesity, and reduced serum cholesterol, triglyceride, and LDL-C levels. In addition, GP ameliorated insulin resistance and prevented hepatic lipid accumulation and meta-inflammation in both liver and adipose tissues in obese mice. Remarkably, GP treatment restored the Firmicutes/Bacteroidetes ratio, induced growth of beneficial bacteria including Clostridium XlVa, Parvibacter, and Enterorhabdus, and decreased in inflammation-related bacteria Mucispirillum in mice fecal samples, accompanied with enhanced production of colonic short chain fatty acids especially butyric acid. However, the metabolic benefits of GP diminished in antibiotics-treated HFD-fed mice. Overall, GP improved metabolic profiles in HFD-induced obese mice via the mediation of gut microbiota-dependent pathways. GP might be developed and utilized as prebiotics in nutraceutical and food industry.

The chemical characteristics and hypolipidemic effects of alkylphenols in the fruit of Syzygium jambos were investigated in this study. Three cardanols (1-3; 1 as a new compound) and three alkylresorcinols (4-6) were isolated and identified from S. jambos fruit. Cardanols 1 and 2 (10-40 μM) suppressed lipids accumulation and reduced triglyceride content in oleic acid-overloaded HepG2 cells via the activation of AMPK/PPARα signaling pathways. Furthermore, the biological distribution of cardanols after an oral intake in mice was investigated. Compound 2 was detected in mice plasma, feces, and adipose tissues after a single oral intake (80 mg/kg body weight). In addition, an alkylphenols-enriched S. jambos fruit extract containing two bioactive compounds (95.9 and 198.6 μg/mg of compounds 1 and 2, respectively) was prepared. Findings from the current study highlight the potential usage of cardanols as well as S. jambos fruit for the management of dyslipidemia.

ObjectiveTo investigate the effect of Fufang Huangqi Decoction on the gut microbiota in patients with class I or II myasthenia gravis (MG) and to explore the correlation between gut microbiota and MG (registration number, ChiCTR2100048367; registration website, http://www.chictr.org.cn/listbycreater.aspx; NCBI: SRP338707).MethodsIn this study, microbial community composition and diversity analyses were carried out on fecal specimens from MG patients who did not take Fufang Huangqi Decoction (control group, n = 8) and those who took Fufang Huangqi Decoction and achieved remarkable alleviation of symptoms (medication group, n = 8). The abundance, diversity within and between habitats, taxonomic differences and corresponding discrimination markers of gut microbiota in the control group and medicated group were assessed.ResultsCompared with the control group, the medicated group showed a significantly decreased abundance of Bacteroidetes (P < 0.05) and significantly increased abundance of Actinobacteria at the phylum level, a significantly decreased abundance of Bacteroidaceae (P < 0.05) and significantly increased abundance of Bifidobacteriaceae at the family level and a significantly decreased abundance of Blautia and Bacteroides (P < 0.05) and significantly increased abundance of Bifidobacterium, Lactobacillus and Roseburia at the genus level. Compared to the control group, the medicated group had decreased abundance, diversity, and genetic diversity of the communities and increased coverage, but the differences were not significant (P > 0.05); the markers that differed significantly between communities at the genus level and influenced the differences between groups were Blautia, Bacteroides, Bifidobacterium and Lactobacillus.ConclusionsMG patients have obvious gut microbiota-associated metabolic disorders. Fufang Huangqi Decoction regulates the gut microbiota in patients with class I or II MG by reducing the abundance of Blautia and Bacteroides and increasing the abundance of Bifidobacterium and Lactobacillus. The correlation between gut microbiota and MG may be related to cell-mediated immunity.

Clinacanthus nutans Lindau (Family: Acanthaceae) is a medicinal herb widely distributed in the tropic and subtropic areas of Asia. C. nutans is traditionally consumed as vegetable or herbal tea, as well as a folk medicine for anticancer and antifungal activities. However, to date, chemical constituent responsible for observed health beneficial effects of this medicinal plant is not clear. In the current study, 32 compounds (1−32), including three new megastigmanes (1–3) were isolated from the aerial parts of C. nutans. Their structures were elucidated on the basis of comprehensive NMR, MS, and CD spectroscopic data analysis, as well as chemical hydrolysis. Among the isolates, cycloartane triterpenoids (9, 10, and 12) displayed moderate anti-proliferative effects against HepG2 cell growth with IC50 values ranging from 9.12 to 19.89 μM. Data obtained from flow cytometry analysis and western blotting assays revealed that compounds 9 and 12 induced apoptosis of HepG2 cells by modulating the expression of proteins associated to mitochondrial-mediated apoptotic pathway. Furthermore, megastigmanes 1, 2, 7, and 8 enhanced the anti-Candida albicans activity of amphotericin B (AmB), supporting the synergistic effects between megastigmanes and AmB. This is the first report of anticancer and antifungal potential of cycloartane triterpenoids and megastigmanes in C. nutans, which shed useful insights on the relationship between C. nutans's chemical constituent and its beneficial effects to health. Findings from this study support further development of this medicinal plant for potential pharmaceutical applications.

Three new phenazine metabolites, strepphenazine A-C (1-3), along with a known compound baraphenazine E 4 were isolated from the culture broth of a Streptomyces strain YIM PH20095. The structures were elucidated based on the spectral data. Compounds 1-4 showed different antifungal activity against Fusarium oxysporum, Plectosphaerella cucumerina, Alternaria panax, and Phoma herbarum, which caused root-rot disease of Panax notoginseng with minimal inhibitory concentrations (MICs) of 16-64 μg/mL; compared with compound 4, compounds 1-3 showed better antifungal activity against some of these pathogenic fungi with MICs of 16-32 μg/mL, while compound 4 showed antifungal activity against F. oxysporum, P. cucumerina, and A. panax with the same MICs of 64 μg/mL. Thus, strain YIM PH20095 provides new sources for the development of biological control agents to prevent the infection of pathogenic fungi of P. notoginseng.

Reactive oxygen species and subsequent oxidative stress are reported to play important roles in chronic metabolic diseases. Plant-derived polyphenols, especially food-derived phenolics, have attracted a lot of attention due to their potential usage against oxidative stress-related diseases. The leaf of Psidium guajava (known as guava) is regarded as a good resource of polyphenols and its products are commercially available in Japan as functional foods against multiple chronic metabolism disorders. In the course of finding novel polyphenols with antioxidative activities from guava leaf, 11 acylated phenolic glycosides (1-11), including 5 new oleuropeic acid-conjugated phenolic glycosides, named guajanosides A-E (1, 2, and 5-7), along with 17 known meroterpenoides (12-28), were isolated and identified. Their structures were determined by spectroscopic data analysis, chemical degradation, and acid hydrolysis. Compounds 1, 2, and 5-11 displayed potent reactive oxygen species-scavenging activity in lipopolysaccharide-stimulated RAW 264.7 macrophage cells. Western blot revealed that compound 6 markedly increased the expression levels of nuclear factor-erythroid 2-related factor 2 (Nrf2), NAD(P)H quinone dehydrogenase 1 (NQO1), and the glutamate-cysteine ligase catalytic subunit. The current study revealed the presence of oleuropeic acid-derived phenolic glycosides in guava leaf and highlighted the potential usage of this type of phenolics against oxidative stress-related metabolic diseases via activation of the Nrf2 signaling pathway.

Background Recent studies have revealed that vitamin D deficiency may increase the risk of Alzheimer's disease, and vitamin D supplementation may be effective strategy to ameliorate the neurodegenerative process in Alzheimer's disease patients. Paricalcitol (PAL), a low-calcemic vitamin D receptor agonist, is clinically used to treat secondary hyperparathyroidism. However, the potential application of PAL for treating neurodegenerative disorders remains unexplored. Methods The APP/PS1 mice were intraperitoneally injected with PAL or vehicle every other day for 15 weeks. The β-amyloid (Aβ) production was confirmed using immunostaining and enzyme linked immunosorbent assay. The underlying mechanism was verified by western blot and immunostaining in vivo and in vitro. Findings Long-term PAL treatment clearly reduced β-amyloid (Aβ) generation and neuronal loss in APP/PS1 transgenic mouse brains. PAL stimulated the expression of low-density lipoprotein receptor-related protein 1 (LRP1) possibly through inhibiting sterol regulatory element binding protein-2 (SREBP2); PAL also promoted LRP1-mediated β-site APP cleavage enzyme 1 (BACE1) transport to late endosomes, thus increasing the lysosomal degradation of BACE1. Furthermore, PAL diminished 8-hydroxyguanosine (8-OHdG) generation in neuronal mitochondria via enhancing base excision repair (BER), resulting in the attenuation of calpain-1-mediated neuronal loss. Interpretation The present data demonstrate that PAL can reduce Aβ generation through accelerating BACE1 lysosomal degradation and can inhibit neuronal loss through suppressing mitochondrial 8-OHdG generation. Hence, PAL might be a promising agent for treating Alzheimer's disease. Fund This study was financially supported by the Natural Science Foundation of China (U1608282).

Strains YIM 102796T and YIM 102701-2T were isolated from the feces of Macaca mulatta and Hylobates hoolock, respectively, living in the Yunnan Wild Animal Park, Yunnan province of China. The two strains were Gram-stain-negative, non-gliding, produced flexirubin pigments, non-flagellated and aerobic bacteria. The 16S rRNA gene-based phylogenetic analysis indicate that both YIM 102796T and YIM 102701-2T are members of the genus Flavobacterium, closely related to F. ummariense DS-12T (95.9% similarity) and F. ceti 454-2T (93.8% similarity), respectively. The two strains shared 95.1 % 16S rRNA gene sequence similarity. The average nucleotide identity and digital DNA–DNA hybridization values between the two strains were 76.5% and 22.9%, respectively, indicating that they are separate species. DNA G+C contents of YIM 102796T and YIM 102701-2T were 32.3 mol% and 34.0 mol%, respectively. Strains are able to grow at 4–37 °C, at pH 7.0–8.0 and in 0–2% (w/v) NaCl. Predominant fatty acid constituents (>7 %) were iso-C15:0, summed feature 3 (C16 : 1ω6c and/or C16 : 1ω7c) and summed feature 9 (iso-C17:1ω9c and/or 10-methylC16:0). Menaquinone 6 is major respiratory quinone. The predominant polar lipids were very similar to each other, comprising phosphatidylethanolamine, and multiple unknown aminolipids and unidentified polar lipids, and an unidentified aminophospholipid. On the basis of phenotypic and phylogenetic distinctiveness, it is suggested that the two strains represent two novel Flavobacterium species with strain YIM 102796T (=KCTC 52101T=CCTCC AB 2016015T) as the type strain of Flavobacterium viscosus sp. nov. and strain YIM 102701-2T (=KCTC 52100T=CCTCC AB 2016028T) as the type strain of Flavobacterium tangerina sp. nov.

Twenty seven dihydro-β-agarofuran sesquiterpenoids, including fifteen new congeners, wilforsinines I-W (1-9, 12-13, 24-27), and twelve known compounds were isolated from the dried root of Tripterygium wilfordii. The structures of the new sesquiterpenoids, wilforsinines I-W, were elucidated by extensive spectroscopic data analysis. The anti-inflammatory activity of isolates 1-27 were evaluated by examining their inhibitory effects on nitric oxide (NO) production in LPS-induced RAW 264.7 macrophage cells. Among them, wilforsinine K (3) and angulatin M (16) exerted optimal inhibitory effects on the production of NO in LPS-induced RAW 264.7 cells. Moreover, Western blot results revealed that their anti-inflammatory activities were correlated with the suppression of the expression of nitric oxide synthase (iNOS) and down-regulation of the level of NF-κB p65 phosphorylation.

Violacin A, a chromanone derivative, isolated from a fermentation broth of Streptomyces violaceoruber, has excellent anti-inflammatory potential. Herein, a biogenetically modeled approach to synthesize violacin A and twenty-five analogues was described, which involved the preparation of aromatic polyketide precursor through Claisen condensation and its spontaneous cyclization. The inhibitory effect on nitric oxide (NO) production of all synthetic molecules was evaluated by lipopolysaccharide (LPS)-induced Raw264.7 cells. The results revealed that introduction of aliphatic amine moieties on C-7 obviously improved the anti-inflammation effect of violacin A, and also the aromatic ether instead of ketone group at side chain was favorable to increase the activity. Among them, analogue 7a and 16d were screened as the most effective anti-inflammatory candidates. Molecular mechanism research revealed that 7a and 16d acquired anti-inflammatory ability due to the inhibition of NF-κB signaling pathway.

Eleven metabolites, six echinosporins (

Asian elephant is large herbivorous animal with elongated hindgut. To explore fecal microbial community composition with various ages, sex and diets, and their role in plant biomass degrading and nutrition conversation. We generated 119 Gb by metagenome sequencing from 10 different individual feces and identified 5.3 million non-redundant genes. The comprehensive analysis established that the Bacteroidetes, Firmicutes and Proteobacteria constituted the most dominant phyla in overall fecal samples. In different individuals, the alpha diversity of the fecal microbiota in female was lower than male, and the alpha diversity of the fecal microbiota in older was higher than younger, and the fecal microbial diversity was the most complex in wild elephant. But the predominant population compositions were similar to each other. Moreover, the newborn infant elephant feces assembled and maintained a diverse but host-specific fecal microbial population. The discovery speculated that Asian elephant maybe have start to building microbial populations before birth. Meanwhile, these results illustrated that host phylogeny, diets, ages and sex are significant factors for fecal microbial community composition. Therefore, we put forward the process of Asian elephant fecal microbial community composition that the dominant populations were built first under the guidance of phylogeny, and then shaped gradually a unique and flexible gut microbial community structure under the influences of diet, age and sex. This study found also that the Bacteroidetes were presumably the main drivers of plant fiber-degradation. A large of secondary metabolite biosynthetic gene clusters, and genes related to enediyne biosynthesis were found and showed that the Asian elephant fecal microbiome harbored a diverse and abundant genetic resource. A picture of antibiotic resistance genes (ARGs) reservoirs of fecal microbiota in Asian elephants was provided. Surprisingly, there was such wide range of ARGs in newborn infant elephant. Further strengthening our speculation that the fetus of Asian elephant has colonized prototypical fecal microbiota before birth. However, it is necessary to point out that the data give a first inside into the gut microbiota of Asian elephants but too few individuals were studied to draw general conclusions for differences among wild and captured elephants, female and male or different ages. Further studies are required. Additionally, the cultured actinomycetes from Asian elephant feces also were investigated, which the feces of Asian elephants could be an important source of actinomycetes.

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by β-amyloid (Aβ) protein deposition, neurofibrillary tangle (NFT) formation, and neuronal loss in the brain. The current study was designed to investigate the potential mechanisms by which levistolide A affects the pathogenesis of AD in an amyloid precursor protein/presenilin 1 (APP/PS1) transgenic (Tg) mouse model of AD and N2a/APP695swe cells. Specifically, behavioral changes in levistolide A–treated APP/PS1 Tg mice were assessed by the nest-building and Morris water maze (MWM) tests. Levistolide A treatment clearly ameliorated memory deficits and cognitive decline in APP/PS1 Tg mice. Aβ generation and the inflammatory response in APP/PS1 Tg mouse brains were clearly reduced after long-term levistolide A application. Mechanistically, levistolide A concurrently stimulated the expression of α-secretase and decreased the generation of β- and γ-secretases. In addition, levistolide A inhibited the phosphorylation of tau in the brains of the Tg mice. Furthermore, in vitro and in vivo experiments suggested that peroxisome proliferator–activated receptor γ (PPARγ) is the key transcription factor that mediates the regulatory effects of levistolide A on the expression of α-, β-, and γ-secretases and phosphorylation of tau. Collectively, these findings show that levistolide A may be a candidate for the treatment of AD. [Image: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13311-020-00943-1) contains supplementary material, which is available to authorized users.

Benzophenone glycosides are a major type of polyphenols present in guava. To date, there is still poor understanding of the relationship between benzophenone glycosides and the hepatoprotective effects attributed to this edible fruit. Herein, the protective effects of guavinoside B (GUB), a main benzophenone glycoside present in guava fruit, against acetaminophen (APAP)-induced liver injury were investigated in vitro and in vivo. Fluorescence measurement demonstrated that GUB (at a concentration of 30 μM) significantly reduced the intracellular ROS levels in APAP-treated HepG2 cells. In addition, GUB (100 mg kg-1 d-1) pretreatment markedly alleviated APAP-induced hepatocyte infiltration and necrosis in C57BL/6 mice, and improved serum and hepatic biochemical parameters, such as ALT, AST, SOD, GSH, ROS, MDA, and TNF-α levels. RT-PCR and western blot experiments revealed that GUB up-regulated Nrf2, GCLC and NQO1, while reducing p-JNK gene expression in the liver. The fermentation experiment further revealed that the displayed beneficial effects of GUB in vivo might be related to the gut microbial metabolite gallic acid. These promising data suggested that GUB showed potent hepatoprotective effects through regulating the Nrf2 and JNK signaling pathways. Further investigation of the absorption and metabolism of benzophenones would be warranted to promote the utilization of these phenolics as functional food ingredients against oxidative stress-induced chronic diseases.