Structural elucidation and complete NMR spectral assignments of Monascus monacolin analogues.

Three new monacolin analogues, 3,6-dihydroxy-monacolin P (1), 6-methoxy monacolin S (2), and 6-methoxy dehydromonacolin S (3), were isolated from a fraction that strongly inhibited 3-hydroxy-3-methylglutaryl-CoA reductase from the ethyl acetate portion of red yeast rice ethanol extract. Their structures were determined through a combination of 1D and 2D NMR experiments, mass spectrometry analysis, and known literature reports.

Triterpene esters of cirsium setosum and their anti-inflammatory activity.

Two new triterpene fatty acid esters, 3ß-palmityloxy-12,27-cyclofriedoolean-14-en-11α-ol (1) and 3ß-palmityloxy-19α-hydroxyursane (2), together with 3ß-hydroxy-11-oxo-olean-12-enyl palmitate (3) were isolated from the potent anti-inflammatory active fraction of the petroleum ether-soluble part of Cirsium setosum ethanol extract. Compound 1 was found to be a rare 12,27-cyclopropane triterpenoid. Their structures were determined through spectral data analysis combined with literature reports. Furthermore, in vitro experiment, compounds 1-3 exhibited significant inhibitory effects on nitric oxide production in lipopolysaccharide-activated mouse RAW264.7 macrophages.

Seco-nortriterpenoids from Cirsium setosum and their anti-inflammatory activity.

Five unusual seco-nortriterpenoids, 3ß-hydroxy-20,21-seco-30-nortaraxastan-20,21-dioic acid (1), 3ß-hydroxy-20,21-seco-30-nortaraxastan-20-oic-21-oate (2), 3ß-hydroxy-20-oxo-21,22-seco-30-nortaraxastan-22-oic acid (3), 3ß-hydroxy-19-oxo-20,21-seco-29,30-nortaraxastan-21-oic acid (4) and 3ß-hydroxy-19-oxo-20,21-seco-19-norlupan-21-oic acid (5) were isolated and elucidated from the anti-inflammatory activity fraction of the ethanol extract of Cirsium setosum. The structures of these compounds were established through spectroscopic methods. Preliminary biological assays showed that compounds 1-5 had significant inhibitory effect on NO production on lipopolysaccharide-stimulated RAW 264.7 cells, and compound 1 showed the strongest anti-inflammatory activity. This type of ring-opening compound is the first seco-triterpenoid structure discovered from the genus of Cirsium.

Stachyose in combination with L. rhamnosus GG ameliorates acute hypobaric hypoxia-induced intestinal barrier dysfunction through alleviating inflammatory response and oxidative stress.

High altitude is closely related to intestinal mucosal damage and intestinal microbiota imbalance, and there is currently no effective prevention and treatment measures. In this study, the effects of stachyose (STA), L. rhamnosus GG (LGG) and their combination on inflammatory response, oxidatve stress and intestinal barrier function in mice exposed to acute hypobaric hypoxia were investigated. Our results indicated the combination of STA and LGG could more effectively regulate intestinal microbiota disorders caused by hypobaric hypoxia than STA or LGG alone. When mice were administered with STA + LGG, the content of short chain fatty acids (SCFAs) especially butyric acid significantly increased, which helped intestinal cells to form tight connections, improve the level of anti-inflammatory cytokine (TGF-ß) and antioxidant enzymes (SOD, CAT, GSH-Px), and decrease the expression of pro-inlammatory cytokines and hypoxia-inducing factors (IFN-γ, IL-1ß, IL-6, TNF-α and HIF-1α), thereby enhance the strong intestinal barrier function. Furthermore, the synbiotics significantly reduced the ratio of Firmicutes to Bacteroidetes, while significantly increased the relative abundance of Rikenella, Bacteroides, Odoribacter, Ruminiclostridium_5 and Gordonibacter, which were correlated with production of SCFAs and anti-inflammatory role. Correlation analysis showed that the protective effect of synbiotics on intestinal barrier function was associated with its anti-inflammatory activity and antioxidant capacity. It provided a strong foundation for further research on the role of STA and LGG in maintaining normal intestinal function at high altitude. Our study has identified and demonstrated a new synbiotic that may be one of the ideal intervention measures for preventing and treating intestinal dysfunction at high altitude.

The potential role of nondigestible Raffinose family oligosaccharides as prebiotics.

Based on factual scientific health claims, prebiotics have gained significant importance in ever-growing food and pharmaceutical industries. The diverse nature of distinct prebiotics influences the host differently in distinguishable patterns. Functional oligosaccharides are either plant-derived or commercially prepared. Raffinose, stachyose, and verbascose are the 3 types of raffinose family oligosaccharides (RFOs) that have been extensively used as medicine, cosmetic, and food additives. These dietary fiber fractions avert the adhesion and colonization by enteric pathogens and add nutrition metabolites for a healthy immune system. Enrichment of RFOs in healthy foods should be promoted as these oligosaccharides augment gut microecology by enhancing the health conferring microbes i.e. bifidobacteria and lactobacilli. RFOs influence the host's multiorgan systems due to their physiological and physicochemical properties. For example, the fermented microbial products of such carbohydrates affect neurological processes, including memory, mood, and behavior in humans. Raffinose-type sugar uptake is thought to be a ubiquitous property of bifidobacteria. This review paper summarizes the source of RFOs and their metabolizing entities, highlighting bifidobacterial carbohydrate utilization and health benefits.

Two unusual novel iridoid glycosides from Cornus officinalis fruit and their biological activities.

Two unusual novel iridoid glycosides, cornsecoside A (1) and cornsecoside B (2), were isolated from a 40% ethanol elution fraction of a 50% ethanol extract of Cornus officinalis fruit. Their structures were determined by spectroscopic data analysis combined with hydrolysis and ECD spectroscopy. In addition, compounds 1 and 2 exhibited cytotoxic activity against Bel-7402 cells with IC50 values of 8.12 and 9.31 µM, and were neuroprotective against H2O2-induced SH-SY5Y cell injure at a concentration of 10 µM.

Changes of serum HMGB1 and IDO levels in patients with esophageal squamous cell carcinoma and their clinical significance / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：检测食管鳞状细胞癌（ESCC）患者血清中高迁移率族蛋白B1（HMGB1）和吲哚胺-2，3-双加氧酶（IDO）的表达水平并探讨两者与临床病理特征及淋巴细胞亚群的相关性。方法：选取2021年3月至2022年8月在河北医科大学第四医院初次住院治疗的95例ESCC患者作为ESCC组，另选取40例健康体检人群作为对照组。ELISA法检测全部研究对象的血清HMGB1和IDO水平及不同组ESCC细胞培养上清中HMGB1、IDO和p65水平，流式细胞术检测全部研究对象外周血淋巴细胞亚群水平。WB法检测仅敲低HMGB1基因表达或敲低HMGB1后再加入NF-κB信号通路激活剂对ESCC细胞HMGB1、IDO和p65表达的影响。结果：ESCC组患者血清HMGB1和IDO水平明显高于对照组（均P<0.01）；血清HMGB1和IDO表达水平升高是ESCC临床进展的独立危险因素（均P<0.01），二者联合检测对ESCC临床进展预测价值更高（P<0.01）；血清HMGB1和IDO与ESCC患者的T分期、N分期和临床分期有明显关联（均P<0.05）； ESCC组患者血清HMGB1与外周血CD3+ T细胞、CD4+ T细胞、B细胞和NK细胞绝对计数值呈显著负相关，而与Treg细胞百分率呈显著正相关（均P<0.05），血清IDO与外周血CD3+ T细胞百分率和绝对计数值、CD4+ T细胞百分率和绝对计数值、CD8+ T细胞和B细胞绝对计数值呈显著负相关，而与Treg细胞百分率呈显著正相关（均P<0.05）；血清HMGB1和IDO表达水平呈显著正相关（P<0.01）。si-HMGB1组KYSE30和ECA109细胞及其培养上清液中IDO和p65表达水平明显低于si-NC组和si-HMGB1+PMA组（均P<0.05）。结论：血清HMGB1和IDO与ESCC临床进展和机体免疫功能密切相关，具有成为ESCC肿瘤标志物和免疫治疗新靶点的潜力。HMGB1可能通过NF-κB信号通路促进IDO表达，进行双靶点联合治疗可能会取得更好的疗效。

The potential role of prebiotics, probiotics, and synbiotics in adjuvant cancer therapy especially colorectal cancer.

Cancer is a global health issue that is rising swiftly with younger people and an increased number of patients. The role of human microbiota in the pathophysiology of tumors has been paid more and more attention. Microecologics including prebiotics, probiotics, and synbiotics are among the best validated/proven resources for the application of microbiological prophylaxis and therapy. There is strong evidence that microecologics have anti-cancer activity and their potential association with cancer is significant. In this review, we will focus on the role of prebiotics, probiotics, and synbiotics in tumor suppression in maintaining the colon barrier, metabolism, immune regulation, inhibition of host tumor cell proliferation, and epidemiological-based recommendations. Besides, other signs illuminate the role of microecological agents to adjunct the cancer treatment and counter the toxic side effects of cancer drugs. In addition, we will explore their role in chemotherapy, where these probiotics can be used as an adjunct to chemotherapy, counteracting the toxic side effects of chemotherapy drugs to minimize or optimize the therapeutic effect. In the treatment of cancer, we can see the role of prebiotics, probiotics, synbiotics, and their application in cancer patients, and the effectiveness effect can be considered as a clinical benefit. PRACTICAL APPLICATIONS: A large number of studies have shown that microecologics including prebiotics, probiotics, and synbiotics play an important role in regulating intestinal microecology and contribute to the prevention and treatment of cancer, indicating that prebiotics, probiotics, and synbiotics have the potential to be used as microecological modulators in the adjuvant therapy of cancer. However, it is not clear what is the anti-tumor mechanism of these microecologics and how they antagonize the side effects of cancer chemotherapy and protect normal cells. This paper reviews the role of prebiotics, probiotics, and synbiotics in tumor suppression in maintaining the colon barrier, metabolism, immune regulation, and prevention of rapid growth of host cells, as well as their potential role in cancer chemotherapy. This review helps to better understand the relationship between prebiotics, probiotics, and synbiotics with immune regulation, intestinal microecology, metabolic regulation, and cell proliferation and provides strong evidence for their potential application as microecologics in cancer adjuvant therapy.

Chemical characterization of the antioxidant and α-glucosidase inhibitory active fraction of Malus transitoria leaves.

Chinese Tibetan tea made from the tender leaves of Malus transitoria is a widely consumed health drink, but there are few reports on its chemical composition and biological activity. In this study, we found that a 50% ethanol extract of M. transitoria had good antioxidant and α-glucosidase inhibitory activities in vitro. Guided by in vitro bioassays, chromatographic separation and purification were conducted, and the most active fraction in M. transitoria was determined. UPLC-Orbitrap-MS/MS was used to further quickly and comprehensively characterize the chemical composition. Library searches, MS/MS fragmentation patterns of two isolated reference compounds, and bibliography were used to annotate 81 compounds, of which 2 were new compounds, and 79 were identified from M. transitoria for the first time. This study provides a scientific basis for the development of antioxidant and anti-diabetic functional foods from M. transitoria.

Screening of Siderophore-Producing Bacteria and Their Effects on Promoting the Growth of Plants.

Iron deficiency is a major global agricultural problem. Siderophores can help organisms to uptake iron in form of siderophore-Fe3+ complexes and then in the cell cytosol, iron is reducted and released in ferrous form. This research aimed to obtain some efficient siderophore-producing bacterial strains and evaluate their plant growth-promoting effects in the iron-deficit environment. Two strains, Brucella sp. E7 and Pseudomonas brassicae W7, were isolated from rhizosphere soil. Both strains could produce maximum siderophores under the optimal conditions. Plant promoting experiment showed that many indicators of Vigna radiata seedling were all increased significantly by strain E7/W7 or the consortium of E7 + W7. Under no-iron and high iron stress, the inoculation treatment also showed growth promotion effects on both Vigna radiata and Lolium multiflorum. These results indicated that the potential ability of strain E7 and W7 in increasing agricultural production as a growth-promoting agent in iron-deficit soil.

Three new ursane-type triterpenoids from Rosmarinus officinalis and their biological activities.

Three new ursane-type triterpenoids, 3-oxours-12-en-20, 28-olide (1), 3ß-hydroxyurs-12-en-20, 28-olide (2) and 3ß-hydroxyurs-11, 13(18)-dien-20, 28-olide (3), were isolated from a potent anti-inflammatory and antibacterial fraction of the ethanolic extract of Rosmarinus officinalis. Their structures were elucidated by a combination of extensive 1D- and 2D-NMR experiments, MS data and comparisons with literature reports. Compounds 1-3 exhibited significantly inhibitory effects on nitric oxide production in lipopolysaccharide-activated mouse RAW264.7 macrophages, but no antibacterial activity was found at a concentration of 128 µg·mL-1.

New polymerized sesquiterpene lactones from Ainsliaea yunnanensis and their activity evaluation.

Two new dimeric and trimeric sesquiterpene lactones (1-2), and nine known sesquiterpene lactones (3-11) were isolated from the EtOAc phase of the ethanolic extract of Ainsliaea yunnanensis. Their structures were identified by NMR, IR and HR-ESIMS spectroscopic methods, and compound 1 was confirmed by single crystal X-ray diffraction experiment. All the compounds were tested for their cytotoxic, anti-microbial and anti-inflammatory activities. Compounds 1, 2, 3, 5, 7, 9 and 11 showed very significant selective cytotoxic activities on MDA-MB-468, PANC-1, HEPG2 or A549 cells. Compounds 6 and 11 showed very significant inhibiting effect on Epicoccum sp. (CPCC 400307), Fusarium solani (CPCC 800013) or Bacillus subtilis. Meanwhile, compounds 6 and 7 can inhibit the NLRP3 inflammasome's activation at the concentration of 10 µM.

Secoiridoid glycosides from the fruits of Cornus officinalis.

Five new secoiridoid glycosides, cornusphenosides E-I (1-5), were isolated and characterized from an active fraction of ethanol extract of the fruits of Cornus officinalis. Their structures were determined by extensive spectroscopic data analysis, including 2 D NMR and HRESIMS experiments. In the preliminary assay, compound 5 (when evaluated at 10 µM) showed the neuroprotective effect against H2O2-induced SH-SY5Y cell damage.

Norursane-type triterpenoids from Rosmarinus officinalis and their anti-inflammatory activity evaluation.

Five norursane-type triterpenoids, including three novel of 3ß-28-norursa-12,17,19,21-tetraene-3-ol (1), 3ß-28-norursa-12,20(30)-dien-3-ol (2) and 3ß-28-norursa-12,16,20(30)-triene-3-ol (3), as well as two known 3ß-28-norursa-17,19,21-trien-3-ol (4) and 3ß-28-norursa-12-ene-3-ol (5) were isolated from the ethyl acetate dissolved fraction of the ethanol extract from Rosmarinus officinalis. Their structures were elucidated by HR-ESI-MS, IR, 1D- and 2D-NMR spectroscopic methods. Compounds 1-5 exhibited significant inhibitory effect on NO production in LPS-activated RAW264.7 cells, and compounds 2, 3 and 5 shown better anti-inflammatory activity.

Chemical characterization of a PD-1/PD-L1 inhibitory activity fraction of the ethanol extract from Gymnadenia conopsea.

Searching for PD-1/PD-L1 inhibitor from medicinal plants has become a potential method to discover small molecular cancer immunotherapy drugs. Using PD-1/PD-L1 inhibitory activity assay in vitro, a bioactive fraction was obtained from the ethanol extract of Gymnadenia conopsea. A sensitive UPLC-HRMS/MS method was established for the rapid screening and identification of compositions from bioactive fraction. Based on the characteristic fragmentation patterns of standards analysis and extracted ion chromatogram (EIC) method, 46 compounds were rapidly screened and identified (including 35 succinic acid ester glycosides and 11 other compounds), among which 17 compounds were tentatively identified as new compounds.

Chemical characterization of the polar antibacterial fraction of the ethanol extract from Rosmarinus officinalis.

Rosmarinus officinalis L. has been widely used as a spice to extend the shelf life of foods. Most studies in the literature indicate that its essential oil is its major antibacterial component. In this study, a polar fraction from rosemary exhibited considerably stronger antibacterial activity against Bacillus subtilis than its essential oil. Guided by rapid characterization of the chemical compositions based on UPLC-Orbitrap-MS/MS, further investigation resulted in the isolation and identification of sixteen compounds. Among them, two new and six known compounds were identified in rosemary for the first time. Most isolated compounds exhibited significant antibacterial activities with minimum inhibitory concentration values of 2-128 µg/mL; however, these activities were weaker than that of the polar fraction. Thus, the polar fraction demonstrated a promising potential to serve as a food additive, as an alternative to the essential oil, because of its stronger antibacterial activity.

Prebiotic properties of different polysaccharide fractions from Artemisia sphaerocephala Krasch seeds evaluated by simulated digestion and in vitro fermentation by human fecal microbiota.

Artemisia sphaerocephala Krasch polysaccharide (ASKP) and its two fractions-60P (branched xylan) and 60S (branched glucomannan), were subjected to simulated gastrointestinal digestion and in vitro fermentation by human fecal microbiota. The results showed that all polysaccharide fractions could transit through gastrointestinal tract without dramatic degradation and be utilized by gut microbiota. ASKP exhibited the highest depletion rate and highest capability to decrease the pH than its fractions. Meanwhile, 60S showed the stronger capability to increase the production of propionic acid and reduce the ratio of acetic acid to propionic acid. At the phylum level, all polysaccharides efficiently reduced the Firmicutes/Bacteroidetes ratio and relative abundance of Proteobacteria, with ASKP being the most capable to suppress the proliferation of Proteobacteria. At the genus level, ASKP and 60P markedly promoted the growth of Bacteroidetes, and 60S promoted the growth of Parabacteroides and Collinsella. Prediction on metabolic function revealed that polysaccharide administration could dramatically change the metabolic profile of bacteria compared with fructooligosaccharides. Besides, all the polysaccharides dramatically promoted the bile acid metabolism. Compared with 60S, ASKP and 60P showed stronger ability to suppress the metabolisms on carbohydrate and amino acid. In summary, both ASKP and its two fractions showed the prebiotic potentials.

Rapid Characterizaiton of Chemical Constituents of the Tubers of Gymnadenia conopsea by UPLC-Orbitrap-MS/MS Analysis.

Gymnadenia conopsea R. Br. is a traditional Tibetan medicinal plant that grows at altitudes above 3000 m, which is used to treat neurasthenia, asthma, coughs, and chronic hepatitis. However, a comprehensive configuration of the chemical profile of this plant has not been reported because of the complexity of its chemical constituents. In this study, a rapid and precise method based on ultra-high performance liquid chromatography (UPLC) combined with an Orbitrap mass spectrometer (UPLC-Orbitrap-MS/MS) was established in both positive- and negative-ion modes to rapidly identify various chemical components in the tubers of G. conopsea for the first time. Finally, a total of 91 compounds, including 17 succinic acid ester glycosides, 9 stilbenes, 6 phenanthrenes, 19 alkaloids, 11 terpenoids and steroids, 20 phenolic acid derivatives, and 9 others, were identified in the tubers of G. conopsea based on the accurate mass within 3 ppm error. Furthermore, many alkaloids, phenolic acid derivates, and terpenes were reported from G. conopsea for the first time. This rapid method provides an important scientific basis for further study on the cultivation, clinical application, and functional food of G. conopsea.

Purification, identification and properties of a new blue pigment produced from Streptomyces sp. A1013Y.

A novel blue pigment was first isolated from Streptomyces sp. A1013Y. The purified component was identified as 4,8,13-trihydroxy-6,11-dione-trihydrogranaticins A (TDTA). Its physical properties were found to be: Molecular weight 462 Da; Color value, E0.1%1cm580 nm = 80; Solubility, it dissolved in organic solvents. In addition, the color of TDTA changed with pH but was found to be relatively stable between 20 and 100 °C, from pH 3 to pH 11, and under UV-light or darkness. TDTA's functional properties was as follows: TDTA showed excellent free radical scavenging properties, IC50 41.04 µg/mL and 13.75 µg/mL using 2, 20-diphenyl-1-picrylhydrazyl (DPPH) and 2,2-n-(3, 2-ethyl-benzothiazole-6-sulfonic acid) ammonium salt (ABTS) respectively. TDTA might be a promising source of natural pigment and bioactive compound used as additive in food industry.