BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
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2024
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IF 2.5
Xinlei Liu,Rui Liu,Yancheng Wang
Drug-induced liver injury (DILI) occurs frequently and can be life-threatening. Increasing researches suggest that acetaminophen (APAP) overdose is a leading cause of drug-induced liver injury. Indole-3-carboxaldehyde (I3A) alleviates hepatic inflammation, fibrosis and atherosclerosis, suggesting a potential role in different disease development. However, the question of whether and how I3A protects against acetaminophen-induced liver injury remains unanswered. In this study, we demonstrated that I3A treatment effectively mitigates acetaminophen-induced liver injury. Serum alanine/aspartate aminotransferases (ALT/AST), liver malondialdehyde (MDA) activity, liver glutathione (GSH), and superoxide dismutase (SOD) levels confirmed the protective effect of I3A against APAP-induced liver injury. Liver histological examination provided further evidence of I3A-induced protection. Mechanistically, I3A reduced the expression of apoptosis-related factors and oxidative stress, alleviating disease symptoms. Finally, I3A treatment improved survival in mice receiving a lethal dose of APAP. In conclusion, our study demonstrates that I3A modulates hepatotoxicity and can be used as a potential therapeutic agent for DILI.
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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产品关联
DOI
PubMed
高影响因子
International Journal of Environmental Research and Public Health
·
2019
·Vol. 17
·期 1
·138
·
IF 2.468
Chang Liu,Yaohui Zhu,Zhenxiang Lu,Weina Guo,Bayaer Tumen,Yalan He,Chao Chen,Shanshan Hu,Kangzhi Xu,Yan Wang,Lei Li,Shenghe Li
Acute Cadmium (Cd) exposure usually induces hepatotoxicity. It is well known that oxidative stress and inflammation causes Cd-induced liver injury. However, the effect of nuclear factor erythroid 2-related factor 2 (Nrf2) in Cd-induced liver injury is not completely understood. In this study, we observed Cd-induced liver damage and the potential contribution of Nrf2, nuclear factor-κB (NF-κB), Nod-like receptor 3 (NLRP3), and mitogen-activated protein kinases (MAPKs) signaling pathways. Changes in serum transaminases and proinflammatory cytokines expression showed that Cd could induce acute hepatotoxicity. Moreover, Nrf2 and its downstream heme oxygenase 1 (HO-1) were inhibited by Cd exposure, and Kelch-like ECH-associated protein 1 (Keap1), the inhibitory protein of Nrf2, was increased. Furthermore, NF-κB, NLRP3, and MAPKs signaling pathways were all activated by Cd intoxication. In conclusion, the inhibition of Nrf2, HO-1, and the activation of NF-κB, NLRP3, and MAPKs all contribute to Cd-induced liver injury.Keywords:Cadmium;acute liver injury;Nrf2;NLRP3;NF-κB;MAPKs
研究领域:
毒理学
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分子生物学
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免疫学
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产品关联
DOI
PubMed
高影响因子
Food Bioscience
·
2024
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IF 4.8
Lin Lan,Jingxin Wang,Hao Luo,Min Cao,Nianhong Guo,Guiling Fan,Shengyu Wang,Zaixing Sun,QiaoLing He,Yufeng Li
Cordyceps militaris , a medicinal and edible fungus, has garnered significant interest for its polysaccharides, known for their diverse physiological activities and health benefits. The purpose of this study was to extract polysaccharides (CM-1) from Cordyceps militaris fruiting bodies using hot water extraction and column chromatography, and evaluate its structural characteristics, antioxidant capacity, and in vivo absorption effects. Additionally, the study aimed to assess its protective effects against carbon tetrachloride (CCl 4 ) induced liver injury in mice. The results showed that CM-1 significantly decreased the expression levels of serum ALT, AST, TNF-α, IL-6, and IL-1β. Pre-treatment with CM-1 also increased the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px). Furthermore, histopathological examination of liver tissues confirmed the protective effects of CM-1 against acute liver injury induced by CCl 4 . These results indicate CM-1 promising potential as a dietary supplement for liver injury prevention and treatment.
研究领域:
药理学
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生物化学
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产品关联
DOI
高影响因子
MOLECULES
·
2023
·Vol. 28
·期 14
·5496
·
IF 4.6
Ting Li,Chaoyue Yang,Houkang Cao,Siyi Mo,Bo Li,Zhipeng Huang,Ruobing Zhang,Jianzhao Wu,Kefeng Zhang,Ya Gao
Bergenin (BER), a natural component of polyphenols, has a variety of pharmacological activities, especially in improving drug metabolism, reducing cholestasis, anti-oxidative stress and inhibiting inflammatory responses. The aim of this study was to investigate the effects of BER on liver injury induced by isonicotinic acid hydrazide (INH) and rifampicin (RIF) in mice. The mice model of liver injury was established with INH (100 mg/kg)+RIF (100 mg/kg), and then different doses of BER were used to intervene. The pathological morphology and biochemical indicators of mice were detected. Meanwhile, RNA sequencing was performed to screen the differentially expressed genes and signaling pathways. Finally, critical differentially expressed genes were verified by qRT-PCR and Western blot. RNA sequencing results showed that 707 genes were significantly changed in the INH+RIF group compared with the Control group, and 496 genes were significantly changed after the BER intervention. These differentially expressed genes were mainly enriched in the drug metabolism, bile acid metabolism, Nrf2 pathway and TLR4 pathway. The validation results of qRT-PCR and Western blot were consistent with the RNA sequencing. Therefore, BER alleviated INH+RIF-induced liver injury in mice. The mechanism of BER improving INH+RIF-induced liver injury was related to regulating drug metabolism enzymes, bile acid metabolism, Nrf2 pathway and TLR4 pathway.Keywords:bergenin;isonicotinic acid hydrazide;rifampicin;liver injury;RNA sequencing
研究领域:
药理学
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分子生物学
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毒理学
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产品关联
DOI
PubMed
高影响因子
FOOD RESEARCH INTERNATIONAL
·
2025
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IF 8
Mengyao Zhang,Jiali Tang,Jiaying Wang,Chenchen Qi,Guohui Chen,Wei Chen,Chengtao Wang
This study explores the grafting of syringic acid onto fucoidan and assesses the resultant graft's (F S) enhanced functional properties and therapeutic potential in a histamine-induced liver injury model. Utilizing a redox system of ascorbic acid and hydrogen peroxide, the grafting process achieved a grafting rate of 290.45 mg CAE/g, confirmed through UV–Vis spectroscopy, FT-IR spectroscopy, scanning electron microscopy, and thermogravimetric analysis. In vivo investigations using histamine-sensitive mice demonstrated that F S significantly mitigated histamine-induced damage, evidenced by improvements in body weight, organ index, and colon length. F S exhibited superior efficacy in restoring liver function indices (ALT, AST, ALP, GGT), enhancing antioxidant defenses (GSH, SOD), and reducing oxidative stress markers (MDA). Anti-inflammatory effects included reduced levels of pro-inflammatory cytokines (TNF- α , IL-6, IL-1 β ) and modulation of apoptosis-related proteins (BCl 2 , BAX). Additionally, F S upregulated key antioxidant genes in the Nrf2/KEAP1 pathway and downregulated inflammatory genes in the NF- κ B pathway. Restoration of colonic tight junction proteins (ZO-1, Occludin, Claudin-1) and normalization of gut microbiota composition further underscored the therapeutic potential of F S. The study highlights the significant enhancement in functional properties of fucoidan through SA grafting, presenting F S as a promising candidate for developing functional foods and nutraceuticals aimed at preventing and mitigating liver damage and related disorders.
研究领域:
生物化学
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药理学
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营养学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2017
·
IF 2.981
Zi-wei Li,Yi Kuang,Shu-nan Tang,Kai Li,Yun Huang,Xue Qiao,Si-wang Yu,Yew-min Tzeng,Jen-Yu Lo,Min Ye
Ethnopharmacology relevance Antrodia camphorata (AC) is a rare and precious fungus indigenous to Taiwan used as a traditional medicine for the treatment of liver injury. Triterpenoids are the major bioactive constituents of A. camphorata and have been reported to possess hepatoprotective activities. To meet the increasing demand, artificial cultivation techniques have been developed. Aim of the study This study aims to evaluate the hepatoprotective activities of AC samples derived from different cultivation techniques and to dissect the main active triterpenoid compounds. Materials and methods The ethanol extracts of five batches of AC samples, including wild growing fruiting bodies, cutting wood culture fruiting bodies, dish cultures, cutting wood culture mycelia, and submerged fermentation mycelia were orally administered (50 mg/kg or 200 mg/kg) to ICR mice for 7 days. On the last day, CCl 4 (0.2%, 7 mL/kg, i.p.) was used to induce liver injury, and the activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined 24 h after the injection. Moreover, a HepG2 cell model treated with CCl 4 (0.35%) was used to screen the protective activities of 29 AC triterpenoids. After incubation for 6 h, viabilities of the cells were tested using MTS assay. The in vivo hepatoprotective activities of antcin B and antcin K were further studied on the mice model by ALT and AST tests and histopathologic examinations. To elucidate the mechanisms, the mRNA levels of iNOS , COX2, TNF-α and IL-1β, and the protein levels of NF-κB (p65/p-p65), iNOS and COX2 in liver tissues were determined. Results The wild growing or cutting wood culture fruiting bodies, and the dish cultures of AC showed more potent activities than the mycelia ( P <0.001). At 20 μM, 16 of 29 triterpenoids showed significant protective activities, increasing HepG2 cell viability from 46% of the CCl 4 group to >90%. Antcin B and antcin K could dose-dependently (10 or 50 mg/kg, 7 days, i.g.) decrease the serum levels of ALT and AST, and decrease the incidence of liver necrosis . The effects of 50 mg/kg of antcin K or antcin B were almost identical to those of 100 mg/kg silymarin . Furthermore, qRT-PCR and Western blotting analyses revealed they could down-regulate IL-1β, TNF-α, iNOS, COX-2 and NF- κ B in liver tissues at both transcriptional and translational levels. Conclusion The results indicate that cultivation techniques remarkably affect the hepatoprotective activities of AC. Antcin K and antcin B are the major hepatoprotective compounds of A. camphorata , and the mechanism is related with anti-inflammation. Given its high natural abundance and good oral absorption, antcin K could be a promising drug candidate for liver injury.
研究领域:
药理学
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中药学
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肝脏病学
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产品关联
DOI
PubMed
高影响因子
Cell Death & Disease
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2022
·Vol. 13
·期 9
·1-9
·
IF 9.685
Bi Jianbin,Zhang Jia,Ke Mengyun,Wang Tao,Wang Mengzhou,Liu Wuming,Du Zhaoqing,Ren Yifan,Zhang Shuqun,Wu Zheng,Lv Yi,Wu Rongqian
Heat shock proteins (HSPs) depletion and protein misfolding are important causes of hepatocyte death and liver regeneration disorder in liver injury. HSF2BP, as its name implies, is a binding protein of HSF2, but the specific role of HSF2BP in heat shock response (HSR) remains unknown. The aim of this study is to identify the role of HSF2BP in HSR and acute liver injury. In this study, we found that HSF2BP expression increased significantly within 24 h after APAP administration, and the trend was highly consistent with that of HSP70. hsf2bp - KO and hsf2bp - TG mouse models demonstrated HSF2BP reduced hepatocyte death, ameliorated inflammation, and improved liver function in APAP- or D-GalN/LPS- induced liver injury. Meanwhile, a significant increase of the survival rate was observed in hsf2bp - TG mice after APAP administration. Further studies showed that HSF2BP upregulated the expression of HSF2 and HSP70 and inhibited the activation of Jnk1/2 and P38 MAPK. Additionally, HSP70 siRNA pretreatment abolished the effect of HSF2BP on the MAPK pathway in APAP-treated hepatocytes. The results reveal that HSF2BP is a protective factor in acute liver injury, and the HSF2BP/HSP70/MAPK regulatory axis is crucial for the pathogenesis of liver injury. HSF2BP is a potential therapeutic target for liver injury.
研究领域:
分子生物学
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医学
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肝脏研究
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DOI
高影响因子
Journal of Environmental Sciences
·
2025
·
IF 6.3
Hongfei Hu,Guangji Wei,Hai Lan,Yang Feng,Shihua Luo,Yaqin Pang,Yanxin Huang,Huixiong Yuan,Huixin Peng,Wencheng Chen
The liver, a critical metabolic organ, is particularly vulnerable to damage upon aluminum exposure. However, the precise molecular mechanisms through which aluminum induces hepatotoxicity remain to be fully elucidated. This study aimed to investigate the adverse effects of aluminum exposure on mouse liver tissue. The results indicated that AlCl 3 exposure induced significant liver dysfunction, characterized by reduced adenosine triphosphate levels, elevated plasma alanine aminotransferase and aspartate aminotransferase. Histopathological analysis of liver tissue revealed marked histological damage, accompanied by substantial iron deposition. Further examinations demonstrated elevated hepatic levels of malondialdehyde, 4-hydroxynonenal, and reactive oxygen species, decreased levels of glutathione (GSH) and superoxide dismutase, increased levels of Oxidized glutathione (GSSG), and a reduced GSH/GSSG ratio. The mRNA and protein expression of ferroptosis-related molecules, including downregulated glutathione peroxidase 4 and solute carrier family 7 member 11, were significantly downregulated, while acyl-CoA synthetase long-chain family member 4, ferritin heavy chain 1, and iron regulatory protein 1 levels were significantly upregulated. Treatment with Ferrostatin-1 markedly ameliorated liver dysfunction and histopathological damage, attenuating signs of ferroptosis. These findings highlight the potential of ferroptosis-targeted therapies as a viable treatment strategy for aluminum exposure-induced hepatocyte injury.
研究领域:
毒理学
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肝脏病学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cell Host & Microbe
·
2025
·
IF 18.7
Yunong Zeng,Rong Wu,Yi He,Qian Zhang,Ze Wang,Ping Qin,Fangyuan Yang,Yingshi Han,Mingjing Hao,Yujian Zheng,Lei Gao,Xia Chen,Xiaoshan Zhao,Zhenhua Zeng,Zhe-Xiong Lian,Weidong Xiao,Zhanguo Liu,Zhi-Bin Zhao,Shenhai Gong
Acetaminophen overuse is a leading cause of acute liver injury (ALI). Although ALI is linked to inter-individual differences in microbiome composition, the mechanisms remain unclear. We demonstrate that horizontal transmission of gut microbiota between male and female mice impacts ALI and identify Rikenella microfusus- mediated isoflavone transformation as determinants of ALI severity. R. microfusus increases upon cohabitation with bacterial β-galactosidase enhancing intestinal absorption of isoflavone biochanin-A (Bio-A). R. microfusus mono-colonization reduced ALI severity following acetaminophen overdose. Genetic or chemical-mediated inhibition of β-galactosidase blocked Bio-A release and negated the hepatoprotective effects of R. microfusus . Bio-A directly binds to pyruvate carboxylase (PC) and propionyl-CoA carboxylase subunit alpha (PCCA), augmenting the tricarboxylic acid cycle and promoting protective glutathione synthesis in hepatocytes. Additionally, immunohistochemical analysis revealed reduced hepatic PC and PCCA expression in liver failure (LF) patients. These findings highlight the impacts of microbiome composition on ALI and the ability of microbial isoflavone absorption to mitigate ALI severity.
研究领域:
医学
·
微生物学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Jie Li,Xiaolong Lian,Baojian Li,Quhuan Ma,Lingling Yang,Guangmiao Gao,Tingmei Yin,Xiaoyan Fu,Yi Deng,Zhijun Yang,Xiujuan Yang
Ethnopharmacological relevance Cisplatin (CP), a widely used antineoplastic agent, is a leading cause of drug-induced liver injury (DILI) due to its hepatotoxic effects. Licorice (GC), an established remedy in traditional Chinese medicine (TCM), has shown promise in addressing liver diseases and DILI. Nonetheless, the specific active components and underlying mechanisms of GC in mitigating CP-induced liver injury remain inadequately investigated. Aim of the study This study examined the active components and efficacy of GC in addressing CP-induced hepatotoxicity, focusing on its mechanisms related to bile acid metabolism and gut microbiota regulation. Materials and methods Utilizing a CP-induced rat liver injury model, this study evaluated changes in liver coefficient, liver function indices, and pathological morphology while assessing the efficacy of GC for both prevention and treatment of CP-induced liver injury. Subsequently, UPLC-Q-TOF-MS qualitatively analyzed GC's blood-entering components, elucidating its pharmacodynamic material basis. Network pharmacology analysis identified potential pathways and targets of GC's blood components in relation to CP-induced liver injury. Furthermore, metabolomics and 16S rRNA sequencing were employed to clarify the pharmacodynamic mechanisms of GC in modulating bile acid metabolism and gut microbiota, offering insights into its preventive and therapeutic roles. Results The pharmacodynamic results revealed that GC significantly reduced liver function biomarkers and improved pathological changes in liver tissue. UPLC-Q-TOF-MS analysis identified 16 blood-entering components as potential pharmacodynamic agents of GC for preventing and treating CP-induced liver injury. Network pharmacology analysis suggested a link between GC's efficacy and the bile acid metabolic pathway. Furthermore, metabolomics analysis, immunoblotting, and 16S rRNA sequencing demonstrated that GC regulated bile acid metabolites in both liver and feces, enhanced FXR and BSEP expressions in the liver, and decreased CYP27A1 expression. Additionally, GC mitigated CP-induced intestinal dysbiosis by altering the abundance of gut microbiota. Conclusions UPLC-Q-TOF-MS performed a qualitative analysis of 16 blood-entering components linked to GC, providing a basis for further exploration of the pharmacodynamic material underpinning GC. The protective role of GC in CP-induced liver injury appears connected to enhanced bile acid metabolism and restoration of gut microbiota balance.
研究领域:
民族药理学
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药理学
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代谢组学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2018
·Vol. 19
·期 7
·2047
·
IF 3.687
Yao Li,Sheng Guo,Quanjin Ren,Dandan Wei,Ming Zhao,Shulan Su,Zhishu Tang,Jin-Ao Duan
Jujubae Fructus, the dried fruit ofZiziphus jujuba, has been used as Chinese medicine and food for centuries. Triterpenic acids have been found to be the major bioactive constituents inJujubae Fructusresponsible for their hepatoprotective activity in previous phytochemical and biological studies, while few pharmacokinetic studies have been conducted. To reveal the kinetics of the triterpenic acids under the pathological liver injury state, an established ultra-performance liquid chromatography coupled with a mass spectrometry method was applied for the simultaneous quantitation of seven triterpenic acids (ceanothic acid, epiceanothic acid, pomonic acid, alphitolic acid, maslinic acid, betulinic acid, and betulonic acid) in plasma samples of normal and acute liver injury rats induced by CCl4. The results showed that there were significant differences (p< 0.05) in the pharmacokinetic parameters of seven triterpenic acids between model and normal groups. The AUC0–tand AUC0–∞of epiceanothic acid (5227 ± 334 μg⋅h/L vs. 1478 ± 255 μg⋅h/L and 6127 ± 423 μg⋅h/L vs. 1482 ± 255 μg⋅h/L, respectively) and pomonic acid (4654 ± 349 μg⋅h/L vs. 1834 ± 225 μg⋅h/L and 4776 ± 322 μg⋅h/L vs. 1859 ± 230 μg⋅h/L, respectively) in model rats were significantly higher than those in normal rats, and the CLz/F of them were significantly decreased (0.28 ± 0.02 L/h/kg vs. 1.36 ± 0.18 L/h/kg and 19.96 ± 1.30 L/h/kg vs. 53.15 ± 5.60 L/h/kg, respectively). In contrast, the above parameters for alphitolic acid, betulinic acid and betulonic acid exhibited the quite different trend. This pharmacokinetic research might provide useful information for the clinical usage of triterpenic acids fromJujubae Fructus.Keywords:Ziziphus jujuba;triterpenic acids;pharmacokinetic study;acute liver injury
研究领域:
中药学
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药理学
✓ 已验证
DOI
PubMed
高影响因子
CURRENT TOPICS IN MEDICINAL CHEMISTRY
·
2024
·
IF 2.9
Su Hongbing,Lei Hong,Cao Ling,Zhou Xiaoying,Liu Yumeng,Li Ying,Yan Lili,Shaowa Lv,Wang Yanhong,Guan Qingxia
Background: Self-emulsifying nano-phase of traditional Chinese medicine are a research
hotspot. Xiao-Chai-Hu decoction is a commonly used compound decoction in clinical practice,
which is of great research significance. The aim of this study was to isolate and characterize
the self-emulsifying nano-phase and other phases of Xiao-Chai-Hu decoction, and to study the effects
of each phase on acute liver injury.
Methods: The liquid medicine was prepared employing centrifugation followed by dialysis. Single-
factor investigation methodology was utilized to optimize the preparation parameters for both
phases. Characterization of the formulated phase involved analyses such as surface morphology assessment,
measurement of nanoparticle size and Zeta potential using an analyzer, observation of
the Tyndall effect, conducting diffusion and dilution tests, examination under a microscope, and
structural visualization via transmission electron microscopy (TEM). Furthermore, an acute liver
injury model was established in rats through intraperitoneal injection of D-Galactosamine (D-Gal-
N). To assess hepatic function and oxidative stress status, serum levels of alanine aminotransferase
(ALT) and aspartate aminotransferase (AST), superoxide dismutase (SOD) activity, and
malondialdehyde (MDA) content in liver tissue were quantified. The liver coefficients for each
group were calculated as an additional parameter. For histopathological evaluation, liver tissue sections
from the experimental group were stained with Hematoxylin and Eosin (H&E) and examined
microscopically under light conditions. These revisions aim to enhance clarity, correct minor
grammatical errors (such as capitalization of “HE” to “H&E”), and ensure a smoother flow of
information without altering the scientific content of your original text.
Results: Successful establishment and separation of four distinct phases were achieved, including
the self-emulsifying nano-phase, precipitation phase, suspension phase, and true solution phase.
The self-emulsifying nano-phase was characterized as spherical particles with an average diameter
of approximately 100 nm. Pharmacodynamic assessments revealed that both Xiao-Chai-Hu decoction
and its self-emulsifying nano-phase significantly reduced liver coefficients and alanine aminotransferase
(ALT) levels compared to controls (P<0.05). However, no statistically significant differences
were observed in regards to aspartate aminotransferase (AST) concentrations, malondialdehyde
(MDA) content, or superoxide dismutase (SOD) activity between the treatment groups
and control (P>0.05). These findings indicate that both Xiao-Chai-Hu decoction and its self-emulsifying
nano-formulation ameliorated D-GalN-induced acute liver injury, albeit without statistically
distinguishable efficacy between them (P>0.05).
Conclusion: The presence of a self-emulsifying nano-phase within Xiao-Chai-Hu decoction is
confirmed, and this nano-phase emerges as a therapeutically efficacious component in mitigating
acute liver injury.
研究领域:
中药学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
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