1.Microbial-lipid Metabolism Mechanism of Liver Injury in Wistar Rats Caused by Dictamni Cortex- Flavescens Sophora
Luna NIU ; Chunguo WANG ; Lu JING
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(11):34-42
ObjectiveTo observe the microbial changes in Wistar rats with liver injury caused by the Dictamni Cortex-Flavescens Sophora by high-throughput sequencing technology and investigate the potential mechanism of liver injury caused by the Dictamni Cortex-Flavescens Sophora. MethodFemale Wistar rats were randomly divided into four groups: normal group, as well as low-dose, medium-dose, and high-dose groups of traditional Chinese medicine (TCM). The rats were gavaged with the Dictamni Cortex-Flavescens Sophora in different doses (4.125, 8.25, 16.5 g·kg-1 of raw drug respectively) for 28 days, and the general condition was recorded. The liver-body weight ratio was calculated, and the biochemical indexes of serum were observed. The Hematoxylin-eosin (HE) staining was used to observe pathological changes in the liver, and 16S rDNA high-throughput sequencing was utilized to detect fecal microbial changes in rats. ResultCompared with the normal group, Dictamni Cortex-Flavescens Sophora increased the liver weights and liver-body weight ratios of Wistar rats. The difference in liver weight between the medium-dose and high-dose groups of TCM was statistically significant (P<0.05), and the liver-body weight ratios of the low-dose, medium-dose, and high-dose groups of TCM were all statistically significant (P<0.05). Compared with the normal group, serum albumin and cholesterol levels increased in the medium-dose and high-dose groups of TCM (P<0.05). The histopathology of the liver in the medium-dose and high-dose groups of TCM showed tiny vacuole-like changes. Compared with the normal group, there were obvious intestinal flora disorders after administration of Dictamni Cortex-Flavescens Sophora, and alpha diversity increased in the medium-dose and high-dose groups of TCM. The principal coordinates analysis showed that species increasingly deviated from the normal group as the administered dose increased. Compared with the normal group, the proportion of Firmicutes and Bacteroidota decreased after the drug administration, and the genus level of Parasutterella, Romboutsia, Turicibacter, Allobaculum, and Dubosiella increased. The genus level of Lachnospiraceae_NK4A136_group, Blautia, Erysipelatoclostridium, Muribaculum, and Ruminococcus_gnavus_group decreased. The correlation analysis showed that Parasutterella, Romboutsia, Turicibacter, Allobaculum, and Dubosiella were positively correlated with serum cholesterol and liver-body weight ratio, and lanchnospiraceae_NK4A136_group, Blautia, Muribaculum, Erysipelatoclostridium, and Ruminococcus_gnavus_group were negatively associated with serum cholesterol and liver-body weight ratio. ConclusionThe liver injury caused by Dictamni Cortex-Flavescens Sophora is manifested as a lipid metabolism disorder, and the mechanism is related to the increase in lipid metabolism-related microorganisms.
2.Pharmacodynamic Effect and Mechanism of Xiaoke Drink in Ameliorating Insulin Resistance in ob/ob Mice
Baoying LI ; Baosheng ZHAO ; Yuling ZHA ; Mi DENG ; Luna NIU ; Xuefei LI ; Ruowei ZHU ; Yu DONG ; Lu JING
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(23):254-260
ObjectiveTo observe the effect of Xiaoke drink on insulin resistance in ob/ob mice and explore the mechanism. MethodEighteen ob/ob mice were randomly assigned into model, Xiaoke drink (17.68 g·kg-1), and atorvastatin (0.01 g·kg-1) groups (n=6), and six C57BL/6 mice were selected as the normal group. Mice in the normal and model groups were administrated with the same amount of distilled water. Fasting body weight, weekly food intake, and weekly water intake were measured at a fixed time. Fasting plasma glucose (FPG) and 2-hour post-load plasma glucose (2 hPG) were measured before and after 8-week intervention. After intervention, total cholesterol (TC), triglyceride (TG), fasting insulin (FINS), Homeostasis Model Assessment-Insulin Resistance (HOMA-IR), blood routine, and alkaline phosphatase (ALP) were measured. Western blot was employed to determine the expression levels of ubiquitin-specific protease 20 (USP20) and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) in the liver. The pancreas was stained with hematoxylin-eosin for observation. ResultCompared with the model group, the Xiaoke drink group showed decreased body weight of ob/ob mice (P<0.05, P<0.01), declined growth trend of body weight (P<0.05, P<0.01), reduced weekly average water intake, lowered levels of FPG, 2 hPG, TC, and HOMA-IR (P<0.05, P<0.01), and down-regulated expression level of USP20 in the liver (P<0.05). HMGCR content was positively correlated with USP20 expression. In addition, Xiaoke drink promoted the recovery of islet tissue morphology and function in ob/ob mice. ConclusionXiaoke drink can ameliorate insulin resistance in ob/ob mice by inhibiting USP20/HMGCR expression, reversing cholesterol biosynthesis process, and reducing cholesterol level.