Bioactive terpenoids from Croton laui.

Two new highly-oxygenated neo-clerodane diterpenoids, 3S-acetoxyl-mollotucin D dilactone ester (1) and 6S-crotoeurin C (2), and a new lupane-type triterpene, 16ß-hydroxyl-3ß-O-trans-coumaroyl-betulin (6), as well as three known analogues (3-5) were obtained from the leaves of Croton laui. The structures of the new compounds were determined by extensive spectroscopic methods, and their absolute configurations were determined by combination of single-crystal X-ray diffraction analysis, electronic circular dichroism (ECD) spectra, and literature data. Compounds 2 and 3 exhibited inhibitory activities of lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7 macrophages with IC50 values of 1.2 and 1.6 µM, respectively. Additionally, compound 6 exhibited activity against Col205 and HepG2 cell lines with IC50 values of 12.9 and 17.7 µM, respectively.

Indigo Naturalis Ameliorates Dextran Sulfate Sodium-Induced Colitis in Mice by Modulating the Intestinal Microbiota Community.

Indigo naturalis (IN) is a traditional Chinese medicine, named Qing-Dai, which is extracted from indigo plants and has been used to treat patients with inflammatory bowel disease (IBD) in China and Japan. Though there are notable effects of IN on colitis, the mechanisms remain elusive. Regarding the significance of alterations of intestinal flora related to IBD and the poor water solubility of the blue IN powder, we predicted that the protective action of IN on colitis may occur through modifying gut microbiota. To investigate the relationships of IN, colitis, and gut microbiomes, a dextran sulfate sodium (DSS)-induced mice colitis model was tested to explore the protective effects of IN on macroscopic colitis symptoms, the histopathological structure, inflammation cytokines, and gut microbiota, and their potential functions. Sulfasalazine (SASP) was used as the positive control. Firstly, because it was a mixture, the main chemical compositions of indigo and indirubin in IN were detected by ultra-performance liquid chromatography (UPLC). The clinical activity score (CAS), hematoxylin and eosin (H&E) staining results, and enzyme-linked immunosorbent assay (ELISA) results in this study showed that IN greatly improved the health conditions of the tested colitis mice, ameliorated the histopathological structure of the colon tissue, down-regulated pro-inflammatory cytokines, and up-regulated anti-inflammatory cytokines. The results of 16S rDNA sequences analysis with the Illumina MiSeq platform showed that IN could modulate the balance of gut microbiota, especially by down-regulating the relative quantity of Turicibacter and up-regulating the relative quantity of Peptococcus. The therapeutic effect of IN may be closely related to the anaerobic gram-positive bacteria of Turicibacter and Peptococcus. The inferred metagenomes from 16S data using PICRUSt demonstrated that decreased metabolic genes, such as through biosynthesis of siderophore group nonribosomal peptides, non-homologous end-joining, and glycosphingolipid biosynthesis of lacto and neolacto series, may maintain microbiota homeostasis during inflammation from IN treatment in DSS-induced colitis.

Tryptanthrin Protects Mice against Dextran Sulfate Sodium-Induced Colitis through Inhibition of TNF-α/NF-κB and IL-6/STAT3 Pathways.

Inflammatory bowel disease (IBD) is a notable health problem and may considerably affect the quality of human life. Previously, the protective roles of tryptanthrin (TRYP) against dextran sulfate sodium (DSS) induced colitis has been proved, but the concrete mechanism remained elusive. It has been suggested that TRYP could diminish the weight loss and improve the health conditions of mice with DSS induced colitis. Hematoxylin and eosin staining revealed that TRYP could improve the histopathological structure of the colon tissue. Two signaling pathways (TNF-α/NF-κBp65 and IL-6/STAT3) were investigated using immunochemistry and western blot. The detected concentrations of the two cytokines TNF-α and IL-6 showed that their levels decreased after TRYP treatment of the colitis. The protein expression level of NF-κBp65 in cytoplasm increased after TRYP treatment of the induced colitis. However, the protein level of NF-κBp65 in the nucleus decreased after administration of TRYP. The expression level of IκBα, the inhibitory protein of NF-κBp65, was tested and the results suggested that TRYP could inhibit the degradation of IκBα. The phosphorylation level of STAT3 was inhibited by TRYP and the expression level of STAT3 and p-STAT3 decreased after administration of TRYP. We conclude that TRYP improves the health condition of mice with DSS induced colitis by regulating the TNF-α/NF-κBp65 and IL-6/STAT3 signaling pathways via inhibiting the degradation of IκBα and the phosphorylation of STAT3.

The chemistry and pharmacology of Ligularia przewalskii: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: Ligularia przewalskii (Maxim.) Diels (LP) (called zhangyetuowu in Chinese), is generally found in moist forest areas in the western regions of China. The root, leaves and flower of LP are utilized as a common traditional medicine in China. It has been utilized conventionally in herbal remedies for the remedy of haemoptysis, asthma, pulmonary phthisis, jaundice hepatitis, food poisoning, bronchitis, cough, fever, wound healing, measles, carbuncle, swelling and phlegm diseases. AIM OF THE STUDY: The review aims to provide a systematic summary of LP and to reveal the correlation between the traditional uses and pharmacological activities in order to provide updated, comprehensive and categorized information and identify the therapeutic potential for its use as a new medicine. MATERIALS AND METHODS: The relevant data were searched by using the keywords "Ligularia przewalskii" "phytochemistry", "pharmacology", "Traditional uses", and "Toxicity" in "Scopus", "Scifinder", "Springer", "Pubmed", "Wiley", "Web of Science", "China Knowledge Resource Integrated databases (CNKI)", "Ph.D." and "M.Sc. dissertations", and a hand-search was done to acquire peer-reviewed articles and reports about LP. The plant taxonomy was validated by the databases "The Plant List", "Flora Reipublicae Popularis Sinicae", "A Collection of Qinghai Economic Plants", "Inner Mongolia plant medicine Chi", Zhonghua-bencao and the Standard of Chinese herbal medicine in Gansu. RESULTS: Based on the traditional uses, the chemical nature and biological effects of LP have been the focus of research. In modern research, approximately seventy-six secondary metabolites, including thirty-eight terpenoids, nine benzofuran derivatives, seven flavonoids, ten sterols and others, were isolated from this plant. They exhibit anti-inflammatory, antioxidative, anti-bacterial and anti-tumour effects, and so on. Currently, there is no report on the toxicity of LP, but hepatotoxic pyrrolizidine alkaloids (HPA) were first detected with LC/MSn in LP, and they have potential hepatotoxicity. CONCLUSIONS: The lung-moistening, cough-relieving and phlegm-resolving actions of the root of LP are attributed to the anti-inflammatory properties of flavonoids and terpenoids. The heat-clearing, dampness-removing and gallbladder-normalizing (to cure jaundice) actions of the flowers of LP are based on the anti-inflammatory, antioxidant and hepatoprotective activity properties of terpenoids, flavonoids and sterols. The Traditional Chinese Medicine (TCM) characteristics of LP (bitter flavour) corroborate its potent anti-inflammatory effects. In addition, the remarkable anti-inflammatory and antioxidant capacities of LP contribute to its anti-tumour and antitussive activities. Many conventional uses of LP have now been validated by modernized pharmacological research. For future research, further phytochemical and biological studies need to be conducted on LP, In particular, the safety, mechanism of action and efficacy of LP could be of future research interest before beginning clinical trials. More in vivo experiments and clinical studies are encouraged to further clarify the relation between traditional uses and modern applications. Regarding the roots, leaves and flowers of LP, their chemical compositions and clinical effects should be compared. The information on LP will be helpful in providing and identifying its therapeutic potential and economic value for its use as a new medicine in the future.

Long non-coding RNA DANCR, a prognostic indicator, promotes cell growth and tumorigenicity in gastric cancer.

Gastric cancer remains the third leading cause of cancer-related mortality worldwide, and proliferation of gastric cancer represents the major reason for its poor prognosis. Recent evidence indicates that long non-coding RNAs play crucial roles in development and progression of gastric cancer. Long non-coding RNA differentiation antagonizing non-protein coding RNA is upregulated in hepatic cell carcinoma, but the role of lncRNA differentiation antagonizing non-protein coding RNA in gastric cancer has not been explored. In this article, we found that differentiation antagonizing non-protein coding RNA is also upregulated in gastric cancer. Experiments revealed that silencing differentiation antagonizing non-protein coding RNA significantly inhibited gastric cancer cell proliferation in vitro and in vivo. Overexpression of differentiation antagonizing non-protein coding RNA notably increases gastric cancer cell proliferation. From RNA-seq and gene ontology annotations, we found that differentiation antagonizing non-protein coding RNA influences the gene expression programs in cell metabolic and cycle process. Taken together, our findings suggest that the long non-coding RNA differentiation antagonizing non-protein coding RNA promotes the proliferation of gastric cancer and is a potential prognostic biomarker and therapeutic target in gastric cancer.

High expression of long non-coding RNA CCAT2 indicates poor prognosis of gastric cancer and promotes cell proliferation and invasion.

BACKGROUND: Numerous studies have demonstrated that long non-coding RNAs (lncRNAs) have many biological functions and play crucial roles in various human cancers, including cancer development, metastasis and prognosis of cancer patients. CCAT2, a novel long non-coding RNA, has been identified as correlating with several different types of cancers. However, the role of lncRNA CCAT2 in gastric cancer (GC) patients is unknown. The purpose of our research was to investigate the function and prognostic significance of lncRNA CCAT2 expression in GC patients. METHODS: Expression of lncRNA CCAT2 was examined in 208 paired normal and cancerous gastric tissues. Molecular and cellular techniques were used to explore the biological function of lncRNA CCAT2 in GC cells. Kaplan-Meier method and Cox proportional hazards model were used to analyze the prognostic significance of lncRNA CCAT2 expression. RESULTS: The results showed that lncRNA CCAT2 was upregulated in GC tissues (P=0.000), and positively correlated with TNM stage (P=0.029), lymphatic invasion (P=0.042) and nervous invasion (P=0.024) in GC patients. Furthermore, we also found that high expression of lncRNA CCAT2 was an unfavorable prognostic factor in GC patients. Silencing of lncRNA CCAT2 inhibits gastric cancer cell proliferation and invasion. CONCLUSIONS: lncRNA CCAT2 may serve as a tumor promoter and a new predictive prognostic factor for human gastric cancer.

Continuation calculations of boron- (aluminum-, titanium-, and nickel-) doped La13 clusters.

In this work, we have calculated boron-, aluminum-, titanium-, and nickel-doped La13 clusters by DMOL method based on the density-functional theory. Two doping modes are employed: surface and center doping. The boron, aluminum, and nickel atoms prefer to occupy the surface sites while the titanium atom prefers to occupy the center site. The doped La13 clusters with these four kinds of atoms have lower binding energy than pure La13 clusters. The icosahedral isomers are of lower binding energy than cubotahedral and decahedral isomers for La12B(-1), La12Al(-1), and La12Ni, while doping makes the cubotahedral La12Ti stable with a binding energy a little lower than icosahedral La12Ti. There are electronic shell effects in icosahedral La12B(-1) and La12Al(-1). The icosahedral La12B(-1) is promising to be formed during the doped process experimentally. Furthermore, we have also discussed the distorted structures of center doping by bond lengths, density of states, and charge transfers.