Increased brain uptake of venlafaxine loaded solid lipid nanoparticles by overcoming the efflux function and expression of P-gp

Yan Zhou,Xin’an Wu,Guo-Qiang Zhang,Zhi Rao,Yang Yang,Qian Zhou,Hongyan Qin,Yuhui Wei 대한약학회 2015 Archives of Pharmacal Research Vol.38 No.7

Venlafaxine (VLX) could be pumped out of the brain by P-glycoprotein (P-gp). Moreover, the expression of P-gp distributed in blood–brain barrier could be significantly induced by VLX. Thus, P-gp could be considered as the nature barrier for delivering of VLX to the brain. The aim of this study was to investigate whether the efflux function and increased expression of P-gp could be reversed by utilizing solid lipid nanoparticles (SLN). VLX solid lipid nanoparticles (VLX - SLN) were prepared and evaluated. Pharmacokinetics and brain distribution of VLX in different formulations were conducted after oral or intravenous administration. P-gp efflux function to VLX was evaluated by the brain uptake amount of VLX, while P-gp expression was investigated by Western blotting. Results indicated that the entrapment, mean size and zata potential of VLX - SLN was 74.9 ± 3.0 %, 186.3 ± 69.26 nm and -22.8 ± 7.78 mv, respectively. After vein injection of VLX formulations, the brain uptake amount of VLX from VLX - SLN was significantly higher than that of VLX solution, VLX solution with empty SLN (VLX? empty SLN) and VLX solution with Verapamil (VLX ? Ver), respectively. Furthermore, the protein mass of P-gp in VLX - SLN treated group was the lowest among all the investigated groups. These results indicated that SLN could overcome P-gp and achieve brain target by intravenous administration.

Chlorogenic Acid Decreased Intestinal Permeability and Ameliorated Intestinal Injury in Rats via Amelioration of Mitochondrial Respiratory Chain Dysfunction

Yan Zhou,Zheng Ruan,Lili Zhou,Yuhui Yang,Shumei Mi,Ze-Yuan Deng,Yulong Yin 한국식품과학회 2016 Food Science and Biotechnology Vol.25 No.1

Chlorogenic acid (CGA), an abundant polyphenol compound in plants, exhibits anti-oxidant effects. The protective effect of CGA in the rat intestine with endotoxin infusion was evaluated. CGA administration ameliorated endotoxin-induced intestinal injury, and decreased the ratio of lactulose/ mannitol, the ileum pathological grade, the myeloperoxidase activity in the ileum, and the malondialdehyde content in the ileum and in ileum mitochondria. The small intestine weight, activities of alkaline phosphatase and superoxide dismutase in the ileum, and β-nicotinamide adenine dinucleotide reduce form (NADH) dehydrogenase and succinate dehydrogenase activities in ileum mitochondria were increased. Intestinal permeability was positively correlated with intestinal mitochondrial injury indicated as the level of malondialdehyde in ileum mitochondria, and negatively correlated with NADH dehydrogenase activity. Dietary administration of CGA protected against increased intestinal permeability caused by endotoxin infusion. The protective effect of CGA was probably associated with a decrease in mitochondrial lipid peroxidation levels and an increase in NADH dehydrogenase activity.

Effect of supplying a carbon extracting solution on denitrification in horizontal subsurface flow constructed wetlands

Denghua Yan,Yi Ding,Xinshan Song,Yuhui Wang 한국화학공학회 2013 Korean Journal of Chemical Engineering Vol.30 No.2

Denitrification strongly depends on the availability of carbon source in constructed wetlands (CWs). In this study, several relevant carbon source extracting solutions made from hydrolyzate of selected wetland litters were added to CWs for nitrogen removal enhancement. The feasibility of supplying a carbon extracting solution to improve potential denitrification rate in horizontal subsurface flow constructed wetland was deeply investigated. Combinations of different hydraulic retention time (HRT, especially for 2-day and 4-day) with different influent COD/N ratios were designed to prove the enhancement on denitrification by carbon source supplement. In addition, specific denitrification rate (SDNR) was calculated for the comparison of the nitrogen removal at different COD/N ratios. The sequential operation results on total nitrogen (TN) and nitrate (NO3−-N) removal efficiencies were obtained in CW system with an influent COD/N ratio of 4.0. The accumulation of nitrite (NO2−-N) was found to be closely related to the removal of NO3−-N. Meanwhile, no obvious accumulation of NO2−-N was found when the removal of NO3−-N was relatively high.

Mesenchymal stem cell-derived exosome mir-342-3p inhibits metastasis and chemo-resistance of breast cancer through regulating ID4

Yu Shuyao,Zhou Yuhui,Niu Ligang,Qiao Yan,Yan Yu 한국유전학회 2022 Genes & Genomics Vol.44 No.5

Background: The mesenchymal stem cell-derived exosome (MSCs-exo) carrying microRNAs have been proved to regulate tumor biological activities. Clarifying molecular mechanism and identifying predictive microRNAs will be of great value in anti-tumor therapy improvement. Objective: We aimed to investigate the regulatory role of microRNA-342-3p (miR-342-3p) in MSCs-exo on breast cancer. Methods: Breast cancer tissues and cell lines were used to evaluate miR-342-3p expression in patients with or without lymph node/distal organ metastasis. The impact of MSCs-exo expression on tumor cell chemo-resistance and invasion/migration was measured. Dual-luciferase reporter gene assay was applied to identify binding site. Inhibitor of differentiation 4 (ID4) siRNA and miR-342-3p inhibitor transfection was conducted to further explore the miR-342-3p/ID4 axis on chemo-resistance and metastasis of breast cancer cells. Results: Breast cancer cells revealed significantly lower level of miR-342-3p in patients with metastatic diseases. miR-342-3p suppressed invasive and chemo-resistant behavior of breast cancer tumor cells. Binding site between miR-342-3p and ID4 was proved. ID4 could reverse the influence of miR-342-3p on chemo-resistance. The tumor inhibition effect of IDA siRNA in vivo was also identified. Conclusions: This study demonstrated that miR-342-3p acted as potential tumor suppressor by inhibiting metastasis and chemo-resistance of breast cancer cells through targeting ID4. This study might provide potential therapy targets for the treatment of breast cancer.

Gastroprotective effect of cirsilineol against hydrochloric acid/ethanol-induced gastric ulcer in rats

Guojin Gong,Rigetu Zhao,Yuhui Zhu,Jinfeng Yu,Bin Wei,Yan Xu,Zhaoxun Cui,Guoying Liang 대한생리학회-대한약리학회 2021 The Korean Journal of Physiology & Pharmacology Vol.25 No.5

This study was designed to evaluate the gastroprotective activity of cirsilineol in hydrochloric acid (HCl)/ethanol-induced gastric ulcer model. Cirsilineol was administered at the doses of 20 and 40 mg/kg in HCl/ethanol-induced rats. The gastroprotective ability was verified by determining the ulcer score, total acidity, hemoglobin, inflammatory cytokines, lipid peroxides, and enzymatic antioxidants superoxide dismutase (SOD) and catalase (CAT) in gastric tissue and serum biochemical analysis. The results showed a favorable increase in the hemoglobin level, antioxidant enzymes (SOD and CAT), restored electrochemical balance (carbon dioxide & anion gap) while a noticeable decrease in ulcer index, total acidity, lipid peroxides, inflammatory cytokines (interleukin-1 beta [IL-1β], IL-6, and tumor necrosis factor alpha) in rats treated with the cirsilineol. The serum biochemical analysis on liver markers (alkaline phosphatases, alanine aminotransferase, and aspartate aminotransferase), kidney markers (urea, creatinine, albumin, globulin, total protein), and lipid profile (triglyceride, high-density lipoprotein, total cholesterol) were attenuated by cirsilineol treatment in rats. Histopathology showed enhanced gastric protection and preserved the integrity of gastric mucosa upon cirsilineol administration. These results ultimately suggest that cirsilineol has gastroprotective effects that prevent the development of gastric ulcer.

Substitution of soybean meal with detoxified Jatropha curcas kernel meal: Effects on performance, nutrient utilization, and meat edibility of growing pigs

Li, Yang,Chen, Ling,Zhang, Yuhui,Wu, Jianmei,Lin, Yan,Fang, Zhengfeng,Che, Lianqiang,Xu, Shengyu,Wu, De Asian Australasian Association of Animal Productio 2018 Animal Bioscience Vol.31 No.6

Objective: The study was conducted to investigate the effects of replacing soybean meal (SBM) with different levels of detoxified Jatropha curcas kernel meal (DJM) in growing pig diets on growth performance, nutrients digestibility and meat edibility. Methods: A total of 144 pigs with initial body weight of $20.47{\pm}1.44kg$, were randomly allocated to 6 dietary treatments with 6 replications per treatment and 4 pigs per replication for a period of 79 days. Six diets (DJM0, DJM15, DJM30, DJM45, DJM60, and DJM75) were formulated using DJM to replace 0%, 15%, 30%, 45%, 60%, and 75% of SBM. From d 37 to 42, feces and urine were total collected from six barrows in each treatment. At day 79, thirty-six pigs were slaughtered for sampling. The feed intake and weight gain were recorded, while the intestinal morphology, digestive enzyme activities, nutrient digestibility and the content of residual phorbol esters in muscles were determined. Results: The results showed that increasing the replacement of SBM with DJM decreased the parameters including body weight, average daily gain, average daily feed intake, gain-to-feed ratio, weight and villus heights of duodenum, villus height and villus height/crypt depth of jejunum, digestive enzymes (protease, amylase, lipase, and trypsin) activities, and nutrients digestibility (nitrogen deposition, digestibility of nitrogen, energy digestibility, and total nitrogen utilization) (linear, p<0.05; quadratic, p<0.05) and there was no significant difference among DJM0, DJM15, and DJM30 in all measured indices. The highest diarrhea morbidity was observed in DJM75 (p<0.05). Phorbol esters were not detected in pig muscle tissues. Conclusion: The DJM was a good protein source for pigs, and could be used to replace SBM up to 30% (diet phorbol esters concentration at 5.5 mg/kg) in growing pig diets with no detrimental impacts on growth performance, nutrient utilization, and meat edibility.

Effects of Pluronic F68 and Labrasol on the Intestinal Absorption and Pharmacokinetics of Rifampicin in Rats

Li Ma,Xin'an Wu,Yuhui Wei,Yan Zhou,Xiaohua Ma 대한약학회 2011 Archives of Pharmacal Research Vol.34 No.11

The aim of this study was to investigate the effects of Pluronic F68 and Labrasol on the intestinal absorption and pharmacokinetics of rifampicin. Intestinal permeability of rifampicin with or without excipients was evaluated by an in situ single-pass perfusion method. A highperformance liquid chromatographic method was applied to study the pharmacokinetics of rifampicin with or without excipients. Labrasol or Pluronic F68 (0.1% and 0.05%, v/v), co-perfused with rifampicin (60 μg/mL), significantly increased in situ permeability. Similarly, verapamil (a typical P-gp inhibitor) also increased in situ permeability, but to a lesser extent. In vivo, the oral administration of rifampicin with or without Pluronic F68, Labrasol or verapamil resulted in statistically significant effect on t1/2 (4.83 to 7.75, 6.42 and 7.46 h) and total body clearance (0.46 to 0.26, 0.28, 0.24 L/h/kg). In addition, Pluronic F68, Labrasol and verapamil produced minor changes in AUC_0-t, which improved 1.55-, 1.54-, and 1.73-fold in comparison to control group, respectively. These results showed that Labrasol and Pluronic F68 might inhibit the function of P-gp in the intestine, thereby increasing intestinal absorption and changing the pharmacokinetic parameters of rifampicin. Therefore, excipient selection is an important factor to consider in rational formulation design.

Lactate exacerbates lung damage induced by nanomicroplastic through the gut microbiota–HIF1a/PTBP1 pathway

Xuan Lihui,Xu Zheng,Luo Jinhua,Yin Wang,Yan Yuhui,Qu Can,Xie Zuozhong,Skonieczna Magdalena,Zhou Ping-Kun,Huang Ruixue 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-

Exposure to nanomicroplastics (nano-MPs) can induce lung damage. The gut microbiota is a critical modulator of the gut–lung axis. However, the mechanisms underlying these interactions have not been elucidated. This study explored the role of lactate, a key metabolite of the microbiota, in the development of lung damage induced by nano-MPs (LDMP). After 28 days of exposure to nano-MPs (50–100 nm), mice mainly exhibited damage to the lungs and intestinal mucosa and dysbiosis of the gut microbiota. Lactate accumulation was observed in the lungs, intestines and serum and was strongly associated with the imbalance in lactic acid bacteria in the gut. Furthermore, no lactate accumulation was observed in germ-free mice, while the depletion of the gut microbiota using a cocktail of antibiotics produced similar results, suggesting that lactate accumulation in the lungs may have been due to changes in the gut microbiota components. Mechanistically, elevated lactate triggers activation of the HIF1a/PTBP1 pathway, exacerbating nano-MP-induced lung damage through modulation of the epithelial–mesenchymal transition (EMT). Conversely, mice with conditional knockout of Ptbp1 in the lungs (Ptbp1flfl) and PTBP1-knockout (PTBP1-KO) human bronchial epithelial (HBE) cells showed reversal of the effects of lactate through modulation of the HIF1a/PTBP1 signaling pathway. These findings indicate that lactate is a potential target for preventing and treating LDMP.

Nematicidal activity against Aphelenchoides besseyi and Ditylenchus destructor of three biflavonoids, isolated from roots of Stellera chamaejasme

Hui Jin,Haiyan Cui,Xiaoyan Yang,Lihong Xu,Xudong Li,Rentao Liu,Zhiqiang Yan,Xiuzhuang Li,Weili Zheng,Yuhui Zhao,Xiaoxia Song,Lihua Zhong,Anxiang Su,Bo Qin 한국응용곤충학회 2018 Journal of Asia-Pacific Entomology Vol.21 No.4

Aphelenchoides besseyi and Ditylenchus destructor can cause serious problems for a number of important agricultural crops and vegetables. In this study, the ethanol extract of Stellera chamaejasme L. roots showed strong nematicidal activity against Aphelenchoides besseyi and Ditylenchus destructor. By using a bioactivity-driven fractionation, three biflavonoids were isolated from the extract and their structures were identified by mass and nuclear magnetic resonance spectral data. Nematicidal activity bioassays revealed that isoneochamaejasmin A had the strongest nematicidal activity against A. besseyi and D. destructor with LC 50 values of 2.32 and 0.18 mM at 72 h, respectively. Chamaejasmenin B displayed weaker nematicidal activity against A. besseyi with an LC 50 value of 3.94 mM at 72 h. Neochamaejasmin B induced the lowest mortality against D. destructor with an LC 50 values of 15.6 mM at 72 h. These results suggested that the kind and position of substitutions and the relative configuration of 2-H/3-H and 2”-H/3”-H could be considered as important factors responsible for the nematicidal activity of these purified C-3/C-3″ biflavonoids.