JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2015
·
IF 2.912
Chuanyang Su,Xiaomin Xia,Qiong Shi,Xiufang Song,Juanli Fu,Congxue Xiao,Hongjun Chen,Bin Lu,Zhiyin Sun,Shanmei Wu,Siyu Yang,Xuegang Li,Xiaoli Ye,Erqun Song,Yang Song
Neohesperidin dihydrochalcone (NHDC), a sweetener derived from citrus, belongs to the family of bycyclic flavonoids dihydrochalcones. NHDC has been reported to act against CCl4-induced hepatic injury, but its mechanism is still unclear. We first discovered that NHDC showed a strong ability to scavenge free radicals. In addition, NHDC induces the phase II antioxidant enzymes heme oxygenase 1 (HO-1) and NAD(P)H/quinone oxidoreductase 1 (NQO1) through the activation of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/antioxidant response element (ARE) signaling. Further assays demonstrated that NHDC induces accumulation of Nrf2 in the nucleus and augmented Nrf2-ARE binding activity. Moreover, NHDC inhibits the ubiquitination of Nrf2 and suggests the modification of Kelch-like ECH-associated protein 1 (Keap1) and the disruption of the Keap1/Nrf2 complex. c-Jun N-terminal kinase (JNK) and p38 but not extracellular signal-regulated protein kinase (ERK) phosphorylations were up-regulated by NHDC treatment. Taken together, NHDC showed its protective antioxidant effect against CCl4-induced oxidative damage via the direct free radical scavenging and indirect Nrf2/ARE signaling pathway.
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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产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2024
·
IF 15.8
Meng Sun,Min Li,Min Hu,Yueyun Fan,Yanhong Liu,Jian Sun,Jinfeng Zhang
Acute liver failure (ALF) is a serious global disease characterized by rapid onset and high mortality. Currently, the clinical treatment of ALF faces considerable hurdles due to limited medication options and the scarcity of liver transplants. Despite biomacromolecules such as hepatocyte growth factor (HGF) and glutathione (GSH) having been applied for ALF symptom relief in the clinic, they still face substantial challenges including poor stability, difficulty in acting on intracellular targets, and inadequate therapeutic outcome. In this work, by taking advantage of the innate targeting and regenerative capabilities of mesenchymal stem cells (MSCs), we harnessed MSC-derived exosomes as natural bioactive carriers for the simultaneous delivery of HGF and GSH, forming a fully bioactive nanodrug termed HG@Exo. Impressively, the HG@Exo demonstrated potent therapeutic effects against both carbon tetrachloride (CCl4)- and extreme hepatectomy-induced ALF through multiple mechanisms, including regulation of oxidative stress, reduction of inflammation, and promotion of hepatocyte regeneration, which were facilitated by its inflammation-targeting to damaged liver tissues. Furthermore, an FDA-approved near-infrared fluorescent dye, indocyanine green (ICG), has been incorporated into the exosomes (HGI@Exo) to endow them with real-time in vivo tracking capability, which showed favorable liver accumulation of the HGI@Exo in both CCl4- and surgery-induced ALF animal models, providing crucial insights into their biodistribution and therapeutic efficacy. Overall, the presented fully bioactive nanodrugs with targeting and theranostic abilities hold significant promise for potentiating the therapeutic efficacy of biomacromolecules for the improved treatment of ALF and other inflammatory diseases.
研究领域:
药理学
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纳米医学
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干细胞治疗
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肝脏疾病
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Nutrients
·
2025
·Vol. 17
·期 21
·3463
·
IF 5
Yang Liu,Jingzhong Zheng,Xin Zheng,Dan Zhou,Hang Ma,Xue Zhou,Fahuan Ge
Background:Cili (Rosa roxburghiiTratt) is a unique fruit native to China’s Yunnan–Guizhou Plateau, rich in vitamin C, polyphenols, and triterpene, with broad health-promoting effects. Although cili’s hepatoprotective properties are reported, the bioactive components and underlying mechanisms remain poorly defined.Methods:We enriched proanthocyanidins from cili using column chromatography, identified their components via UPLC-Q-TOF-MS/MS, and validated their anti-liver fibrosis effects through in vitro and in vivo experiments.Results:Herein, we developed a novel proanthocyanidin-rich cili fruit extract (PACs-CFE) containing 84.2% total proanthocyanidins, comprising catechins, epicatechins, and diverse B-type dimers, trimers, tetramers, and gallate esters, as characterized by UPLC-Q-TOF-MS/MS. PACs-CFE inhibited LX-2 activation, suppressed collagen III and α-SMA expression, and induced ferroptosis via mitochondrial injury, reactive oxygen species accumulation, and GPX4/ferritin downregulation. In vivo, PACs-CFE ameliorated liver fibrosis, restored hepatic architecture, and improved serum alanine aminotransferase, aspartate aminotransferase, and bilirubin profiles. Moreover, PACs-CFE modulated the TGF-β1/Smad3 signaling pathway and beneficially reshaped the gut microbiota, enriching anti-inflammatory and hepatoprotective genera while reducing pathogenic taxa.Conclusions:Our findings show that PACs-CFE exerts multi-targeted anti-fibrotic effects through hepatic stellate cell inactivation, ferroptosis induction, TGF-β1/Smad3 suppression, and gut–liver axis modulation. This study provides useful insight into the hepatoprotective potential of cili fruit and supports its development as standardized functional ingredients for liver health.
研究领域:
药理学
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营养科学
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肝病学
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微生物组研究
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天然产物化学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2020
·
IF 3.943
Ruoyu Wang,Dong Zhang,Dan Tang,Kewei Sun,Jianping Peng,Wenfang Zhu,Sihan Yin,Yunan Wu
The activation of hepatic stellate cells (HSCs) has been considered one of the major events in hepatic fibrosis. Amygdalin has been used to treat cancers and alleviate pain; however, its role and mechanism in HSC activation and hepatic fibrosis remain unclear. In the present study, transforming growth factor-beta 1 (TGF-β1) stimulated the activation of HSCs, as indicated by significantly increased alpha-smooth muscle actin (α-SMA), desmin, collagen I, and tissue inhibitor of metalloproteinase-1 (TIMP-1) protein levels. Amygdalin treatment dramatically suppressed TGF-β1-induced HSC proliferation and activation. Moreover, amygdalin treatment also reduced the TGF-β1-induced secretion of cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), platelet-derived growth factor (PDGF), and chemokine (C-C motif) ligand 2 (CCL2), as well as the phosphorylation of Smad2, Smad3, and p65. In the CCl 4 -stimulated liver fibrosis rat model, amygdalin treatment improved liver fibrosis and liver damage by reducing focal necrosis, collagen fiber accumulation, and the protein levels of α-SMA, desmin, collagen I, and TIMP-1 in hepatic tissue samples and reducing serum alanine transaminase (ALT) and aspartate transaminase (AST) levels. In conclusion, we demonstrated the suppressive effects of amygdalin in TGF-β1-induced HSC activation through modulating proliferation, fibrogenesis, and inflammation signaling in vitro and the antifibrotic effects of amygdalin in CCl 4 -stimulated hepatic fibrosis in rats in vivo .
研究领域:
药理学
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肝病学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY
·
2023
·
IF 1.9
Wenchao Pan,Yadong Wang,Caiyan Zhao
Objective To explore the protective effect and related mechanism of miR-140-5p on liver fibrosis by interfering with TGF-β/Smad signaling pathway.Methods Liver fibrosis mice models were established by intraperitoneal injection of CCL4. Hematoxylin and eosin (HE) staining was used to detect the structural and morphological changes of the liver. Masson staining was used to detect collagen deposition. Human hepatic stellate cells (HSCs, LX-2) were transfected with miR-140-5p mimic or inhibitor then treated with TGF-β1. The qRT-PCR and Western blotting was used to detect the expression of related molecules. The luciferase reporter assay was used to identify the target of miR-140-5p.Results Our results indicated that miR-140-5p expression was downregulated in fibrotic liver tissues of model mice and LX-2 cells treated with TGF-β1. The overexpression of miR-140-5p decreased the expression of collagen1(COL1) and α-smooth muscle actin(α-SMA), inhibited the phosphorylation of Smad-2/3 (pSmad-2/3) in LX-2 cells. Conversely, the knockdown of miR-140-5p upregulated COL1 and α-SMA expression, increased Smad-2/3 phosphorylation. A dual-luciferase reporter assay showed that TGFβR1 was a target gene of miR-140-5p. The overexpression of miR-140-5p suppressed TGFβR1 expression in LX-2 cells. Additionally, knockdown of TGFβR1 decreased the expression of COL1 and α-SMA. Conversely, the overexpression of TGFβR1 reversed the inhibitory effect of miR-140-5p upregulation on expression of COL1 and α-SMA.Conclusion miR-140-5p bound to TGFβR1 mRNA 3′-untranslated region(3′UTR) and inhibited the expression of TGFβR1, pSmad-2/3, COL1 and α-SMA, thereby exerting a potential therapeutic effect on hepatic fibrosis.
研究领域:
分子生物学
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肝病学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Bioscience
·
2024
·
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
Frontiers in Pharmacology
·
2024
·
IF 4.4
Wu Qiong,Zhu Fangsi,Yao Yu,Chen Luyun,Ding Yijie,Su Yong,Ge Chaoliang
Introduction: Si-Ni-San (SNS), a traditional Chinese medicine, is effective in treating liver fibrosis with an unclear mechanism. Although disturbance of intestinal flora and the subsequent secretion of short-chain fatty acids (SCFAs) is suggested to be involved in the progression of liver fibrosis, whether SNS produces the anti-fibrosis effect through the regulation of intestinal flora and SCFAs remains unclear.Methods: In the current study, carbon tetrachloride (CCl4)-treated mice were dosed with SNS to examine the anti-fibrotic effects and the involved mechanism. Biochemical parameters, histological staining, and analyses of fibrotic gene expression were used to evaluate the anti-fibrotic effect of SNS, while intestinal flora and SCFA content were determined by 16S rRNA and LC–MS to evaluate the mechanism.Results: In vivo results showed that SNS improved liver function, reduced hepatocyte apoptosis and FFAR2/3 expression, and restored intestinal dysbiosis and reduced PA, BA, and IsA levels. In vitro experiments showed that PA, BA, and IsA exacerbated TNF-α-induced HepG2 apoptosis. Notably, the protective effects of SNS were compromised in pseudo-sterile mice.Discussion: In conclusion, our experimental results suggest that the disturbance in intestinal flora results in elevated SCFA levels, which further exacerbates hepatocyte apoptosis in liver fibrosis, while SNS suppresses CCl4-induced liver fibrosis at least partially by reinstating intestinal flora homeostasis and reducing SCFA levels.
研究领域:
药理学
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肝病学
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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
Metabolites
·
2021
·Vol. 11
·期 6
·374
·
IF 4.932
Nanlin Zhu,Suling Huang,Qingli Zhang,Zhuohui Zhao,Hui Qu,Mengmeng Ning,Ying Leng,Jia Liu
The pathophysiology of nonalcoholic fatty liver disease (NAFLD) is a complex process involving metabolic and inflammatory changes in livers and other organs, but the pathogenesis is still not well clarified. Two mouse models were established to study metabolic alteration of nonalcoholic fatty liver and nonalcoholic steatohepatitis, respectively. The concentrations of metabolites in serum, liver and intestine content were measured by the AbsoluteIDQ®p180 Kit (Biocrates Life Sciences, Innsbruck, Austria). Multivariate statistical methods, pathway analysis, enrichment analysis and correlation analysis were performed to analyze metabolomic data. The metabolic characteristics of liver, serum and intestine content could be distinctly distinguished from each group, indicating the occurrence of metabolic disturbance. Among them, metabolic alteration of liver and intestine content was more significant. Based on the metabolic data of liver, 19 differential metabolites were discovered between DIO and control, 12 between DIO-CCl4and DIO, and 47 between DIO-CCl4and normal. These metabolites were mainly associated with aminoacyl-tRNA biosynthesis, nitrogen metabolism, lipid metabolism, glyoxylate and dicarboxylate metabolism, and amino metabolism. Further study revealed that the intervention of obeticholic acid (OCA) could partly reverse the damage of CCl4. The correlation analysis of metabolite levels and clinical parameters showed that phosphatidylcholines were negatively associated with serum alanine aminotransferase, aspartate aminotransferase, NAFLD activity score, and fibrosis score, while lysophosphatidylcholines, sphingomyelins, amino acids, and acylcarnitines shared the reverse pattern. Our study investigated metabolic alteration among control, NAFLD model, and OCA treatment groups, providing preclinical information to understand the mechanism of NAFLD and amelioration of OCA.Keywords:nonalcoholic fatty liver disease (NAFLD);nonalcoholic fatty liver (NAFL);nonalcoholic steatohepatitis (NASH);differential metabolites;metabolic pathways;obeticholic acid (OCA)
研究领域:
代谢组学
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肝脏疾病
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2021
·
IF 6.953
Chao Xin,Shuang Liu,Hang Qu,Zhenyu Wang
Chemical liver injury threatens seriously human health, along with the shortage of efficiency and low-toxicity drugs. Herein, the novel oral nanocomplexes composed of deoxycholic acid-grafted chitosan and oleanolic acid were constructed to reverse the CCl 4 -induced acute liver damage in mice. Results indicated core-shell nanocomplexes, maintained by the hydrophobic interaction between deoxycholic acid and oleanolic acid, could be dissociated in the intestine. Notably, the nanocomplexes possessed superior hepatoprotective effect in vivo , possibly due to the synergistic effect between grafted chitosan and oleanolic acid. Mechanism investigations suggested that nanocomplexes reversed CCl 4 -induced liver injury through improving hepatic antioxidant capacity via NrF2/Keap1 pathway and regulating inflammation response via NF-κB signaling pathway. The novel oral nanocomplexes represent an effective strategy for chemical liver injury therapy.
研究领域:
药学
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毒理学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Pharmacology Research & Perspectives
·
2020
·Vol. 8
·期 5
·e00660
·
IF 2.052
Jingyi Zhao,Ying Chen,Lijun Dong,Xin Li,Ruijie Dong,Dongmei Zhou,Chengzhi Wang,Xiangdong Guo,Jieyou Zhang,Zhenyi Xue,Qing Xi,Lijuan Zhang,Guangze Yang,Yan Li,Rongxin Zhang
Acute peritonitis is an acute inflammatory response of the peritoneal cavity to physical injury and chemical stimulation. Timely resolution of this response is critical to prevent further damage to the body, which can eventually lead to more severe chronic inflammation. Arctigenin (ATG) is the main active ingredient of the Chinese medicine Arctium lappa . In recent years, there have been an increasing number of studies on the anti-inflammatory effect of ATG, but there have been few studies on the effect of ATG on acute inflammation, especially in acute peritonitis, which has not been reported. In this study, a mouse model of experimental acute peritonitis induced by thioglycolate (TG) solution was used to study the protective anti-inflammatory effect of ATG against acute peritonitis and the relevant mechanism. Our results showed that, after 12 hours of TG treatment, ATG significantly reduced inflammatory cell infiltration in mouse tissues and inhibited the secretion and expression of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in mice. ATG significantly reduced the percentage of CD11b + Ly6G + neutrophils and F4/80 + macrophages in the spleen and peritoneal exudate. In addition, ATG significantly inhibited the expression of the chemokines CCL3 and CCL4 and the adhesion molecule CD62L on the surface of CD11b-positive monocytes. ATG was observed to inhibit the phosphorylation of p65 and p38 in LPS-stimulated RAW264.7 cells. In conclusion, ATG can improve the symptoms of TG-induced acute peritonitis through immune regulation. ATG can reduce the inflammatory response in TG-induced acute peritonitis in mice.
研究领域:
药理学
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免疫学
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炎症性疾病
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产品关联
DOI
PubMed
高影响因子
Applied Materials Today
·
2024
·
IF 7.2
Yu Xu,Wen Jiang,Xin-Chuang Wang,Feng-Xian Luo,Jiang-Ning Hu
As a global public health issue, the treatment of acute liver injury (ALI) is facing serious challenges due to the lack of specific drugs. Selenium nanoparticles (Se NPs), due to their robust antioxidant attributes, have shown considerable potential in ALI prevention. However, the application of Se NPs is impeded by their instability, propensity to aggregate, and tendencies towards precipitation. In this study, we modified the surface of Se NPs with phlorotannin (PT) to synthesize PT-Se NPs. Our initial results suggested that PT-Se NPs, having a reduced particle size of 107.10 ± 4.04 nm, exhibited superior stability, enhanced cellular absorption, and sustained liver accumulation in comparison to Se NPs. In concordance with our expectations, PT-Se NPs demonstrated enhanced therapeutic performance in mitigating CCl 4 -induced ALI, as demonstrated by the preservation of liver functionality, decrease in oxidative stress markers, reduction of inflammatory factor levels, and improvement in histological damage. This research contributes a promising strategy for effectively improving the stability of Se NPs and preventing ALI, broadening the horizon for effective liver protection and potential clinical translation.
研究领域:
纳米技术
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药理学
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肝病学
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材料科学
✓ 已验证
产品关联
DOI
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2022
·
IF 6.064
Peng Wei,Zhang Shiwen,Zhou Wei,Zhao Xinchen,Wang Kexue,Yue Chengxu,Wei Xinyu,Pang Siyan,Dong Wei,Chen Sulian,Chen Changjie,Yang Qingling,Wang Wenrui
A core feature of liver fibrosis is the activation of hepatic stellate cells (HSCs), which are transformed into myofibroblasts and lead to the accumulation of extracellular matrix (ECM) proteins. In this study, we combined in vitro cellular efficacy with in vivo antifibrosis performance to evaluate the outcome of sorafenib (SRF) loaded layered double hydroxide (LDH) nanocomposite (LDH-SRF) on HSCs. The cellular uptake test has revealed that sorafenib encapsulated LDH nanoparticles were efficiently internalized by the HSC-T6 cells, synergistically inducing apoptosis of hepatic stellate cells. Moreover, the apoptosis rate and the migration inhibition rate induced by LDHs-SRF were 2.5 and 1.7 times that of SRF. Western Blot showed that the TGF-β1/Smad/EMT and AKT signaling pathway was significantly inhibited in HSC-T6 cells treated with LDHs-SRF. For the in vivo experiment, LDHs-SRF were administered to rat models of CCl4-induced liver fibrosis. H&E, masson and sirius red staining showed that LDHs-SRF could significantly reduce inflammatory infiltrate and collagen fiber deposition and immunohistochemical results found that LDHs-SRF treatment significantly inhibited the protein expressions of α-SMA in the liver, these results suggesting that LDHs-SRF exhibited better anti-fibrotic effect than SRF alone and significantly inhibited the proliferation and activation of rat hepatic stellate cells and collagen fiber synthesis.
研究领域:
药理学
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细胞生物学
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肝病学
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纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）