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China Journal of Chinese Materia Medica ; (24): 3317-3326, 2023.
Article in Chinese | WPRIM | ID: wpr-981469


In recent years, reports of adverse reactions related to traditional Chinese medicine(TCM) have been on the rise, especially some traditionally considered "non-toxic" TCM(such as Dictamni Cortex). This has aroused the concern of scholars. This study aims to explore the metabolomic mechanism underlying the difference in liver injury induced by dictamnine between males and females through the experiment on 4-week-old mice. The results showed that the serum biochemical indexes of liver function and organ coefficients were significantly increased by dictamnine(P<0.05), and hepatic alveolar steatosis was mainly observed in female mice. However, no histopathological changes were observed in the male mice. Furthermore, a total of 48 differential metabolites(such as tryptophan, corticosterone, and indole) related to the difference in liver injury between males and females were screened out by untargeted metabolomics and multivariate statistical analysis. According to the receiver operating characteristic(ROC) curve, 14 metabolites were highly correlated with the difference. Finally, pathway enrichment analysis indicated that disorders of metabolic pathways, such as tryptophan metabolism, steroid hormone biosynthesis, and ferroptosis(linoleic acid metabolism and arachidonic acid metabolism), may be the potential mechanism of the difference. Liver injury induced by dictamnine is significantly different between males and females, which may be caused by the disorders of tryptophan metabolism, steroid hormone biosynthesis, and ferroptosis pathways.

Female , Male , Animals , Mice , Tryptophan , Metabolomics , Fatty Liver , Steroids , Hormones
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 77-85, 2022.
Article in Chinese | WPRIM | ID: wpr-940488


ObjectiveTo explore the differences in response to bakuchiol-induced hepatotoxicity between Institute of Cancer Research (ICR) mice and Kunming (KM) mice. MethodThe objective manifestations of bakuchiol-induced hepatotoxicity in mice were confirmed by acute and subacute toxicity animal experiments, and enrichment pathways of differential genes between normal ICR mice and KM mice were compared by transcriptomics. The real-time quantitative polymerase chain reaction (real-time qPCR) assay was used to verify the mRNA expression of key genes in the related pathways to confirm the species differences of bakuchiol-induced liver injury. ResultIn the subacute toxicity experiment, compared with the normal mice, the ICR mice showed increased serum content of alkaline phosphatase (ALP), and 5′-nucleotidase (5′-NT), without significant difference, and no manifest change was observed in KM mice. Pathological results showed that hepatocyte hypertrophy was the main pathological feature in ICR mice and hepatocyte steatosis in KM mice. In the acute toxicity experiment, KM mice showed erect hair, mental malaise, and near-death 3 days after administration. The levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in KM mice (400 mg·kg-1) significantly increased(P<0.01), and the activity of total reactive oxygen species (SOD) in liver significantly decreased(P<0.01)compared with those in normal mice, while the serum content of 5′-NT and cholinesterase (CHE) in ICR mice (400 mg·kg-1) were significantly elevated (P<0.01). The liver/brain ratio in ICR mice increased by 20.34% and that in KM mice increased by 29.14% (P<0.01). The main pathological manifestation of the liver in ICR mice was hepatocyte hypertrophy, while those in KM mice were focal inflammation, hepatocyte hypertrophy, and hepatocyte steatosis. Kyoto Encyclopedia of Genes and Genomes(KEGG)and Reactome pathway enrichment analyses showed that the differential gene expression between ICR mice and KM mice was mainly involved in oxidative phosphorylation, bile secretion, bile acid and bile salts synthesis, and metabolism pathway. CYP7A1 was up-regulated in all groups with drug intervention (P<0.01) and MRP2 was reduced in all groups with drug intervention of KM mice (P<0.01) and elevated in all groups with drug intervention of ICR mice (P<0.01) compared with those in the normal group. The expression of BSEP was lowered in ICR mice with acute liver injury (400 mg·kg-1) (P<0.05). SHP1 was highly expressed in KM mice with acute liver injury (400 mg·kg-1). The expression of FXR was diminished in ICR mice with subacute liver injury (200 mg·kg-1) (P<0.01). SOD1, CAT, and NFR2 significantly decreased in KM mice with acute liver injury (400 mg·kg-1), and CAT dwindled in KM mice with subacute liver injury (200 mg·kg-1) (P<0.01). GSTA1 and GPX1 significantly increased in KM mice with acute liver injury (400 mg·kg-1) (P<0.01) and SOD1, CAT, NRF2, and GSTA1 significantly increased in ICR mice with subacute liver injury (200 mg·kg-1) (P<0.01). CAT and NRF2 significantly increased in ICR mice with acute liver injury (400 mg·kg-1) (P<0.01). ConclusionWith the increase in the dosage of bakuchiol, the liver injury induced by oxidative stress in KM mice was gradually aggravated, and ICR mice showed stronger antioxidant capacity. The comparison of responses to bakuchiol-induced hepatotoxicity between ICR mice and KM mice reveals that ICR mice are more suitable for the investigation of the mechanisms related to bile secretion and bile acid metabolism in the research on bakuchiol-induced hepatotoxicity in mice. KM mice are more prone to liver injury caused by oxidative stress.

Chinese Journal of Hematology ; (12): 989-993, 2018.
Article in Chinese | WPRIM | ID: wpr-1011903


Objective: To study the effect of WT1 expression on the prognosis of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in acute leukemia (AL) and its significance as molecular marker to dynamically monitor minimal residual disease (MRD) . Methods: Retrospectively analyzed those AL patients who underwent allo-HSCT in the First Hospital Affiliated to Zhejiang University School of Medicine during Jan 2016 to Dec 2017, a total number of 314 cases, 163 males and 151 females, median age was 30 (9-64) years old. Comparing the difference of WT1 expression at diagnosed, pre-HSCT and after HSCT. Using the receiver operating characteristic (ROC) curve to determine the WT1 threshold at different time so as to predict relapse. The threshold of WT1 expression before transplantation was 1.010%, within 3 months after HSCT was 0.079% and 6 months after HSCT was 0.375%. According to these thresholds, WT1 positive patients were divided into low expression groups and high expression groups. Analyzed the relationship between overall survival (OS) , disease-free survival (DFS) , cumulative incidence of relapse (CIR) and WT1 expression. Results: The OS and DFS of high expression group pre-HSCT were lower than low expression group [69.2% (9/13) vs 89.1% (57/64) , χ(2)=4.086, P=0.043; 53.8% (7/13) vs 87.5% (56/64) , χ(2)=9.766, P=0.002], CIR was higher than low expression group [30.8% (4/13) vs 7.8% (5/64) , P=0.017]. There was no significant difference of OS and DFS between high expression and low expression group of 3 months after HSCT (P=0.558, P=0.269) . The OS and DFS of high expression group of 6 months after transplantation were both lower than low expression group (P=0.049, P=0.035) . Multivariate analysis showed that WT1>0.375% when 6 months after transplantation was the only independent prognostic factor for shorter DFS (P=0.022) . There was no statistically significant difference in CIR between the high-expression group and the low-expression group 3 months after transplantation and 6 months after transplantation (P=0.114, P=0.306) . Conclusion: High expression of WT1 before and after HSCT was an adverse prognosis factor. It is of clinical practical value to use WT1 as a transplant recommendation index for patients with acute leukemia and as a marker to monitor MRD dynamically.

Adolescent , Adult , Child , Female , Humans , Male , Middle Aged , Young Adult , Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute/therapy , Neoplasm, Residual , Prognosis , Retrospective Studies , Transplantation, Homologous , WT1 Proteins
China Journal of Chinese Materia Medica ; (24): 2325-2329, 2015.
Article in Chinese | WPRIM | ID: wpr-337936


Toxicity of different processed was evaluated Polygoni Multiflori Radix by determining the hepatotoxic potency for selecting processing technology. Process Polygoni Multiflori Radix using high pressure steamed, Black Bean high pressure steamed, atmospheric steamed for different time. Using normal human hepatocytes (L02) as evaluation model, hepatotoxic potency as index to evaluate hepatotoxic potency of different processed Polygoni Multiflori Radix. Analysis chemical composition of some processed products by UPLC-MS. Hepatotoxic bioassay method cloud evaluate the toxicity of different Polygoni Multiflori Radix samples. Different processing methods can reduce the toxicity of Polygoni Multiflori Radix, high pressure steamed three hours attenuated was better. Different processing methods have different effects on chemical constituents of Polygoni Multiflori Radix. Comparing with crude sample, the contents of gallic acid, 2,3,5,4-tetrahydroxyl diphenylethylene-2-O-glucoside, emodin-8-O-beta glucoside and emodin were decreased in processed products with 3 kinds of different methods. The change trend of 2,3,5,4-tetrahydroxyl diphenylethylene-2-O-glucoside content was similar with hepatotoxic potency. Different processing methods can reduce the toxicity of Polygoni Multiflori Radix. Processing methods and time attenuated obvious impact on toxicity. Recommended further research on the attehuated standard control of Polygoni Multiflori Radix concocted.

Humans , Biological Assay , Cell Line , Chemistry, Pharmaceutical , Methods , Chromatography, High Pressure Liquid , Drugs, Chinese Herbal , Chemistry , Toxicity , Fallopia multiflora , Chemistry , Toxicity , Hepatocytes , Plant Roots , Chemistry , Toxicity
China Journal of Chinese Materia Medica ; (24): 654-660, 2015.
Article in Chinese | WPRIM | ID: wpr-330182


To investigate the difference of liver injury in rats gavaged with crude and processed Polygoni Multiflori Radix. The 75% ethanol extract of crude and processed Polygoni Multiflori Radix (50 g · kg(-1) crude medicine weight/body weight) were continuous oral administered to rats for 6 weeks. Serum biochemical indicators were dynamically detected, the change of liver histopathology was assessed 6 weeks later. Principal component analysis (PCA) was adopted to screen sensitive indicator of the liver damage induced by polygoni multiflori radix. Biochemical tests showed that the crude Polygoni Multiflori Radix group had significant increase of serum ALT, AST, ALP, DBIL and TBIL (P < 0.01 or P < 0.05) and significant decreases of serum IBIL and TBA (P < 0.01 or P < 0.05), while the processed Polygoni Multiflori Radix group showed no obvious changes, compared to the untreated normal group. Histopathologic analysis revealed that crude Polygoni Multiflori Radix group exhibited significant inflammatory cells infiltration in portal area around the blood vessels, tissue destruction and local necrosis of liver cells. There were not obvious pathological changes in processed Polygoni Multiflori Radix group. The results demonstrated that the injury effect of processed Polygoni Multiflori Radix on liver injury of rats was significantly lower than that of unprocessed, and that processing can effectively reduce the hepatotoxicity of Polygoni Multiflori Radix. Traditional transaminase liver function indicators were not sensitive for crude Polygoni Multiflori Radix induced liver damage. The serum content of DBIL and TBIL can reflect the liver damage induced by crude Polygoni Multiflori Radix early and can be sensitive indicators for clinical monitoring the usage of it.

Animals , Female , Male , Rats , Chemical and Drug Induced Liver Injury , Chemistry, Pharmaceutical , Methods , Drugs, Chinese Herbal , Chemistry , Toxicity , Liver , Wounds and Injuries , Plant Roots , Chemistry , Toxicity , Polygonum , Chemistry , Toxicity