1.Mechanism of Bielong Ruangan decoction in treatment of liver cancer based on network pharmacology and molecular docking
Sihan YIN ; Wei YUAN ; Lingwei LUO ; Kewei SUN ; Tao ZHANG
Journal of Chinese Physician 2023;25(3):348-354,359
Objective:To explore the key targets and mechanism of Bielong Ruangan decoction in the treatment of liver cancer based on network pharmacology and molecular docking.Methods:Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database, PubChem database and PharmMapper database were used to search and screen the chemical components and related targets of Bielong Ruangan decoction and the targets of liver cancer diseases. The network diagram of " Bielong Ruangan decoction-traditional Chinese medicine-active ingredient-predicted target-disease" was constructed; Protein-protein interaction (PPI) network were analyzed through String database; gene ontology (GO) enrichment analysis was performed through WebGestalt database; Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was carried out through KEGG Orthology Based Annotation System (KOBAS) database; Molecular docking of the active components and core target proteins of Bielong Ruangan decoction was carried out by using PyMOL, Auto DockVina and other software.Results:Bielong Ruangan decoction had 67 active components, 154 liver cancer targets and 244 pathways. According to the analysis of network pharmacology, Bielong Ruangan decoction may play an anti-cancer role through key targets such as epidermal growth factor receptor (EGFR), mitogen activated protein kinase 1 (MAPK1), estrogen receptor 1 (ESR1), MAPK8, serine threonine protein kinase 1 (AKT1), MAPK14, cysteine protease 3 (CASP3), cyclin-dependent kinase 2 (CDK2), bone morphogenetic protein 2 (BMP2), aldose reductase (AKR1B1) and other key targets. KEGG enrichment analysis showed that the treatment of liver cancer by Bielong Ruangan decoction involved the regulation of vascular endothelial growth factor (VEGF) signaling pathway, tumor necrosis factor (TNF) signaling pathway, thyroid hormone signaling pathway, T cell receptor signaling pathway and other pathways. The results of molecular docking showed that the binding energy of all compounds to protein was less than -5.6 kcal/mol, indicating that each compound and each protein could bind well.Conclusions:Bielong Ruangan decoction participates in the treatment of liver cancer through " multi-component, multi-target and multi-channel" ways, and plays an anti-cancer role mainly by regulating the proliferation and invasion of tumor cells and tumor inflammatory microenvironment.
2.Prevalence of subclinical thyroid disease in the faculty and staff of a university and their affecting factors
Shihuan LUO ; Ying NIE ; Xinhuan ZHANG ; Xue BAI ; Yahui SUN ; Lingwei KONG ; Yifei WANG
Chinese Journal of General Practitioners 2023;22(10):1032-1037
Objective:To investigate the status quo of subclinical thyroid diseases in the faculty and staff of a university and to explore their affecting factors.Methods:A total of 4 219 faculty and staff members who met the exclusion criteria and underwent the health examination in the Community Health Service Center of Beijing Jiaotong University in 2021 were enrolled in the study. General clinical data and laboratory findings of the enrolled subjects were collected. According to the upper and low reference range of thyroid stimulating hormone (TSH) in our laboratory (0.35-5.5 μIU/ml), subjects were classified into subclinical hyperthyroidism group, subclinical hypothyroidism group and normal thyroidism group. The association of gender, age and body mass index (BMI), as well as the metabolic indices with the prevalence of subclinical thyroid disease was analyzed.Results:The prevalence rates of subclinical hypothyroidism and subclinical hyperthyroidism were 4.10% (173/4 219) and 0.69% (29/4 219), respectively. The prevalence of subclinical thyroid diseases in females was higher than that in males(5.90% (77/2 101) vs. 3.66%(125/2 018),χ 2=11.58, P<0.05); there was a significant difference in prevalence among different age groups(χ 2=39.49, P<0.05)and the prevalence increased with the age. There were significant differences in levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), diastolic blood pressure(DBP), fasting blood glucose (FBG), free triiodothyronine (FT 3), free thyroxine (FT 4), thyroglobulin antibody (TGAb) and thyroid peroxidase antibody (TPOAb) among three groups ( P<0.05). TSH levels were positively correlated with the age ( r=0.58, P<0.001), and levels of TG ( r=0.66, P<0.001), TC ( r=0.67, P<0.001), LDL-C ( r=0.62, P<0.001), TPOAb ( r=0.78, P<0.001), TGAb ( r=0.77, P<0.001); was negatively correlated with FBG ( r=-0.50, P<0.001). Conclusion:The prevalence of subclinical thyroid diseases among faculty and staff of the studied university is relatively high, and it is related to gender, age, thyroid antibodies, blood glucose and lipid levels.
3.Effects and mechanism of Bielong ruangan decoction on liver cancer model rats
Sihan YIN ; Jing PENG ; Lingwei LUO ; Yi ZHOU ; Li HU
China Pharmacy 2024;35(18):2219-2224
OBJECTIVE To explore the effects and mechanism of Bielong ruangan decoction on liver cancer model rats. METHODS Thirty-two male SD rats were randomly divided into control group, model group, and Bielong ruangan decoction low- dose and high-dose groups [6.84, 27.36 g/(kg·d), by raw material], with 8 rats in each group. Except for the control group, other groups were intraperitoneally injected with diethylnitrosamine (DEN) 50 mg/kg (once a week, for 16 consecutive weeks) to induce liver cancer model. At the 8th week of DEN injection, Bielong ruangan decoction low-dose and high-dose groups were orally administered with the corresponding medication, twice a day, until the 16th week. The general condition of rats in each group was observed during the experimental period. After the final administration, the body weight and liver mass were weighed, and the liver indexes were calculated; serum contents of alanine transaminase (ALT) and aspartate transaminase (AST) were determined; the appearance, pathological morphology and degree of fibrosis of liver were observed; Ishak scoring for liver fibrosis was performed; the mRNA and protein expressions of nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3), caspase-1, gasdermin D (GSDMD), interleukin-18 (IL-18), IL-1β in liver tissue were detected. RESULTS Compared with the model group, the general condition of rats (except for the low-dose group), liver texture, surface nodules and tumors, inflammatory cell infiltration and abnormal cell amount were all improved in Bielong ruangan decoction low-dose and high-dose groups. Liver index (except for low-dose group), Ishak score (except for low-dose group), the serum contents of ALT and AST, as well as the mRNA and protein expressions of NLRP3, caspase-1, GSDMD, IL-18 and IL-1β in liver tissue were reduced significantly (P<0.05), with some of above indicators in high-dose group being significantly lower than those in low-dose group (P<0.05). CONCLUSIONS Bielong ruangan decoction can inhibit the progression of liver cancer in rats and reduce liver damage. Its mechanism of action may be related to the inhibition of the NLRP3/caspase-1/GSDMD signaling pathway and the improvement of inflammatory response.