Objective:To study the hypoglycemic effect of Quercus mongolica leaves total flavonoids on alloxan-induced hyperglycemia mice; To discuss its underlying mechanism and pharmacodynamic material basis.Methods:The healthy ICR mice were divided into control group and diabetic mice group according to random number table method. The diabetic mouse model was established by intravenously injected with streptozotocin solution (45 mg/kg) via the tail vein. The model diabetic mice were divided into model group, positive drug group (150 mg/kg metformin hydrochloride), total flavonoids low (100 mg/kg), medium (200 mg/kg) and high (400 mg/kg) dose groups, and monomer flavonoids low (25 mg/kg), medium (50 mg/kg) and high (100 mg/kg) dose groups. Each group of mice received 0.2 ml/10 g body weight for gavage, once a day for 14 consecutive days. The control and model group were given an equal volume of physiological saline. On the 7th and 14th day of administration, the body weight, fasting blood glucose, area under the curve (AUC) of blood glucose, serum insulin and insulin receptor beta concentrations, and insulin sensitivity index were measured. The main chemical components of total flavonoids from Quercus mongolica leaves were analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) technology.Results:Compared with the model group, after 14 days of administration, the total flavonoids of Quercus mongolica leaves at different doses and quercetin-3-O-β-D-glucopyranoside and astragalin at different doses all significantly reduced blood glucose levels ( P<0.01 or P<0.05), decreased AUC ( P<0.01 or P<0.05), and increased insulin sensitivity index ( P<0.01 or P<0.05). The 12 flavone glycosides and aglycone components were identified by UPLC-MS/MS. Conclusions:Flavonoids are speculated to be the material basis for the hypoglycemic effect of Quercus mongolica leaves. Among them, total flavonoids of Quercus mongolica leaves and monomeric flavonoids such as quercetin 3-O-β-D-glucopyranoside and astragalin have certain hypoglycemic activity, which can lower blood glucose levels by improving insulin resistance.

Objective:This study aims to investigate the effects of Zhibao Sanbian Pills on learning and memory ability and explore its mechanism.Methods:Cognitive decline and memory impairment in mice was induced by scopolamine. Morris water maze test, platform jumping test and dark avoidance test were used to evaluate the learning and memory ability of mice. TCMSP, TCMID database and literature search were used to search the chemical components of Zhibao Sanbian Pills. The potential active components were screened through ADMETlab 2.0. The targets were predicted by Swiss Target Prediction. GO function and KEGG pathway enrichment analysis were conducted through the Metascape database, and a PPI network was constructed for MCODE module analysis.Results:Compared with the model group, the latency of water maze test in the high-dose group of Zhibao Sanbian Pills was shortened ( P<0.05), and the time of platform quadrant and the number of crossing increased ( P<0.05). 863 active components and 401 potential targets of Zhibao Sanbian Pills were collected. The enrichment analysis of MCODE, GO and KEGG pathways found that the action pathways of Zhibao Sanbian Pills to improve cognitive impairment involve neuroactive ligand receptor pathway, calcium signal pathway, Rap1 signal pathway, PI3K-Akt signal pathway, MAPK signal transduction pathway, 5-hydroxytryptamine receptor pathway, etc. Conclusion:Zhibao Sanbian Pills have the potential to improve the learning and memory ability of mice, which may be realized through MAPK signaling pathway and other neural related signaling pathways.

Tripterygium glycosides tablet(TGT),the classical commercial drug of Tripterygium wilfordii Hook.F.has been effectively used in the treatment of rheumatoid arthritis,nephrotic syndrome,leprosy,Behcet's syndrome,leprosy reaction and autoimmune hepatitis.However,due to its narrow and limited treatment window,TGT-induced organ toxicity(among which liver injury accounts for about 40％of clinical reports)has gained increasing attention.The present study aimed to clarify the cellular and molecular events underlying TGT-induced acute liver injury using single-cell RNA sequencing(scRNA-seq)technology.The TGT-induced acute liver injury mouse model was constructed through short-term TGT exposure and further verified by hematoxylin-eosin staining and liver function-related serum indicators,including alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase and total bilirubin.Using the mouse model,we identified 15 specific subtypes of cells in the liver tissue,including endothelial cells,hepatocytes,cholangiocytes,and hepatic stellate cells.Further analysis indicated that TGT caused a significant inflammatory response in liver endothelial cells at different spatial locations;led to marked inflammatory response,apoptosis and fatty acid metabolism dysfunction in hepatocytes;activated he-patic stellate cells;brought about the activation,inflammation,and phagocytosis of liver capsular macrophages cells;resulted in immune dysfunction of liver lymphocytes;disturbed the intercellular crosstalk in liver microenvironment by regulating various signaling pathways.Thus,these findings elaborate the mechanism underlying TGT-induced acute liver injury,provide new insights into the safe and rational applications in the clinic,and complement the identification of new biomarkers and ther-apeutic targets for liver protection.

ObjectiveTo investigate the pharmacodynamic characteristics and explore the molecular mechanism of Honghua oral liquid （HOL） in relieving neuropathic pain （NP）. MethodHealthy male SD rats were randomly assigned into sham group， model group， low-， medium-， high-dose （0.5， 1.0， 2.0 mL·kg^-1·d^-1， respectively） HOL groups， and a positive drug （pregabalin， 25 mg·kg^-1·d^-1） group， with 6 rats in each group. Spinal nerve ligation （SNL） of L5 was conducted in other groups except the sham group. Drug administration was performed 3 days after the SNL surgery for 2 consecutive weeks， and samples were collected after the end of the administration. During the treatment period， the mechanical pain threshold and cold pain threshold were determined to measure the pain-relieving effect of HOL. Transcriptome sequencing was performed on hippocampal tissue samples from the sham， model， and high-dose HOL groups， and differentially expressed genes between the sham group and the model group as well as the model group and HOL high-dose group were obtained. After pathway enrichment analysis， we selected the targets which were closely related to neuroinflammation for validation， and predicted the specific binding sites of the major active components in HOL with the targets through molecular docking. In addition， the serum levels of tumor necrosis factor-α （TNF-α） and interleukin-10 （IL-10） were determined by enzyme-linked immunosorbent assay （ELISA） to evaluate the effect of HOL on neuroinflammation in NP rats. ResultCompared with the sham group， SNL decreased the mechanical pain threshold and cold pain threshold （P<0.05）. Compared with the model group， HOL recovered the mechanical pain threshold and cold pain threshold （P<0.05）. The transcriptome data showed that 376 differentially expressed genes （DEGs） were identified between the model group and the sham group， including 124 upregulated genes and 252 downregulated genes， and 194 DEGs between the model group and the high-dose HOL group， including 33 upregulated genes and 161 downregulated genes. Among them， insulin-like growth factor 1（IGF1）， matrix metallopeptidase-2 （MMP-2）， matrix metallopeptidase-14 （MMP-14）， erb-B2 receptor tyrosine kinase 2 （ERBB2）， and integrin subunit alpha 5 （ITGA5） associated with NP were selected for further validation. The Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） results showed that compared with the sham group， the modeling up-gurelated the mRNA levels of the above five molecules in the hippocampus （P<0.01）. Compared with model group， HOL down-regulated the mRNA levels of these molecules （P<0.01）. The molecular docking results showed that the main active components of safflower， hydroxysafflor yellow A， kaempferol， and quercetin， formed stable hydrogen bonds with the amino acid residues of IGF1， MMP-2， MMP-14， ERBB2， and ITGA5. The enzyme-linked immunosorbent assay（ELISA） results showed that compared with those in the sham group， the serum levels of TNF-α and IL-10 were out of balance in the model rats （P<0.01）. Compared with the model group， HOL lowered the level of the pro-inflammatory cytokine TNF-α （P<0.01） and elevated that of the anti-inflammatory cytokine IL-10 （P<0.05）. ConclusionHOL exerts analgesic effect on SNL rats by inhibiting neuroinflammation.

Objective:To establish a method of evaluating the reproducibility of the preparation process of Xiaozheng-Zhitong cataplasm. Methods:Used fingerprint spectrum technology and in vitro release test to evaluate the reproducibility preparation process of Xiaozheng-Zhitong cataplasm. By using HPLC to establish the fingerprint of Xiaozheng-Zhitong cataplasm. The chromatographic column was an Agilent HC-C18 column (4.6 mm×250 mm, 5 μm); the detection wavelength was 280 nm; the flow rate was 1 ml/min; the column temperature was 25 ℃. The mobile phase was acetonitrile-0.2% phosphoric acid aqueous solution, used gradient elution method. An HPLC method for the determination of tetrahydropalmatine content was established, and the vertical Franz diffusion cell method was used to investigate its in vitro release. Results:The results showed that the similarity between the 10 batches of Xiaozheng-Zhitong cataplasm and the control map was above 0.95, indicating that the process of Xiaozheng-Zhitong cataplasm was stable and feasible; the cumulative release amount of tetrahydropalmatine was 0.23 mg in 24 hours, and the cumulative release rate in 8 hours was 91.54%, and the RSD of 6 samples at each time point was <3%. Conclusion:The method of evaluating the reproducibility of the preparation process of Xiaozheng-Zhitong cataplasm was established by using fingerprint technology and in vitro release; it can provide a reference and scientific basis for the evaluation of the reproducibility of the preparation process of the plaster.

Objective In this paper, the extraction process of Xiaozhong-Zhitong granule (XZG) was investigated. Methods In Process 1, the Panax notoginseng (Burk.) F.H.Chen was extracted with other drugs, and in the process 2, the Panax notoginseng (Burk.) F.H.Chen was crushed and directly used as medicine. Rats were randomly divided into blank group, process 1 group, process 2 group and mixture group.The sample concentration of the process 1 group 1 for the stomach was 2.07 g/ml, and the sample concentration of the process 2 group 1 for the stomach was 1.06 g/ml, and the sample concentration of the mixture group for the stomach was 0.015 g/ml, and blank group gavaged equal volume saline. Anti-inflammatory and analgesic effects of acetic acid writhing test, hot plate test, auricle swelling test and egg white-induced plantar swelling test were evaluated. Results Compared with the blank group after 1, 2, 3, and 4 h after administration, the average writhing number of the mice in the process group 1 and the process 2 group (35.50％ ± 8.06％, 35.00％ ± 7.63％vs. 47.00％ ± 1.45％) significantly decreased (P<0.01), and the auricular swelling degree (46.31％ ± 22.25％, 45.41％ ± 21.43％ vs. 73.89％ ± 15.55％) significantly decreased. And compared with the blank group after 0.5, 1, 2, and 4 h after inflammation, the percentage of pain threshold in the first group and the second group increased (P<0.01). While there was no significant difference in the inhibition rate of paw swelling in each group (P>0.05). Conclusions The design of extraction process of XZG was reasonable; when treating swelling and pain, it was better to put the powder of Panax notoginseng (Burk.) F.H.Chen in XZG.

Objective To study the effects of microemulsion/ethosomes on transdermal absorption properties and efficacy of Huoxue Zhitong Cataplasm. Methods The improved Franz diffusion cells were used for the in-vitro permeation experiment with rat skins as the barriers, which was used to evaluate the transdermal absorption properties. In the erxeriment, the contents of paeonol, eugenol and methyl salicylate were used as markers, and detected by ultra performance liquid chromatography to evaluate the transdermal absorption effects. The anti-inflammatory and analgesia activity were evaluated through the writhing plate experiments. Results The cumulative release rate of paeonol in Huoxue Zhitong Cataplasm, Microemulsion Huoxue Zhitong Cataplasm and Ethosomes Huoxue Zhitong Cataplasm were, in order, 65.30%, 61.30%and 60.20%in 24 h;eugenol were, in order, 51.08%, 54.71% and 55.66% in 24 h; methyl salicylate were, in order, 49.20%, 65.17% and 72.15% in 24 h. Furthermore, Microemulsion Huoxue Zhitong Cataplasm high-dose group and Ethosomes Huoxue Zhitong Cataplasm medium-dose group had good effects on reducing the inflammatory exudate of peritoneal capillary and capillary permeability (P<0.05) in animal models. Conclusion Huoxue Zhitong Cataplasm based on microemulsion/ethosomesnano-technology has good transdermal absorption properties and efficacy.

Objective To optimize refinement of water extract from Bushen Yangxue Granules by chitosan flocculation.Methods According to the content of icariin detected by HPLC, the waters amount, extraction time and extraction times were evaluated by orthogonal design. The effects of the solution concentration, clarifying temperature and the amount of clarifying agent on the flocculation clarification processes were optimized with the content of icariin and polysaccharides.Results The optimum water extraction processes A2B1C3 were follows: 10 times amount of water, three times extraction and 1 h for each extraction process. The optimized flocculation clarification processes A1B2C3 were as follows: solution concentration was 0.4 g/mL, the clarifying temperature was 40℃ and the addition of chitosan was 0.1%.Conclusion The optimized refining process is stable and feasible.

Artemisinin is the antimalarial active ingredient, which is discovered by Chinese scientists in 1970s. The chemical structure of artemisinin is modified or altered to obtain a series of analogues to satisfy the medication requirements. According to the physicochemical properties of medicines and actual clinical necessities, the preparations of artemisinins are developed and the common preparations include tablet, suppository, injection, etc.. With the developing of technology, researchers have conducted a large number of studies on the artemisinins nanoparticles injection, transdermal drug delivery systems, mucosal drug delivery systems and etc. This article systematically collected and discussed the recent studies on the antimalarial preparations of artemisinins in line with different administration routes.

Objective To establish the determination method of gallic acid in Yuanhu Zhitong Soft Capsule by HPLC. Methods Chromatography was performed on a Unitary C18 column (250 mm× 4.6 mm, 5 μm) at 254 nm. The mobile phase consisted of a mixture of methanol and 0.5%phosphate acid (5∶95) at flow rate of 1.0 mL/min. Results The standard curve of linear relationship was 0.024 8-0.496 μg and r=0.999 9. The RSD of precision, repeatability and stability was 0.27%, 0.21%, 1.40%, respectively. The average recovery was 99.81%, RSD was 0.72%. Conclusion The established method was accurate and reliable for the determination of gallic acid in Yuanhu Zhitong Soft Capsule.