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Regulation of metabolic targets in hepatic and tumor cells
WU Xu-Dong
, Available online  
Abstract:
Piperine Treating Sciatica Through Regulating Inflammation and MiR-520a/P65 Pathway
Yu Jiu-wang, Li Sha, Bao Li-dao, Wang Lu, Bo Agula
, Available online  
Abstract:
  Background  Mongolian medicine, Naru-3, is composed of the radix aconiti agrestis, the fructus chebulae and the long pepper, which has the effects of reducing swelling, relieving pain and treating sciatica. Previous researchs have found that piperine, an intrinsic ingredient in the long pepper, may has analgesic and anti-inflammatory effects.  Objective  To verify the regulatory relationship between miR-520a and p65, and to explore how miR-520a/p65 affects the levels of pro-inflammatory cytokines (IL-1β,TNF-α) and anti-inflammatory cytokines (IL-10,TGF-β1) under the action of piperine.  Methods  The rat model of sciatica was firstly made. The factors of sciatica inflammatory response were evaluated by ELISA. Gene chip analysis of the miRNAs was then performed to analyze the miRNA expressed differently in the model group and the drug-administered group, and to predict the downstream targeting of the miRNA. Real-time quantitative PCR was used to detect the expressions of miR-520a, P65, pro-inflammatory cytokines (IL-1β and TNF-ɑ) and anti-inflammatory cytokines (IL-10 and TGF-β1) at the mRNA level. The protein expressions of P65, pro-inflammatory cytokines (IL-1β and TNF-ɑ) and anti-inflammatory cytokines (IL-10 and TGF-β1) was detected by Western blot; HE staining and immunohistochemistry were used to analyze the pathological changes and the expression of P65 in the sciatic nerve. Finally, the regulatory relationship between miR-520a and P65 was detected again by double luciferase reporter gene assay.  Results  ELISA experiments suggested that IL-1β,TNF-ɑ,IL-10 and TGF-β1 can be used as indicators for evaluation of sciatica. The miRNA with different expression was screened out by chip technology as miR-520a, and the downstream target of miR-520a was detected as P65 by bioinformatics. Real-time quantitative PCR confirmed that the expression of miR-520a was negatively correlated with pro-inflammatory factors, positively correlated with anti-inflammatory factors, and negatively correlated with the expression of P65 at the mRNA level. Western blot showed that P65 expression was positively correlated with pro-inflammatory factors and negatively correlated with anti-inflammatory factors at protein level. HE staining showed that the nerves in the sham group were closely arranged and orderly, in the model group, the nerve damage was extremely severe, with obvious vacuoles and severe deformation of nerve fibers. After drug administration, nerve fibers were repaired, vacuoles were significantly reduced, and the damage degree of nerve fibers was also improved. Immunohistochemical analysis showed that P65 was not expressed in the sham group, P65 was severely expressed in the model group, and the expression of P65 was decreased after administration. The dual luciferase reporter assay again confirmed that luciferase signal was significantly decreased when co-transfected with the recombinant plasmid of miR-520a mimics and P65 3'UTR compared with the other groups (P < 0.01). When miR-520a mimics was expressed at high or low, there was no significant decrease in luciferase signal after co-transfection with the mutated P65 3'UTR recombinant plasmid, suggesting that miR-520a had a specific target effect on P65.  Conclusion  In the rat model of non-compressed lumbar disc herniation, the administration of piperine has a significant effect on analgesia. MiR-520a can specifically and directly target p65. Piperine can promote the expression of miR-520a, inhibiting the expression of P65. It can down-regulate pro-inflammatory factors IL-1β, TNF-ɑ and upregulate the effects of anti-inflammatory factors IL-10, TGF-β1, so as to treat sciatica.
cjnm-2020-02 Contents
, Available online  
Abstract:
2020-03ml Contents
, Available online  
Abstract:
Preparation and evaluation of a water-in-oil nanoemulsion drug delivery system loaded with salidroside
LIANG Chun-Xia, QI Dong-Li, ZHANG Li-Na, LU Peng, LIU Zhi-Dong
, Available online  
Abstract:
Salidroside is a phenolic substance with high solubility and low permeability, which make it easy to cause the efflux effect of p-glycoprotein and degradation of intestinal flora, resulting in lower bioavailability. The aim of this study was to develop and optimize a water-in-oil nanoemulsion of salidroside (w/o SAL-N) to explore its suitability in oral drug delivery systems. In this work, SAL-N was successfully prepared by water titration method at Km=1 to construct the pseudo-ternary phase diagrams. Physical characterization including the average viscosity, pH, refractive index, particle size, PDI, TEM, DSC, the content of SAL, and stability study were performed. It was evaluated for drug release in vitro and pharmacokinetic studies in vivo. The optimized nanoemulsion formulation consisted of Labrafil M 1944CS (63%), Span80/Tween80/EtOH (27%) and 200 mg/mL salidroside solution (SAL-SOL) (10%). Low viscosity and suitable pH were expected for the nanoemulsion. The spherical morphology and nanoscale size of SAL-N enhanced the stability of the nanoemulsion system. In vitro drug release showed that SAL-N had a better controlled release property than SAL-SOL at earlier time points. The pharmacokinetic studies exhibited that SAL-N had significantly higher in T1/2 (2.11-fold), AUC0-48h (1.75-fold) and MRT0-48h (2.63-fold) than SAL-SOL (p<0.01). The w/o SAL-N prepared in this work can be effectively delivered via the oral route. It can be seen w/o nanoemulsion is a strategy for the drug with polyphenols to delay the release, enhance oral absorption and reduce metabolic rate.
Liver metabonomics study on the protective effect of glycyrrhetinic acid against realgar-induced liver injury
Huo Taoguang, Fang Ying, Zhang Yinghua, Feng Cong, Jiang Hong
, Available online  
Abstract:
Glycyrrhetinic acid (GA) is the bioactive ingredient in Glycyrrhizae Radx et Rhizoma. Our previous study has reported that GA has protective effect on realgar- induced hepatotoxicity. However, the details of the hepatoprotective mechanisms of GA on realgar-induced liver injury remain to be elucidated. In the study, mice were divided into control, GA-control, realgar, and co-treated groups. Their liver tissues were used for metabonomics study by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) method. The results illustrate that GA significantly ameliorate the liver injury and metabolic perturbations caused by realgar. Some metabolites, such as phenylalanine, pyroglutamic acid (PGA), proline, carnitine, nicotinamide, choline, lysophosphatidylcholine (LPC) 16:0 and LPC 18:2 were found responsible for the hepatoprotective effect of GA. These metabolites are associated with the methylation metabolism of arsenic, cell membrane structure, energy metabolism and oxidative stress. From the results of this study, we infer that the potential hepatoprotective mechanism of GA on realgar-induced liver injury may be associated with reducing arsenic accumulation and its methylation metabolism in the liver, promoting the conjugation of arsenic and GSH to play detoxification effect, and ameliorating the liver metabolic perturbations caused by realgar.
Prediction of the Globally Ecological Suitability of Panax quinquefolius by the Geographic Information System for Global Medicinal Plants (GMPGIS)
Liang SHEN, Xi-Wen LI, Xiang-Xiao MENG, Jie WU, Huan TANG, Lin-Fang HUANG, Shui-Ming XIAO, Jiang XU, Shi-Lin CHEN
, Available online  , doi: 10.3724/SP.J.1009.2019.00000
Abstract:
American ginseng (Panax quinquefolius L.) is a well-known Asian traditional herbal medicine with a large market demand. The plant is native to eastern North America, and its main producing areas worldwide are decreasing due to continuous cropping obstacles and environmental changes. Therefore, the identification of maximum similarities of new ecological distribution of P. quinquefolius, and prediction of its response to climate change in the future are necessary for plant introduction and cultivation. In this study, the areas with potential ecological suitability for P. quinquefolius were predicted using the geographic information system for global medicinal plants (GMPGIS) based on 476 occurrence points and 19 bioclimatic variables. The results indicate that the new ecologically suitable areas for P. quinquefolius are East Asia and the mid-eastern Europe, which are mainly distributed in China, Russia, Japan, Ukraine, Belarus, North Korean, South Korea, and Romania. Under global climate change scenarios, the suitable planting areas for P. quinquefolius would be increased by 9.16%–30.97%, and expanding north and west over the current ecologically suitable areas by 2070. The potential increased areas that are ecologically suitable include northern Canada, Eastern Europe, and the Lesser Khingan Mountains of China, and reduced regions are mainly in central China, the southern U.S., and southern Europe. Jackknife tests indicate that the precipitation of the warmest quarter was the important climatic factor controlling the distribution of P. quinquefolius. Our findings can be used as a useful guide for P. quinquefolius introduction and cultivation in ecologically suitable areas.