RSC Advances
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2023
·Vol. 13
·期 4
·2635-2648
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IF 3.9
Ying Li,Yingxin Tian,Qixue Wang,Xinyi Gu,Long Chen,Yiqun Jia,Shan Cao,Ting Zhang,Mingmei Zhou,Xiaojun Gou
Gynura segetum (Lour.) Merr. (GS), has been widely used in Chinese folk medicine and can promote circulation, relieve pain and remove stasis. In recent years, the hepatotoxicity caused by GS has been reported, however its mechanism is not fully elucidated. Metabolomic techniques are powerful means to explore the toxicological mechanism and therapeutic effects of traditional Chinese medicine. The purpose of this study was to establish a serum metabolomics method based on Gas Chromatography-Mass Spectrometry (GC-MS) to explore the hepatotoxicity mechanism of different exposure times and doses of GS in rats. Sprague Dawley (SD) rats were administered daily with distilled water, 7.5 g kg−1 GS, or 15 g kg−1 GS by intragastrical gavage for either 10 or 21 days. The methods adopted included enzyme-linked immunosorbent assay (ELISA), Hematoxylin and Eosin (H&E) staining and GC-MS-based serum metabolomics. Serum biochemistry analysis showed that the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglycerides (TG), total bilirubin (TBIL) and total bile acid (TBA) significantly (P < 0.05) increased while the levels of albumin (ALB) and high-density lipoprotein (HDL) significantly (P < 0.05) decreased in GS-treated groups, compared with the control group. Interestingly, the ALT, AST, TG and ALB levels changed in a time- and dose-dependent manner. The results of H&E staining showed the degree of liver damage after administration of GS gradually deepened with the extension of administration time and the increase of the dose. According to the results of metabolomics analysis, 26 differential metabolites were identified, which were involved in 8 metabolic pathways including phenylalanine metabolism, glyoxylic acid and dicarboxylic acid metabolism and so on. Meanwhile, the number of differential metabolites in different GS-treated groups was associated with GS exposure time and dose. Therefore, we concluded that GS might induce hepatotoxicity depending on the exposure time and dose.
研究领域:
药理学
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毒理学
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代谢组学
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传统中药
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DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2023
·
IF 7.5
Guoqin Zhang,Jianhua Sun,Meiqi Liu,Zhixiang Tian,Zicheng Ma,Bingyu Hao,Jintang Ning,Xiaoliang Ren,Meng Wang,Ping Wang,Jiunian Li,Hailin Li,Jian Ni,Yi Liu
Polygoni multiflori radix (PM) is a well-known tonic herb. It has been reported that PM could cause idiosyncratic inflammatory liver injury in some individuals. In this study, we investigated the mechanism of PM-induced idiosyncratic inflammatory liver injury in zebrafish and rat models based on pharmacodynamics and pharmacokinetics. The zebrafish were administered with polygoni multiflori radix extract (PME), emodin (EMO), and 2,3,5,4′-tetrahydroxystilbene-2-Ο-β- D -glucoside (TSG) after lipopolysaccharide (LPS) treatment, to establish an idiosyncratic inflammation model. In zebrafish with idiosyncratic inflammation, PME, EMO, and TSG decreased liver area and brightness and increased the number of immune cells around the colliculi. PME+LPS produced hepatocyte damage, aggravated mitochondrial and endoplasmic reticulum damage, and increased AST and ALT activity. RT-PCR showed that PME and EMO up-regulated the expression of IL-6, IL-1β, and INF-γ, and PME down-regulated expression of FXR and SHP. In rats with idiosyncratic inflammation, AST and ALT activities increased significantly, and liver tissues showed pathological damage. An efficient and sensitive LC-MS/MS method was established for the pharmacokinetic study of EMO and TSG in rats with idiosyncratic inflammation. The AUC 0−t was higher for EMO and TSG in the model group compared with the normal group. The MRT 0−t was significantly prolonged in EMO, while CL z/F was significantly reduced. The present results suggested that the absorption of potentially toxic components of PM increased and metabolism slowed down under inflammatory stress, and PM induced idiosyncratic liver injury via the FXR-SHP axis.
研究领域:
药理学
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毒理学
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肝病学
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药代动力学
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斑马鱼模型
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大鼠模型
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DOI
PubMed
高影响因子
ACS Nano
·
2022
·
IF 18.027
Ruijia Huang,Xiaoqing Cai,Jihui Du,Jie Lian,Ping Hui,Minxuan Gu,Feng Li,Jidong Wang,Wenwen Chen
Delayed use of appropriate antibiotics for superbugs, particularly for extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pn), has caused extensive morbidity and mortality worldwide. Therefore, rapid and on-site antimicrobial susceptibility testing (AST) is urgently required. Unfortunately, currently, no phenotypic AST can realize a sample-to-answer result within 2 h directly from a clinical sample and without using laboratory equipment or customized devices. Inspired by observing that E. coli and K. pn can rapidly catalyze H2O2, we developed a plasmonic nanosensor that responds to the proliferation of bacteria for realizing rapid AST. The results can be determined with the naked eye, digitized using a smartphone, and validated using ultraviolet–visible spectrometry. Our assay achieved superb area under the curves of 0.9752 and 1 in a receiver operating characteristic analysis directly obtained from uncultured clinical urine samples infected by E. coli and K. pn, respectively. The entire process from sample collection to analysis takes 100 min for E. coli and 85 min for K. pn detection. Our platform provides a practical approach for performing on-site AST in clinics to improve the survival of patients. It releases the burden of superbugs and avoids the abuse of antibiotics.
研究领域:
生物技术
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纳米技术
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医学诊断
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微生物学
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临床化学
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DOI
PubMed
高影响因子
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
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2022
·Vol. 395
·期 10
·1283-1295
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IF 3.195
Xiong Ziwei,Cui Yushun,Wu Jiahui,Shi Lingyu,Quan Wen,Yang Shilin,Feng Yulin
Pteris cretica L. var. nervosa is one of the most well-known Chinese medicines. Although it is widely used to treat jaundice hepatitis, the main ingredient for its treatment was not thoroughly explored until recently. Essentially, the purpose of this study is to find the monomer compound in Pteris cretica L. var. nervosa , which is most likely to be effective in treating liver injury. Through the model of LPS/D-gal-induced liver injury in mice, the best therapeutic site of the total extract was explored, the chemical components of the parts with the best therapeutic effect were separated, a total of 10 flavonoids were isolated, and the RAW264.7 cells induced by LPS were used as the experimental model to explore the preliminary anti-inflammatory activity of NO production in vitro. Finally, the anti-inflammatory activity and the highest content in this plant Luteolin-7-O-rutinoside (LUT) were selected, as the object of study in vivo. It was found that LUT could not only reduce alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, but also significantly reduce the release of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β), and inhibit PI3K/AKT/AMPK/NF-κB pathway. In addition, LUT can increase levels of SOD and GSH to reduce oxidative stress. It has an obvious therapeutic effect on acute liver injury induced by LPS/D-gal in mice. Therefore, infer LUT is a functional substance in Pteris cretica L. var. nervosa. Graphical abstract
研究领域:
药理学
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免疫学
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肝脏病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2019
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IF 3.775
Jiankang Wang,Yutong He,Deqing Yu,Liang Jin,Xiaobao Gong,Baoshun Zhang
Perilla oil (PerO), a natural oil with a high unsaturated fatty acid content derived from the mature seeds of Perilla frutescens , is a homology of medicine and food . The type 2 diabetes mellitus (T2DM) model was successfully established using a high-fat and high-sugar diet combined with a single low-dose of streptozocin (STZ). PerO intervention reduced the levels of fasting blood glucose and the level, size and accumulation of lipid droplets , increased the insulin level and diminished the body weight loss. PerO pretreatment markedly promoted the serum levels of alanine transaminase (ALT) and aspartate transaminase alanine (AST) and inhibited the levels of glucose (GLU), glucose-6-phosphate dehydrogenase (G6PD), triglycerides (TGs) and total cholesterol (TC). Moreover, PerO treatment enhanced the expression of phosphoinositide-3 kinase (PI3K)/protein kinase B (AKT) and activated the expression of glucose transporter 4 (Glut4) and phospho-AKT serine/threonine kinase (p-AS160) in the liver. Additionally, PerO treatment distinctly decreased the abundance of Aerococcus and facilitated the richness of Alloprevotella in the intestine, as well as accelerated the restoration of the gut microflora diversity. Thus, PerO regulates intestinal microbiota and alleviates insulin resistance through the PI3K/AKT signaling pathway in type-2 diabetic KKAy mice and may be a potential functional food for diabetic treatment.
研究领域:
营养学
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糖尿病
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分子生物学
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微生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2019
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IF 4.784
Hang Qu,Xin Gao,Zhen-Yu Wang,Juan-Juan Yi
A novel polysaccharide (PNP80b-2) was obtained from Pinus koraiensis pine nut, which has been proved to possess good hepatoprotective effects in vitro . This study comprehensively investigated its hepatoprotective activities against different types of chemical-induced liver injury in vivo . Carbon tetrachloride, alcohol and acetaminophen were used as hepatic toxicants to establish chemical pollutant-induced liver injury (CILI) model, alcohol induced-liver injury (AILI) model and drug-induced liver injury (DILI) model, respectively. The results showed that PNP80b-2 prevented elevation of biomarkers for liver injury in each model, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and total bilirubin (TBIL). The expression of cytochrome P450 in damaged hepatocytes was also downregulated. Additionally, PNP80b-2 enhanced hepatic antioxidant capacity through upregulating the expression of NRF2 and HO-1, thereby increasing superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) activities and decreasing malondialdehyde (MDA) levels. The uncontrolled production of inflammatory factors including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2) in CILI, AILI and DILI models was also suppressed by PNP80b-2. By contrast, PNP80b-2 exerted the strongest hepatoprotection against AILI model, through improving hepatic antioxidant capacity via NRF2/ARE pathway and regulating inflammation response. Thus, PNP80b-2 is a promising functional food to prevent AILI.
研究领域:
药理学
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肝病学
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功能性食品
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毒理学
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DOI
PubMed
高影响因子
AMB Express
·
2024
·Vol. 14
·期 1
·1-16
·
IF 3.5
Yan Yan,Yuan Haisheng,Yang Fan,Na Heiya,Yu Xiuling,Liu Jingran,Wang Yuzhen
Non-alcoholic fatty liver disease (NAFLD) is becoming a significant global public health threat. Seabuckthorn ( Hippophae rhamnoides L.) has been used in traditional Chinese medicine (TCM). The hypolipidemic effects of Seabuckthorn polysaccharides (SP) against high-fat diets (HFD)-induced NAFLD were systematically explored and compared with that of Bifidobacterium lactis V9 ( B. Lactis V9). Results showed that HFD-induced alanine transaminase (ALT) and aspartate aminotransferase (AST) levels decreased by 2.8-fold and 4.5-fold, respectively, after SP supplementation. Moreover, the alleviating effect on hepatic lipid accumulation is better than that of B. Lactis V9. The ACC and FASN mRNA levels were significantly reduced by 1.8 fold ( P < 0.05) and 2.3 folds ( P < 0.05), respectively, while the CPT1α and PPARα mRNA levels was significantly increased by 2.3 fold ( P < 0.05) and 1.6 fold ( P < 0.05), respectively, after SP administration. SP activated phosphorylated-AMPK and inhibited PPARγ protein expression, improved serum oxidative stress and inflammation ( P < 0.05). SP supplementation leads to increased hepatic expression of nuclear factor erythroid 2-related factor 2 (Nrf-2), heme oxygenase-1 (HO-1) and Superoxide dismutase-2 (SOD-2). Furthermore, SP treatment improved HFD-induced intestinal dysbiosis. Lentisphaerae , Firmicutes , Tenericutes and Peptococcus sp., RC9_gut_group sp., and Parabacteroides sp. of the gut microbiota were significantly associated with hepatic steatosis and indicators related to oxidative stress and inflammation. Therefore, SP can mitigate hepatic lipid accumulation by regulating Nrf-2/HO-1 signaling pathways and gut microbiota. This study offers new evidence supporting the use of SP as a prebiotic treatment for NAFLD.
研究领域:
药理学
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肝病学
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营养学
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微生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Yan Lin,Xing-Jun Chen,Jing-Jing Li,Lei He,Ya-Ru Yang,Fei Zhong,Ming-Hui He,Yi-Tong Shen,Bo Tu,Xu Zhang,Zhu Zeng
Ethnopharmacology relevance Sophora flavescens Aiton, was a crucial source of Traditional Chinese Medicine (TCM) that has benefited human health for hundreds of years. Alkaloids and flavonoids were the major bioactive constituents from S. flavescens , which had been widely used for liver disease treatment in China. However, the liver-protective components of flavonoids from S. flavescens and their mechanism of action were not clear. Aim of the study This work aimed to evaluate the in vitro hepatoprotective activities of 35 flavonoids from S. flavescens and screen active compounds. Furthermore, it was conducted to demonstrate the hepatoprotective effects of a new active compound (kurarinol A, 1 ) was isolated by authors and the ethyl acetate (EtOAc) extract form S. flavescens against carbon tetrachloride (CCl 4 )-induced hepatic injury in Kunming (KM) mice, meanwhile revealed the potential mechanism. Materials and methods The 35 flavonoids from S. flavescens were co-incubated with HepG2 cells and treated with 0.35% CCl 4 for 6 h cell viability was measured by (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) (MTS) assay. Then, in vivo animal experiments, the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) in the serum were analyzed, the degree of hepatic injury was examined using hematoxylin-eosin (H&E) staining, the mRNA expression of Superoxide Dismutase 2 (SOD2), Nuclear factor E2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), Interleukin 6 (IL-6), Tumor Necrosis Factor-α (TNF-α), interleukin-1β (IL-1β), and the protein levels of nuclear factor-kappa B p65/p-p65 (NF-κB p65/p-p65), toll-like receptor 2 (TLR2), IL-1β and cyclooxygenase-2 (COX2) in hepatic tissues were detected. Results The lavandulyl flavonoid (kurarinol A, 1 ) and the EtOAc extract from S. flavescens showed protective effects on CCl 4 -injured HepG2 cells, increasing cell viability from 24.5% to 61.3% and 91.8%, respectively. What’s more, we found that treatment with kurarinol A ( 1 ) and the EtOAc extract lead to a significant reduction in hepatotoxicity in response to acute CCl 4 exposure. Compared with the model group, experimental results exhibited kurarinol A (10 mg/kg, i.p.) and the EtOAc extract (300 mg/kg, i.p.) could decrease the levels of AST, ALT, ALP and tissue damage. Further mechanistic investigations revealed that up-regulated the mRNA expression of SOD2, Nrf2, OH-1 and down-regulated the IL-1β in liver tissues, respectively. Additionally, Western blot analyses elucidated that inhibition of IL-1β, TLR2, COX-2, NF-κB (p65/p-p65) via TLR2/NF-κB signaling pathway by kurarinol A and the EtOAc extract contribute to its hepatoprotective activity. Conclusion These findings demonstrated that the novel compound (kurarinol A, 1 ) possessed notable hepatoprotective activity against CCl 4 . It was confirmed that kurarinol A had a certain effect on mice with liver damage induced by CCl 4 , and its mechanism could be include inhibiting inflammation and reducing of oxidative stress reaction by regulating expression of related genes and proteins. Thus, kurarinol A could as a novel active agent that contributes to the hepatoprotective activity of S. flavescens for the treatment of live injury.
研究领域:
药理学
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民族药理学
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分子生物学
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细胞生物学
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毒理学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
Wang Kaiping,Yang Linlin,Zhou Jing,Pan Xianglin,He Zihao,Liu Junxi,Zhang Yu
The alleviation of oxidative stress is considered an effective treatment for acetaminophen (APAP)-induced acute liver injury (AILI). However, it remains unknow whether the potential antioxidant Smilax china L. polysaccharide (SCLP) protects against AILI. In this study, in vitro and in vivo experiments were conducted to verify the hepatoprotective effect of SCLP against AILI and explore the potential mechanism. We found that SCLP relieved liver histopathological changes; reversed the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), malondialdehyde (MDA) and reactive oxygen species (ROS); reversed the change in liver myeloperoxidase (MPO) activity; and enhanced liver antioxidant (GSH, GSH-Px, and t-SOD) levels in APAP-treated mice, thereby significantly reducing APAP-induced liver toxicity. SCLP rescued the cell viability and alleviated oxidative stress in H2O2-treated mouse AML12 (Alpha mouse liver 12) hepatocytes. The results of the mechanistic studies showed that SCLP upregulated nuclear factor E2 related factor (Nrf2) expression, promoted Nrf2 nuclear translocation, and enhanced the ability of Nrf2 to bind antioxidant response elements (AREs). Furthermore, SCLP activated Nrf2-ARE pathway, thus upregulating the expression of oxidative stress-related proteins heme oxygenase 1(HO-1), NAD(P)H quinone dehydrogenase 1(NQO-1) and glutamic acid cysteine ligase catalytic subunit (GCLC). In conclusion, this study confirmed the close correlation between liver protection by SCLP upon exposure to APAP and activated of the Nrf2-ARE pathway. These findings suggest that SCLP is an attractive therapeutic candidate drug for the treatment of AILI.
研究领域:
药理学
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毒理学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
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