1.Exploration on the liver-protective effect of Peipi Shugan Decoction on liver fibrosis in rats based on network pharmacology
Guangshun CHEN ; Mingzhong CAO ; Rongming ZHANG ; Ruxia WU ; Zhen XIE ; Jiangfeng HAO
International Journal of Traditional Chinese Medicine 2025;47(12):1708-1717
Objective:To investigate the liver-protective effect of Peipi Shugan Decoction (PSD) in rats with liver fibrosis through network pharmacology and experimental animal models.Methods:TCMSP was used to retrieve the active components of Peipi Shugan Decoction, GeneCards database was used to obtain the liver fibrosis related targets, and Venny 2.1 was used to obtain the intersection targets. A protein-protein interaction (PPI) network was constructed using the STRING 12.0 database, and Go function and KEGG pathway enrichment analysis were performed through David database. A total of 60 male Sprague-Dawley (SD) rats were divided into two groups: a blank control group ( n=10) and a model establishment group ( n=50) with random number table method. Liver fibrosis models were induced in the model group by intraperitoneal injection of a 40% CCl?- olive oil solution. After successful modeling, the rats were randomly assigned to the following groups ( n=10 per group): model group, colchicine group, and Peipi Shugan Decoction low-, medium-, and high-dosage groups. The colchicine group received colchicine suspension at 0.2 ml/kg via intragastric administration. Peipi Shugan Decoction low-, medium-, and high-dosage groups were administered the decoction at dosages of 2.81, 5.63, and 11.25 g/kg, respectively. The blank control and model groups received an equal volume of normal saline. All treatments were administered once daily for 8 consecutive weeks. HE staining and Masson staining were used to observe the morphological changes of liver tissue and the deposition of collagen fibers. he levels of GPT, GOT and ALP were detected by automatic biochemical analyzer. The expressions of JAK2/STAT1 signaling pathway related proteins, α - smooth muscle actin (α-SMA) and Collagen Ⅰ in rat liver were detected by Western blot. The expression of α-SMA protein in liver tissue was detected by immunohistochemistry. The number and ratio of CD4 + T cells and CD8 + T cells in liver tissue were analyzed by flow cytometry. The levels of IL-6, IL-1β and TNF-α in serum were detected by ELISA. Results:A total of 94 active components were screened out from Peipi Shugan Decoction; the prediction analysis results revealed that this compound formula shared 122 common targets with liver fibrosis diseases; The top five core targets with degree values in the PPI network are AKT1, TNF, IL-6, TP53, and IL-1β. GO enrichment analysis further indicated that Peipi Shugan Decoction mainly achieved anti-liver fibrosis effects by regulating JAK2/STAT1 signaling pathway and other mechanisms. Compared with the model group, the colchicine group and Peipi Shugan Decoction low-, medium-, and high-dosage groups exhibited decreased serum levels of GPT, GOT, ALP, IL-6, TNF-α, and IL-1β ( P<0.05), as well as reduced expression of α-SMA in liver tissue ( P<0.05). Peipi Shugan Decoction medium- and high-dosage groups showed increased protein expression of p-STAT1/STAT1 in liver tissue ( P<0.05), while Peipi Shugan Decoction high-dosage group demonstrated decreased α-SMA protein expression ( P<0.05). Additionally, Peipi Shugan Decoction medium- and high-dosage groups exhibited reduced expressions of CD4 + and CD8 + ( P<0.05). Conclusions:Peipi Shugan Decoction has the characteristics of multi-component, multi-target and multi-pathway in the treatment of liver fibrosis. Its mechanism is mainly related to activating the JAK2/STAT1 signaling pathway, inhibiting cellular inflammatory responses and hindering the activation of hepatic stellate cells (HSC).
2.Study on Toxic Effect of the Extract from Tripterygium hypoglaucum on Embryo-fetal Development of New Zealand Rabbits
Tinglan SHI ; Li ZHANG ; He HUANG ; Xiaoli MEI ; Ruxia TU ; Silan WU ; Bo LAN ; Henghua LI
China Pharmacy 2020;31(14):1710-1714
OBJECTIVE:To study the toxic effect of the extract from Tripterygium hypoglaucum on pregnant animal and embryo-fetal development . METHODS :Successfully mated New Zealand female rabbits were randomly divided into solvent control group,positive control group (cyclophosphamide,20 mg/kg)and T. hypoglaucum extract high-dose ,medium-dose and low- dose groups(15.0,7.50,3.75 g/kg,by the amount of crude drug )according to their body weight ,with 18 rabbits in each group at least. The female rabbits in solvent control group and T. hypoglaucum extract groups were given water or the corresponding T. hypoglaucum extract solution from 6th to 18th day of pregnancy ,5 mL/kg,once a day. Positive control group was given cyclophosphamide subcutaneously into the neck from 10th to 13th day of pregnancy ,1 mL/kg,once a day. According to the related requirements of Technical Guidelines for the Study of Drug Reproductive Toxicity ,the general situation ,body weight ,body weight increase and food intake of female rabbits were observed and recorded during the experiment ,and euthanasia was carried out on 28th day of pregnancy ;the relative indexes of main organs ,fetal uterus ,placenta uterus ,placenta,ovary,implantation gland , absorption fetus ,stillbirth,live fetus and corpus luteum were observed and recorded after anatomy ;the relative indexes of body weight,appearance,visceral and skeletal alterations of the fetus were detected . RESULTS :Compared with solvent control group , the body weight ,body weight increase ,food intake ,main organs ,pregnancy of pregnant rabbits ,as well as reproductive function,embryo formation ,fetal growth and development ,appearance,visceral and skeletal development indexes in T. hypoglaucum extract groups had no significant abnormal changes (P>0.05);above indexes in the positive control group had significant changes (P<0.05),and significant maternal toxicity and embryotoxicity were found. CONCLUSIONS :T. hypoglaucum extract 15.00-3.75 g/kg(by the amount of crude drug )have no significant maternal toxicity ,embryotoxicity or fetal development toxicity to New Zealand rabbits.

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