1.The interactions between natural products and OATP1B1.
Meizhi SHI ; Yu LIU ; Jialin BIAN ; Meng JIN ; Chunshan GUI
Acta Pharmaceutica Sinica 2015;50(7):848-53
Organic anion transporting polypeptide 1B1 (OATP1B1) is an important liver-specific uptake transporter, which mediates transport of numerous endogenous substances and drugs from blood into hepatocytes. To identify and investigate potential modulators of OATP1B1 from natural products, the effect of 21 frequently used natural compounds and extracts on OATP1B1-mediated fluorescein methotrexate transport was studied by using Chinese hamster ovary cells stably expressing OATP1B1 (CHO-OATP1B1) in 96-well plates. This method could be used for the screening of large compound libraries. Our studies showed that some flavonoids (e.g., quercetin, quercitrin, rutin, chrysanthemum flavonoids and mulberrin) and triterpenoids (e.g., glycyrrhetinic acid and glycyrrhizic acid) were inhibitors of OATP1B1 with IC50 values less than 16 µmol · L(-1). The IC50 value of glycyrrhetinic acid on OATP1B1 was comparable to its blood concentration in clinics, indicating an OATPlB1-mediated drug-drug interaction could occur. Structure-activity relationship analysis showed that flavonoids had much higher inhibitory activity than their glycosides. Furthermore, the type and length of saccharides had a significant effect on their activity. In addition, we used OATP1B1 substrates fluvastatin and rosuvastatin as probe drugs to investigate the substrate-dependent effect of several natural compounds on the function of OATP1B1 in vitro. Our results demonstrated that the effect of these natural products on the function of OATPlB1 was substrate-dependent. In summary, this study would be conducive to predicting and avoiding potential OATP1B1-mediated drug-drug and drug-food interactions and thus provide the experimental basis and guidance for rational drug use.
2.Metabolomic study on preventive effect of Aqueous extract and Volatile oil of Dalbergia Odorifera on myocardial ischemia/reperfusion injury in rats
Fei MU ; Jialin DUAN ; Haixu BIAN ; Rui LIN ; Peijin SHANG ; Zhihui ZHU ; Aidong WEN ; Miaomiao XI
Chinese Pharmacological Bulletin 2016;32(10):1377-1382
Aim To investigate the changes of serum metabolism after the treatment of DOA and DOO on myocardial ischemia reperfusion ( MI/R ) injury in rats, and to explore the pathogenesis of MI/R injury and drug action mechanism. Method The serum samples of Sham group, Model group, DOA group and DOO group of rats were acquired, gas phase time of flight mass spectrometry ( GC-TOF-MS) was applied to analyze the metabolic profiles of the samples. After da-ta preprocessing, they were processed into SIMCA 14. 1 software for multivariate statistical analysis. Results By principal components analysis ( PCA ) , partial least squares analysis ( PLS-DA) and orthogonal partial least squares analysis ( OPLS-DA ) , the Model group and Sham group were obviously separated, the drug in-tervention group and Model group were separated and close to Sham group. The therapeutic effect of DOO and DOA on MI/R injury in rats was proved. The ex-perimental results identified 13 endogenous biomark-ers, which were related to the glucose metabolism,lipid metabolism and amino acid metabolism pathway. Con-clusion DOA and DOO may protect the MI/R injured rats by regulating the glucose metabolism, lipid metab-olism and amino acid metabolism pathway.
3.Clinical value of preoperative nutritional support therapy in the hepatectomy of patients with nutritional risk: a prospective study
Bing HAN ; Yitao DING ; Xiaojie BIAN ; Yafu WU ; Xinhua ZHU ; Haozhen REN ; Ning TANG ; Jialin GAO ; Xiaolei SHI
Chinese Journal of Digestive Surgery 2017;16(12):1183-1190
Objective To investigate the clinical value of preoperative nutritional support (PNS) therapy in the hepatectomy of patients with nutritional risk.Methods The prospective study was conducted.The clinical data of 133 patients with nutritional risk who were admitted to the Drum Tower Hospital Affiliated to Nanjing University Medical School from August 2012 to June 2016 were collected.All the patients undergoing PNS and traditional therapy were divided into the PNS group and the control group by random number table method,respectively.Observation indicators:(1) comparisons of laboratory indexes between groups;(2) comparisons of postoperative situations between groups;(3) comparisons of postoperative complications between groups.Measurement data with normal distribution were represented as-x±s.Comparisons between groups were evaluated with the independent-sample t test.Comparisons of count data were analyzed using the chi-square test,and repeated measures data were analyzed by the repeated measures ANOVA.Results All the 133 patients were screened for eligibility,including 68 in the PNS group and 65 in the control group.(1) Comparisons of laboratory indexes between groups:alanine transaminase (ALT),aspartate transaminase (AST),total bilirubin (TBil),cholinesterase,albumin (Alb),prealbumin,transferrin and C-reactive protein (CRP) in the PNS group were respectively (36± 13) U/L,(29± 10) U/L,(18.5±2.4) mmol/L,(5 738± 1 824) U/L,(37.4±5.1) g/L,(155±48) mg/L,(2.2±0.5)g/L,(10±4) g/L at admission and (33 ± 9) U/L,(27 ± 8) U/L,(17.9± 1.8) mmol/L,(5 796± 2 016) U/L,(38.5 ± 4.7) g/L,(181 ± 40) mg/L,(2.4± 0.5) g/L,(8± 4) g/L before operation and (285±100)U/L,(218±93)U/L,(33.5±6.3)mmol/L,(4 847±1 044)U/L,(32.6±3.8)g/L,(105±34)mg/L,(1.3±0.4) g/L,(55±28) g/L at 1 day postoperatively and (149±84) U/L,(76±42) U/L,(22.7±4.9) mmol/L,(3 866±893) U/L,(34.2±2.4) g/L,(125±30) mg/L,(1.6±0.4) g/L,(51±34) g/L at 3 days postoperatively and (64±33) U/L,(44±18) U/L,(19.4±2.8) mmol/L,(4 257± 1 032) U/L,(37.0±2.1) g/L,(148±42) mg/L,(1.9±0.4)g/L,(16±11)g/L at 7 days postoperatively;ALT,AST,TBil,cholinesterase,Alb,prealbumin,transferrin and CRP in the control group were respectively (36± 15)U/L,(31± 12)U/L,(18.3±2.9)mmol/L,(5 762±1 693)U/L,(37.3±6.1)g/L,(162±51)mg/L,(2.3±0.5)g/L,(10±4)g/L at admission and (36±11)U/L,(30±11)U/L,(18.2±2.8)mmol/L,(5 789±1 673)U/L,(37.8±7.1)g/L,(166±57) mg/L,(2.3±0.6) g/L,(9±5) g/L before operation and (305±127) U/L,(246± 104) U/L,(34.2±7.8) mmol/L,(4 842±1 173)U/L,(32.0±4.1) g/L,(83±32) mg/L,(1.2±0.4) g/L,(61 ±31) g/L at 1 day postoperatively and (163±104)U/L,(82±62)U/L,(23.1±6.0)mmol/L,(3 672±937) U/L,(33.8±3.6) g/L,(106±30)mg/L,(1.4±0.4)g/L,(61±40)g/L at 3 days postoperatively and (77±48) U/L,(52±27) U/L,(20.2±3.5) mmol/L,(3 925±987) U/L,(36.6±2.8) g/L,(125±40) mg/L,(1.7±0.4) g/L,(22± 12) g/L at 7 days postoperatively,showing no statistically significant difference in changing trends of above indicators between groups (F =1.007,2.223,0.579,0.014,0.235,3.533,2.970,2.143,P>0.05).Results of further analysis showed that there were statistically significant differences in the levels of ALT,AST and cholinesterase at 7 days postoperatively between groups (t=1.832,2.073,1.899,P<0.05),and in the levels of prealbumin before operation and at 1,3 and 7 days postoperatively between groups (t =1.698,3.738,3.625,3.178,P<0.05) and in the levels of transferrin and CRP at 3 and 7 days postoperatively between groups (t=2.917,2.709,1.667,2.990,P<0.05).(2) Comparisons of postoperative situations between groups:time to initial exsufflation,time of initial defecation,infused volume of exogenous albumin and duration of postoperative hospital stay were respectively (46± 15)hours,(64±16)hours,(23±10)g,(9.2±2.6)days in the PNS group and (55±18)hours,(78±21)hours,(39±25)g,(11.7±5.3) days,with statistically significant differences in the above indicators between groups (t =2.830,4.157,5.044,3.497,P<0.05).(3) Comparisons of postoperative complications between groups:23 and 33 patients in the PNS and control groups had postoperative complications,showing a statistically significant difference between groups (x2=3.915,P<0.05).Eight and 17 patients in the PNS and control groups were respectively complicated with peritoneal effusion,with a statistically significant difference between groups (x2 =4.508,P< 0.05).Conclusion PNS therapy in the hepatectomy of patients with nutrition risk can effectively improve pre-and post-operative nutrition statuses,reduce liver damage,accelerate recoveries of liver and gastrointestinal functions,reduce complications,shorten duration of postoperative hospital stay and accelerate patients' recovery.
4.A multicenter, randomized, controlled study on the treatment of pediatric influenza (wind-heat invading lung) with Qingxuan Zhike granules
Xi MING ; Xiaodong SHEN ; Jinni CHEN ; Jinya WANG ; Jiemin WANG ; Fengzhan CHEN ; Huiping SHEN ; Huihui HUANG ; Yingzhu LU ; Jialin ZHENG ; Ziwei WANG ; Ji BIAN ; Zihao FENG ; Naichao FENG ; Siqi CHEN ; Xunzhou LIU ; Xiaohua YAN ; Xiaoyan WANG ; Wen XIE ; Lei XIONG
Chinese Journal of Applied Clinical Pediatrics 2024;39(8):597-601
Objective:To evaluate the efficacy and safety of Qingxuan Zhike granules in improving cough symptoms and shortening the course of influenza (wind-heat invading lung) in children.Methods:In this multicenter, randomized, controlled clinical trial, a total of 240 outpatient influenza patients from 7 hospitals, including the First Affiliated Hospital of Yunnan University of Traditional Chinese Medicine, from April 2023 to December 2023 were collected.The subjects were randomly divided into the control group and the experimental group via SAS software using the block randomization method.The differences between two groups were compared with t test, corrected t test and χ2 test.Subjects in the control group were given Oseltamivir phosphate granules, orally, twice a day (weight ≤15 kg, 30 mg/time; weight >15-23 kg, 45 mg/time; weight >23-40 kg, 60 mg/time; weight >40 kg, 75 mg/time; age≥13 years, 75 mg/time).In addition to Oseltamivir phosphate granules, subjects in the experimental group were also given Qingxuan Zhike granules, orally, 3 times a day (1-3 years old, 1/2 bag each time; >3-6 years old, 3/4 bag each time; >6-14 years old, 1 bag each time).After 5 days of treatment, the medication was suspended for 2 days.The effect of cough, antipyretic effect, clinical recovery rate, clinical recovery time, Canadian Acute Respiratory Illness and Flu Scale (CARIFS) score, traditional Chinese medicine (TCM) syndrome effect, complication rate, and adverse reactions were evaluated between the two groups. Results:Finally, 232 cases were included in the study, including 115 cases in the experimental group and 117 cases in the control group.Before and after treatment, there were no significant difference in CARIFS cough score between the experimental group and the control group (all P>0.05).After treatment, the change in CARIFS cough score in the experimental group [(-1.00±0.91) scores]was significantly higher than that in the control group [(-0.75±0.98) scores] ( t=-1.995, P=0.047).After treatment, the change in TCM syndrome cough score in the experimental group [(-1.69±1.51) scores] was significantly higher than that in the control group [(-0.97±1.63) scores] ( t′=-0.035, P=0.001).The time of complete regression of fever in the experimental group [(44.82±22.72) h] was shorter than that in the control group [(51.35±27.07) h], and the difference between the two groups was statistically significant ( t=-1.966, P=0.050).The fever score showed that the area under the curve between the CARIFS symptom fever score and time in the experimental group was 4.40±2.42, while that in the control group was 5.12±2.44, and the difference between the two groups was statistically significant ( t=-2.252, P=0.025).The clinical recovery rate was 93.91%(108/115) in the experimental group and 92.31%(108/117) in the control group, and there was no significant difference between the two groups ( χ2=0.233, P>0.05).The clinical recovery time in the experimental group [(2.93±1.21) d] was shorter than that in the control group [(3.29±1.15) d], and the difference between the two groups was statistically significant ( t=-2.279, P=0.024).After treatment, there was a significant difference in TCM syndrome score variation between the experimental group [(-12.00±4.13) scores] and the control group [(-10.85±4.31) scores] ( t′=-2.067, P=0.040).No complication occurred in both groups, and there was no significant difference in the incidence of adverse events between the two groups ( χ2=1.299, P>0.05). Conclusions:Qingxuan Zhike granules combined with Oseltamivir phosphate can effectively improve the cough symptoms associated with influenza in children, shorten the time and course of fever, and improve the TCM syndrome score; thus, they are safe in clinical application.