Publications by authors named "Yi-Sheng He"

13 Publications

  • Page 1 of 1

Circadian clock genes as promising therapeutic targets for autoimmune diseases.

Autoimmun Rev 2021 Aug 10;20(8):102866. Epub 2021 Jun 10.

Department of Nephrology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China. Electronic address:

Circadian rhythm is a natural, endogenous process whose physiological functions are controlled by a set of clock genes. Disturbance of the clock genes have detrimental effects on both innate and adaptive immunity, which significantly enhance pro-inflammatory responses and susceptibility to autoimmune diseases via strictly controlling the individual cellular components of the immune system that initiate and perpetuate the inflammation pathways. Autoimmune diseases, especially rheumatoid arthritis (RA), often exhibit substantial circadian oscillations, and circadian rhythm is involved in the onset and progression of autoimmune diseases. Mounting evidence indicate that the synthetic ligands of circadian clock genes have the property of reducing the susceptibility and clinical severity of subjects. This review supplies an overview of the roles of circadian clock genes in the pathology of autoimmune diseases, including BMAL1, CLOCK, PER, CRY, REV-ERBα, and ROR. Furthermore, summarized some circadian clock genes as candidate genes for autoimmune diseases and current advancement on therapy of autoimmune diseases with synthetic ligands of circadian clock genes. The existing body of knowledge demonstrates that circadian clock genes are inextricably linked to autoimmune diseases. Future research should pay attention to improve the quality of life of patients with autoimmune diseases and reduce the effects of drug preparation on the normal circadian rhythms.
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http://dx.doi.org/10.1016/j.autrev.2021.102866DOI Listing
August 2021

Association between ambient air pollution and tuberculosis risk: A systematic review and meta-analysis.

Chemosphere 2021 Aug 23;277:130342. Epub 2021 Mar 23.

Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, China; Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, 81 Meishan Road, Hefei, Anhui, China. Electronic address:

There is a growing body of evidence suggesting an association between air pollution exposure and tuberculosis (TB) incidence, but no meta-analysis has assembled all evidence so far. This review and meta-analysis aimed to derive a more reliable estimation on the association between air pollution and TB incidence. PubMed, Embase and Web of Science electronic databases were systemically searched for eligible literature. The PECO framework was used to form the eligibility criteria. Effect estimates and 95% confidence intervals (CIs) published in the included studies were pooled quantitatively. Seventeen articles met the inclusion criteria. The pooled estimates showed that long-term exposure to particulate matter with an aerodynamic diameter ≤10 μm (PM) was associated with increased incidence of TB (per 10 μg/m increase in concentrations of PM: risk ratios (RR) = 1.058, 95% CI: 1.021-1.095). Besides, long-term exposure to sulfur dioxide (SO) and nitrogen dioxide (NO) were significantly associated with TB incidence (per 1 ppb increase, SO: RR = 1.016, 95% CI: 1.001-1.031; NO: 1.010, 95% CI: 1.002-1.017). We did not find a significant association of PM, ozone (O) or carbon monoxide (CO) with TB risk, regardless of long-term or short-term exposure. However, in view of the 2016 ASA Statement and the biological plausibility of PM damaging host immunity, the association between PM and TB risk remains to be further established. This meta-analysis shows that long-term exposure to PM, SO or NO is associated with increased odds of TB, and the specific biological mechanisms warrant further research.
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http://dx.doi.org/10.1016/j.chemosphere.2021.130342DOI Listing
August 2021

Association of PER2 gene single nucleotide polymorphisms with genetic susceptibility to systemic lupus erythematosus.

Lupus 2021 Apr 26;30(5):734-740. Epub 2021 Jan 26.

Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Anhui, China.

The circadian clock plays a crucial role in the progress of systemic lupus erythematosus (SLE). In this study, we performed a case-control study to explore the association between 2 (PER2) gene single nucleotide polymorphisms (SNPs) and the susceptibility of systemic lupus erythematosus (SLE). A total of 492 SLE patients and 493 healthy controls were included. The improved multiple ligase detection reaction (iMLDR) was used for genotyping. The correlations between four SNPs of PER2 (rs10929273, rs11894491, rs36124720, rs934945) and the genetic susceptibility and clinical manifestations of SLE were analyzed. Significant differences were observed in the distributions of allele frequencies and genotype under dominant model in rs11894491 between SLE patients and controls ( = 0.030,  = 022, respectively). We hypothesized that PER2 gene SNPs was related to the genetic susceptibility and clinical manifestations, implying the potential role of PER2 in the pathogenesis of SLE.
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http://dx.doi.org/10.1177/0961203321989794DOI Listing
April 2021

Emerging role of Fli1 in autoimmune diseases.

Int Immunopharmacol 2021 Jan 21;90:107127. Epub 2020 Nov 21.

Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, China; Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, 81 Meishan Road, Hefei, Anhui, China. Electronic address:

The Ets transcription factor family exerts crucial role in cell proliferation, apoptosis, differentiation and migration. Friend leukemia integration 1 (Fli1), a member of the Ets family, is expressed in fibroblasts, endothelial cells and immune cells. Fli1 gene is participated in the development, proliferation, activation, migration and other processes of immune cells. Fli1 can also affect the function of immune cells by regulating cytokines and chemokines. Emerging evidence has shown that Fli1 is implicated in the etiology of several autoimmune diseases, including systemic sclerosis (SSc) and systemic lupus erythematosus (SLE). In this review, we mainly discuss the current evidence for the role of Fli1 in these diseases.
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http://dx.doi.org/10.1016/j.intimp.2020.107127DOI Listing
January 2021

Association between traffic-related air pollution and hospital readmissions for rheumatoid arthritis in Hefei, China: A time-series study.

Environ Pollut 2021 Jan 1;268(Pt A):115628. Epub 2020 Oct 1.

Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, China; Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, 81 Meishan Road, Hefei, Anhui, China. Electronic address:

Air pollution is an important risk factor for autoimmune diseases, but its association with the recurrence of rheumatoid arthritis (RA) remains unclear so far. This study aimed to investigate the short-term association between traffic-related air pollutants and hospital readmissions for RA in Hefei, China. Data on daily hospital readmissions for RA and traffic-related air pollutants, including particulate matter (PM and PM), nitrogen dioxide (NO), and carbon monoxide (CO), from 2014 to 2018 were retrieved. A time-series approach using generalized linear regression model was employed. The analysis was further stratified by sex, age and season. A total of 1153 readmissions for RA were reported during the study period. A significant association between high-concentration PM (90th percentile) and RA readmissions was observed on lag1 (relative risk (RR) = 1.09, 95% confidence interval (CI): 1.01-1.19) and lasted until lag3 (RR = 1.06, 95%CI: 1.01-1.12). From lag2 to lag5, high-concentration NO (90th percentile) was associated with increased risk of RA readmissions, with the highest RR observed at lag 4 (1.11, 95%CI: 1.05-1.17). Stratified analyses indicated that females and the elderly appeared to be more vulnerable to high-concentration PM and NO exposure. High-concentration PM and NO in cold seasons were consistently significantly associated with increased risk of RA readmissions. Exposure to high-concentration PM and NO was associated with increased risk of RA readmissions. Protective measures against the exposure to high-concentration PM and NO should be taken to reduce the recurrence risk in RA patients, especially in females, the elderly and during cold seasons.
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http://dx.doi.org/10.1016/j.envpol.2020.115628DOI Listing
January 2021

Circulating Meteorin-like Levels in Patients with Type 2 Diabetes Mellitus: A Meta-Analysis.

Curr Pharm Des 2020 ;26(44):5732-5738

Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, China.

Background: Meteorin-like (Metrnl) is a newly identified adipokine implicated in the pathogenesis of type 2 diabetes mellitus (T2DM), yet data on the circulating levels of Metrnl in patients with T2DM are controversial. To derive a more precise estimation on circulating Metrnl levels in T2DM patients, we conducted this meta-analysis.

Methods: The existing studies on the circulating levels of Metrnl in patients with T2DM published up to 16 January 2020 were comprehensively retrieved from PubMed, Web of Science, EMBASE, and The Cochrane library database. Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated using random-effects model. Heterogeneity was assessed and quantified by Cochrane's Q and I2 statistic. All statistical analyses were performed using Stata 12.0 software.

Results: Nine studies with 867 T2DM patients and 831 normal glucose tolerance (NGT) controls were included in the final analysis according to the inclusion criteria. No significant difference in circulating Metrnl levels was found between T2DM patients and NGT individuals (pooled SMD = -0.429, 95% CI = -1.077 to 0.219). Compared to controls, circulating Metrnl levels were significantly higher in the subgroups with BMI <25 kg/m2, using plasma sample and patient sample size ≥100, while circulating Metrnl levels were significantly lower in subgroups with age ≤50 years and homeostatic model assessment for insulin resistance (HOMA-IR) ≥4.

Conclusion: This meta-analysis indicates no significant change in circulating Metrnl levels in T2DM patients. However, this result may be influenced by age, BMI, sample type, HOMA-IR and patients sample size. Further longitudinal studies are warranted to offer more insights into the relationship between Metrnl and T2DM.
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http://dx.doi.org/10.2174/1381612826666201007163930DOI Listing
April 2021

The dual roles of ginsenosides in improving the anti-tumor efficiency of cyclophosphamide in mammary carcinoma mice.

J Ethnopharmacol 2021 Jan 24;265:113271. Epub 2020 Aug 24.

Department of Pharmaceutical Analysis, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China; Department of Metabolomics, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, China. Electronic address:

Ethnopharmacological Relevance: Cyclophosphamide (CTX) is a first line chemotherapeutic agent, but often limited for its unstable therapeutic effect and serious side effects. Ginsenosides could facilitate the anti-tumor efficiency of CTX, including benefiting therapeutic effect and decreasing side effects.

Aim Of The Study: To investigate the potential mechanism of ginsenosides on benefiting the anti-tumor efficiency of CTX.

Materials And Methods: Mammary carcinoma mice were applied to investigate the anti-tumor efficiency and potential mechanism of combinational treatment of ginsenosides and CTX. Therapeutic effect was evaluated based on survival rate, tumor burden, tumor growth inhibition rate, and apoptosis and histological changes of tumor tissues. Anti-tumor immunity was studied by measuring serum level of anti-tumor cytokines. Gut mucositis, one of lethal side effects of CTX, was evaluated by diarrhea degree, gut permeability and tight junction proteins expressions. Gut microbial diversity was analyzed by 16S rRNA gene sequencing, and fecal transplant and antibiotics sterilized animals were performed to evaluate the therapeutic effect of gut microbiota on tumor suppression.

Results: Ginsenosides facilitated the therapeutic effect of CTX in mice, which manifested as prolonged survival rate, decreased tumor burden, as well as enhanced tumor growth inhibition rate and apoptosis. The favoring effect was related to elevation of anti-tumor immunity which manifested as the increased anti-tumor cytokines (INF-γ, IL-17, IL-2 and IL-6). Further studies indicated the elevation was ascribed to ginsenosides promoted reproduction of gut probiotics including Akkermansia, Bifidobacterium and Lactobacillus. Moreover, co-administration of ginsenosides in mice alleviated CTX-induced gut mucositis, including lower gut permeability, less diarrhea, less epithelium damage and higher tight junction proteins. Further researches suggested the alleviation was related to ginsenosides activated Nrf2 and inhibited NFκB pathways.

Conclusion: Ginsenosides show dual roles to facilitate the anti-tumor efficiency of CTX, namely promote the anti-tumor immunity through maintaining gut microflora and ameliorate gut mucositis by modulating Nrf2 and NFκB pathways.
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http://dx.doi.org/10.1016/j.jep.2020.113271DOI Listing
January 2021

Prevalence and influential factors of thrombocytopaenia in systemic lupus erythematosus patients: a retrospective analysis of 3140 cases in a Chinese population.

Lupus 2020 Jun 1;29(7):743-750. Epub 2020 May 1.

School of Nursing, Anhui Medical University, Anhui, PR China.

Introduction: The present study aimed to investigate the prevalence and influential factors of thrombocytopaenia in systemic lupus erythematosus (SLE) patients among the Chinese population in order to provide evidence for improving the treatment and nursing of SLE patients.

Methods: A retrospective analysis of 3140 SLE patients admitted to two large tertiary hospitals was conducted in Anhui, China, from 2011 to 2018. In addition, the influential factors related to SLE with thrombocytopaenia were analysed through univariate and multivariate analysis.

Results: A total of 804 SLE patients had thrombocytopaenia (25.6%). The top 5 clinical manifestations of SLE inpatients were proteinuria (51.0%), lupus nephritis (45.9%), new rash (38.4%), haematuria (36.7%) and pyuria (32.2%). The incidence of neurological manifestations, oral mucosal ulceration, pleurisy, pericarditis, hyperglycaemia, leucocytopaenia, urinary casts, haematuria, pyuria and high disease activity in the thrombocytopaenia group were higher than those in the non-thrombocytopaenia group ( < 0.05). Multivariate analysis showed age (odds ratio (OR) = 1.009,  = 0.005), neurological manifestations (OR = 1.373,  = 0.048), pericarditis (OR = 1.394,  = 0.048), hyperglycaemia (OR = 1.717,  < 0.001), leucocytopaenia (OR = 2.551,  < 0.001), haematuria (OR = 1.582,  < 0.001), serum C3 level <0.85 g/L (OR = 1.525,  = 0.001), serum C4 concentration <0.10 g/L (OR = 1.287,  = 0.020), serum CRP concentration <8 ng/L (OR = 1.314,  = 0.005), prothrombin time >15.30 seconds (OR = 1.479,  = 0.032), activated partial thromboplatin time >45 seconds (OR = 1.924,  < 0.001) and thrombin time >21 seconds (OR = 1.629,  = 0.015) were associated with thrombocytopaenia.

Conclusion: Thrombocytopaenia has a high prevalence in SLE patients and is related to some baseline, clinical and laboratory characteristics, affecting multiple organs and systems.
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http://dx.doi.org/10.1177/0961203320922301DOI Listing
June 2020

Pharmacokinetic profiles of falcarindiol and oplopandiol in rats after oral administration of polyynes extract of Oplopanax elatus.

Chin J Nat Med 2016 Sep;14(9):714-720

State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China. Electronic address:

Polyynes, such as facarindiol (FAD) and oplopandiol (OPD), are responsible for anticancer activities of Oplopanax elatus (O. elatus). A novel approach to pharmacokinetics determination of the two natural polyynes in rats was developed and validated using a liquid chromatography-electrospray ionization-mass spectrometry (LC-MS) method. Biosamples were prepared by liquid-liquid extraction using ethyl acetate/n-hexane (V : V = 9 : 1) and the analytes were eluted on an Agilent ZORBAX Eclipse Plus C18 threaded column (4.6 mm × 50 mm, 1.8 μm) with the mobile phase of acetonitrile-0.1% aqueous formic acid at a flow-rate of 0.5 mL·min(-1) within a total run time of 11 min. All analytes were simultaneously monitored in a single-quadrupole mass spectrometer in the selected ion monitoring (SIM) mode using electrospray source in positive mode. The method was demonstrated to be rapid, sensitive, and reliable, and it was successfully applied to the pharmacokinetic studies of the two polyynes in rat plasma after oral administration of polyynes extract of O. elatus.
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http://dx.doi.org/10.1016/S1875-5364(16)30085-1DOI Listing
September 2016

Hepatotoxic assessment of Polygoni Multiflori Radix extract and toxicokinetic study of stilbene glucoside and anthraquinones in rats.

J Ethnopharmacol 2015 Mar 31;162:61-8. Epub 2014 Dec 31.

State Key Laboratory of Natural Medicines (China Pharmaceutical University), No. 24 Tong jia Lane, Nanjing 210009, China. Electronic address:

Ethnopharmacological Relevance: Polygoni Multiflori Radix (PMR) has been traditionally used as a tonic and an anti-aging remedy for centuries; however, hepatic lesions linked to PMR have been frequently reported.

Aim Of The Study: This work attempted to investigate the hepatotoxic potential of PMR extract and the toxicokinetics of stilbene glucoside and anthraquinones in PMR extract following repeated administration.

Materials And Methods: Histopathological and biochemical tests were performed to assess the hepatotoxicity of PMR extract. A rapid and sensitive liquid chromatography-mass spectrometry (LC-MS) assay was developed for toxicokinetic analysis of the main constituents of PMR extract, including 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside (TSG), emodin-8-O-β-D-glucoside and emodin.

Results: The histopathological and biochemical tests indicated that repeated administration of high-dose PMR extract (20 g/kg) for 3 weeks could cause hepatic lesions, while the low-dose treatment (1 g/kg) was safe. Necrosis and steatosis of hepatic cells, inflammatory cell infiltration and mild fibrosis were the main toxicity symptoms caused by high-dose PMR extract in rat liver. The aspartate aminotransferase (AST) levels increased by approximately 17%, from 110.80±0.84 to 129.75±10.83 IU/L, in the high-dose group compared with the control group. The proposed LC-MS method was proven to be suitable for the simultaneous quantification of these three constituents by affording desirable linearity (r(2)>0.998) and satisfactory precision (error less than 10%). The toxicokinetic study showed that emodin could not be detected in the low-dose group, but the AUC and Cmax of emodin displayed a gradual increase with repeated treatments in the high-dose group. The toxicokinetics of TSG in the low- and high-dose groups exhibited similar trends after repeated administration.

Conclusions: Consideration needs to be given to the rational application of PMR in the clinic to balance its benefits and risks. The increased emodin exposure in vivo provided a putative explanation for the observed hepatic lesions induced by PMR extract, although further studies to confirm the potentially causal link between emodin exposure and hepatic lesions are still necessary.
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http://dx.doi.org/10.1016/j.jep.2014.12.045DOI Listing
March 2015

Effects of American ginseng on pharmacokinetics of 5-fluorouracil in rats.

Biomed Chromatogr 2015 May 22;29(5):762-7. Epub 2014 Oct 22.

State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.

The pharmacokinetics of 5-fluorouracil (5-FU) in combination with or without American ginseng (seven-consecutive days oral dose) in rats were evaluated using liquid chromatography-electrospray ionization-mass spectrometry (LC-MS). Chromatographic separation was performed on a reverse LC column within a total run time of 6.5 min, which allowed for a relatively quick analysis. The limit of quantification for 5-FU was 15 ng/mL and this method was linear over 15-50,000 ng/mL. This method supported stabilizing determination of the plasma concentration of 5-FU over a period of 24 h. Precision both interday and intraday (coefficient of variation) was within 14% and accuracy (relative error) ranged from -5 to 14%. In view of the observed pharmacokinetic parameters, including maximum concentration, time to maximum concentration, area under the concentration-time curve (AUC), mean residence time, elimination half-life and clearance, our results showed no significant differences in all of the pharmacokinetic parameters between the ginseng co-treated group and 5-FU alone group. Some increase in AUC was observed in 5-FU plus ginseng group; however, the difference did not reach statistical significance compared with 5-FU alone. It appeared that American ginseng administration did not significantly alter the kinetics of 5-FU. More studies are still needed to confirm our results.
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http://dx.doi.org/10.1002/bmc.3354DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4405504PMC
May 2015

Metabonomic analysis of the therapeutic effect of Potentilla discolor in the treatment of type 2 diabetes mellitus.

Mol Biosyst 2014 Nov;10(11):2898-906

State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.

Type 2 diabetes mellitus (T2DM) is increased worldwide in parallel with the obesity epidemic. Potentilla discolor is one of the most important crude materials in Traditional Chinese medicine (TCM) for therapy of hyperglycemia and hyperlipidemia. In this work, a plasma metabonomic approach based on the combination of UPLC-Q-TOF with multivariate data analysis was applied to investigate the therapeutic effects of the extract of P. discolor (EPD) and corosolic acid (CA), the main bioactive compounds of P. discolor. Male C57BL/6 mice were fed with high-fat diet (HFD-fed group) for 8 weeks and then treated with EPD (EPD-treated group) or CA (CA-treated group) for another 8 weeks. After the experimental period, samples of plasma were collected and analyzed by ultra-performance liquid chromatography/quadrupole time of flight mass spectrometry (UPLC-Q-TOF). The principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) models were built to find biomarkers of T2DM and investigate the therapeutic effects of EPD and CA. 26 metabolites, which are distributed in several metabolic pathways, were identified as potential biomarkers of T2DM. It was found that EPD and CA could reverse the pathological process of T2DM through regulating the disturbed pathway of metabolism. The metabonomic results are beneficial not only for the evaluation of the therapeutic effect of TCM but also for the elucidation of the underlying molecular mechanism.
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http://dx.doi.org/10.1039/c4mb00278dDOI Listing
November 2014

Stilbene glucoside inhibits the glucuronidation of emodin in rats through the down-regulation of UDP-glucuronosyltransferases 1A8: application to a drug-drug interaction study in Radix Polygoni Multiflori.

J Ethnopharmacol 2013 May 21;147(2):335-40. Epub 2013 Mar 21.

State Key Laboratory of Natural Medicines (China Pharmaceutical University), No. 24 Tong jia Lane, Nanjing 210009, China.

Ethnopharmacological Relevance: The integrated effects of herbal medicines were the outcome of all of the inherent components. Currently, few studies have focused on the multicomponent interactions in an herbal medicine to elucidate its pharmacological and/or toxicological effects. In this study, an attempt was made to investigate the interaction between stilbene glucosides and the anthraquinones contained in Radix Polygoni Multiflori (RPM) and to explore the interaction's mechanism from the perspective of UDP-glucuronosyltransferase (UGT) regulation.

Materials And Methods: The extract of RPM was separated into a stilbene glucoside fraction and a emodin fraction. A rapid high-performance liquid chromatography-mass spectrometry method was developed and validated to disclose the influence of stilbene glucoside on the pharmacokinetics of emodin in rats. Drug and Statistics 2.0 was used for the estimation of the pharmacokinetic parameters. Gene expression analysis in liver and intestinal tissues was performed by a semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) method.

Results: The analytical method appeared to be suitable for the analysis of emodin with desirable linearity, accuracy, precision and stability, and the total analysis time was less than 2 min on a short column. Glucuronide of emodin, which is the major metabolite of emodin, was determined after β-glucuronidase hydrolysis. As the in vivo pharmacokinetic studies had indicated, the AUC, Cmax and T1/2 of emodin were increased after the stilbene glucoside treatment, and the glucuronidation of emodin was significantly inhibited. The mRNA levels from UGT1A8 and UGT1A2 were decreased by stilbene glucoside treatment. In contrast, the expression of UGT1A1, UGT1A6 and UGT1A9 mRNA was increased in the liver following treatment.

Conclusions: The influence of stilbene glucoside on the pharmacokinetics of emodin may be attributed to the inhibition of UGT1A8 mRNA expression. Thus, it is important to extend this research to deepen our understanding of the pharmacological and/or toxicological effects of RPM.
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http://dx.doi.org/10.1016/j.jep.2013.03.013DOI Listing
May 2013
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