Complex disease is a cascade process which is associated with functional abnormalities in multiple proteins and protein-protein interaction (PPI) networks. One drug one target has not been able to ...perfectly intervene complex diseases. Increasing evidences show that Chinese herb formula usually treats complex diseases in the form of multi-components and multi-targets. The key step to elucidate the underlying mechanism of formula in traditional Chinese medicine (TCM) is to optimize and capture the important components in the formula. At present, there are several formula optimization models based on network pharmacology has been proposed. Most of these models focus on the 2D/3D similarity of chemical structure of drug components and ignore the functional optimization space based on relationship between pathogenetic genes and drug targets. How to select the key group of effective components (KGEC) from the formula of TCM based on the optimal space which link pathogenic genes and drug targets is a bottleneck problem in network pharmacology. To address this issue, we designed a novel network pharmacological model, which takes Lang Chuang Wan (LCW) treatment of systemic lupus erythematosus (SLE) as the case. We used the weighted gene regulatory network and active components targets network to construct disease-targets-components network, after filtering through the network attribute degree, the optimization space and effective proteins were obtained. And then the KGEC was selected by using contribution index (CI) model based on knapsack algorithm. The results show that the enriched pathways of effective proteins we selected can cover 96% of the pathogenetic genes enriched pathways. After reverse analysis of effective proteins and optimization with CI index model, KGEC with 82 components were obtained, and 105 enriched pathways of KGEC targets were consistent with enriched pathways of pathogenic genes (80.15%). Finally, the key components in KGEC of LCW were evaluated by in vitro experiments. These results indicate that the proposed model with good accuracy in screening the KGEC in the formula of TCM, which provides reference for the optimization and mechanism analysis of the formula in TCM.
Compound Kushen Injection (CKI) is a widely used TCM formula for treatment of carcinomatous pain and tumors of digestive system including hepatocellular carcinoma (HCC). However, the potential ...mechanisms of CKI for treatment of HCC have not been systematically and deeply studied.
A metabolic data-driven systems pharmacology approach was utilized to investigate the potential mechanisms of CKI for treatment of HCC.
Based on phenotypic data generated by metabolomics and genotypic data of drug targets, a propagation model based on Dijkstra program was proposed to decode the effective network of key genotype-phenotype of CKI in treating HCC. The pivotal pathway was predicted by target propagation mode of our proposed model, and was validated in SMMC-7721 cells and diethylnitrosamine-induced rats.
Metabolomics results indicated that 12 differential metabolites, and 5 metabolic pathways might be involved in the anti-HCC effect of CKI. A total of 86 metabolic related genes that affected by CKI were obtained. The results calculated by propagation model showed that 6475 shortest distance chains might be involved in the anti-HCC effect of CKI. According to the results of propagation mode, EGFR was identified as the core target of CKI for the anti-HCC effect. Finally, EGFR and its related pathway EGFR-STAT3 signaling pathway were validated in vivo and in vitro.
The proposed method provides a methodological reference for explaining the underlying mechanism of TCM in treating HCC.
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Astragali Radix polysaccharides (APSs) have a wide range of biological activities. Our preliminary experiment showed that APS-Ⅱ (10 kDa) was the main immunologically active component of APSs. ...However, the characteristic structure related to activity of APS-Ⅱ needs further verification and clarification. In this study, APS-II was degraded by endo α-1,4-glucosidase. The degraded products with different degrees of polymerization 1-3 (P1), 3-6 (P2), 7-14 (P3), and 10-18 (P4) were obtained using a polyacrylamide gel chromatography column. The structural features of the different products were characterized by HPGPC, monosaccharide composition, Fourier transform infrared spectrum, GC-MS, nuclear magnetic resonance, and UPLC-ESI-QTOF-MS analysis. Specific immune and non-specific immune cell tests were used to identify the most immunogenic fractions of the products. The backbone of P4 was speculated to be α-D-1,4-linked glucans and rich in C2 (25.34%) and C6 (34.54%) branches. Immune screening experiments indicated that the activity of P4 was better than that of APS-II and the other three components. In this research, the relationship between the structure of APS-Ⅱ and the immune activity from the degradation level of polysaccharides was studied, laying a foundation for the quality control and product development of APSs.
Paeoniae Radix Alba (PRA, dried root of Paeonia lactiflora Pall.) is a widely used as traditional Chinese medicine and tannins are one of their main bioactive ingredients. However, there are rarely ...systematically investigated in this study. This study aimed to establish a rapid, high selective, high sensitive and effective method based on UHPLC-Q-Exactive Orbitrap MS for simultaneous identification the tannins in PRA. Separation was performed on Thermo Scientific Hypersil GOLD™ aQ (100 mm × 2.1 mm, 1.9 μm) using gradient elution consist of 0.1% formic acid acetonitrile and 0.1% formic acid water as the mobile phase at a flow rate of 0.3 mL/min. The mass spectrometer was operated with Q-Exactive Orbitrap spectrometer in negative ion mode. Finally, a total of 106 constituents were identified in PRA by UHPLC-Q-Exactive Orbitrap MS, 75 of those were reported from PRA for the first time. This result laid the foundation for in-depth research on the material basis efficacy and provided scientific basis for the selection of quality marker of PRA.
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•The protective effect of TFA against nephropathy model were studied.•Metabolomics coupled with system pharmacology were applied.•The bioactive components responsible for the function ...of TFA were identified.•The endogenous metabolites correlated with the effect of TFA were also identified.
Astragali Radix (AR) has been used in the traditional Chinese medicine (TCM) in the treatment of various renal diseases for many years. In this study, a NMR based metabolomic approach coupled with biochemical assay and histopathological inspection had been employed to study the protective effect of total flavonoids (TFA) in AR against adriamycin-induced nephropathy using rats model. Multivariate analysis revealed that 11 of perturbed metabolites could be reversed by TFA, and the MetaboAnalyst analysis revealed that the anti-nephrotic syndrome effect of TFA was probably related with regulation of alanine, aspartate and glutamate metabolism, citrate cycle, pyruvate metabolism, cysteine and methionine metabolism and glyoxylate and dicarboxylate metabolism. The regulatory effects on the gene expression (ACE, nephrin, podocin) suggested that the anti-nephrotic syndrome effect of TFA was also related with the protection of renal filtration function and regulation of blood pressure. The system pharmacology analysis revealed 43 potential targets for TFA, and suggested that the protective effect of TFA on the nephrotic syndrome was probably related with the regulation of immune and renin-angiotensin system. These metabolic changes and the associated pathways, as well as the compound-target-disease network provide insights into the mechanisms of TFA for the treatment of nephrotic syndrome, and further studies are needed to validate the bioactive compounds responsible for the anti-nephrotic syndrome effect of TFA.
Foxtail millet is a traditional excellent crop with high nutritional value in the world, belong to cereals. The bran of foxtail millet is rich in polyphenol that has antioxidant, anti-inflammatory, ...and anti-tumorigenic effects. Previously, we extracted bound polyphenols from the inner shell of foxtail millet bran (BPIS). Here, we report that BPIS specifically induced breast cancer cell death and elevated the autophagy level simultaneously. The addition of an autophagy inhibitor blocked BPIS-induced breast cancer cell death, indicating that excessive autophagy induced cell death. Furthermore, oil red O and BODIPY staining also confirmed that lipids, which are important inducers of autophagy, accumulated in breast cancer cells treated with BPIS. Lipidomics research revealed that glycerophospholipids were the main accumulated lipids induced by BPIS. Further study showed that elevated PCYT1A expression was responsible for glycerophospholipid accumulation, and BPIS contained ferulic acid and p-coumaric acid, which induced PCYT1A expression and breast cancer cell death. Collectively, our results revealed that BPIS resulted in autophagic death by enhancing lipid accumulation in breast cancer cells, and BPIS contains ferulic acid and p-coumaric acid, which provided new insights into developing nutraceuticals and drugs for breast cancer patients.
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•BPIS specifically induced the death of breast cancer cells, but not the normal.•BPIS-triggered excessive autophagy was the inducement of breast cancer cell death.•BPIS-induced lipid accumulation promoted autophagic death in breast cancer cells.•PCYT1A was the key of BPIS-induced lipid accumulation of breast cancer cells.•BPIS has the potential as a nutraceutical for breast cancer patients.
In this paper, we propose to implement the heralded pair-coherent source into the measurement-device-independent quantum key distribution. By comparing its performance with other existing schemes, we ...demonstrate that our new scheme can overcome many shortcomings existing in current schemes, and show excellent behavior in the quantum key distribution. Moreover, even when taking the statistical fluctuation into account, we can still obtain quite high key generation rate at very long transmission distance by using our new scheme.
•Implement the heralded pair-coherent source into the measurement-device-independent quantum key distribution.•Overcome many shortcomings existing in current schemes and show excellent behavior.•Obtain quite high key generation rate even when taking statistical fluctuation into account.
Huangqi (HQ) is a commonly Chinese herb that has been widely used in China for thousands of years. Many classic traditional Chinese medicine (TCM) prescriptions consist of HQ, which is known as ...“eight Huangqi out of ten prescriptions”. However, its contribution to the whole formula remains unclear. In this study, a classical prescription Huangqi jianzhong tang (HQJZ) was selected to evaluate the “monarch” role of HQ against chronic atrophic gastritis (CAG) rats based on pharmacology and metabonomic strategy. Traditional pharmacology indexes, including body weight variety, pathological examination and biochemical indexes of gastric juice showed that the efficacy of HQJZ and HQ were better than HY (HQJZ without HQ). Serum metabonomics analysis also showed that the same separation of metabolic features among them. 9 differential endogenous metabolites were screened and involved into the metabolic alterations induced by CAG. Among them, 7, 6 and 4 metabolites were regulated by HQJZ, HQ and HY, respectively. Three important pathways, including pyruvate metabolism, glycolysis or gluconeogenesis, aminoacyl-tRNA biosynthesis, were further screened out as the most important pathways related to the efficacy of HQ contributing to HQJZ by integrating MetaboAnalyst, systemsDock and binding ability weighted polypharmacology index (BAWP). Our work provided a novel method to study the metabolic contribution of HQ to the whole HQJZ in the treatment of CAG, which might be beneficial to understand the fundamental idea behind formula construction of TCM.
•A first study to reveal the role of HQ contributing to HQJZ.•Metabolic pathway analysis integrating of metabonomics, molecular docking and BAWP.•Metabonomics approach applied in the TCM compatible study.
Cathepsin B (CatB) cDNA of 759 bp from Jian carp (Cyprinus carpio var. Jian) with amino acid similarity of 99.6% to common carp was cloned. The mature CatB was expressed in Escherichia coli BL21 ...transferred with vector CatB‐pET‐30a. It was purified and identified as a single band (29 kDa) on SDS‐PAGE. Optimum CatB activity was observed at 40 °C and pH 5.5. Mouse anti‐CatB polyclonal antibody with a high titer of 1:256000 was prepared successfully and shown to specifically recognize the antigen both in prokaryotic cells and in the tissues of Jian carp according to western blotting and immunohistochemistry results. Immunolocation analysis showed that CatB distribution at protein level varied among the tested tissues. The results presented in this study may provide a significant reference for future research on the inherent relationship between CatB and the quality of fish or fish products at both the gene and protein levels.
Practical Application
The investigation on the cDNA cloning and biochemical characteristics of Jian carp CatB and its immunolocalization is essential for utilizing piscine Cathepsins, or researching the inherent relationship between CatB and the quality of fish or fish products.
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