Rare flavanone-diarylheptanoid hybrids from Typha angustifolia shows anti breast cancer activity via activating TGF-ß1/Smad signaling pathway.

Four new flavanone-diarylheptanoid hetero dimers, typhatifolins A-D (1-4), were separated from the pollen of a widely distributed medicinal plant Typha angustifolia. Structures of these rare hybrids were elucidated by detailed interpretation of spectroscopic data, and their absolute configurations were determined on the basis of Mosher's method and ECD analyses. All the four compounds showed moderate to significant cytotoxicities against a panel of tumor cell lines with IC50 values ranging from 0.67 to 12.48 µM. Further in vitro antitumor evaluation for typhatifolin B (TTB, 2) on two breast cancer cells (4T1 and MDA-MB231) revealed that it could remarkably induce cell apoptosis and G0/G1 cycle arrest, as well as block cell migration and invasion. Mechanistically, TTB could exert its antitumor effect via activating the TGF-ß1 (transforming growth factor beta 1) signaling pathway as evidenced by RNA-seq analysis and immunoblotting experiments, which was further corroborated by treating cancer cells with a TGF-ß signaling inhibitor. Lastly, the in vivo anti breast cancer activity was demonstrated by applying the mixture of typhatifolins A-D to a preclinical animal model.

An optimized machine learning method for predicting wogonin therapy for the treatment of pulmonary hypertension.

Human health is at risk from pulmonary hypertension (PH), characterized by decreased pulmonary vascular resistance and constriction of the pulmonary vessels, resulting in right heart failure and dysfunction. Thus, preventing PH and monitoring its progression before treating it is vital. Wogonin, derived from the leaves of Scutellaria baicalensis Georgi, exhibits remarkable pharmacological activity. In this study, we examined the effectiveness of wogonin in mitigating the progression of PH in mice using right heart catheterization and hematoxylin-eosin (HE) staining. As an alternative to minimize the possibility of harming small animals, we present a scientifically effective feature selection method (BSCDWOA-KELM) that will allow us to develop a novel simpler noninvasive prediction method for wogonin in treating PH. In this method, we use the proposed enhanced whale optimizer (SCDWOA) in conjunction with the kernel extreme learning machine (KELM). Initially, we let SCDWOA perform global optimization experiments on the IEEE CEC2014 benchmark function set to verify its core advantages. Lastly, 12 public and PH datasets are examined for feature selection experiments using BSCDWOA-KELM. As shown in the experimental results for global optimization, the proposed SCDWOA has better convergence performance. Meanwhile, the proposed binary SCDWOA (BSCDWOA) significantly improves the ability of KELM to classify data. By utilizing the BSCDWOA-KELM, key indicators such as the Red blood cell (RBC), the Haemoglobin (HGB), the Lymphocyte percentage (LYM%), the Hematocrit (HCT), and the Red blood cell distribution width-size distribution (RDW-SD) can be efficiently screened in the Pulmonary hypertension dataset, and one of its most essential points is its accuracy of greater than 0.98. Consequently, the BSCDWOA-KELM introduced in this study can be used to predict wogonin therapy for treating pulmonary hypertension in a simple and noninvasive manner.

Polyhydroxylated eudesmane sesquiterpenoids and sesquiterpenoid glucoside from the flower buds of Tussilago farfara.

Chemical fractionation of the n-BuOH partition, which was generated from the EtOH extract of the flower buds of Tussilago farfara, afforded a series of polar constituents including four new sesquiterpenoids (1-4), one new sesquiterpenoid glucoside (5) and one known analogue (6) of the eudesmane type, as well as five known quinic acid derivatives (7-11). Structures of the new compounds were unambiguously characterized by detailed spectroscopic analyses, with their absolute configurations being established by X-ray crystallography, electronic circular dichroism (ECD) calculation and induced ECD experiments. The inhibitory effect of all the isolates against LPS-induced NO production in murine RAW264.7 macrophages was evaluated, with isochlorogenic acid A (7) showing significant inhibitory activity.

Novel Quinic Acid Glycerates from Tussilago farfara Inhibit Polypeptide GalNAc-Transferase.

The discovery of a bioactive inhibitor tool for human polypeptide N-acetylgalactosaminyl transferases (GalNAc-Ts), the initiating enzyme for mucin-type O-glycosylation, remains challenging. In the present study, we identified an array of quinic acid derivatives, including four new glycerates (1-4) from Tussilago farfara, a traditional Chinese medicinal plant, as active inhibitors of GalNAc-T2 using a combined screening approach with a cell-based T2-specific sensor and purified enzyme assay. These inhibitors dose-dependently inhibited human GalNAc-T2 but did not affect O-linked N-acetylglucosamine transferase (OGT), the other type of glycosyltransferase. Importantly, they are not cytotoxic and retain inhibitory activity in cells lacking elongated O-glycans, which are eliminated by the CRISPR/Cas9 gene editing tool. A structure-activity relationship study unveiled a novel quinic acid-caffeic acid conjugate pharmacophore that directs inhibition. Overall, these new natural product inhibitors could serve as a basis for developing an inhibitor tool for GalNAc-T2.

21,24-Cyclolanostanes revisited: Structural revision and biological evaluation.

Chemical fractionation of the EtOH extract of a medicinal macro fungus, Inonotus obliquus, afforded an array of lanostane-type triterpenoids (1-11) including two new ones (1 and 8). The structures of these compounds were determined on the basis of spectroscopic analyses, single crystal X-ray crystallography of 3-6 and biosynthetic considerations. With the confirmatory structural information provided by X-ray diffraction analysis in hand, several previously reported 21,24-cyclolanostanes, such as inonotsutriols A-C and (20R,21S,24S)-21,24-cyclopenta-3ß,21,25-trihydroxylanosta-8-ene, were structurally corrected. In addition, the NMR data of other types of 21,24-cyclo triterpenoids were also re-examined and structural revisions were thus suggested. Compounds 2, 6 and 8 showed significant cytostatic effects against a panel of tumor cell lines with IC50 values ranging from 7.80 to 18.5 µM. Further assays established that compound 2 exerted promising in vitro anti-breast cancer potential by inhibiting the proliferation and migration of 4T1 cells.

Dietary Clostridium butyricum supplementation modifies significantly the liver transcriptomic profile in weaned piglets.

The addition of probiotics in swine nutrition is known to positively influence both health and growth. The current study investigates differences in the hepatic transcriptome profiles between weaned piglets supplemented with Clostridium butyricum (C. butyricum) and control animals that received no probiotic. The liver is an important metabolic organ that plays a critical role in oxidizing triglycerides for energy production, lipid synthesis and degradation, as well as immune regulation in animals. RNA-Seq analysis was carried out on total RNA harvested from the liver of piglets fed with (n = 3) or without (n = 3) 5 × 105 C. butyricum CFU/g. Compared to the control piglets, 588 of the genes examined (352 up-regulated and 236 down-regulated) were significantly differentially expressed at a fold change > 2 and p < .05 in animals fed with C. butyricum. Quantitative real-time reverse transcription PCR (qRT-PCR) analysis was further used to validate the microarray expression results for 28 genes tested. The functional annotation analyses revealed several genes, processes and pathways with putative involvement in piglet growth and performance. Feeding swine with 5 × 105 C. butyricum CFU/g appears to reinforce their immune status as well as foster the cell cycle and improve the metabolism of carbohydrates, lipids and amino acids. This study provides valuable information about the expression profiles of mRNAs in piglet liver and in-depth functional investigations of these mRNAs that could provide new insights into the molecular networks of growth, immune responses and nutrient metabolism in the porcine liver.

New e:b-Friedo-Hopane Type Triterpenoids from Euphorbia peplus with Simiarendiol Possessing Significant Cytostatic Activity against HeLa Cells by Induction of Apoptosis and S/G2 Cell Cycle Arrest.

Seven rare e:b-friedo-hopane-type triterpenoids including four new (1-4) and three known (5-7) ones with 5 being first reported as a natural product, together with five other known triterpenoids (8-12), were isolated from the nonpolar fractions of the ethanolic extract of Euphorbia peplus. Structural assignments for these compounds were based on spectroscopic analyses and quantum chemical computation method. The structural variations for the C-21 isopropyl group, including dehydrogenation (1 and 3) and hydroxylation at C-22 (simiarendiol, 2), were the first cases among e:b-friedo-hopane-type triterpenoids. Simiarendiol (2) bearing a 22-OH showed significant cytostatic activity against HeLa and A549 human tumor cell lines with IC50 values of 3.93 ± 0.10 and 7.90 ± 0.31 µM, respectively. The DAPI staining and flow cytometric analysis revealed that simiarendiol (2) effectively induced cell apoptosis and arrested cell cycle at the S/G2 phases in a dose-dependent manner in HeLa cells.

[Effects of two controlled-release fertilizers with different proportions of N, P and K on the nutrient uptake and growth of Chrysanthemum morifolium Ramat].

A pot experiment was conducted to study the effects of two controlled-release fertilizers CRFA (4% resin-coated, N: P2O5: K2O = 14: 14: 14) and CRFB (4% resin-coated, N: P2O5: K2O = 20: 8:10) on the nutrient uptake and growth of Chrysanthemum morifolium, with common compound fertilizer CCF (N: P2O5: K2O = 15: 15: 15) as the control. Six treatments were installed, i. e., CCF1 (CCF, 6 g N x pot(-1)), CCF2 (CCF, 3 g N x pot(-1)), CRFA1 (CRFA, 6 g x pot(-1)), CRFA2 (CRFA, 3 g x pot(-1)), CRFB1 (CRFB, 6 g x pot(-1)), and CRFB (CRFB, 3 g x pot(-1)). On the 30th day of applying common compound fertilizer CCF1 and CCF2, soil available N, P and K contents were 163.29 and 145.26 mg x kg(-1), 180.39 and 163.13 mg x kg(-1), and 300.08 and 213.15 mg x kg(-1), respectively, and decreased rapidly since then. In treatments CRFA1, CRFB1, CRFA2, and CRFB, soil available N content increased slowly, and reached the peak on the 60th day after fertilizing, being 129.51, 138.65, 118.36, and 126.31 mg x kg(-1), respectively. Soil available P content had the same variation trend. Its maximum concentration was 169.54 and 133.46 mg x kg(-1) in treatments CRFA1 and CRFA2 on the 30th day after fertilizing, and 137.13 and 84.68 mg x kg(-1) in treatments CRFB1 and CRFB2 on the 60th day after fertilizing, and decreased slowly then. The agronomic traits such as leaf area, leaf area index, branch number, flowering rate, flower number, and flower diameter, etc., in treatments CRFA and CRFB were obviously better than those of the control, and CRFB was better than CRFA, suggesting that CRFB more matched the nutrient demand of C. morifolium. Under the conditions of present experiment, applying CRFB2 obtained the highest yield.