AIM: To compare the permeation enhancing characters of menthol and azone on the model drug of indomethacin and to study the enhancing effect when the two agents were used in combination. METHODS: The transdermal test was conduced on the penetration experiment apparatus of isolated skin. The cumulate penetrated amount, penetrating rate, stable flux and lag time were calculated upon the concentrations. RESULTS: After adding the penetration enhancer, the penetrating rate of indomethacin increased remarkably. It was 6.21 , 4.91 and 6.92 times of that of the controls respectively. When used in combination, the two penetration enhancers increased much more the penetrating rate than being used separately (P

Objective To explore the effect of schisanhenol on adipokine expression in 3T3-L1 adipocyte and its related mechanism. Methods 3T3-L1 adipocyte was cultured in vitro and induced to differentiation and maturity. Glucokinase was added to culture medium to make an oxidative model. The expression of adipocytokines were detected under the circumstance of different doses and at different time points of schisanhenol. Results The expression of adiponectin, leptin, resistin and visfatin were decreased with the increase of glucokinase concentration. Concentration-dependent inhibition effect was most obvious in leptin (25 mU/ml Glucokinase vs Blank group, t =7.29, P＜0.01). With pretreatment of oxidative stress, the adipocytokines increased as the doses of schisanhenol increased (t=6.31,P＜0.01 in adiponectin;t=5.92, P＜0.01 in leptin; t=3.77, P＜0.05 in resistin; t=3.63,P＜0.05 in visfatin). With the extension of schisanhenol effect, the expression of four adipokines showed the process of first decrease-then increase'. The effects of schisanhenol on adipokines were parallel with the alteration of oxidative stress. Conclusions Schisanhenol increased adipocytokines expression in 3T3-L1 adipocyte by reducing oxidative stress, and the increase of leptin and adiponectin were most obvious, which indicated that schisanhenol could play a role in the treatment of diabetes by Chinese herb wuweizi.

Objective To establish the method for the content determination of sinomenine in Qiwei Tongbi oral liquid. Methods Sinomenine ofQiwei Tongbi oral liquid was determined by HPLC, with the column being Waters XTerra column temperature setting at 25℃, flow rate being 1.0 ml/min, and the detective wavelength being 262 nm. Results There was a good linearity of sinomenine in the range of 0.248～2.480 μg, and the average recovery was 98.82% with RSD of 0.13%. Conclusion This method was simple, accurate, reproducible, and thus could be used for quality control of Qiwei Tongbi oral liquid.

Objective To investigate the effect of intrathecal hyperbaric bupivacaine on spinal cord neurons apoptosis in diabetic neuropathic rats.Methods Thirty-two healthy male Sprague-Daw-ley rats weighing 220-300 g,8 normal rats randomly served as control group (group C),the other rats were intraperitoneal injection 1% streptozotocin (STZ)60 mg/kg to induce diabetic neuropathic (DN),and last induced thirty-seven diabetic neuropathic rats.group C and diabetic neuropathic rats administer intrathecal catheter,respectively.Twenty-four rats in which DN was successfully intrathe-cal catheter were randomly divided into 3 groups (n=8):hyperbaric bupivacaine group (group HB), isobaric bupivacaine group (group IB),glucose group (group G).Hyperbaric bupivacaine 10 μl were injected intrathecally in groups C and HB respectively,isobaric lidocaine 10 μl were injected intrathe-cally in group IB,10% glucose 10 μl were injected intrathecally in group G,once daily for 3d.After rats each administration 2 min,motor block duration were recorded;The paw withdrawal threshold to von Frey filament stimulation (PWT)were measured before induced diabetes model (T1 ),before in-jected intrathecally (T2 ),after 30 min administered 1 d (T3 ),2 d (T4 ),3 d (T5 )and end administered 4 d (T6 ).All rats were sacrificed at T6 and their lumbar intumescential spinal cord tissue were re-moved for microscopic examination.And using TUNEL assay to measure spinal neuronal apoptosis. Results PWT was lower at T2-5 in groups HB,IB and G comparing with T1 (P <0.05 ).Comparing with group C,the motor block duration was significantly prolonged(P <0.05)and spinal cord neuro-nal apoptosis cells were increased(P <0.05)in group HB.Comparing with group IB,the motor block duration was significantly prolonged(P <0.05)and spinal cord neuronal apoptosis cells were increased (P <0.05)in group HB,too.PWT was increased at T6 in group HB at T2-T5 (P <0.05).Group G did not appear motor block and spinal cord neuronal apoptosis.Conclusion Intrathecally hyperbaric bupi-vacaine can promote spinal cord neuronal apoptosis in diabetic neuropathic rats.

OBJECTIVE To investigate the protective effects and mechanism of diterpene ginkgolides meglumine injection (DGMI) against oxidative stress induced by oxygen-glucose deprivation (OGD) in SH-SY5Y cells. METHODS SH-SY5Y cells were divided into five groups: normal control, model control (OGD group) and drug(25 mg · L- 1) administration groups including DGMI group, extract of ginkgo biloba leaves injection group (EGBLI) and lactones ginkgo biloba injection group (LGBI). The cells suffered from oxygen-glucose deprivation (OGD) for 4 h, followed by reoxygenation with drugs for 6 h. Then, cell viabilities were detect using CCK-8 assays, reactive oxygen species (ROS) levels using fluorescence probe DCFH-DA and superoxide dismutase (SOD) activities using WST-1 test. Western blotting was used to detected protein levels of hemeoxygenase-1(HO-1), NAD(P)H, quinone oxidore?ductase l (Nqo1), protein kinase B (Akt), phosphorylated Akt (p-Akt), nuclear factor-E2-related factor2 (Nrf2) and phosphorylated Nrf2 (p-Nrf2). The cells were induced by OGD for 4 h, followed by reoxygen?ation and DGMI for 1 h, combined with different concentrations of PI3K inhibitor (LY294002) (at the final concentration of 12.5, 25 and 50 μmol · L-1) before the protein levels of AKT, p-AKT, Nrf2 and p-Nrf2 were detected by Western blotting. RESULTS SH-SY5Y cells induced by OGD for 4 h resulted in an increase in ROS(P<0.01), but a decrease in cell viabilities(P<0.01), SOD activities(P<0.01), and antioxidant protein levels ( Akt, p-Akt, Nrf2, p-Nrf2, HO-1 and Nqo1) (P<0.01). Compared with OGD group, treatment with reoxygenation and drugs (DGMI,EGBLI and LGBI respectively) for 6 h resulted in a decrease in ROS (P<0.01), but an increase in cell viabilities, SOD activities and antioxidant protein levels of p-Nrf2, HO-1, Nqo1 and p-Akt(P<0.05,P<0.01). DGMI group showed the best efficiently. Moreover, after OGD for 4 h, compared with DGMI group, combining reoxygenation and DGMI with LY294002 for 1 h resulted in a concentration-dependent inhibition of the protein levels of p-AKT and p-Nrf2(P<0.01). CONCLUSION DGMI 25 mg · L-1 can inhibit oxidative stress in SH-SY5Y cells induced by OGD by increasing the activity and expression of Nrf2 through PI3K/Akt pathway, which may be one of the mechanisms by which DGMI protects neurons from stroke.

Hydroxycinnamoyl-CoA:shikimate/quinate hydroxycinnamoyltransferase(HCT) is an key enzyme involved in the biosynthesis of chlorogenic acid in Lonicera japonica. In this study, eight putative HCT genes were cloned with RACE (rapid amplification of cDNA ends) technology based on the analysis of transcriptome in L. japonica. Among them, one was suggested as HCT gene (LjHCT) in L. japonica through analysis of sequence similarity, physical and chemical properties, and domain conservation of the proptein. LjHCT gene containing 1 275 bp encodes a protein with the molecular weight of 47 kDa. These results will provide foundation for exploring the function of LjHCT in Lonicera japonica.

SUMO4 Met55Val variation was shown to be related to type 2 diabetes susceptibility and the vascular complications in Asian people. To further examine the related mechanisms, this study was designed to evaluate the association of SUMO4 Met55Val polymorphism with insulin resistance and β cell function in newly diagnosed type 2 diabetic patients in a Chinese population. Four hundred and twenty seven newly diagnosed type 2 diabetic patients were selected for SUMO4 Met55Val polymorphism genotype analysis. All subjects underwent a 75-g oral glucose tolerance test (OGTT) to estimate the insulin sensitivity and β cell function. Anthropometrics and a metabolic profile were used for phenotyping analysis. The results showed that the SUMO4 Met55Val polymorphism was associated with higher insulin resistance (P<0.001) and lower insulin sensitivity (P<0.001). Patients with GG genotype had higher levels of plasma glucose, insulin and C peptide. Insulin sensitivity index (ISI) was closely correlated with body mass index (BMI) in patients with GG genotype in comparison to the counterparts with AG or AA genotype (r= -0.504 vs. r= -0.430 vs. r= -0.340). Multiple regression linear analysis showed that SUMO4 Met55Val polymorphism was an independent determinant for insulin sensitivity (P=0.001), which, along with triglyceride, BMI and sex, could account for 20.1% of the variation in ISI. The result remained the same after adjusting for BMI and sex. No association was found between SUMO4 Met55Val polymorphism and β cell function (all P>0.05). It was concluded that SUMO4 Met55Val variant was associated with increased insulin resistance in Chinese patients with newly diagnosed type 2 diabetes.

Objective To evaluate the role of C-Jun N-Terminal kinase (JNK) signaling pathway in dexmedetomidine-induced reduction of spinal neurotoxicity induced by lidocaine in rats.Methods Seventy-two adult male Sprague-Dawley rats, weighing 280-320 g, in which intrathecal catheters were successfully implanted without complications, were randomly divided into 6 groups (n =12 each) using a random number table: control group (group C);SP600125 (JNK signaling pathway blocker) group (group SP);dexmedetomidine group (group D);lidocaine group (group L);dexmedetomidine + lidocaine group (group DL);SP600125+lidocaine group (group SPL).Dimethyl sulfoxide (DMSO) 20 μl was injected intrathecally in group C.SP600125 30 μg and 10％ lidocaine 20 μl were injected intrathecally in SP and L groups, respectively.At 20 min after intrathecal injection of 10％ lidocaine, dexmedetomidine 75 μg/kg was injected intraperitoneally in group DL, and SP600125 30 μg was injected intrathecally in group SPL.Dexmedetomidine 75 μg/kg was injected intraperitoneally in group D.The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured before intrathecal catheters were implanted (T0), before intrathecal administration (T1), and at 4, 8 and 12 h and 1, 2, 3, 4, 5 and 6 days after intrathecal administration (T2-10).At 24 h after intrathecal administration, 6 rats randomly selected from each group were sacrificed.The lumbar segment (L4-5) of the spinal cord was removed for detection of cell apoptosis (by TUNEL) and phosphorylated JNK (p-JNK) expression (by Western blot).The apoptotic index was calculated.Results Compared with group C, no significant change was found in the MWT, TWL, apoptotic index and expression of p-JNK in SP and D groups (P＞0.05), the MWT at T2-8 in group L, at T2-6 in group DL and at T2-5 in group SPL were significantly increased, the TWL at T2-8 in group L, at T2-5 in group DL and at T2-4 in group SPL were prolonged, and the apoptotic index and expression of p-JNK were increased in DL, SPL and L groups (P＜0.05).Compared with group L, the MWT was significantly decreased, and the TWL was shortened at T2-8, and the apoptotic index and expression of p-JNK were decreased in DL and SPL groups (P＜0.05).Conclusion The mechanism by which dexmedetomidine mitigates spinal neurotoxicity induced by lidocaine is related to inhibited activation of JNK signaling pathway in rats.

Aim To investigate the protective effects of YXETNZ injection on SH-SY5 Y cells damaged by oxygen-glucose deprivation ( OGD ) , and explore its functional mechanisms. Methods After 4 h of OGD, the cells were treated with 25 mg·L-1 drugs for 1 h. Subsequently, cell viabilities were measured by cell counting kit-8 ( CCK-8 kit ) and cell apoptosis was measured by caspase-3/7 assay kit according to manu-facturer’ s instructions. Furthermore, cell death was also detected by ELISA. The levels of phospho-Akt, phospho-PKA,phospho-Bad were evaluated by western blot. Results Oxygen-glucose deprivation significant-ly decreased the cell viabilities of SH-SY5Y cells, while YXETNZ injection significantly increased cell vi-abilities, phospho-Akt, phospho-PKA and phospho-Bad. Furthermore, YXETNZ injection also reduced the activities of caspase-3/7 and cytoplasmic histone-asso-ciated-DNA-fragments contents. Conclusion Our re-searches demonstrat that YXETNZ injection shows good neuroprotective effects on SH-SY5 Y cells after oxygen-glucose deprivation. The underlying mechanisms may be associated with activation of PI3 K/Akt/Bad/caspase-3/7 , cAMP/PKA/Bad/caspase-3/7 signaling pathway.