Objective To observe the effect of paeoniflorin on insulin resistance in rats fed with high-fat diet and to investigate the possible mechanisms.Methods Male Sprague Dawley (SD) rats were randomized into 4 groups:normal control,high-fat diet,high-dosage paeoniflorin (HDP group),and lowdosage paeoniflorin (LDP group).The control group was fed with ordinary diet,while the others with highfat diet,paeoniflorin intervention groups were given low-or high-dosage paeoniflorin by intraperitoneal injection.After 6 weeks,fasting serum triacylglycerol (TG),total cholesterol (TC),free fatty acids (FFA),fasting blood glucose (FBG),and insulin were determined.Insulin sensitivity index (ISI) were calculated and then the animals were sacrificed to acquire epididymal fat mass.The tumor necrosis factor alpha (TNFα) and glucose transporter 4 (Glut4) expressions in adipose tissue were detected by quantitative realtime polymerase chain reaction(PCR).Results Compared with high-fat fed group,HDP group had lower epididymal fat pad weight,reduced level of FBG,insulin and FFA (P ＜0.05) and improved ISI(-5.84 ± 0.24 vs-6.44 ± 0.25,P ＜ 0.05).LDP group had similar trends.In adipose tissue,the TNFα expression in LDP and HDP group was lower,Glut4 expression in HDP group was higher than that of high-fat fed group (P ＜ 0.05).Conclusion Paeoniflorin can reduce visceral adipose content,inhibit TNFα expression and increase Glut4 expression in adipose tissue,eventually lower glucose,and improve insulin resistance caused by high-fat diet.

Objective To study the effects of different transport protein on the transport of 7,4'-dihydroxyflavone (7,4'-DHF) and its metabolite (7,4'-DHF-S) in Caco-2 cell model.Methods Ultra performance liquid chromatography was employed to determinethe content of 7,4'-DHF and 7,4'-DHF-S incubation buffer,their structures were identified by LC-MS/MS.Bidirectional transport of Caco-2 cells model was used to investigate the influence of ko143 (the inhibitor of BCRP) and MK571 (the inhibitor of MRP2) on the transport of 7,4'-DHF and 7,4'-DHF-S,respectively.Results Metabolic product of 7,4'-DHF in Caco-2 monolayer cell was identified as one monosulfate;PDR of 7,4'-DHF was (1.43 ± 0.11),PDR of ko143 and MK571 on the apparent permeability of 7,4'-DHF was (1.59 ± 0.04) and (1.48 ± 0.07) (P ＞ 0.05);PDR of 7,4'-DHF-S was (1.60 ± 0.06);ko143 could significantly reduce the apparent permeability of 7,4'-DHF-S,and the PDR was (0.23 ±0.03) (P ＜ 0.01);MK571 had no significant effect on the apparent permeability of the 7,4'-DHF-S,and the PDR was (1.51±0.04) (P ＞ 0.05).Conclusion Caco-2 cells can mediate the suffonated reaction of 7,4'-DHF;7,4'-dihydroxyflavone sulfonated combination product may be a substrate for BCRP.

Objective To evaluate the efficacy and safety of donepezil in the treatment of cognitive dysfunction caused by radiation-induced encephalopathy.Methods A total of fifty-five patients with radiation-induced cognitive impairment were divided into treatment group with extra donepezil 5-10 mg/d combined with conventional therapy and control group with conventional treatment for 16 weeks.The cognitive function was assessed according to Montreal cognitive assessment (MoCA) and mini-mental state examination (MMSE) before and 16 weeks after treatment.Results After 16 weeks of treatment,the patients in treatment group displayed significantly greater improvement in cognitive function.In treatment group,the scores of patients after donepezil therapy in MoCA and MMSE were obviously higher than the control group (t =5.40,3.88,P ＜ 0.01).The scores in the visual space and executive function,naming,attention,abstract thinking,delayed memories also had improved,which suggested the statistically significant difference(t=-3.55,-3.08,-3.21,-2.58,-3.65,P＜0.05).The scores of control group unchanged accordingly.Conclusions Donepezil combined with conventional treatment was signally effective in the therapy of cognitive dysfunction caused by radiation-induced encephalopathy.

Objective To investigate the metabolic profile of chrysin in SULT1A3 and human small intestine S9.Methods After incubation of chrysin using in vitro SULT1A3 and human small intestine S9 system, high-performance liquid chromatography was utilized to determine the sulfates of chrysin.Mass spectrum(MS) were employed to elucidate the structures of metabolite.Results In the SULT1A3 with PAPS, Km were (3.06 ±1.04) and (0.41±0.06) μM, Vmax were (12.13 ±1.30) and (6.72 ±1.61) nmol/(min· mg), Vmax/Km were 3.96 and 16.39 mL/(min· mg), respectively.In the human small intestine S9 with PAPS, Km were (1.92 ±0.35) and (0.01 ±0.00) μM, Vmax were (0.52 ±0.02) and (0.08 ± 0.02) nmol/(min· mg), Vmax/Km were 0.27 and 8.00 mL/(min· mg).The metabolic behavior of chrysin in SULT1A3 and human small intestine S9 both were followed biphasic kinetics.The sulfation of chrysin in SULT1A3 showed a significant correlation with that in human small intestine S9(R2 =0.985).Conclusion The result indicates that SULT1A3 is the major enzyme to the metabolism of chrysin, human small intestine may be the main metabolic organs of chrysin.

Objective To investigate the kinectics characteristics of sulfation of apigenin mediated by SULTIA3.Methods After incubation of apigenin using in vitro SULT1A3 system, high-performance liquid chromatography was utilized to determine the sulfates of apigenin.Mass spectrum(MS) were employed to elucidate the structure of metabolite.The program GraphPad Prism 5 was used to perform the kinetic characterization of SULT1A3 catalyzed metabolism of apigenin.Results A liner calibration curve for the assay of apigenin was validated in the range of 0.15625 ~30 μM with the recoveries of at least 80% and intra-day and inter-day RSD of less than 15%.Metabolic product of apigenin and SULT1A3 in the incubated system was identified one monosulfate.The metabolic behavior of apigenin in SULT1A3 was followed substrate inhibition kinetics.Apparent kinetic parameters of metabolism of apigenin by SULT1A3, Kmwas(0.355 ±1.04) μM and Ksi was(23.62 ±0.06) μM,Vmax was(65.71 ±1.30) nmol/(min? mg),Vmax/Km was 185.10 mL/(min? mg).Conclusion SULT1A3 can mediate the binding of apigenin sulfonated reaction, and the character of enzymatic kinetics shows substrate inhibition.Sulfation of apigenin mediated by SULTIA3 may play an important role in phaseⅡmetabolic in vivo.

We report a family of glucocorticoid-remediable aldosteronism (GRA). A 20-year-old man presented with early-onset hypertension accompanied by hypokalemia was admitted to our hospital. Clinical data and family history were collected. Following genetic analyses with PCR and Sanger sequencing to document the chimeric gene and crossover site, respectively, we identified CYP11B1/CYP11B2 and determined the breakpoint of unequal crossover to be located in 264-380 nucletide, which was considered as GRA. There were 4 cases of GRA in the family, the average age of onset was 28 years, and all had different degrees of hypertension. Among them, the proband′s uncle suffered from moyamoya disease and died 6 months later due to sudden cerebral hemorrhage. In order to improve the understanding of this rare disease, the pathogenesis, biochemical profiles, diagnosis and treatment of GRA were summarized and analyzed.