Target-Guided Isolation and Purification of Antioxidants from Urtica laetevirens Maxim. by HSCCC Combined with Online DPPH-HPLC Analysis.

Urtica laetevirens Maxim. is used extensively in traditional Chinese medicine (TCM) for its potent antioxidative properties. In this study, three antioxidants were purified from U. laetevirens. using HSCCC guided by online DPPH-HPLC analysis. Firstly, the online DPPH-HPLC analysis was performed to profile out the antioxidant active molecules in U. laetevirens. The ultrasonic-assisted extraction conditions were optimized by response surface methodology and the results showed the targeted antioxidant active molecules could be well enriched under the optimized extraction conditions. Then, the antioxidant active molecules were separated by high-speed countercurrent chromatography ethyl acetate/n-butanol/water (2:3:5, v/v/v) as the solvent system. Finally, the three targets including 16.8 mg of Isovitexin, 9.8 mg of Isoorientin, and 26.7 mg of Apigenin-6,8-di-C-ß-d-glucopyranoside were obtained from 100 mg of sample. Their structures were identified by 1H NMR spectroscopy.

Using proteomics and metabolomics to identify therapeutic targets for senescence mediated cancer: genetic complementarity method.

Background: Senescence have emerged as potential factors of lung cancer risk based on findings from many studies. However, the underlying pathogenesis of lung cancer caused by senescence is not clear. In this study, we try to explain the potential pathogenesis between senescence and lung cancer through proteomics and metabonomics. And try to find new potential therapeutic targets in lung cancer patients through network mendelian randomization (MR). Methods: The genome-wide association data of this study was mainly obtained from a meta-analysis and the Transdisciplinary Research in Cancer of the Lung Consortium (TRICL), respectively.And in this study, we mainly used genetic complementarity methods to explore the susceptibility of aging to lung cancer. Additionally, a mediation analysis was performed to explore the potential mediating role of proteomics and metabonomics, using a network MR design. Results: GNOVA analysis revealed a shared genetic structure between HannumAge and lung cancer with a significant genetic correlation estimated at 0.141 and 0.135, respectively. MR analysis showed a relationship between HannumAge and lung cancer, regardless of smoking status. Furthermore, genetically predicted HannumAge was consistently associated with the proteins C-type lectin domain family 4 member D (CLEC4D) and Retinoic acid receptor responder protein 1 (RARR-1), indicating their potential role as mediators in the causal pathway. Conclusion: HannumAge acceleration may increase the risk of lung cancer, some of which may be mediated by CLEC4D and RARR-1, suggestion that CLEC4D and RARR-1 may serve as potential drug targets for the treatment of lung cancer.

Inhibitory activities and rules of plant gallotannins with different numbers of galloyl moieties on sucrase, maltase and α-amylase in vitro and in vivo.

BACKGROUND: α-Glucosidase inhibitors could effectively reduce postprandial blood glucose (PBG) levels and control the occurrence of complications of diabetes. Gallotannins (GTs) in plants have attracted much attention due to their significant α-glucosidase inhibitory activities in vitro. However, there is still a lack of systematic comparative studies to further elucidate inhibitory activities in vivo and in vitro of these compounds against α-glucosidase, especially for mammalian sucrase and maltase, and analyze their structure-activity relationship. PURPOSE: Determine the in vitro and in vivo inhibitory activities of five GTs with different number of galloyl moieties (GMs) on sucrase, maltase and α-amylase, and elucidate the relationship between α-glucosidase inhibitory activities and the number and connection mode of GMs. METHODS: Molecular docking and dynamics were used to study the binding mode and binding ability of five GTs against sucrase, maltase and α-amylase. Then, the inhibitory activities and inhibitory mechanisms of these compounds on sucrase, maltase and α-amylase in vitro were studied using inhibitory assay and enzyme inhibition kinetics. Further, the hypoglycemic effects in vivo of these compounds were demonstrated by three polysaccharides tolerance experiments on diabetes model mice. RESULTS: The results of molecular docking showed that these compounds could bind to enzymes through hydrogen bonds, hydrophobic interactions, etc. In addition, the α-glucosidase inhibition comparative studies in vitro and in vivo demonstrated that the inhibitory activities of these compounds on all three sucrase, maltase and α-amylase were ranked as TA ≈ PGG > TeGG > TGG > 1GG, and their inhibitory activities increases with the increase in the number of GMs. Moreover, the hypoglycemic effects of 1,2,3,4,6-pentagalloylglucose (PGG) and tannic acid (TA) in vitro and in vivo were also confirmed to be equivalent to or even stronger than that of acarbose. CONCLUSION: α-Glucosidase inhibitory activities in vitro and in vivo of GTs were positively correlated with the number of GTs, and the more the number, the stronger the activity. However, PGG with five GTs and TA with ten GTs showed almost identical α-glucosidase inhibitory activities, possibly due to the reduced binding force with the enzyme caused by spatial hindrance.

Phenomics of Vascular Disease: The Systematic Approach to the Combination Therapy.

Vascular diseases are usually caused by multifactorial pathogeneses involving genetic and environmental factors. Our current understanding of vascular disease is, however, based on the focused genotype/phenotype studies driven by the "one-gene/one-phenotype" hypothesis. Drugs with "pure target" at individual molecules involved in the pathophysiological pathways are the mainstream of current clinical treatments and the basis of combination therapy of vascular diseases. Recently, the combination of genomics, proteomics, and metabolomics has unraveled the etiology and pathophysiology of vascular disease in a big-data fashion and also revealed unmatched relationships between the omic variability and the much narrower definition of various clinical phenotypes of vascular disease in individual patients. Here, we introduce the phenomics strategy that will change the conventional focused phenotype/genotype/genome study to a new systematic phenome/genome/proteome approach to the understanding of pathophysiology and combination therapy of vascular disease. A phenome is the sum total of an organism's phenotypic traits that signify the expression of genome and specific environmental influence. Phenomics is the study of phenome to quantitatively correlate complex traits to variability not only in genome, but also in transcriptome, proteome, metabolome, interactome, and environmental factors by exploring the systems biology that links the genomic and phenomic spaces. The application of phenomics and the phenome-wide associated study (PheWAS) will not only identify a systemically-integrated set of biomarkers for diagnosis and prognosis of vascular disease but also provide novel treatment targets for combination therapy and thus make a revolutionary paradigm shift in the clinical treatment of these devastating diseases.