Integrating network pharmacology, UPLC-Q-TOF-MS and molecular docking to investigate the effect and mechanism of Chuanxiong Renshen decoction against Alzheimer's disease.
作者: Zhuo Jun Shen ; Yun Bo Fu ; Jin Ling Hou ; Lu Ning Lin ; Xiao Yan Wang ; Chang Yu Li ; Yuan Xiao Yang
BACKGROUND AND AIM:
Chuanxiong Renshen decoction (CRD) is a traditional Chinese medicine compound used to treat Alzheimer's disease (AD). However, the effects and active ingredients of CRD and its mechanism have not been clarified. We aimed to determine the neuroprotective effects of CRD in a triple-transgenic mouse model of AD (3 × Tg-AD) and investigate the possible active ingredients and their mechanisms.
Morris water maze (MWM) tests were used to determine the protective effect of CRD on learning and memory ability. Afterward, we used brain tissue staining, immunofluorescent staining and western blotting to detect the neuroprotective effects of CRD. Ultraperformance liquid-chromatography-quadrupole-time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS) was applied to determine the ingredients of CRD, and the potential AD targets were obtained from DisGeNET and the GeneCards database. The protein‒protein interaction (PPI) network was built with the additional use of STRING 11.0. Metascape was used in the pathway enrichment analysis. Discovery Studio 2016 (DS) software was used to analyze the binding ability of CRD and AD-related genes. Finally, we verified the regulatory effect of CRD on the predicted core targets EGFR and CASP3 by western blotting.
Our study indicated that CRD can significantly improve learning and memory, reduce the expression of Aβ and protect neurons. A total of 95 ingredients were identified in the CRD. Then, 25 ingredients were identified in serum, and 5 ingredients were identified in the brain tissue homogenate. PPI network analysis identified CASP3, EGFR, APP, CNR1, HIF1A, PTGS2 and MTOR as hub targets. KEGG and GO analyses revealed that the TNF signaling pathway and MAPK signaling pathway were enriched in multiple targets. The results of molecular docking proved that the binding of the ingredients with potential key targets was excellent. The western blotting results showed that CRD could significantly reduce the expression of CASP3 and EGFR in the hippocampus of 3 × Tg-AD mice. Combined with literature analysis, we assumed the neuroprotective effect of CRD on AD may occur through regulation of the MAPK signaling pathway.
CRD significantly alleviated injury in 3 × Tg-AD mice. The possible active ingredients are ferulic acid, rutin, ginsenoside Rg1 and panaxydol. The therapeutic effect of CRD on AD is achieved through the downregulation of CASP3 and EGFR. The neuroprotective effect of CRD on AD may occur through regulation of the MAPK signaling pathway.
2021-05-21·Drug and alcohol dependence2区 · 医学
Cannabis-related diagnosis in pregnancy and adverse maternal and infant outcomes.
2区 · 医学
作者: Gretchen Bandoli ; Laura Jelliffe-Pawlowski ; Benjamin Schumacher ; Rebecca J Baer ; Jennifer N Felder ; Jonathan D Fuchs ; Scott P Oltman ; Martina A Steurer ; Carla Marienfeld
Cannabis use and cannabis use disorders are increasing in prevalence, including among pregnant women. The objective was to evaluate the association of a cannabis-related diagnosis (CRD) in pregnancy and adverse maternal and infant outcomes.
We queried an administrative birth cohort of singleton deliveries in California between 2011-2017 linked to maternal and infant hospital discharge records. We classified pregnancies with CRD from International Classification of Disease codes. We identified nicotine and other substance-related diagnoses (SRD) in the same manner. Outcomes of interest included maternal (hypertensive disorders) and infant (prematurity, small for gestational age, NICU admission, major structural malformations) adverse outcomes.
From 3,067,069 pregnancies resulting in live births, 29,112 (1.0 %) had a CRD. CRD was associated with an increased risk of all outcomes studied; the strongest risks observed were for very preterm birth (aRR 1.4, 95 % CI 1.3, 1.6) and small for gestational age (aRR 1.4, 95 % CI 1.3, 1.4). When analyzed with or without co-exposure diagnoses, CRD alone conferred increased risk for all outcomes compared to no use. The strongest effects were seen for CRD with other SRD (preterm birth aRR 2.3, 95 % CI 2.2, 2.5; very preterm birth aRR 2.6, 95 % CI 2.3, 3.0; gastrointestinal malformations aRR 2.0, 95 % CI 1.6, 2.6). The findings were generally robust to unmeasured confounding and misclassification analyses.
CRD in pregnancy was associated with increased risk of adverse maternal and infant outcomes. Providing education and effective treatment for women with a CRD during prenatal care may improve maternal and infant health.
Cordycepin (CRD), an adenosine analog derived from traditional Chinese medicine, is an active component in Cordyceps militaris. It has been shown to have many protective effects during liver injury and ameliorate liver disease progression, but little is known about its effect on non-alcoholic fatty liver disease (NAFLD). This study aims to explore the effects of CRD on obesity-induced NAFLD. In this experiment, C57BL/6 J mice were randomly assigned into normal control group (NC), high fat diet group (HFD) and HFD + CRD group for 8 weeks. The body weights were recorded weekly, at the end of the experiments, the liver and serum samples were collected. We found that CRD administration reduced body weight and decreased the weight of adipose and liver, and CRD relieved liver injure through diminishing of histopathological changes and decreasing serum levels of AST, ALT, TG, TC, LDL-C and increased the level of HDL-C. Furthermore, treatment with CRD significantly alleviated expression of inflammatory factors (TNF-α, IL-6 and Il-1β) and macrophage markers (MCP1, MIP2, mKC and VCAM1). On the other hand, compared with HFD group, the CRD treated group markedly down-regulated relative proteins of lipid anabolism (SREBP1-c, ACC, SCD-1, LXRα and CD36) and up-regulated relative proteins of β-oxidation (p-AMPK, AMPK, CPT-1 and PPARα). In summary, our results suggest that CRD can be a potential therapeutic agent in the prevention and treatment of NAFLD, which may be closely related to its effect on lipid metabolism and inflammatory responses.