Mechanism studies underlying the alleviatory effects of isoliquiritigenin on abnormal glucolipid metabolism triggered by type 2 diabetes / 药学学报

Isoliquiritigenin (ISL) is an active chalcone compound isolated from licorice. It possesses anti-inflammatory and anti-oxidative activities. In our previous study, we uncovered a great potential of ISL in treatment of type 2 diabetes mellitus (T2DM). Therefore, this study aims to reveal the mechanism underlying the alleviatory effects of ISL on T2DM-induced glycolipid metabolism disorder. High-fat-high-sugar diet (HFD) combined with intraperitoneal injection of streptozotocin (STZ) were used to establish T2DM mice model. All animal experiments were carried out with approval of the Committee of Ethics at Beijing University of Chinese Medicine. HepG2 cells were used in in vitro experiments, and sodium palmitate (SP) was applied to establish insulin resistance (IR) model cells. The effects of ISL on body weight, fasting blood glucose levels, and pathological changes in the livers of mice were examined. Enzyme-linked immune sorbent assay (ELISA) and real-time quantitative PCR (RT-qPCR) were applied to detect the regulatory effects of ISL on key targets involved in glucolipid metabolism. Additionally, molecular docking and analytical dynamics simulation methods were used to analyze the interaction between ISL and key target protein. The results indicate that ISL significantly downregulates the transcriptional levels and inhibits the activities of key enzymes involved in gluconeogenesis, including pyruvate carboxylase (PC), phosphoenolpyruvate carboxykinase (PEPCK), and fructose-1, 6-bisphosphatase (FBP). It also downregulates the transcriptional and protein levels of hepatocyte nuclear factor 4α (HNF4α) and cAMP response element binding protein (CREB), the two transcriptional factors involved in gluconeogenesis. Thus, ISL inhibits hepatic gluconeogenesis in T2DM mice. In addition, ISL reduces total cholesterol (TC) and triglyceride (TG) levels in the livers of T2DM mice. Moreover, ISL downregulates the mRNA levels of lipogenesis genes and upregulates those of genes involved in fatty acid oxidation, lipid uptake, and lipid export. In conclusion, ISL suppresses hepatic gluconeogenesis, promotes lipolysis, and restrains lipogenesis in T2DM mice, thereby improving the abnormal glycolipid metabolism caused by T2DM.

Isoliquiritigenin alleviates energy metabolism imbalance in type 2 diabetic mice / 药学学报

Isoliquiritigenin (ISL) is a flavonoid compound isolated from licorice. It possesses excellent antioxidant and anti-diabetic activities. This study aims to investigate the molecular mechanism underlying the alleviatory effect of ISL on energy metabolism imbalance caused by type 2 diabetes mellitus (T2DM). 8-week-old male C57BL/6J mice were used in in vivo experiments. The high-fat-high-glucose diet combined with intraperitoneal injection of streptozotocin was applied to establish T2DM animal model. All animal experiments were performed in accordance with the Institutional Guidelines of Laboratory Animal Administration issued by the Committee of Ethics at Beijing University of Chinese Medicine. HepG2 cells were used in in vitro experiments. Enzyme-linked immunosorbent assay (ELISA) and real-time quantitative polymerase chain reaction (RT-qPCR) were used to examine the protein and mRNA levels of mitochondrial function-related targets. The levels of reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) in HepG2 cells were measured by the flow cytometry. Additionally, the molecular docking of ISL and key target proteins was analyzed. It was found that ISL significantly inhibited the activity of mitochondrial respiratory chain complex I and increased the protein levels of uncoupling protein 2 (UCP2) in the livers of mice and HepG2 cells. It also obviously decreased the ROS levels and increased the MMP levels in cultured HepG2 cells. In addition, ISL promoted mitochondrial biogenesis by activating proliferator-activated receptor gamma co-activator 1α (PGC-1α) and enhanced mitophagy by upregulating Parkin. It also improved mitochondrial fusion by increasing the mRNA and protein levels of mitofusin 2 (MFN2). In conclusion, ISL alleviates energy metabolism imbalance caused by T2DM through suppression of excessive mitochondrial oxidative phosphorylation and promotion of mitochondrial biogenesis, mitophagy, and fusion.

Overexpression of (3S)-linalool synthase gene (LIS) regulates the glycyrrhizic acid biosynthesis in Glycyrrhiza uralensis hairy roots / 药学学报

(3S)-Linalool synthase (LIS) is a key enzyme involved in the monoterpene biosynthetic pathway. Based on our previous transcriptome study, the expression level of LIS gene was exceedingly related to glycyrrhizic acid (GA) biosynthesis. Therefore, we used hairy root culturing to further investigate the effect of LIS on the GA biosynthesis. A LIS gene (GenBank accession number: MZ169552) was cloned from Glycyrrhiza uralensis. The plant binary overexpression vector pCA-LIS was constructed by gene fusion. G. uralensis hairy roots overexpressing LIS were induced by the Agrobacterium rhizogenes ATCC15834. The expression levels of LIS were analyzed by real-time quantitative PCR (RT-qPCR) and the contents of GA in hairy root lines were determined by UPLC. It was found that in the hairy root lines overexpressing LIS, the expression levels of LIS were significantly higher than that in the wild type, while the contents of GA were remarkably lower than those in the wild type and negative control. These findings indicate that the expression level of LIS is negatively correlated with the accumulation of GA. In this study, LIS was cloned from G. uralensis for the first time and the negative regulatory effect of LIS on GA biosynthesis was confirmed by reverse genetics. This work provides support for further improvement of the molecular regulatory network of GA biosynthesis in G. uralensis.

Research advance in multi-component pharmacokinetics of Chinese herbal extracts in recent five years / 中国中药杂志

The multi-component pharmacokinetic study of Chinese herbal extracts elaborates the in vivo processes,including absorption,distribution,metabolism,and excretion,of multiple bioactive components,which is of significance in revealing pharmacodynamic material basis of Chinese herbal medicine. In recent years,with the innovation in ideas,and development of techniques and methods on traditional Chinese medicine( TCM) research,the pharmacokinetic studies of Chinese herbal extracts were extensively performed,and notable progress has been made. This paper reviewed the advancement of multi-component pharmacokinetics of Chinese herbal extracts in recent five years from analysis technology of biological sample,the pharmacokinetic characteristics of Chinese herbal medicine with complex system,and the impacts of processing and pathological state on pharmacokinetics of Chinese herbal extracts,aiming to provide a reference for quality control,product development and rational medication of Chinese herbal extracts.

Study on Epileptic EEG Data Analysis Methods Based on Machine Learning / 医学信息学杂志

The paper dilates upon epileptic EEG data treatment and analysis methods based on machine learning,including supervised learning,unsupervised learning,semi-supervised learning,reinforcement learning and machine learning methods of other types,and evaluates the application effects of the methods on inspection of epileptic EEG data.