Integrating Network Pharmacology and Experimental Verification to Explore the Targets and Mechanism for Panax Notoginseng Saponins against Coronary In-stent Restenosis.

BACKGROUND: Despite widespread application of drug-eluting stents in coronary intervention, in-stent restenosis (ISR) is still a daunting complication in clinical practice. Panax notoginseng saponins (PNS) are considered to be effective herb compounds for preventing ISR. OBJECTIVE: This study aimed to elucidate the targets and mechanisms of PNS in ISR prevention using network pharmacology approaches and experimental verification. METHODS: Relevant targets of PNS active compounds were collected from the HERB database and PharmMapper. The ISR-related targets were obtained from the GeneCards database and the Comparative Toxicogenomics Database. The GO and KEGG enrichment analysis was performed using R software. The String database and Cytoscape software were employed to build the PPI and compounds-targets-pathways-disease networks. Finally, Molecular docking performed by Autodock Vina and cellular experiments were used to validate network pharmacology results. RESULTS: There were 40 common targets between PNS targets and ISR targets. GO analysis revealed that these targets focused on multiple ISR-related biological processes, including cell proliferation and migration, cell adhesion, inflammatory response, and anti-thrombosis and so on. The KEGG enrichment results suggested that PNS could regulate multiple signaling pathways to inhibit or delay the development and occurrence of ISR. The molecular docking and cellular experiments results verified the network pharmacology results. CONCLUSION: This study demonstrated that the potential molecular mechanisms of PNS for ISR prevention involved multiple compounds, targets, and pathways. These findings provide a theoretical reference and experimental basis for the clinical application and product development of PNS for the prevention of ISR.

Effect of Dietary Fiber (Oat Bran) Supplement in Heart Rate Lowering in Patients with Hypertension: A Randomized DASH-Diet-Controlled Clinical Trial.

(1) Background: The management goal for patients with essential hypertension (HTN) is not only to lower blood pressure (BP), but also to control increased heart rate (HR). In a previous study, it was found that dietary fiber (DF) supplementation can effectively reduce BP in patients with HTN. The aim of this study was to determine whether a DF supplement can lower HR in patients with HTN. (2) Methods: Seventy patients who met the inclusion and exclusion criteria were randomly allocated into the control group (n = 34) and the intervention group (n = 36). The regular DASH dietary care was delivered to both groups of patients. In addition, one bag of oat bran (30 g/d, containing DF 8.9 g) was delivered to the intervention group. The 24 h ambulatory heart rate was measured at baseline and 3 months. (3) Results: At 3 months, the 24 h maximum heart rate (24h maxHR) in the intervention group was significantly lower than that in the control group. After the intervention, within-group comparisons in the intervention group revealed that there were significant reductions in the 24 h average heart rate (24h aveHR), 24h maxHR, average heart rate during day time (D-aveHR), minimum heart rate during day time (D-minHR), and maximum heart rate during day time (D-maxHR). Similar differences were not found in the control group. (4) Conclusions: Dietary fiber (oat bran) supplementation might be beneficial in lowering HR in patients with HTN.

Nontargeted Metabolomics for Phenolic and Polyhydroxy Compounds Profile of Pepper (Piper nigrum L.) Products Based on LC-MS/MS Analysis.

In the present study, nontargeted metabolomics was used to screen the phenolic and polyhydroxy compounds in pepper products. A total of 186 phenolic and polyhydroxy compounds, including anthocyanins, proanthocyanidins, catechin derivatives, flavanones, flavones, flavonols, isoflavones and 3-O-p-coumaroyl quinic acid O-hexoside, quinic acid (polyhydroxy compounds), etc. For the selected 50 types of phenolic compound, except malvidin 3,5-diglucoside (malvin), l-epicatechin and 4'-hydroxy-5,7-dimethoxyflavanone, other compound contents were present in high contents in freeze-dried pepper berries, and pinocembrin was relatively abundant in two kinds of pepper products. The score plots of principal component analysis indicated that the pepper samples can be classified into four groups on the basis of the type pepper processing. This study provided a comprehensive profile of the phenolic and polyhydroxy compounds of different pepper products and partly clarified the factors responsible for different metabolite profiles in ongoing studies and the changes of phenolic compounds for the browning mechanism of black pepper.

Contribution of Polyphenol Oxidation, Chlorophyll and Vitamin C Degradation to the Blackening of Piper nigrum L.

Black pepper (Piper nigrum L.) is the most widely used spice in the world. Blackening is considered to be beneficial and important in the processing of black pepper because it contributes to its color and flavor. The purpose of this paper is to investigate polyphenol oxidation as well as the chlorophyll and vitamin C (VC) degradation in the blackening of Piper nigrum L. Black pepper was produced by four methods, and changes in polyphenols, chlorophyll and VC were studied by high performance liquid chromatography (HPLC) and ultraviolet-visible and visible (UV-Vis) spectrophotometry. The results show that polyphenol oxidase activity significantly decreased during the preparation of black pepper, and the concentrations of phenolic compounds, VC, and chlorophyll a and b also significantly decreased. Polyphenol oxidation and chlorophyll and VC degradation contribute to the blackening. A crude extract of phenolic compounds from black pepper was prepared by the system solvent method. The greater the polarity of the extraction solvent, the higher the extraction rates of the phenolic compounds and the total phenol content. Pepper phenolic compounds were analyzed by HPLC analysis.

[Therapeutic effect of dahuangzhechong pills on advanced schistosomiasis].

OBJECTIVE: To evaluate the therapeutic effect and safety of Dahuangzhechong pills on advanced schistosomiasis. METHODS: Sixty-two patients with advanced schistosomiasis were divided randomly into two groups, a treatment group and a control group, and treated with Dahuangzhechong pills and routine therapy, respectively. The course of treatment was 52 weeks in the two groups. Before and after the 52-week treatment, the indexes of liver function and hepatic fibrosis, prothrombin time (PT), Child-Pugh scores and changes of B-type ultrasonic images were detected for all the patients. RESULTS: There were significant differences in the levels of alanine aminotransferase (ALT) and total bilirubin (TBIL), the indexes of hepatic fibrosis, portal venous inside diameters and portal venous flow between the two groups after 52 weeks treatment (P < 0.05). In addition, there were no obvious adverse effects during the treatment in the patients of the Dahuangzhechong pill group. CONCLUSION: Dahuangzhechong pill treatment is a safe and effective therapy for the patients with advanced schistosomiasis.

Effect of medical ozone therapy on renal blood flow and renal function of patients with chronic severe hepatitis.

BACKGROUND: Medical ozone therapy system was reported to have certain effects on the treatment of severe hepatitis, but its mechanism is not very clear. One of the causes of death of severe hepatitis is complication of renal damage or hepatorenal syndrome. The present study aimed to observe effects of medical ozone therapy system on plasma renin activity (PRA), angiotensin II (AII), aldosterone (ALD), renal blood flow and renal function of patients with chronic severe hepatitis and explore mechanisms of medical ozone therapy in the treatment of severe hepatitis. METHODS: Eighty-five cases with chronic severe hepatitis were randomly divided into ozone therapy group (43 cases) and control group (42 cases). The patients in the ozone therapy group were treated with basic treatments plus ozone therapy system. Basic autohemotherapy was used. One hundred milliliter venous blood was drawn from each patient, and was mixed with 100 ml (35 µg/ml) medical ozone and then was returned the blood to the patient intravenously, once every other day for 20 days. Only the basic treatments were given to the control group. PRA, AII, ALD, renal blood flow and damage to renal function of the two groups before treatment and 20 days after treatment were compared. Survival rates were also compared. RESULTS: Twenty days after the treatment, in ozone therapy group, PRA was (1.31 ± 0.12) ng·ml⁻¹·h⁻¹, AII (111.25 ± 17.35) pg/ml, ALD (251.31 ± 22.60) pg/ml, which decreased significantly compared with those before treatment (PRA (2.23 ± 0.13) ng·ml⁻¹·h⁻¹, AII (155.18 ± 19.13) pg/ml, ALD (405.31 ± 29.88) pg/ml, t = 4.67 - 14.23, P < 0.01), also lower than those of control group 20 days after the treatment (PRA (2.02 ± 0.11) ng·ml⁻¹·h⁻¹, AII (162.21 ± 15.32) pg/ml, ALD (401.20 ± 35.02) pg/ml, t = 4.97 - 15.61, P < 0.01); renal blood flow was (175.15 ± 28.20) ml/min, which increased compared with that before the treatment ((125.68 ± 21.25) ml/min) and was higher than that of control group 20 days after the treatment ((128.59 ± 23.15) ml/min, t = 4.78, 4.61, P < 0.01). Renal damage occurred in 2 cases (5%) in ozone therapy group, less than that in control group (9 cases, 21%) (χ² = 5.295, P < 0.05). Thirty-three cases (77%) in ozone therapy group vs. 16 cases (38%) in control group survived (χ² = 12.993, P < 0.01). CONCLUSIONS: Basic treatment plus medical ozone therapy for patients with chronic severe hepatitis could decrease PRA, AII and ALD levels significantly increase renal blood flow, prevent renal damage to certain extent and improve survival rate of the patients.