To the present study aimed to investigate the protective effects of Erlong Zuoci Pills on oxidative stress induced by hydrogen peroxide (H2O2) in House Ear Institute-Organ of Corti 1 (HEI-OC1) and to explore the mechanism by cellular metabolomics. There were 6 groups in the experiment: the control group, model group, three dose groups of ELZC (low, medium, and high), and positive control ascorbic acid group. The oxidative stress injury model was established in the HEI-OC1 by inducing 0.9 mmol/L H2O2 for 12 h. The proliferation of HEI-OC1 cells was observed by CCK-8 assay; the contents and activity of lactate hydrogenase (LDH), reactive oxygen species (ROS), and superoxide dismutase (SOD) in HEI-OC1 cells were detected by corresponding kits. Finally, the endogenous substances of cells were analyzed from the perspective of metabolomics. Compared with the model group, ELZC groups could significantly increase the cell proliferation rate after administration. Moreover, they could also ameliorate the increase of ROS and LDH content and the decrease of antioxidant enzyme SOD caused by H2O2. Metabolomic results revealed significant differences among multiple groups in the scores of partial least squares discriminant analysis. The ELZC group could relocate the model group back to the control group. The metabolic regulation of ELZC on oxidative stress in HEI-OC1 cells mainly affects nucleotide metabolism and amino acid metabolism. In summary, the results indicate that ELZC exhibits protective effects on H2O2-induced oxidative stress in HEI-OC1 cells. Additionally, this protective effect may be produced by increasing the content of amino acids such as uridine and phenylalanine, thereby regulating pathways such as pyrimidine metabolism, phenylalanine metabolism, biosynthesis of phenylalanine, tyrosine, and tryptophan, and histidine metabolism.

To establish a quantitative LC-MS/MS method for the simultaneous detection of components of Erlong Zuoci Pill in rat plasma: verbascoside, oxypaeoniflorin, echinacoside and benzoylpaeoniflorin, and to evaluate the pharmacokinetic characteristics of Erlong Zuoci Pill in rats, plasma samples were purified by protein precipitation using methanol as a protein precipitant.Methanol was used as the organic phase and aqueous solution containing 0.1% formic acid was used as the water phase.The quantitative analysis method of verbascoside, oxypaeoniflorin, echinacoside and benzoylpaeoniflorin was established in negative ion mode, and the validation of bioanalytical method was carried out.Healthy SD rats were selected, and 20 mL/kg (equivalent to the original drug 10 g/kg dose) of Erlong Zuoci Pill extract was administered by intragastric administration.The plasma concentration of the target compounds at different time intervals after administration was determined using the established method, and the pharmacokinetic parameters was calculated by the Phoenix WinNonlin8.3 software using the non-compartmental model.The method validation results showed that verbascoside (r = 0.993 7) and oxypaeoniflorin (r = 0.994 6) had good linear relationship in the concentration range of 0.5-50 ng/mL, echinacoside (r = 0.993 6) and benzoylpaeoniflorin (r = 0.992 6) had good linear relationship in the concentration range of 1-100 ng/mL.The relative standard deviations of the inter- and intra- batch precision of the four compounds were all less than 15%, and the inter- batch and intra- accuracies were between 85% and 115%.Extraction recovery, matrix effect and stability met the relevant requirements.After a single gavage of Erlong Zuoci Pill extract in rats, all the four compounds were rapidly absorbed and eliminated.Oxypaeoniflorin, echinacoside, and benzoylpaeoniflorin showed two peaks in their drug concentration-time curves.Compared with the other three compounds, oxypaeoniflorin has the highest concentration in rat plasma with cmax1 of (24.40 ± 4.78) ng/mL and cmax2 of (22.50 ± 2.70) ng/mL. The results show that the validation results of this method are in line with the guiding principles of biological sample analysis methods, and it can be used to evaluate the pharmacokinetic characteristics of Erlong Zuoci Pill extract in rats.

Transcranial alternating current stimulation is a non-invasive electric stimulation therapy and a promising neuromodulation approach to treat brain-related diseases. This article briefly introduces the factors related to treatment efficacy, possible mechanism, clinical application, and future development of transcranial alternating current stimulation.

Transcranial alternating current stimulation is a non-invasive electric stimulation therapy and a promising neuromodulation approach to treat brain-related diseases. This article briefly introduces the factors related to treatment efficacy, possible mechanism, clinical application, and future development of transcranial alternating current stimulation.

In view of gemcitabine resistance has limited clinical activity of gemcitabine as a cellulotoxic drug in pancreatic cancer patients, this study is designed to investigate the effect of emodin on the sensitivity of pancreatic cancer to gemcitabine as well as its mechanism. After gemcitabine-resistant pancreatic cancer cell line (SW1990/GZ) was established by escalating doses of gemcitabine serially in pancreatic cancer cell line (SW1990). The cellular proliferation was detected by cell counting kit-8 (CCK-8) assay. Flow cytometry (FCM) was used to determine apoptosis of pancreatic cancer cells. The activity of NF-kappaB in pancreatic cancer cells was measured by electrophoretic mobility shift assay (EMSA). Western blotting was used to detect the protein expression of Bcl-2 and Survivin in SW1990/GZ cells. Metastatic model simulating human pancreatic cancer was established by orthotopic implantation of histologically intact human tumor tissue into pancreatic wall of nude mice. Also, immunohistochemistry was used to detect the positive expression of Ki-67, NF-kappaB, Bcl-2 and Survivin in the tumors. The results show that pretreatment of cells with emodin followed by gemcitabine induced a higher percentage of growth inhibition and apoptosis of pancreatic cancer cells than that of gemcitabine alone. In addition to in vitro results, emodin in combination with gemcitabine is much more effective as an antitumor agent compared to either agent alone in the orthotopic tumor model. Further study showed that the emodin with or without gemcitabine significantly down-regulates NF-kappaB and its regulated molecules such as Bcl-2 and Survivin proteins both in vitro and in vivo. It is concluded that inactivation of NF-kappaB signaling pathway by emodin resulting in the chemosensitization of pancreatic cancer to gemcitabine, which is likely to be an important and novel strategy for the treatment of pancreatic cancer.

Objective To study the diterpenoids possessed immunosuppressive activity from Tripterygium hypoglaucum. Methods The chemical constituents were isolated from the CHCl3 extracts of T. hypoglaucum by repeated column chromatography, including silica gel, Sephadex LH-20, and preparative HPLC. Their structures were elucidated on the basis of spectroscopic studies. The immunosuppressive activity of these compounds was tested using the lymphocyte transformation test. Results Compounds Ⅰ-Ⅵ were identified as triptobenzene H (Ⅰ), triptoquinone A (Ⅱ), triptoquinone B (Ⅲ), triptoquinone H (Ⅳ), triptonediol (Ⅴ), triptonoterpene (Ⅵ). Conclusion Compound Ⅰ-Ⅲ are isolated from this medicinal plant for the first time and all the compounds show the significant immunosuppressive activity.