[Mechanism of Xinshubao Tablets in exerting anti-inflammatory, vasodilation, and cardioprotective effects based on network pharmacology].

This study aims to explore the anti-inflammatory, vasodilation, and cardioprotective effects of the intestinal absorption liquids containing Xinshubao Tablets or single herbs, and to elucidate the potential mechanism based on network pharmacology. Western blot was then conducted to validate the expression changes of core proteins. Lipopolysaccharide(LPS)-stimulated RAW264.7 cells were used to observe the anti-inflammatory effect. The vasodilation activity was examined by the microvessel relaxation assay in vitro. Oxygen-glucose deprivation(OGD)-induced H9c2 cells were used to investigate the cardioprotective effect. The chemical components were retrieved from Herb databases and composition of Xinshubao Tablets drug-containing intestinal absorption solution. Drug targets were retrieved from SwissTargetPrediction databases. GeneCards was searched for the targets associated with the anti-inflammatory, vasodilation, and cardioprotective effects. The common targets shared by the drug and the effects were used to establish the protein-protein interaction(PPI) network, from which the core targets were obtained. Finally, the core targets were imported into Cytoscape 3.9.1 for Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) analyses. The anti-inflammatory experiment showed that both Xinshubao Tablets and the single herbs constituting this formula had anti-inflammatory effects. Curcumae Radix had the strongest inhibitory effect on the production of tumor necrosis factor-α(TNF-α), and Salviae Miltiorrhizae Radix et Rhizoma had the strongest inhibitory effect on the generation of interleukin-6(IL-6). Xinshubao Tablets, Curcumae Radix, and Crataegi Fructus had vasodilation effect, and Crataegi Fructus had the strongest effect. Xinshubao Tablets, Salviae Miltiorrhizae Radix et Rhizoma, Acanthopanacis Senticosi Radix et Rhizoma seu Caulis, and Paeoniae Radix Alba had cardioprotective effects, and Salviae Miltiorrhizae Radix et Rhizoma had the strongest cardioprotective effect. Network pharmacology results demonstrated that except the whole formula, Salviae Miltiorrhizae Radix et Rhizoma had the most components with anti-inflammatory effect, and Curcumae Radix had the most components with vasodilation and cardioprotective effects, followed by Salviae Miltiorrhizae Radix et Rhizoma. The nitric oxide synthase 3(NOS3) was predicted as the core target for the anti-inflammatory, vasodilation, and cardioprotective effects. Western blot results showed that Xinshubao Tablets significantly up-regulated the expression of NOS3 in OGD-induced H9c2 cells. GO enrichment analysis showed that the effects were mainly related to lipid exported from cell, regulation of blood pressure, and inflammatory response. KEGG pathway enrichment predicted AGE-RAGE and HIF-1 signaling pathways as the key pathways.

Assessing the association of coffee consumption on the relationship of chronic pain with depression and anxiety.

BACKGROUND: A bidirectional relationship between chronic pain (CP) and mental disorders has been reported, and coffee was believed to be associated with both. However, the association of coffee in this bidirectional relationship remains unclear. We aim to analyze the association of coffee consumption on the relationship of CP with depression and anxiety. METHODS: A total of 376,813 participants from UK Biobank were included. We collected data on anxiety, depression and CP from objects of our study population. The association of coffee consumption on the relationship of CP with depression and anxiety was assessed through logistic/linear regression models. Moreover, seemingly unrelated estimation test (SUEST) was used to compare whether the coefficients differed in two different groups. RESULTS: We observed significant associations of coffee consumption in the interaction of CP with depression and anxiety, such as the association of multisite chronic pain (MCP) on self-reported depression (ßcoffee = 0.421, ßnon-coffee = 0.488, PSUEST = 0.001), and the association of MCP on generalized anxiety disorder-7 (GAD-7) scores (ßcoffee = 0.561, ßnon-coffee = 0.678, PSUEST = 0.004) were significantly different between coffee drinking and non-coffee drinking groups. Furthermore, in analysis stratified by gender, we found headache (ßmale = 0.392, ßfemale = 0.214, PSUEST = 0.022) and hip pain (ßmale = 0.480, ßfemale = 0.191, PSUEST = 0.021) had significant associations with self-reported depression between males and females groups in coffee drinkers. CONCLUSIONS: Our results suggested that coffee consumption has a significant association on the relationship of CP with depression and anxiety.

Cardioprotective polyphenols from Geum japonicum var. chinense.

Seven undescribed tannins, namely gejaponin A-G, and one dehydrodigallic acid derivative 3,4-dihydroxy-5-(3,4,5-trihydroxy-1-ethoxycarbonyl phenoxy)benzoic acid, together with eighteen known polyphenols were isolated from the 95% ethanol extract of the aerial part of Geum japonicum Thunb. var. chinense F. Bolle. Their structures were elucidated on the basis of comprehensive analysis of UV, IR, NMR, HRMS, and CD spectroscopy experiments. To evaluate their bioactivities, sixteen major compounds were selected to intervene in hydrogen peroxide (H2O2)-induced oxidative damage on H9c2 rat cardiomyoblasts. Some compounds demonstrated high activity in this assay, of which, the known compounds 16 and 21 exhibited strong protective effects against H2O2-induced injury in H9c2 rat cardiomyoblasts, with a comparable cardioprotective activity as that of the positive control trimetazidine, thereby revealing cardioprotective activities from G. japonicum var. chinense.

Effect the accumulation of bioactive constituents of a medicinal plant (Salvia Miltiorrhiza Bge.) by arbuscular mycorrhizal fungi community.

BACKGROUND: Arbuscular mycorrhizal fungi (AMF) form symbiotic relationships with various terrestrial plants and have attracted considerable interest as biofertilizers for improving the quality and yield of medicinal plants. Despite the widespread distribution of AMFs in Salvia miltiorrhiza Bunge's roots, research on the impact of multiple AMFs on biomass and active ingredient accumulations has not been conducted. In this study, the effects of five native AMFs (Glomus formosanum, Septoglomus constrictum, Rhizophagus manihotis, Acaulospora laevis, and Ambispora gerdemannii) and twenty-six communities on the root biomass and active ingredient concentrations of S. miltiorrhiza were assessed using the total factor design method. RESULTS: Thirty-one treatment groups formed symbiotic relationships with S. miltiorrhiza based on the pot culture results, and the colonization rate ranged from 54.83% to 89.97%. AMF communities had higher colonization rates and total phenolic acid concentration than single AMF, and communities also appeared to have higher root fresh weight, dry weight, and total phenolic acid concentration than single inoculations. As AMF richness increased, there was a rising trend in root biomass and total tanshinone accumulations (ATTS), while total phenolic acid accumulations (ATP) showed a decreasing trend. This suggests that plant productivity was influenced by the AMF richness, with higher inoculation benefits observed when the communities contained three or four AMFs. Additionally, the affinities of AMF members were also connected to plant productivity. The inoculation effect of closely related AMFs within the same family, such as G. formosanum, S. constrictum, and R. manihotis, consistently yielded lower than that of mono-inoculation when any combinations were applied. The co-inoculation of S. miltiorrhiza with nearby or distant AMFs from two families, such as G. formosanum, R. manihotis, and Ac. laevis or Am. gerdemannii resulted in an increase of ATP and ATTS by more than 50%. AMF communities appear to be more beneficial to the yield of bioactive constituents than the single AMF, but overall community inoculation effects are related to the composition of AMFs and the relationship between members. CONCLUSION: This study reveals that the AMF community has great potential to improve the productivity and the accumulation of bioactive constituents in S. miltiorrhiza, indicating that it is an effective way to achieve sustainable agricultural development through using the AMF community.

Identification of Human Brain Proteins for Bitter-Sweet Taste Perception: A Joint Proteome-Wide and Transcriptome-Wide Association Study.

Objective: Bitter or sweet beverage perception is associated with alterations in brain structure and function. Our aim is to analyze the genetic association between bitter or sweet beverage perception and human brain proteins. Materials and methods: In our study, 8356 and 11,518 proteins were first collected from two reference datasets of human brain proteomes, the ROS/MAP and Banner. The bitter or sweet beverage perception-related proteome-wide association studies (PWAS) were then conducted by integrating recent genome-wide association study (GWAS) data (n = 422,300) of taste perception with human brain proteomes. The human brain gene expression profiles were collected from two reference datasets, including the brain RNA-seq (CBR) and brain RNA-seq splicing (CBRS). The taste perception-related transcriptome-wide association studies (TWAS) were finally performed by integrating the same GWAS data with human brain gene expression profiles to validate the PWAS findings. Results: In PWAS, four statistically significant proteins were identified using the ROS/MAP and then replicated using the Banner reference dataset (all permutated p < 0.05), including ABCG2 for total bitter beverages and tea, CPNE1 for total bitter beverage, ACTR1B for artificially sweetened beverages, FLOT2 for alcoholic bitter beverages and total sweet beverages. In TWAS analysis, six statistically significant genes were detected by CBR and confirmed by the CBRS reference dataset (all permutated p < 0.05), including PIGG for total bitter beverages and non-alcoholic bitter beverages, C3orf18 for total bitter beverages, ZSWIM7 for non-alcoholic bitter beverages, PEX7 for coffee, PKP4 for tea and RPLP2 for grape juice. Further comparison of the PWAS and TWAS found three common statistically significant proteins/genes identified from the Banner and CBR reference datasets, including THBS4 for total bitter beverages, CA4 for non-alcoholic bitter beverages, LIAS for non-grape juices. Conclusions: Our results support the potential effect of bitter or sweet beverage perception on brain function and identify several candidate brain proteins for bitter or sweet beverage perception.

Synergistic cytotoxic effects of a combined treatment of a Pinellia pedatisecta lipid-soluble extract and cisplatin on human cervical carcinoma in vivo.

Herbal medicines are known to have numerous benefits, including lower toxicity and fewer side effects than traditional chemotherapeutic drugs. In traditional Chinese medicine, the rhizome of Pinellia pedatisecta (PE) Schott has long been used to treat cancer, undiagnosed swelling and erythema toxicum. However, its medical benefits lack support from scientific evidence. A novel lipid-soluble extract from PE has been previously verified to enhance the cytotoxicity of cis-dichlorodiammineplatinum-II (CDDP) against human cervical cancer cells in vitro. The present study evaluated the synergistic cytotoxic effects of PE and CDDP against human cervical cancer. Combination therapy of PE with CDDP exhibited synergistic cytotoxicity towards CaSki cell growth in mouse xenograft tumors. PE exhibited a cytotoxic effect on tumor size and weight, although the inhibitory ratio of tumor weight was only 26.3% in the PE-treated group. However, when mice were co-treated with PE and CDDP, the inhibitory ratio was higher than that of mice treated with CDDP alone (50.8 vs. 68.4%, respectively). The potential synergistic mechanism was likely via inhibiting the signaling E6/p53 pathway, restoring p53 function and inducing downstream tumor suppressor chain effects on apoptosis. Western blot analysis and immunohistochemistry indicated thatE6protein expression was significantly decreased upon treatment with combined PE and CDDP. The expression of p53 was increased in the combined PE and CDDP treatment group. Upregulation of p53-dependent apoptosis-associated proteins, including Bcl-2-associated X protein and cleaved caspases-9 and -3, was observed in the combined PE and CDDP treatment group. Our results present a molecular basis for the future application of the combination of PE and CDDP in the treatment of cervical cancer as a novel and pharmacologically safe chemotherapeutic strategy.

13-Methyltetradecanoic acid induces mitochondrial-mediated apoptosis in human bladder cancer cells.

OBJECTIVE: 13-Methyltetradecanoic acid (13-MTD), a saturated branched-chain fatty acid purified from soy fermentation products, is known to induce apoptosis in many types of human cancer cells. This study was designed to investigate the molecular mechanisms involved in 13-MTD-induced apoptosis in human bladder cancer cells. METHODS AND MATERIALS: MTT assay was used to investigate the potential effects of 13-MTD on the growth and viability of human bladder cancer cells. To find out whether anti-proliferation and cell death were associated with apoptosis, we used flow cytometry to quantify the extent of apoptosis and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay to measures DNA degradation of apoptotic cells. The proteins involved in the 13-MTD induced apoptosis were examined using Western blot. RESULTS: We show that 13-MTD inhibits cellular proliferation and viability in human bladder cancer cells, which has been attributed to apoptosis. 13-MTD down-regulates Bcl-2 and up-regulates Bax. This promotes mitochondrial dysfunction, leading to the release of cytochrome c from the mitochondria to the cytoplasm, as well as the proteolytic activation of caspases. Moreover, 13-MTD down-regulates AKT phosphorylation and activates phosphorylation of p38 and c-Jun N-terminal kinase (JNK). Up-regulating AKT phosphorylation and down-regulating JNK and P38 phosphorylation could attenuate the13-MTD-induced apoptosis. CONCLUSION: Taken together, these data indicate that 13-MTD induces mitochondrial-mediated apoptosis through regulation of the AKT and MAPK pathways, suggesting 13-MTD is a potential candidate for treatment of human bladder cancer.