Chemical Biology & Drug Design
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2025
·Vol. 105
·期 4
·e70097
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IF 3.3
Wei-fang Song,Sheng-nan Li,Rui-xin Yao,Qiu-yan Jiang,Ting Shi,Dan-dan Fan,Hai-juan Zhang,Wen-hui Zhang,Rui-jun Wang
The primary objective aims to evaluate the therapeutic efficacy of echinacoside in ameliorating hepatic steatosis and exploring its role in modulating autophagic flux through AMP-activated protein kinase (AMPK) signaling, positioning it as a potential treatment for non-alcoholic fatty liver disease (NAFLD). A well-established NAFLD rat model was employed, administering varying concentrations of echinacoside. Biochemical parameters, including triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), alongside liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP), were measured to assess liver function. To elucidate the molecular mechanisms, western blot analyses were performed to assess the expressions of p-AMPK, total AMPK, and key autophagy markers LC-3 I/II and Beclin-1. Echinacoside significantly improved the lipid profile by lowering plasma TG, TC, and LDL-C levels while increasing HDL-C. It also reduced serum ALT, AST, and ALP activities, demonstrating hepatoprotective effects. Notably, echinacoside reversed the p-AMPK levels in NAFLD rats in a dose-dependent manner, with the highest dosage showing the strongest effect. This was accompanied by increased expression of LC-3 I/II and Beclin-1. Echinacoside is expected to be a therapeutic drug for NAFLD by activating AMPK activity and enhancing autophagy to improve liver function. These findings suggest its clinical potential, with autophagy modulation via the AMPK pathway as a possible therapeutic mechanism for NAFLD treatment.
研究领域:
药理学
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代谢生物学
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肝脏疾病研究
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DOI
PubMed
高影响因子
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
·
2025
·
IF 4.6
Dake Wen,Ru Yan,Jian He,Ling Gu,Xu-Yang Chen,Kai Wang
γ -Glutamyltransferase (GGT, EC number: 2.3.2.2) is an enzyme critical for glutathione metabolism and serves as a key biomarker for liver function and disease. Diabetes mellitus, a prevalent metabolic disorder, often complicates liver function and increases the challenge of accurately monitoring hepatic GGT levels due to fluctuating metabolic conditions. In this study, we introduce a sulfonate-modified hemicyanine dye-based probe, HDP-GGT, designed for the targeted and real-time assessment of GGT activity in the liver. HDP-GGT combines the fluorescence and photoacoustic advantages of hemicyanine dyes with a specific peptide sequence that enhances sensitivity and specificity for GGT detection. Utilizing both in vitro and in vivo methodologies, the sulfonate-modified HDP-GGT probe enables dual-modal imaging of hepatic and serum GGT activity by photoacoustic and fluorescence models, respectively. To evaluate the clinical translational potential of HDP-GGT, we applied it to detect GGT in mouse serum, finding that the fluorescence signal intensity was highest in the diabetes mellitus (DM) group and significantly reduced in the diabetes mellitus + metformin (DM + Met) group, suggesting that HDP-GGT has promising clinical application prospects. Our results indicate that HDP-GGT is a potent tool for non-invasive monitoring of liver health and could play a crucial role in diagnosing and managing liver-related disorders, particularly in the context of diabetes.
研究领域:
医学
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生物化学
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影像学
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DOI
PubMed
高影响因子
Biomedical Optics Express
·
2024
·Vol. 15
·期 10
·5803-5817
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IF 2.9
Yingchun Li,Yingchun Li,Haobo Cheng
In this work, we developed a novel microfluidic paper-based analytical device to quantify the blood markers of liver function from human fingertips and whole blood samples. The device can quickly acquire information for screening liver injury and supporting clinical decision-making by simultaneously performing quantitative tests for alanine aminotransferase, aspartate aminotransferase, and albumin. We evaluated the detection accuracy and the storage stability of the device using fingertip samples. The yielded results of our device correlated well with those from Mindray BS350s, even under the conditions of 35 °C and 90%RH. Thus, it offers an effective platform for clinical assessment of liver injury particularly in resource-limited areas.
研究领域:
医学诊断
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生物工程
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PubMed
高影响因子
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
·
2025
·
IF 4.5
Jinyao Liu,Yingying Pang,Wenyan Li,Juanjuan Sun,Yujie He,Yonghong Guo,Jing Dong
Linezolid, an oxazolidinone antibiotic, is used in patients with liver or kidney disease. However, the effects and mechanisms of hepatic impairment or renal failure on the pharmacokinetics of linezolid and its metabolites (PNU-142586 and PNU-142300) remain unclear. We used carbon tetrachloride-induced impaired hepatic function and 5/6 nephrectomy-induced renal failure rat models to investigate linezolid and metabolite pharmacokinetics. Isolated primary rat hepatocytes were used to evaluate the impact of hepatic impairment or renal failure on linezolid metabolism. Uptake and efflux transport studies were also conducted. The influence of hepatic impairment or renal failure on the pharmacokinetics of linezolid and two metabolites did not differ between intragastric gavage and intravenous administration in rats. Linezolid did not accumulate in the brain, heart, lung, liver, kidney, and small intestinal tissues of the hepatic impairment or renal failure rats. And PNU-142300 did not accumulate in the liver or kidney tissue. Compared to the isolated normal rat hepatocytes, the in vitro hepatic clearance of linezolid in hepatic impairment and renal failure rat hepatocytes decreased by 61.3% and 44.1%, respectively. Organic anion transporting polypeptide (OATP)1B1, OATP1B3, OATP2B1, Na+-taurocholate co-transporting polypeptide (NTCP), organic anion transporter (OAT)1, OAT3, multidrug resistance-associated protein 2 (MRP2), or multidrug resistance protein 1 (MDR) did not mediate linezolid transport. Hepatic impairment primarily increases linezolid exposure through reduced hepatic metabolism, whereas renal failure increases both linezolid and two metabolites exposure through reduced hepatic metabolism and renal glomerular filtration. These findings guide adjusting the dose of linezolid in patients with hepatic and renal insufficiency.
研究领域:
药理学
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肝脏病学
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肾脏病学
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DOI
PubMed
高影响因子
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
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2025
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IF 4.6
Bao-Ying Wen,Jing-Wen Zhou,Wen-Xiang Jiang,Yue-Jiao Zhang,Jian-Feng Li
Bilirubin, as a major component of human bile and a byproduct of red blood cell metabolism, plays an essential role in diagnosing jaundice and assessing liver function. Surface-enhanced resonance Raman spectroscopy (SERRS) is a highly sensitive detection technique that emerged from the synergy of resonance Raman spectroscopy and surface-enhanced Raman spectroscopy (SERS). This technology not only provides molecular fingerprint information but also offers rapid detection, interference resistance, and high selectivity, making it particularly suitable for specific biological system detection. Herein, we have developed an innovative SERRS technique for efficiently measuring bilirubin levels in urine. This method involves precisely adjusting the pH of sodium nitrite to 1, oxidizing bilirubin to biliverdin. Subsequently, a portable Raman spectrometer with an excitation wavelength of 785 nm is used to emit its resonance Raman signal, achieving high-sensitivity and selective rapid detection. Through this approach, we have achieved the quantification of a wide linear dynamic range spanning from 860 nmol/L to 34.2 μmol/L, characterized by an excellent correlation coefficient of 0.99 and a remarkably low detection limit of 860 pmol/L, which is significantly below that of traditional detection methods. Moreover, in the analysis of real samples, minimal pre-treatment is required to achieve high sensitivity and expedited detection. The entire procedure is completed in merely 1 min, with recovery rates falling between 80 % and 100 %. This approach paves the way for the specific and rapid detection of biomarkers using Raman spectroscopy.
研究领域:
医学诊断
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光谱学
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生物分析化学
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DOI
PubMed
高影响因子
Journal of Biophotonics
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2024
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IF 2
Runze Chen,Shiyi Peng,Qiming Xia,Tianxiang Wu,Junyan Zheng,Haiyan Qin,Jun Qian
Achieving high-resolution and large-depth microscopic imaging in vivo under conditions characterized by high-scattering and dense-labeling, as commonly encountered in the liver, poses a formidable challenge. Here, through the optimization of multi-photon fluorescence excitation window, tailored to the unique optical properties of the liver, intravital microscopic imaging of hepatocytes and hepatic blood vessels with high spatial resolution was attained. It's worth noting that resolution degradation caused by tissue scattering of excitation light was mitigated by accounting for moderate tissue self-absorption. Leveraging high-quality multi-photon fluorescence microscopy, we discerned structural and functional alterations in hepatocytes during drug-induced acute liver failure. Furthermore, a reduction in indocyanine green metabolism rates associated with acute liver failure was observed using NIR-II fluorescence macroscopic imaging.
研究领域:
生物医学工程
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肝脏病理学
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DOI
PubMed
高影响因子
Biomed Research International
·
2022
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IF 3.246
Hongwei Shi,Yue Yan,Hong Yang,Peng Pu,Heng Tang
Objective. Pirarubicin (THP) is one of anthracycline anticancer drugs. It is widely used in the treatment of various cancers, but its hepatotoxicity cannot be ignored. Schisandrin B (SchB) is a traditional liver-protecting drug, which has the ability to promote mitochondrial function and upregulate cellular antioxidant defense mechanism. However, whether it can resist THP-induced hepatotoxicity has not been reported. The purpose of this study was to observe and explore the effect of SchB on THP-induced hepatotoxicity and its potential mechanism by adding SchB to the diet of rats with THP-induced hepatotoxicity. Methods. The rat model of THP-induced hepatotoxicity was established and partly treated with SchB diet. The changes of serum liver function indexes ALT and AST were observed. The histomorphological changes of liver were observed by HE staining. The biomarker levels of oxidative stress in rat serum and liver were measured to observe oxidative stress state. The expressions of ferroptosis-related protein GPX4 and oxidative stress-related protein were detected by Western blot. Primary hepatocytes were prepared and cocultured with THP, SchB, and Fer-1 to detect the production of reactive oxygen species (ROS) and verify the above signal pathways. Results. THP rats showed a series of THP-induced hepatotoxicity changes, such as liver function damage, oxidative stress, and ferroptosis. SchB diet effectively alleviated these adverse reactions. Further studies showed that SchB had strong antioxidant and antiferroptosis abilities in THP-induced hepatotoxicity. Conclusion. SchB has obvious protective effect on THP-induced hepatotoxicity. The mechanism may be closely related to inhibiting oxidative stress and ferroptosis in the liver.
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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DOI
PubMed
高影响因子
Biomedicines
·
2021
·Vol. 9
·期 10
·1320
·
IF 6.081
Xiaoke Zheng,Hanyu Yang,Lan Qin,Siqian Wang,Lei Xie,Lu Yang,Weimin Kong,Liang Zhu,Li Liu,Xiaodong Liu
Liver failure is associated with increased levels of brain aromatic amino acids (AAAs), whose transport across the blood–brain barrier (BBB) is mainly mediated by L-amino acid transporter 1 (LAT1). We aimed to investigate whether liver failure induced by bile duct ligation (BDL) increases levels of brain AAAs by affecting the expression and function of LAT1. The LAT1 function was assessed using the brain distribution of gabapentin. It was found that BDL significantly increased levels of gabapentin, phenylalanine, and tryptophan in the cortex, hippocampus, and striatum of rats, and upregulated the expression of total LAT1 protein in hippocampus and striatum as well as cortex membrane LAT1 protein. HCMEC/D3 served as in vitro BBB model, and the data showed that both the serum of BDL rats and bilirubin induced LAT1 expression and function, while bilirubin oxidase almost abolished the upregulation of LAT1 protein by bilirubin and the serum of BDL rats. The enhanced function and expression of LAT1 were also observed in the hippocampus and striatum of hyperbilirubinemia rats. Both aryl hydrocarbon receptor (AhR) antagonist α-naphthoflavone and AhR silencing obviously attenuated the upregulation of LAT1 protein by bilirubin or omeprazole. This study provides the first evidence that BDL upregulates LAT1 at the rat BBB, attributed to the activation of AhR by the increased plasma bilirubin. The results highlight the mechanisms causing BDL-increased levels of brain AAAs and their physiological significance.Keywords:L-amino acid transporter;blood–brain barrier;liver failure;unconjugated bilirubin;aryl hydrocarbon receptor
研究领域:
神经科学
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药理学
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肝病学
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DOI
PubMed
高影响因子
ACS Nano
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2023
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IF 17.1
Zhibin Zhang,Dongtao Zhou,Xiaowei Luan,Xuyuan Wang,Zhenxing Zhu,Wen Luo,Jingjing Yang,Shaochun Tang,Yujun Song
Type 2 diabetes (T2D) results from the cells’ insulin resistance, and to date, insulin therapy and diabetes medications targeting glycemic management have failed to reverse the increase in T2D prevalence. Restoring liver functions to improve hepatic insulin resistance by reducing oxidative stress is a potential strategy for T2D treatment. Herein, the liver-targeted biodegradable silica nanoshells embedded with platinum nanoparticles (Pt-SiO2) are designed as reactive oxygen species (ROS) nanoscavengers and functional hollow nanocarriers. Then, 2,4-dinitrophenol-methyl ether (DNPME, mitochondrial uncoupler) is loaded inside Pt-SiO2, followed by coating a lipid bilayer (D@Pt-SiO2@L) for long-term effective ROS removal (platinum nanoparticles scavenge overproduced ROS, while DNPME inhibits ROS production) in the liver tissue of T2D models. It is found that D@Pt-SiO2@L reverses elevated oxidative stress, insulin resistance, and impaired glucose consumption in vitro, and significantly improves hepatic steatosis and antioxidant capacity in diabetic mice models induced by a high-fat diet and streptozotocin. Moreover, intravenous administration of D@Pt-SiO2@L indicates therapeutic effects on hyperlipidemia, insulin resistance, hyperglycemia, and diabetic nephropathy, which provides a promising approach for T2D treatment by reversing hepatic insulin resistance through long-term ROS scavenging.
研究领域:
生物医学工程
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代谢疾病研究
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纳米医学
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产品关联
DOI
PubMed
高影响因子
PHARMACOLOGY
·
2017
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IF 1.442
Zhang Jing,Song Huanchun,Jiang Shuying,Chen Zhibin,Tong Shuhua,Lin Feiyan,Wen Congcong,Zhang Xiuhua,Hu Lufeng
Background: Aspirin and ibuprofen are the most frequently prescribed non-steroidal anti-inflammatory drugs in the world. However, both are associated with a variety of toxicities. We applied serum metabonomics and Fisher discrimination for the early diagnosis of its toxic reaction in order to help diagnose these toxicities. Methods: A total of 45 rats were randomly divided into Control group, Aspirin group, and Ibuprofen groups. The experiment groups were given intragastric aspirin (15 mg/kg) or ibuprofen (15 mg/kg) for 3 weeks. Liver function tests were performed and blood metabonomics were analyzed by gas chromatography-mass spectrometry. Results: The most important compounds altered were trihydroxybutyric acid and l-alanine in the aspirin group, and acetoacetic acid, l-alanine, and trihydroxybutyric acid in the ibuprofen group. With respect to metabolic profiles, all 3 groups were completely distinct from one another. Fisher discrimination showed that 91.1% of the original grouped cases were correctly classified by the third week. However, only 55.6% of liver function tests were able to classify grouped cases correctly. Conclusion: Trihydroxybutyric acid, l-alanine, and acetoacetic acid were the most significant indicators of altered serum metabolites following intragastric administration of aspirin and ibuprofen in rates. These metabolomic data may be used for classification of aspirin and ibuprofen toxicity
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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生物统计学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
·
2023
·
IF 3.6
Xiaofei Ren,Kui Xu,Jianming Xu,Qiao Mei
Melatonin possesses potent hepatoprotective properties, but it remains to be elucidated whether melatonin has a therapeutic effect on monocrotaline (MCT)-induced hepatic sinusoidal obstruction syndrome (HSOS). In this study, male Sprague Dawley rats were intraperitoneally injected with melatonin or the same volume of vehicle at 0 and 24 h after MCT intragastric administration. Next, hematoxylin–eosin staining and electron microscopy were performed to evaluate the hepatic sinusoidal injury of rats. Endothelial cell marker RECA-1 was observed by immunohistochemistry. Hepatic oxidative stress was analyzed by detecting malondialdehyde, glutathione S-transferase, and reactive oxygen species. Assessment of liver function was carried out by analysis of serum aspartate aminotransferase, alanine aminotransferase, total bilirubin, and albumin levels. Real-time polymerase chain reaction and Western blot analysis were used to identify liver Sirtuin-3 (SIRT3) and active matrix metallopeptidase 9 (MMP-9) expression. Besides, liver sinusoidal endothelial cells (LSECs) were used for the in vitro functional verification experiment. Specifically, liver histology of the melatonin-treated groups showed that the pathological damages caused by MCT were significantly attenuated, total HSOS scores were decreased, and the elevation of serum hyaluronic acid observed in the model group was also reduced. Moreover, melatonin treatment also improved the survival of rats after partial hepatectomy. Administration of melatonin ameliorated MCT-induced LSECs injury, hepatic oxidative stress, and hepatic dysfunction. Furthermore, melatonin treatment increased SIRT3 expression while attenuating MMP-9 activity in liver tissues. Cell experiment also demonstrated that SIRT3 might mediate the protective effect of melatonin on LSECs. Collectively, our study provided the potential rationale for the application of melatonin for the prevention of MCT-induced HSOS.
研究领域:
药理学
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肝病学
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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
Evidence-based Complementary and Alternative Medicine
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2016
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IF 1.931
Shengyan Xi,Lifeng Yue,Mengmeng Shi,Ying Peng,Yangxinzi Xu,Xinrong Wang,Qian Li,Zhijun Kang,Hanjing Li,Yanhui Wang
Chronic liver disease is one of the most common diseases that threaten human health. Effective treatment is still lacking in western medicine. Semen Persicae (Taoren) and Flos Carthami (Honghua) are known to relieve acute hepatic injury and inflammation, improve microcirculation, and reduce tissue fiber. The aim of our study is to investigate the potential mechanisms of Taoren-Honghua Herb Pair (THHP) in murine model of chronic liver disease caused by Carbon Tetrachloride (CCl4). Mice were randomly divided into seven groups: (1) blank, (2) model, (3) control (colchicine, 0.1 mg/kg), (4) THHP (5.53, 2.67, and 1.33 g/kg), and (5) Tao Hong Siwu Decoction (THSWD) (8.50 g/kg). Histological change and microvessels density were examined by microscopy. Hepatic function, serum fibrosis related factors, and hepatic vascular endothelial growth factor (VEGF) were measured with ELISA. VEGF, kinase insert domain-containing receptor (KDR), Flt-1, and Akt mRNA expression in hepatic tissue were determined with PCR. Tissues of Akt, pAkt, KDR, and Flt-1 were measured with western blotting. Data from this study showed that THHP improved hepatic function and restrained the hepatic inflammation and fibrosis. Its role in inhibiting pathological angiogenesis and hepatic fibrogenesis may be through affecting the angiogenesis-associated VEGF and its upstream and downstream signaling pathways.
研究领域:
药理学
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肝病学
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分子生物学
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病理学
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DOI
PubMed
高影响因子
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