The Effect of Broccoli Sprout Extract on Seasonal Grass Pollen-Induced Allergic Rhinitis.

Patients exposed to pollutants are more likely to suffer from allergic rhinitis and may benefit from antioxidant treatment. Our study determined if patients diagnosed with grass-induced allergic rhinitis could benefit from broccoli sprout extract (BSE) supplementation. In total, 47 patients were confirmed with grass-induced allergic rhinitis and randomized to one of four groups: group 1 (nasal steroid spray + BSE), group 2 (nasal steroid spray + placebo tablet), group 3 (saline nasal spray + BSE) and group 4 (saline nasal spray + placebo tablet). Peak Nasal Inspiratory Flow (PNIF), Total Nasal Symptoms Scores (TNSS) and nasal mucus cytokine levels were analyzed in samples collected before and after the 3-week intervention. Comparing before and after the intervention, PNIF improved significantly when comparing Groups 1 and 2, vs. placebo, at various time points (p ≤ 0.05 at 5, 15, 60 and 240 min) following nasal challenge, while TNSS was only statistically significant at 5 (p = 0.03), 15 (p = 0.057) and 30 (p = 0.05) minutes. There were no statistically significant differences in various cytokine markers before and after the intervention. Combining nasal corticosteroid with BSE led to the most significant improvement in objective measures.

A Chinese Patent Medicine JiaYanKangTai Alleviates Inflammatory Lesions of Experimental Autoimmune Thyroiditis by Regulating Interleukin-17 Signaling.

Objective: This study was aimed to investigate the effects of JiaYanKangTai (JYKT) on regulating interleukin-17 (IL-17) signaling in rats with autoimmune thyroiditis. Methods: Lewis rats were administrated with JYKT for eight weeks after a seven-week subcutaneous injection of thyroglobulin with adjuvant and feeding iodine water. Ultrasonography was performed and total volume of thyroid was calculated. The expressions of autoantibodies and hormones were detected. Morphological changes of thyroid were observed. Metabolomics profile and metabolic network analysis were conducted. IL-17 signaling was detected by polymerase chain reaction and immunohistochemistry separately. Results: JYKT reduced the mean volumes of thyroid, decreased both levels of TPOAb and TGAb, and alleviated lymphocytic infiltration of the thyroid. Metabolic network analysis of metabolomics proved IL-17 signaling pathway as a critical pathway in JYKT administration for autoimmune thyroiditis. JYKT downregulated expressions of IL-17A, TRAF6, p-ERK1/2 and TNF-α. Conclusion: JYKT alleviated inflammatory lesions of experimental autoimmune thyroiditis by regulating IL-17 signaling.

Prediction of the mechanisms of action of Shenkang in chronic kidney disease: A network pharmacology study and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine provides a unique curative treatment of complex chronic diseases, including chronic kidney disease (CKD), which is not effectively treated with the current therapies. The pharmacological mechanisms of Shenkang (SK), a herbal medicine containing rhubarb (Rheum palmatum L. or R. tanguticum Maxim. ex Balf.), red sage (Salvia miltiorrhiza Bunge), safflower (Carthamus tinctorius L.), and astragalus (Astragalus mongholicus Bunge), widely used to treat CKD in China, are still unclear. AIM OF THE STUDY: In this study, the comprehensive approach used for elucidating the pharmacological mechanisms of SK included the identification of the effective constituents, target prediction and network analysis, by investigating the interacting pathways between these molecules in the context of CKD. These results were validated by performing an in vivo study and by comparison with literature reviews. MATERIALS AND METHODS: This approach involved the following main steps: first, we constructed a molecular database for SK and screened for active molecules by conducting drug-likeness and drug half-life evaluations; second, we used a weighted ensemble similarity drug-targeting model to accurately identify the direct drug targets of the bioactive constituents; third, we constructed compound-target, target-pathway, and target-disease networks using the Cytoscape 3.2 software and determined the distribution of the targets in tissues and organs according to the BioGPS database. Finally, the resulting drug-target mechanisms were compared with those proposed by previous research on SK and validated in a mouse model of CKD. RESULTS: By using Network analysis, 88 potential bioactive compounds in the four component herbs of SK and 85 CKD-related targets were identified, including pathways that involve the nuclear factor-κB, mitogen-activated protein kinase, transient receptor potential, and vascular endothelial growth factor, which were categorized as inflammation, proliferation, migration, and permeability modules. The results also included different tissues (kidneys, liver, lungs, and heart) and different disease types (urogenital, metabolic, endocrine, cardiovascular, and immune diseases as well as pathological processes) closely related to CKD. These findings agreed with those reported in the literature. However, our findings with the network pharmacology prediction did not account for all the effects reported for SK found in the literature, such as regulation of the hemodynamics, inhibition of oxidative stress and apoptosis, and the involvement of the transforming growth factor-ß/SMAD3, sirtuin/forkhead box protein O (SIRT/FOXO) and B-cell lymphoma-2-associated X protein pathways. The in vivo validation experiment revealed that SK ameliorated CKD through antifibrosis and anti-inflammatory effects, by downregulating the levels of vascular cell adhesion protein 1, vitamin D receptor, cyclooxygenase-2, and matrix metalloproteinase 9 proteins in the unilateral ureteral obstruction mouse model. This was consistent with the predicted target and pathway networks. CONCLUSIONS: SK exerted a curative effect on CKD and CKD-related diseases by targeting different organs, regulating inflammation and proliferation processes, and inhibiting abnormal extracellular matrix accumulation. Thus, pharmacological network analysis with in vivo validation explained the potential effects and mechanisms of SK in the treatment of CKD. However, these findings need to be further confirmed with clinical studies.

Investigating the Multi-Target Pharmacological Mechanism of Hedyotis diffusa Willd Acting on Prostate Cancer: A Network Pharmacology Approach.

Hedyotis diffusa Willd (HDW) is one of the most well-known herbs used in the treatment of prostate cancer. However, the potential mechanisms of its anti-tumor effects have not been fully explored. Here, we applied a network pharmacology approach to explore the potential mechanisms of HDW against prostate cancer (PCa). We obtained 14 active compounds from HDW and 295 potential PCa related targets in total to construct a network, which indicated that quercetin and ursolic acid served as the main ingredients in HDW. Mitogen-activated Protein Kinase 8 (MAPK8), Interleukin 6 (IL6), Vascular Endothelial Growth Factor A (VEGFA), Signal Transducer and Activator of Transcription 3 (STAT3), Jun Proto-Oncogene (JUN), C-X-C Motif Chemokine Ligand 8 (CXCL8), Interleukin-1 Beta (IL1B), Matrix Metalloproteinase-9 (MMP9), C-C Motif Chemokine Ligand 2 (CCL2), RELA Proto-Oncogene (RELA), and CAMP Responsive Element Binding Protein 1 (CREB1) were identified as key targets of HDW in the treatment of PCa. The protein-protein interaction (PPI) cluster demonstrated that CREB1 was the seed in this cluster, indicating that CREB1 plays an important role in connecting other nodes in the PPI network. This enrichment demonstrated that HDW was highly related to translesion synthesis, unfolded protein binding, regulation of mitotic recombination, phosphatidylinositol and its kinase-mediated signaling, nucleotide excision repair, regulation of DNA recombination, and DNA topological change. The enrichment results also showed that the underlying mechanism of HDW against PCa may be due to its coordinated regulation of several cancer-related pathways, such as angiogenesis, cell differentiation, migration, apoptosis, invasion, and proliferation.

Shenkang injection improves coagulation in patients with chronic kidney disease: a systematic review and Meta-analysis.

OBJECTIVE: To investigate the effect of Shenkang injection (SKI) on chronic kidney disease (CKD). METHODS: Seven databases including Cochrane Central Register of Controlled Trials, PubMed, EMBASE, MEDLINE, China National Knowledge Infrastructure, Wanfang Database, and CQVIP from their inception to March 2018 were searched. Only randomized controlled trials that evaluated conventional treatment and conventional treatment with SKI in CKD patients were investigated. Outcomes such as fibrinogen (FIB), D-dimer, prothrombin time (PT), activated partial thromboplastin time (APTT), and the side effects of SKI were analyzed using Revman 5.3 software. The quality of the studies was assessed using the Cochrane Collaboration's Risk of Bias tool and the quality of evidence was assessed using GRADEpro. RESULTS: Four randomized controlled trials were investigated in our analysis, and these studies were of moderate quality. For FIB and D-dimer, SKI had a superior effect compared with the control group [mean difference (MD)= －1.23, 95% confidence interval (CI): －1.46, －1.99, P < 0.01; MD = －1.36, 95% CI: －1.51, －1.21, P < 0.01, respectively]. SKI increased APTT and PT compared with the control (MD = 7.34, 95% CI: 3.05, 11.62, P < 0.01; MD = 3.40, 95% CI: 2.2, 4.61, P < 0.01, respectively). In the four studies, there were no side effects that were related to SKI. CONCLUSION: SKI may be effective in improving coagulation in patients with CKD without obvious adverse reactions. However, more well-designed studies are required to confirm the findings.

Trans-cinnamaldehyde promotes nitric oxide release via the protein kinase-B /v-Akt murine thymoma viral oncogene -endothelial nitric oxide synthase pathway to alleviate hypertension in SHR.Cg-Leprcp/NDmcr rats.

OBJECTIVE: To evaluate whether endothelial dysfunction and hypertension are prevented by trans-cinnamaldehyde (tCA) through the activation of endothelial nitric oxide synthase (eNOS). METHODS: Human umbilical vein endothelial cells (HUVECs) were cultured in vitro and stimulated with tCA to determine cell viability using the methyl thiazolyl tetrazolium assay. The effect of tCA on nitric oxide (NO) production was determined by diaminofluorescein-dyes in the absence or presence of inhibitors of eNOS, AMPK, PKA, and AKT. The effect of tCA on blood pressure was determined by the tail-cuff method in obesity spontaneous hypertension (SHR. Cg-Leprcp/NDmcr) rats. The phosphorylation of eNOS and protein expression of the insulin-signaling pathway (InsR-IRS1-PI3K-AKT) were measured by western blot. RESULTS: tCA at concentrations less than 100 ¦ÌM did not affect cell viability in cultured HUVECs. Stimulation with tCA promoted NO release in a time-dependent manner compared with the control group. tCA-treated HUVECs also significantly increased AKT-Ser473 and eNOS- Ser1177 phosphorylation. In SHR-CP rats, treatment with tCA at a dose of 40 mg/kg/day for 6 weeks markedly reduced the systolic blood pressure and diastolic blood pressure, increased the phosphorylation of AKT and eNOS, and increased urinary nitric oxidation. CONCLUSION: tCA attenuated endothelial dysfunction and reduced blood pressure in SHR-CP rats. The underlying mechanisms may involve the increase in AKT and eNOS phosphorylation and the release of eNOS-derived NO.