Effect of ezetimibe-statin combination therapy vs. statin monotherapy on coronary atheroma phenotype and lumen stenosis in patients with coronary artery disease: a meta-analysis and trial sequential analysis.

Background: Evidence indicates that the addition of ezetimibe to statin therapy reduces cardiovascular events. However, the impact of ezetimibe-statin combination therapy on coronary plaque regression, plaque stabilization, and diameter stenosis remains a matter of controversy. Methods: We performed electronic searches in PubMed, Web of Knowledge, and the Cochrane Central Register of Controlled Trials to identify eligible trials assessing the effects of ezetimibe-statin combination therapy versus statin monotherapy reporting at least one outcome among total atheroma volume (TAV), minimum fibrous cap thickness (FCT), lumen volume (LV), and lumen area (LA) derived from intravascular imaging modalities of intravascular ultrasound (IVUS) and optical coherence tomography (OCT). We used the random-effects model and performed trial sequential analysis (TSA) during this meta-analysis. Results: Eleven articles with a total of 926 individuals (460 in the dual-lipid-lowering therapy group and 466 in the statin monotherapy group) were included in the final meta-analysis. Compared to statin monotherapy, ezetimibe-statin combination therapy was associated with significantly decreased TAV [WMD = -3.17, 95% CI (-5.42 to -0.92), and p = 0.006], with no effect on the LV of the coronary artery [WMD = -0.52, 95% CI (-2.24 to 1.21), and p = 0.56], the LA of the coronary artery [WMD = 0.16, 95% CI (-0.10-0.42), and p = 0.22], or minimum FCT thickness [WMD = 19.11, 95%CI (-12.76-50.97)]. Conclusion: In patients with coronary artery disease, ezetimibe-statin combination therapy resulted in a significant regression in TAV compared to statin monotherapy, whereas no overall improvements of minimum FCT or lumenal stenosis were observed.

α-HBDH is a superior to LDH in predicting major adverse cardiovascular events in patients with acute aortic dissection.

Objective: Acute aortic dissection (AAD) with a high mortality and postoperative complications remains presently no effective indicators to conjunctly predict the short-term mortality and the prognosis. This study aimed to investigate the predictive role of α-HBDH on in-hospital mortality and postoperative Major adverse cardiovascular events (MACE) in patients with AAD. Methods: In this retrospective study, a total of 369 enrolled patients from 2015 to 2021 were divided into three groups (T1: low, T2: medium and T3: high) based on the tertiles of α-HBDH levels on admission. In terms of the preoperative, intraoperative and postoperative indicators among 3 groups, the relationship between α-HBDH and studying endpoints was determined by logistic regression models, along with the consolidation using Kaplan-Meier and restricted cubic spline (RCS) analysis for predicting the in-hospital death and MACE complications. Last, subgroup analysis further verified the predictive value of α-HBDH. Results: Logistic regression analysis showed that α-HBDH was independently associated with in-hospital mortality of patients with AAD [OR(95CI): 4.771(1.043-21.832), P = 0.044] and MACE [OR(95CI): 9.869(2.148-45.349), P = 0.003]. Moreover, Kaplan-Meier analysis also showed an increased α-HBDH levels associated with poor survival within 30 days (log rank test, P < 0.01), especially in acute Stanford A dissection. RCS presented that 204 U/L was the optimal cut-off value of α-HBDH for in-hospital mortality and postoperative MACE, which facilitated clinical stratification of patients with AAD. Subgroup analysis confirmed a stable correlation between α-HBDH level and hospital mortality and MACE (P > 0.05). Conclusions: α-HBDH is a predictor of the in-hospital mortality and postoperative MACE, guiding admission stratification of patients with AAD.

The residues and health risk assessment of polychlorinated biphenyls (PCBs) in Pheretima (an earthworm-derived traditional medicine) from southeastern China.

Minimal research exists on polychlorinated biphenyl (PCB) exposure from traditional Chinese medicines (TCMs), despite their significant contributions to domestic and international health protection. This study is the first to investigate the levels, profiles, and health risks of PCB residue in Pheretima, a typical TCM produced from earthworm. Seventy-seven Pheretima samples from different regions of China were analyzed for 45 PCB congeners. PCBs were found in all samples exhibiting species-dependent discrepancies. ∑45PCBs was ranging from 0.532 to 25.2 µg/kg (mean 4.46 µg/kg), with CB-11 being the most abundant congener contributing 71.8% ± 10.8% to ∑45PCBs, followed by CB-47, which were all non-Aroclor congeners called unintentionally produced PCBs (UP-PCBs). The average estimated daily intake of ∑45PCBs, ∑7ID-PCBs (indicative polychlorinated biphenyls), and CB-11 were 0.71, 0.04, and 0.51 ng/kg bw/d, respectively. The ∑HQ of PCBs in Pheretima samples was 2.97 × 10-4-2.46 × 10-2 (mean 2.77 × 10-3, 95th 4.21 × 10-3), while the ∑RQ ranged from 1.19 × 10-8 to 2.88 × 10-6 (mean 4.87 × 10-7, 95th 2.31 × 10-6). These findings indicate that Pheretima ingestion does not pose significant non-carcinogenic risks. However, certain individual samples exhibit an acceptable level of potential risks, particularly when considering that PCBs are recognized as endocrine disruptors and classified as probable carcinogens. These results contribute to the safety evaluation of traditional medicines and suggest the potential use of Pheretima as a bioindicator for PCB pollution. It is advisable to monitor UP-PCBs as indicator congeners and gather additional toxicological data.

Predictive value of admission CO2 combining power combined with serum sodium for the prognosis in acute Stanford type A aortic dissection patients.

Acute Stanford type A aortic dissection (ATAAD) with sudden onset and high mortality requiries a standard Bentall operation and a accurate prognosis in common, together with alteration of CO2 combining power (CO2CP) and serum sodium rase concern, hence, we evaluated the prognostic value of CO2CP combined with serum sodium in ATAAD patients. This retrospective study included 183 patients who underwent Bentall operation for ATAAD from 2015 to 2021 in the Fourth Hospital of Hebei Medical University, subsequently followed grouping by the levels of CO2CP and serum sodium. The study endpoint was 30-day all-cause mortality, and the prognostic value of CO2CP combined with serum sodium levels in ATAAD patients were evaluated with multivariate logistic regression method. The postoperative incidence of in-hospital death and adverse events in patients with ATAAD were 18% and 25.7%, respectively. Combination of CO2CP and serum sodium for predicting ATAAD death and adverse events presented a higher predictive value than each single indicator with ROC curve analysis (the AUC of CO2CP combined with serum sodium was 0.786, 95% CI 0.706-0.869, P < 0.001), along with CO2CP < 22.5 mmol/L + serum sodium > 138.5 mmol/L group had the worst prognostic. Multivariate regression analyse showed that CO2CP < 22.5 mmol/L combined with serum sodium > 138.5 mmol/L preferably predicted the prognosis of ATAAD (OR =6.073, 95% CI 2.557-14.425, P < 0.001). Consistently, the cumulative 30-day survival after surgery in ATAAD patients with the low CO2CP and high serum sodium simultaneously was the worst (log-rank P < 0.05). The combination of CO2CP and serum sodium increases the predictive value of prognosis, which is conducive to risk stratification of patients with ATAAD.

Bifunctional Separator with Ultra-Lightweight MnO2 Coating for Highly Stable Lithium-Sulfur Batteries.

The severe shuttling behavior in the discharging-charging process largely hampers the commercialization of lithium-sulfur (Li-S) batteries. Herein, we design a bifunctional separator with an ultra-lightweight MnO2 coating to establish strong chemical adsorption barriers for shuttling effect alleviation. The double-sided polar MnO2 layers not only trap the lithium polysulfides through extraordinary chemical bonding but also ensure the uniform Li+ flux on the lithium anode and inhibit the side reaction, resulting in homogeneous plating and stripping to avoid corrosion of the Li anode. Consequently, the assembled Li-S battery with the MnO2-modified separator retains a capacity of 665 mA h g-1 at 1 C after 1000 cycles at the areal sulfur loading of 2.5 mg cm-2, corresponding to only 0.028% capacity decay per cycle. Notably, the areal loading of ultra-lightweight MnO2 coating is as low as 0.007 mg cm-2, facilitating the achievement of a high energy density of Li-S batteries. This work reveals that the polar metal oxide-modified separator can effectively inhibit the shuttle effect and protect the Li anode for high-performance Li-S batteries.

Association of Ethnicity, Sex, and Age With Cancer Diagnoses and Health Care Utilization Among Children in Inner Mongolia, China.

Importance: China is experiencing a sustained increase in childhood cancer. However, whether differences exist in disease burden by ethnicity remains unclear. Objective: To compare differences in cancer diagnoses and health care utilization in Inner Mongolia among children subgrouped by ethnicity (Han vs Mongolian), sex, and age. Design, Setting, and Participants: This retrospective cohort study in Inner Mongolia, China, used data on children aged 0 to 14 years with cancer from the Inner Mongolia Regional Health Information Platform, which comprises the National Basic Medical Insurance database and the Inner Mongolia cause-of-death reporting system, from January 1, 2013, to December 31, 2019. Ethnicities analyzed included Han and Mongolian; patients of other ethnicities were not included in the analysis because of the small sample size. Cancer was broadly defined as a primary malignant tumor or hematologic cancer; benign central nervous system tumors were also included. A 2-year washout period was used to exclude prevalent cases. After diagnosis, the patients were followed up until the date of death or the end of the insured status, whichever came first. Exposures: Ethnicity (Han vs Mongolian), sex (male vs female), and age (0-4, 5-9, and 10-14 years). Main Outcomes and Measures: Crude incidence, 5-year prevalence, and survival rates at 1 year and 3 years after diagnosis; health care utilization, represented by medical costs during the first year and first 3 years after diagnosis; and hospital attendance with level (tertiary vs secondary and lower-level hospitals) and location of each unique visit. Results: From 2013 to 2019, 1 106 684 (2013), 1 330 242 (2014), 1 763 746 (2015), 2 400 343 (2016), 2 245 963 (2017), 2 901 088 (2018), and 2 996 580 (2019) children aged 0 to 14 years were registered in the NBMI database. Among the 2 996 580 children enrolled in 2019, the mean (SD) age was 6.8 (4.3) years, of whom 1 572 096 (52.5%) were male, 2 572 091 (85.8%) were Han, and 369 400 (12.3%) were Mongolian. A total of 1910 patients with cancer were identified (1048 were male [54.9%]; 1559 were Han [81.6%], and 300 were Mongolian [15.7%]). There were 764 hematologic cancers (40.0%) and 1146 solid tumors (60.0%). The overall crude incidence of cancer from 2015 to 2019 was 129.85 per million children (95% CI, 123.63-136.06), with a higher incidence among Mongolian than among Han children (155.12 [95% CI, 136.81-173.43] vs 134.39 [95% CI, 127.46-141.32]). The 5-year prevalence was 428.97 per million (95% CI, 405.52-452.42) in 2020, with a higher prevalence among Mongolian than among Han children (568.49 [95% CI, 91.62-645.36] vs 404.34 [95% CI, 379.77-428.91]). The combined 1-year (2015-2019) and 3-year (2015-2017) survival rates were 72.5% (95% CI, 67.5%-77.5%) and 66.8% (95% CI, 61.6%-71.9%), respectively. The 1-year (median [IQR], $1991 [$912-$10 181] vs $3991 [$1171-$15 425]) and 3-year (median [IQR], $2704 [$954-$13 909] vs $5375 [$1283-$22 466]) postdiagnosis costs were lower among Mongolian than among Han children. A higher proportion of Mongolian patients attended low-level hospitals (45.9% vs 17.4%). Conclusions and Relevance: In this cohort study, Mongolian children had a higher incidence and prevalence of cancer but a lower demand for medical care, suggesting that further investigations are needed to identify mechanisms underlying ethnic disparities and ensure that care is equitable.

Exploration of severe Covid-19 associated risk factor in China: Meta-analysis of current evidence.

AIM: This meta-analysis aimed to explore potential risk factors for severe Covid-19. METHODS: We systemically and comprehensively retrieved the eligible study evaluating clinical differences between severe vs non-severe Covid-19. Main effect sizes were demographic characteristics, comorbidities, signs and symptoms, laboratory findings as well as radiological features of chest CT. RESULTS: A total of 2566 Covid-19 people (771 in the severe group and 1795 in the non-severe group) from 14 studies were eligible for this meta-analysis. It was demonstrated that older age and males were more likely to have severe Covid-19. Patients with underlying comorbidities, such as hypertension, diabetes, heart disease and COPD were significantly more susceptible to severe Covid-19. Patients with dyspnoea were more likely to be severely ill. Depressed total lymphocytes were observed in this article. Meanwhile, although reticulation (30.8%), intrathoracic lymph node enlargement (20.5%) and pleural effusions (30.8%) were relatively infrequent, meta-analysis revealed that patients with these presentations in chest CT were associated with increased risk of severe Covid-19. CONCLUSIONS: There are significant differences in clinical characteristics between the severe and non-severe Covid-19 patients. Many factors are related to the severity of the disease, which can help clinicians to differentiate severe patients from non-severe patients.

Evaluation of the effect of Bovis Calculus Artifactus on eight rat liver cytochrome P450 isozymes using LC-MS/MS and cocktail approach.

Bovis Calculus Artifactus (BCA) is the main substitute for natural Calculus bovis, a traditional drug in China used to treat high fever, convulsion, and sore throat. The effect of BCA on cytochrome P450 (CYP) activities is unknown. This study was to investigate the effect of BCA on eight rat hepatic microsomal CYPisozymes to evaluate the potential drug interactions using the cocktail approach.Metabolites of the eight isoform probe substrates of CYP isozymes were quantified by LC-MS/MS. The method was validated by incubating known CYP inhibitors α-naphthoflavone (CYP1A2), thiotepa (CYP2B1), quercetin (CYP2C7), sulfaphenazole (CYP2C6), ticlopidine (CYP2C11), quinidine (CYP2D1), ketoconazole (CYP3A1),4-methylpyrazole (CYP2E1) with individual probe substrate and rat liver microsomes. The formation rates of the corresponding metabolites of the eight probe substrates were determined to evaluate the activity of each isozyme.The results showed that BCA has different degrees of inhibitory effect on four CYP450 isoforms (CYP2C6, CYP2C11, CYP2D1, CYP3A1) (p < 0.05), but no significant influence on CYP1A2, 2B1, 2C7 or 2E1 (p > 0.05). Attention should be paid to the BCA-drug interactions by careful monitoring and appropriate dosage adjustments in the concurrent use of the drugs which are metabolized by CYP1A2, CYP2C19, and CYP3A4. Abbreviations: BCA, bovis calculus artifactus; CYP, cytochrome P450; DDIs, drug-drug interactions; ESI, electrospray ionization; MRM, multiple reaction monitoring; NBC, Natural Bovis Calculus; QC, quality control; T CM, traditional Chinese medicine.

Losartan Protects Podocytes against High Glucose-induced Injury by Inhibiting B7-1 Expression.

The role of B7-1 in podocyte injury has received increasing attention. The aim of this study was to investigate whether losartan protects podocytes of patients with diabetic kidney disease (DKD) by regulating B7-1 and the underlying mechanisms. Rats with streptozotocin-induced DKD were treated with losartan for 8 weeks. Biochemical changes in blood and urine were analyzed. Kidneys were isolated for electron microscopy, immunofluorescence, real-time quantitative PCR (RT-PCR), and Western blot analysis. Immortalized mouse podocyte cells were cultured in normal or high glucose medium in the presence or absence of losartan for 48 h, and then the cells were collected for immunofluorescence, PCR, Western blotting and monolayer permeability detection. The phosphatidylinositol 3-kinase (PI3K) 110α subunit and angiotensin II type 1 receptor (AT1R) plasmids were transfected into podocytes, respectively, and then Western blotting was performed to assess the expression of B7-1 protein. The results showed that losartan ameliorated podocyte structure and function in the rat model of DKD, and reduced the expression of B7-1 protein. Overexpression of PI3K 110α subunit in podocytes attenuated the inhibitory effect of losartan on B7-1 expression in high glucose-stimulated podocytes. The expression of B7-1 was significantly increased by overexpression of AT1R and significantly reduced by blocking PI3K 110α subunit. We conclude that losartan protects podocytes against high glucose-induced injury by inhibiting AT1R-mediated B7-1 expression. This effect is dependent on the AT1R-PI3K 110α subunit pathway.

Melamine-based polymer networks enabled N, O, S Co-doped defect-rich hierarchically porous carbon nanobelts for stable and long-cycle Li-ion and Li-Se batteries.

Li-Se battery is a promising energy storage candidate owing to its high theoretical volumetric capacity and safe operating condition. In this work, for the first time, we report using the whole organic Melamine-based porous polymer networks (MPNs) as a precursor to synthesize a N, O, S co-doped hierarchically porous carbon nanobelts (HPCNBs) for both Li-ion and Li-Se battery. The N, O, S co-doping resulting in the defect-rich HPCNBs provides fast transport channels for electrolyte, electrons and ions, but also effectively relieve volume change. When used for Li-ion battery, it exhibits an advanced lithium storage performance with a capacity of 345 mAh g-1 at 500 mA g-1 after 150 cycles and a superior rate capacity of 281 mAh g-1 even at 2000 mA g-1. Further density function theory calculations reveal that the carbon atoms adjacent to the doping sites are electron-rich and more effective to anchor active species in Li-Se battery. With the hierarchically porous channels and the strong dual physical-chemical confinement for Li2Se, the Se@ HPCNBs composite delivers an ultra-stable cycle performance even at 2 C after 1000 cycles. Our work here suggests that introduce of heteroatoms and defects in graphite-like anodes is an effective way to improve the electrochemical performance.

Manipulating the scattering pattern with non-Hermitian particle arrays.

We show that an array of non-Hermitian particles can enable advanced manipulations of the scattering pattern, beyond what is possible with passive structures. Active linear elements are shown to provide zero forward scattering without sacrificing the total scattered power, and by adding more particles, it is possible to control the zero-scattering direction at will. We apply our theory to realistic implementations of scatterer arrays, using loaded dipole antennas in which we tune the load impedance and investigate the stability of these arrays based on a realistic dispersion model for the gain elements. Finally, we discuss the possibility of controlling multiple frequencies to enable broadband control of the scattering pattern.

Association of PAR-2 Gene Polymorphisms with the Inflammatory Response and Susceptibility to Knee Osteoarthritis in the Chinese Han Population.

OBJECTIVE: To investigate the relationship between single nucleotide polymorphisms (SNPs) of protease-activated receptor 2 (PAR-2) and the susceptibility to knee osteoarthritis (KOA) and synovial expression of inflammatory factors in the Chinese Han population. METHODS: Three hundred fifty KOA patients (KOA group) and 345 healthy volunteers (control group) were recruited for the study. Five milliliters of venous blood was taken from each subject to detect the PAR-2 rs1529505, rs631465, and rs2242991 locus genotypes. The expression of PAR-2 mRNA in the synovial tissue and the levels of matrix metalloproteinase (MMP-1), MMP-9, interleukin (IL)-6, and IL-1ß in the joint effusion were detected in 205 KOA patients who had undergone joint replacement surgery. RESULTS: The PAR-2 rs1529505 T allele and the rs2242991 G allele carriers had a higher risk of KOA (p < 0.001). The severity of KOA in patients with the PAR-2 rs1529505 and rs2242991 mutations were higher than in the wild-type controls (p < 0.05). The expression levels of the PAR-2 mRNA in wild types, heterozygotes, and homozygotes of the rs1529505 and rs2242991 loci increased in turn (p < 0.001). The levels of MMP-1, MMP-9, IL-6, and IL-1ß in the synovial fluid of the PAR-2 rs1529505 and rs2242991 locus mutants were distinctly higher than those with the wild-type alleles (p < 0.01). There was no correlation between the rs631465 SNP and susceptibility to KOA, severity of KOA, nor levels of PAR-2 mRNA, MMP-1, MMP-9, IL-6, and IL-1ß. CONCLUSIONS: The PAR-2 SNPs rs1529505 and rs2242991 are associated with the susceptibility to KOA. KOA is more severe in patients harboring the T and G alleles of these two SNPs, respectively. The levels of inflammatory factors in synovial tissue and blood are higher than those in wild-type patients.

Efficacy and safety of empagliflozin for type 2 diabetes mellitus: Meta-analysis of randomized controlled trials.

BACKGROUND: This study was designed to evaluate the efficiency and tolerability of empagliflozin (EMPA) as monotherapy or add-on to existing therapy in patients with type 2 diabetes mellitus (T2DM). METHODS: Randomized controlled trials (RCTs) comparing efficacy and safety of EMPA vs placebo or EMPA plus other antidiabetes drugs vs placebo plus other oral antidiabetes drugs (OADs) in T2DM were recruited from electronic database Pubmed, Web of Knowledge, and Cochrane Central Register of Controlled Trials (CENTRAL), supplemented by a hand search of the reference lists of selected articles. Main effect sizes were change from baseline on glycemia control, body weight, blood pressure, and complications (i.e., incidence of urinary and genital tract infections, and morbidity of hypoglycemia and hyperglycemia). Random-effects model was used to account for clinical or methodologic heterogeneity across studies. RESULTS: Fifteen RCTs with a total number of 7891 individuals (5374 in EMPA group and 2517 in control group) were suitable for this meta-analysis. The results demonstrated that significant improvements in glycemia control, body weight, and blood pressure were associated with EMPA application (i.e., monotherapy and add-on therapy) in patient with T2DM when compared with placebo. Meanwhile, EMPA 10 and 20 mg improved glycemia, body weight, and blood pressure control for patients with T2DM. There was no significant difference in incidence of hypoglycemia and urinary tract infections across EMPA and placebo group. Significant reduced risk of hyperglycemia was revealed in EMPA group vs placebo (risk ratio: 0.34, 95%confidence interval: 0.23-0.49, P < .00001), except in patients on background insulin therapy. However, increased risk of genital infection was noted across EMPA vs placebo (risk ratio: 2.59, 95% confidence interval: 1.80-3.71, P < .00001). CONCLUSION: Our evidence supports the application of EMPA in treatment of patients with T2DM who are obesity or at risk of weight gain.

[Bushen Jiedu Recipe Protected Radiation Induced Hematopoietic Injury].

Objective To observe the protective effects of Bushen Jiedu Recipe (BJR) on radia- tion induced hematopoietic injury. Methods C57BL/10J mice TLR4 gene (TLR4 +/+) and knockout mice (TLR4 -/-) were randomly divided into 3 groups, the blank control group, the radiation model group, the BJR group. Sampling was respectively performed at day 1 , 14, and 30 after radiation. The general condi- tion of mice was observed. White blood cell (WBC) , red blood cell ( RBC) , and platelet ( PLT) were counted in each group. Thigh bone of mice was collected for bone marrow specimen. Bone marrow slice was prepared. Pathomorphological changes were observed under electron microscope. Results Com- pared with the blank control group, WBC, RBC, and PLT all decreased or showed a decreasing tendency after one day radiation. RBC and PLT significantly decreased after 14 days of radiation (P <0. 01 , P < 0. 05). Counts of WBC and RBC were higher in the TLR4 +/+ BJR group than in the rest 2 groups (P < 0. 01 , P <0. 05). No statistical difference in RBC or PLT between mice after 30 days of radiation and mice in the blank control group (P >0. 05). PLT count in the TLR4 +/+ BJR group was most approximate to the normal value. WBC count obviously increased, but still with statistical difference as compared with the blank control group (P <0.01). WBC count recovered most rapidly in the TLR4 +/+ BJR group. Results under light microscope showed the structure of bone marrow was injured to different degrees in all mice except those in the TLR4 +/+ BJR group. Conclusion BJR could attenuate radiation induced hematopoi- etic injury possibly through TLR4 signal pathway, thus playing significant radioprotective roles.

[Arsenic speciation in rat plasma after oral administration of realgar and Niu Huang Jie Du Pian].

The arsenic species in rat plasma were studied after oral administration of realgar and Niu Huang Jie Du Pian (NHJDP) and the possible compatible effects of realgar was evaluated by comparing the pharmacokinetics of arsenic species after administration of realgar and NHJDP. The separation of the arsenicals was performed by a high performance liquid chromatography-hydride generation-atomic fluorescence spectrometry (HPLC-HG-AFS) technique. Dimethylarsinic acid (DMA) was found to be the main species in rats' plasma after dosing. No traces of arsenite [As(Ⅲ)], monomethylarsonic acid (MMA) or arsenate [As(Ⅴ)] were detected at any sampling time points. Compared with realgar administration alone, dose-normalized peak concentration(C(max)) and AUC(0-t) of DMA were significantly decreased by NHJDP administration, while the t(max) was significantly delayed with the clearance and apparent volume of distribution significantly increased, indicating that the pharmacokinetics of As from realgar was affected by other ingredients in the compound prescription of NHJDP.

Pharmacokinetics of phenolic compounds of Danshen extract in rat blood and brain by microdialysis sampling.

AIM OF THE STUDY: To evaluate the pharmacokinetics of phenolic compounds after oral administration of Danshen extract in rat brain. MATERIALS AND METHODS: Blood and brain microdialysis probes were inserted into jugular vein and cerebral cortex of rat under anesthesia and perfused with ringer's solution at the rate of 2.0 and 0.8 µL/min, respectively. Blank microdialysates were collected after 2h post-implantation equilibrium time. Danshen extract (danshensu 40 mg/kg BW, protocatechuic aldehyde 149 mg/kg BW, and salvianolic acid B 50mg/kg BW) was administrated intragastrically, and then blood and brain microdialysates were collected at 15 and 30 min time intervals for 4h, respectively. The concentrations of phenolic compounds were determined by high-performance liquid chromatography coupled with chemiluminescence detection. Pharmacokinetic parameters were estimated using non-compartmental methods. RESULTS: Danshensu and protocatechuic acid could be detected in both blood and brain microdialysates, while protocatechuic aldehyde and salvianolic acid B were not detected. Brain-to-blood (AUC(brain)/AUC(blood)) distribution ratio were 0.25±0.04 and 0.09±0.02 for danshensu and protocatechuic acid, respectively. CONCLUSIONS: Danshensu can readily permeate the blood brain barrier after oral administration of Danshen extract, and protocatechuic acid is a potential oxidative metabolite of protocatechuic aldehyde.