Rhynchophylline attenuates migraine in trigeminal nucleus caudalis in nitroglycerin-induced rat model by inhibiting MAPK/NF-кB signaling.

Migraine causes severe health and social issues worldwide. Rhynchophylline (Rhy) is one of the major active components of Uncaria rhynchophylla that is used for the treatment of headache in Traditional Chinese Medicine. In the current study, the effect of Rhy on nitroglycerin (NTG)-induced migraine was assessed and the associated mechanism was also explored to explain its function. Rats were pre-treated with Rhy of two doses (10 mg/kg and 30 mg/kg) and then subjected to NTG to induce migraine symptoms. Thereafter, the electroencephalogram (EEG) signaling, spontaneous behaviors, levels of indicators related to oxidative stress, and expression of calcitonin gene-related peptide (CGRP) were measured to assess the anti-migraine function of Rhy. Moreover, the activities of MAPK/NF-κB pathway under the administrations of Rhy were also detected. The results showed that NTG induced EEG and behavior disorders in rats, which was associated with the initiation of oxidative stress and increased expression of CGRP. Nevertheless, the pre-treatments with Rhy attenuated the damages induced by NTG by reversing the levels of all the above indicators. The results of western blotting demonstrated that the anti-migraine effect of Rhy was accompanied by the inhibition of MAPK/NF-кB pathway. The findings outlined in the current study revealed an alternative mechanism of Rhy in protecting brain tissues against migraine: the agent exerted its effect by suppressing MAPK/NF-кB pathway, which would ameliorate impairments associated with migraine.

Tumor-originated exosomal lncUEGC1 as a circulating biomarker for early-stage gastric cancer.

Conventional tumor markers for non-invasive diagnosis of gastric cancer (GC) exhibit insufficient sensitivity and specificity to facilitate detection of early gastric cancer (EGC). We aimed to identify EGC-specific exosomal lncRNA biomarkers that are highly sensitive and stable for the non-invasive diagnosis of EGC. Hence, in the present study, exosomes from the plasma of five healthy individuals and ten stage I GC patients and from culture media of four human primary stomach epithelial cells and four gastric cancer cells (GCCs) were isolated. Exosomal RNA profiling was performed using RNA sequencing to identify EGC-specific exosomal lncRNAs. A total of 79 and 285 exosomal RNAs were expressed at significantly higher levels in stage I GC patients and GCCs, respectively, than that in normal controls. Through combinational analysis of the RNA sequencing results, we found two EGC-specific exosomal lncRNAs, lncUEGC1 and lncUEGC2, which were further confirmed to be remarkably up-regulated in exosomes derived from EGC patients and GCCs. Furthermore, stability testing demonstrates that almost all the plasma lncUEGC1 was encapsulated within exosomes and thus protected from RNase degradation. The diagnostic accuracy of exosomal lncUEGC1 was evaluated, and lncUEGC1 exhibited AUC values of 0.8760 and 0.8406 in discriminating EGC patients from healthy individuals and those with premalignant chronic atrophic gastritis, respectively, which was higher than the diagnostic accuracy of carcinoembryonic antigen. Consequently, exosomal lncUEGC1 may be promising in the development of highly sensitive, stable, and non-invasive biomarkers for EGC diagnosis.

Aucubin and its hydrolytic derivative attenuate activation of hepatic stellate cells via modulation of TGF-ß stimulation.

Eucommia ulmoides is an important traditional Chinese medicine and has been used as a tonic with a long history. Aucubin is an active component extracted from Eucommia ulmoides, which has liver-protection effects. However the mechanisms are still unclear. To investigate the inhibitory effects and the underlying mechanisms of aucubin on TGF-ß1-induced activation of hepatic stellate cells and ECM deposition, Human hepatic stellate cells (LX-2 cells) were incubated with TGF-ß1 to evaluate the anti-fibrotic effect of aucubin. Western blot was used to investigate the expression of α-SMA, Col I, Col III, MMP-2 and TIMP-1. ROS production was monitored using DCFH-DA probe, and NOX4 expression was detected by Real-time PCR. Results indicated that TGF-ß1 stimulated the activation and ECM deposition of LX-2 cells. Compared with the control group, aucubin and aucubigenin both reduced the protein expression of α-SMA, Col I, Col III and MMP-2 in LX-2 cells. Aucubin and aucubigenin also suppressed the generation of ROS and down-regulated the NOX4 mRNA expression. Taken together, aucubin and aucubigenin both inhibit the activation and ECM deposition of LX-2 cells activated by TGF-ß1. Aucubin and aucubigenin are potential therapeutic candidate drugs for liver fibrosis.

The effect of SLCO1B1 polymorphism on the pharmacokinetics of atorvastatin and 2-hydroxyatorvastatin in healthy Chinese people.

The pharmacokinetics of statins show substantial inter-subject variability. Increasing systemic exposure of statins may lead to adverse drug reactions such as myopathy. The variation in statin pharmacokinetics is partly explained by genetic factors. OATP1B1, coded by SLCO1B1 transports a large number of therapeutic drugs, such as atorvastatin. Here we investigated the effect of SLCO1B1 polymorphism on the pharmacokinetics of atorvastatin and its metabolites. Two pharmacokinetic studies were conducted in Chinese Han volunteers and 132 volunteers were enrolled in our study as 72 in trial 1 and 60 in trial 2. A LC-MS/MS method was developed for the identification and quantification of atorvastatin acid and its metabolites. S LCO1B1 c.521T>C (rs4149056) was identified by the MALDI-TOF MS and Sequenom MassARRAY system. The distribution frequencies of SLCO1B1 c.521T>C were in agreement with Hardy-Weinberg equilibrium both in trial 1 and trial 2. In subjects with 521C allele the mean Cmax, AUC0-24h and AUC0-∞ of atorvastatin acid and 2-hydroxyatorvastatin acid were significantly higher than subjects with 521TT genotype, while the mean CL was lower. In conclusion, our results suggested that SLCO1B1 c.521T>C had an effect on the pharmacokinetics of atorvastatin and 2-hydroxyatorvastatin in Chinese Han population. Subjects with 521C allele have an increased risk of toxic effects caused by atorvastatin.

Lignans from the bark of Eucommia ulmoides inhibited Ang II-stimulated extracellular matrix biosynthesis in mesangial cells.

BACKGROUND: Tree bark of Eucommia ulmoides Oliv., (commonly well-known as "Du-zhong" in China), has been used to treat hypertension, hypercholesterolemia, hyperglycemia, hepatic fibrosis and renal injury. This study aims to investigate the effects of lignans extracted from the bark of Eucommia ulmoides Oliv. on Ang II-induced proliferation and extracellular matrix biosynthesis in rat mesangial cells. METHODS: Rat mesangial cells (RMCs) were cultured in vitro and divided into six groups (control, Ang II, losartan, and low, middle and high concentration lignans groups). RMC proliferation was measured by MTT assay. RT-qPCR and western blotting were used to detect mRNA and protein expression of collagen type I (Col I), collagen type III (Col III), collagen type IV (Col IV), fibronectin and aldose reductase (AR). RESULTS: Cellular proliferation induced by Ang II was significantly suppressed by Eucommia lignans of different concentrations (P = 0.034, P < 0.001, and P < 0.001). Treatment of cells with Ang II increased Col I, Col III, Col IV, and fibronectin mRNA expression, which was observed at the protein level (P < 0.001, P < 0.001, P = 0.004, and P = 0.004, respectively). The increased mRNA expression and protein levels of Col I, Col III, Col IV, and fibronectin were diminished remarkably with by treatment Eucommia lignans, and elevated AR expression stimulated by Ang II was significantly inhibited by Eucommia lignans. CONCLUSIONS: Eucommia lignans (Du-zhong) inhibited Ang II-stimulated extracellular matrix biosynthesis in mesangial cells.