OBJECTIVE To synthesize scutellarein derivatives and study their solubility and bioactivity. METHODS Based on the lead compound scutellarein, 12 compounds were designed and synthesized using functional group substitution, parent nucleus ring opening, and electron rearrangement principles. The structures of the compounds were characterized through ¹H-NMR, ¹³C-NMR and MS, their solubility was tested, and their transient receptor potential vanilloid 3 (TRPV3) inhibitory activities were evaluated through calcium flow detection. An animal model of psoriasis induced by imiquimod (IMQ) was established and the three most active compounds were selected for anti-psoriasis evaluation. RESULTS All compounds had higher solubility than scutellarein. In the calcium flow experiment, compounds I-01, I-04, and I-06 showed stronger TRPV3 inhibition than scutellarein, with I-06 having the strongest activity. Animal experiments on psoriasis showed that I-01, I-04, and I-06 could significantly improve the pathological appearance and inflammatory response of psoriasis mice, and I-06 performed the best. CONCLUSION This type of modified scutellarein has potential therapeutic value for psoriasis and provides a new approach for targeting TRPV3 to treat various skin diseases.

Chemotherapy induced nausea and vomiting (CINV) is the most common adverse reaction in cancer patients during chemotherapy. 5-HT₃ receptor antagonists are recommended as the first-line drugs against CINV. However, the commonly used clinical dosage forms of 5-HT₃ receptor antagonists are mainly oral and intravenous administration, among which intravenous administration is easy to produce adverse reactions and requires professional medical operation. Oral administration has first-pass effect, especially for patients with severe vomiting after chemotherapy, so the commonly used clinical dosage forms have certain defects and limited clinical application. Transdermal drug delivery system has the advantages of avoiding gastrointestinal first-pass effect, less toxic and side effects, and good patient compliance, so the transdermal drug delivery system of anti-tumor nausea and vomiting drugs has been widely concerned and studied. In this paper, the research status of transdermal delivery of 5-HT₃ receptor antagonists at home and abroad is reviewed, which provides reference for the research and development of new preparations and new delivery routes of these drugs.

OBJECTIVE To explore the mechanism of action of coptisine derivative Q3 against dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice from the perspective of changes in the inflammatory signaling pathway TLR4/NF-κB and compositions of the intestinal microbiota. METHODS Fifty mice were randomly divided into normal control group, model group, sulfasalazine (SASP) group, Q3-low dose group, Q3-high dose group, with 10 in each group. Mice in the groups except the control group were orally administered with 2.5% DSS solution to induce UC model. The SASP was given 700 mg·kg^-1·d^-1 of sulfasalazine by intragastric administration, and the Q3 low and high dose groups were given 50 and 100 mg·kg^-1·d^-1 of Q3, respectively. The other groups were given an equal amount of distilled water. After 6 days of administration, the mouse colon tissues were taken for DAI score and length measurement. HE staining was used to detect the degree of pathological damage in each group. 16S rRNA high-throughput sequencing was used to detect changes in intestinal flora in the intestinal contents of mice. Immunohistochemistry and Western blot were used to detect the expression of TLR4 and p-p65 in colon tissue. The protein expressions of TLR4, p-p65 and p-IκBα and the nuclear translocation of NF-κB p65 in IEC6 cells and RAW264.7 cells were detected by Western blot and immunofluorescence. RESULTS In the DSS-induced mouse ulcerative colitis model, compared with the model group, in vivo Q3 could significantly improve the weight loss, colon length, and increase in DAI scores of UC mice. HE staining results showed that Q3 significantly improved the intestinal pathological damages such as tract epithelial damage, crypt structure disorder and goblet cell reduction; immunohistochemistry and Western blot results showed that Q3 could significantly reduce the expression of TLR4 and p-p65 in the colon tissue of mice in the model group. The results of 16S rRNA showed that Q3 could increase the biodiversity of intestinal microbiota and regulate the composition of intestinal microbiota after DSS administration. It was also shown that in vitro Q3 could inhibit the nuclear translocation of NF-κB p65 in both IEC6 and RAW264.7 cells by immunofluorescence. CONCLUSION Q3 can improve intestinal inflammation by inhibiting the TLR4/NF-κB pathway and regulating the composition of intestinal flora, exerting anti-UC effects, which is expected to become a candidate compound for the treatment of UC.

OBJECTIVE To investigate the potential therapeutic effects and underlying mechanisms of total alkaloids derived from processed Aconitum carmichaelii Debx (ACA) on ulcerative colitis (UC) in mice. METHODS The chemical composition of ACA was analyzed using liquid chromatography-mass spectrometry. A mouse model of UC was induced using dextran sodium sulfate (DSS) to assess the effects of continuous administration of salicylazosulfapyridine(SASP) (200 mg·kg^-1) and ACA (10 and 20 mg·kg^-1) over seven days, evaluating parameters such as body weight, disease activity index, colon length, and pathological damage to the colon. The anti-inflammatory activity and mechanisms of ACA were investigated through in vitro experiments, enzyme-linked immunosorbent assay, and Western blotting. RESULTS ACA is primarily composed of various characteristic monomeric alkaloids. Treatment with ACA (10 and 20 mg/kg) significantly mitigated weight loss, disease index elevation, colon shortening, and pathological damage induced by DSS in the mice. Additionally, ACA reduced the levels of inflammatory factors, including IL-1β, IL-18, and IL-6, elevated by DSS in colitis. The in vitro inflammatory model further demonstrated that ACA functions as a specific inhibitor, MCC950, similar to the NLRP3 inflammasome, which suppresses the secretion of the aforementioned inflammatory factors in the supernatant of LPS- and Nigericin-induced THP-1 cells. Protein expression analysis suggested that this effect may be linked to the inhibition of the NLRP3 signaling pathway. CONCLUSION ACA contains multiple structurally similar monomeric alkaloids that exhibit anti-UC activity in mice, potentially exerting anti-inflammatory effects through the inhibition of the NLRP3 inflammasome.

It is important to select a suitable in vitro experimental model to study the pathology and pharmacological mechanisms of inflammatory bowel disease (IBD), thereby developing advanced therapeutic drugs. Immortalized cell lines, as a classic in vitro model, offer several advantages in the research and drug evaluation of IBD, such as high efficiency, low cost, simple operation and intuitive experimental results. However, these models cannot recapitulate the multicellular composition and intercellular interaction of intestinal tissue in vivo and may lose genetic characteristics after multiple passages in vitro. The development of organoids and organs-on-a-chip has promoted the technological innovation of in vitro models by significantly improving our capability to simulate the architecture and function of IBD. The enhanced reproducibility of the organoid model to the microenvironment of the source tissue also confers improved predictive capability for patient treatment response. This paper reviews the current research status of these models by discussing their characteristics, advantages, disadvantages, and their applications in evaluation of IBD therapeutic drugs and development of advanced therapeutic drugs, as well as in the exploration of pharmacological mechanisms.

OBJECTIVE To idenntify the whole chemical components of different extracts of alangium chinense root and fibrous root using ultra high performance liquid chromatography-mass spectrometry(UPLC-MS/MS), and screen the index components of different medicinal parts”. METHODS UPLC-MS/MS technology was used to analyze the total components of alcoholic extract (ALE), water extract (ALW) of Alangium chinense root, alcoholic extract (AFE) and water extract (AFW) of Alangium chinense fibrous root. Principal component analysis (PCA), orthogonal partial least squares-discriminant analysis (OPLS-DA) and other multivariate statistical analysis were used to screen and analyze the chemical components with significant differences in different medicinal parts of Alangium chinense. RESULTS A total of 406 active chemical components were identified from the extract of Alangium chinense. The mass spectrometry cracking rules of phenolic acids, flavonoids, alkaloids and terpenoids were summarized and analyzed in different medicinal parts. Twenty Index components such as fraxin, loganic acid and benzoyleneurea were screened from different medicinal parts. CONCLUSION There were obvious differences in the components of different medicinal parts and different extracts of Alangium chinense. Phenolic acids, flavonoids and alkaloids are the main compounds, and they were mainly concentrated in flavonoid biosynthesis pathway. This study provides a scientific basis for clarifying the pharmacodynamic material basis and quality differences of different parts of Alangium chinense, and lays a foundation for rapid identification, quality control and further development and utilization of Alangium chinense.

OBJECTIVE To establish a liquid chromatography tandem mass spectrometry (LC-MS/MS) method for determination of cinnamic acid (CA), vanillic acid (VA) and 3,3'-O-dimethylellagic acid (DMA) concentrations in rat plasma and evaluate the pharmacokinetics and the correlations between dose and systemic exposure levels of CA, VA and DMA in rats after single dose administration of Anshen Buxin Liuwei Pills (ASBX). METHODS Blood was collected from male SD rats at different time points after different dose administration. The plasma was processed by protein precipitation method. The concentrations of CA, VA and DMA in plasma were determined by LC-MS/MS method. Pharmacokinetic parameters were calculated with MaS Studio software. The correlations between dose and systemic exposure level were analyzed by confidence interval method. RESULTS The linear relationship of the calibration curves of the three compounds were good within the tested ranges, and the specificity, precision and accuracy, recovery, matrix effect and stability of the method all met the requirements for biological sample assay. After single intragastric administration of ASBX, the t_max of CA, VA and DMA were 0.22-0.40, 0.08 and 5.40-8.20 h, the t_1/2 were 0.79-2.04, 0.37-0.65 and 4.26-9.58 h, the ρ_max were 279.70-302.88, 16.42-43.33, and 2.81-7.20 ng·mL^-1, and the AUC_0-∞ were 351.83-537.96, 7.20-18.82, and 29.27-119.64 ng·h·mL^-1, respectively. The results of confidence interval analysis showed that the ρ_max and AUC of VA and DMA, and AUC of CA were positively correlated with dose, but the ρ_max of CA was not clearly correlated with dose. CONCLUSION The LC-MS/MS analysis method is proved to be rapid, sensitive, and accurate, so it can be applied to the pharmacokinetic study of ASBX after intragastric administration in rats. This sdtudy provides a reference for future research on the pharmacodynamic material basis and safe and effective clinical use of ASBX.

OBJECTIVE To analyze the dynamic changes of cell types and protein expression during the occurrence and development of ulcerative colitis. METHODS Single-cell sequencing technology was used to analyze the intestinal tissues of ulcerative colitis model mice and normal mice. After quality control, a total of 58 714 cells were used to construct a colitis dataset for downstream analysis. Then, the changes of epithelial compartments in the process of colitis occurrence and development were analyzed by means of dimensionality reduction clustering, GO analysis and Monocle quasi-time analysis. RESULTS Compared with the normal samples, the interaction between cell subsets in colitis samples changed significantly. The analysis revealed that most epithelial cell subtypes were destroyed and reduced in number during the colitis phase. The Wnt pathway was inhibited, which is important for maintaining stem cell function. The Ppia-Bsg ligand receptor pair was highly expressed in normal samples. CONCLUSION The depletion of Ppia secreted by stromal cells in the inflammatory state leads to stem cell senescence, which ultimately disrupts the homeostasis of epithelial cells and aggravates colitis.

OBJECTIVE To develop a method for the determination of dracorhodin in Draconis Sanguis scald ointment based on the concept of quality by design (QbD), and to study its preparation process for quantitative transfer. METHODS Using the content of dracorhodin as key quality attribute, the key analytical parameters in preparation of test solution were selected through Plackett-Burman design. The relationship between key quality attribute and key analysis parameters was evaluated through Box-Behnken design. According to characteristics of the medicinal material, intermediate and finished product of scald ointment, the different methods for determining content of dracorhodin were established, and the law of quantity transfer was studied. The preparation conditions of test solution for content determination of Draconis Sanguis scald ointment were as follows: lanolin was removed by petroleum ether, extraction solvent was 7% phosphoric acid methanol solution, and extraction was carried out in a water bath at 60 ℃ for 30 min. The chromatographic conditions were as follows: the mobile phase was consisted of acetonitrile and 0.05 mol·L^-1 sodium dihydrogen phosphate solution using a gradient elution. Temperature was 40 ℃ and flow rate was 1.0 mL·min^-1, at a detector wavelength of 440 nm. RESULTS The feasibility of preparation process of Draconis Sanguis scald ointment was proven. The transfer rate of dracorhodin from medicinal material to finished product was over 90%. CONCLUSION The analytical method developed based on concept of QbD could accurately determine content of dracorhodin in Draconis Sanguis scald ointment, which is conducive to product quality evaluation and process value transfer research.

OBJECTIVE To analyze the characteristics and drug cost of hepatoprotective drugs among outpatients in domestic hospitals and provide references for rational drug use. METHODS The outpatient prescription data of 119 hospitals in 9 cities from January 2016 to December 2023 was collected, and the clinical application of hepatoprotective drugs was analyzed. RESULTS A total of 8 635 977 prescriptions from 3 194 167 patients were obtained in this study. The most frequent diagnoses of hepatoprotective drugs were hepatitis B (7.59%), liver cirrhosis (5.11%) and non-alcoholic steatohepatitis (4.53%).98.15% of prescriptions for 1-2 hepatoprotective drugs are prescribed, and oral dosage forms account for 97.29%. The total drug cost of hepatoprotective drugs increased from 85.38 million yuan to 109.8 million yuan, and the average drug cost per time increased from 85.15 yuan to 95.52 yuan. The glycyrrhizin preparation was the most used regimen, and the polyene phosphatidylcholine+glycyrrhizin preparation was the most used regimen. CONCLUSIONS The aggregate costs on hepatoprotective medications appears a consistent annual increase, which brings economic burden to medical insurance. This study analyzes the trend of hepatoprotective drug costs in the past 8 years, which is of great significance to the drug management of patients with liver disease.