Materials Today Bio
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2026
·
IF 11
Jiaqi Liu,Wenting Cheng,Hailong Tian,Zhihan Wang,Canhua Huang,Qifu Li
Glioblastoma (GBM), a highly malignant central nervous system tumor, poses a major therapeutic challenge due to the poor blood-brain barrier (BBB) permeability and an immunosuppressive tumor microenvironment. Notably, silymarin, a natural compound known for its anti-inflammatory and liver-protective properties, has emerged as a promising candidate for GBM immunotherapy through the inhibition of glycolysis and induction of mitochondrial damage. In this study, we developed a silymarin-repurposed, site-specific delivery photo-chemotherapy nanoplatform, designed to synergistically suppress mitochondria for efficient GBM immunotherapy. The platform utilizes a self-assembly strategy incorporating brain-targeted lactoferrin (LF), triphenylphosphine-modified chlorin e6 (TCe6), and silymarin. Mechanistically, LF facilitates targeted binding to low-density lipoprotein receptor-related protein-1 (LRP1), enabling BBB penetration and inducing mitochondrial dysfunction in GBM cells through TCe6-mediated intracellular reactive oxygen species (ROS) generation and silymarin-induced glycolysis suppression. This mitochondrial dysfunction triggers the activation of the AMPK pathway, leading to the degradation of programmed cell death ligand-1 (PD-L1) and the activation of the cGAS-STING pathway, thereby enhancing the anti-tumor immune response. As anticipated, this nanoplatform significantly improves BBB permeability and antitumor immunity, providing an innovative drug repurposing strategy for effective GBM immunotherapy.
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ANALYTICA CHIMICA ACTA
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2026
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IF 6.1
Yue-qiang Chen,Xiao-xia Dong,Li Liu,Xiu-ping Chen,Chen-guo Feng,Li-xing Zhan,Yue Su,Fang Zhang,Yin-long Guo
Background Alterations in the amine submetabolome are closely associated with cellular metabolic status and are important for understanding metabolic regulation under intervention conditions. In this study, a stable isotope labeling derivatization combined with liquid chromatography–mass spectrometry (LC–MS) was employed to characterize alterations in the cellular amine submetabolome. Optimization of chromatographic separation and cellular metabolic quenching procedures improved the separation performance of amine metabolites while enabling more accurate preservation of the metabolic state at the time of sampling. Results The established method was applied to a D-lactate–treated BEAS-2B cell model to evaluate amine submetabolome alterations under different compound intervention conditions. The results demonstrated that selenomethionine (SeMet) and berberine alleviated D-lactate induced abnormalities in the amine submetabolome and showed metabolic regulatory effects consistent with tumor-suppressive trends observed under in vivo experiments. Significance Overall, this analytical strategy enables characterization of the amine submetabolome in complex biological samples and provides a reliable methodological reference for metabolome-based investigations of cellular metabolic alterations.
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JOURNAL OF ETHNOPHARMACOLOGY
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2026
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IF 6.8
Ma-Long Qin,Yan-Ling Qian,Xi Wen,Yun-Li Zhao,Xiao-Dong Luo
Ethnopharmacological relevance Kadsura longipedunculata is a Yi ethnic herb for hepatic disorders treatment in China. However, its effects on herb- and chemical-induced liver injury remain unknown. Aim of the study To validate traditional ethnomedicinal applications of K. longipedunculata and characterize its bioactive constituents. Materials and methods The hepatoprotective effect was evaluated using a triptolide-induced mice liver injury model. Bio-guided isolates were screened in an acetaminophen (APAP)-induced HepG2 cell model. Underlying signaling pathways were investigated using transcriptomics, network pharmacology, molecular docking, molecular dynamics simulations, and subsequent Western blotting validation. Results Abnormal biochemical indices, antioxidant defenses, and liver pathological necrosis in triptolide-induced mice were all adjusted by treatment with K. longipedunculata extract, exhibiting effects superior to those of the positive control, silymarin. The PI3K/AKT/NF-κB signaling pathway was identified as a core therapeutic pathway through transcriptomic profiling, supported by the upregulation of phosphorylated AKT and MTOR concurrent with the downregulation of NF-κB and TNF-α. Four compounds were isolated, among which catechin-5- O -β-D-glucopyranoside (Catechin GP) showed potent anti-apoptotic and antioxidative bioactivities in APAP-induced hepatocytes through the same pathway. The formation of a stable Catechin GP-AKT1 complex was further supported by computational analyses of binding stability and safety. Conclusion The protective effect of K. longipedunculata and its bioactive compound, Catechin GP, against liver injury triggered by both herbal (triptolide) and chemical (acetaminophen) agents is regulated via the PI3K/AKT/NF-κB pathway.
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ELECTROCHIMICA ACTA
·
2026
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IF 5.8
Yuchuan Zhu,Xinyu Huang,Ruoxi Yang,Ruoyao Tong,Changqing Lu,Ruirui Yue
One-pot synthesis of rGO/PEDOT:PSS/Ru composite for targeted flavonoid sensing. • PEDOT:PSS prevents rGO restacking and enables uniform Ru nanoparticle dispersion. • Interfacial coupling downshifts Ru d-band center to accelerate oxidation kinetics. • Ternary architecture greatly minimizes charge-transfer resistance at the interface. Flavonoid quantification is essential for pharmaceutical and food quality control, yet direct electrochemical detection is hindered by sluggish heterogeneous electron-transfer kinetics and limited current responses at trace concentrations on unmodified electrodes. We report an electrochemical sensing platform based on an rGO/PEDOT:PSS/Ru nanocomposite. Structural characterization indicates that π-π stacking between rGO and PEDOT:PSS prevents graphene restacking, enabling uniform Ru nanoparticle distribution. Crucially, interfacial electronic coupling within the ternary network downshifts the d-band center of the Ru nanoparticles, thereby accelerating the electro-oxidation kinetics. Electrochemical kinetic analyses reveal that the analytes undergo an adsorption-controlled, two-electron and two-proton (2e - /2H + ) transfer pathway. This architecture significantly minimizes charge-transfer resistance and expands the electroactive surface area. Differential pulse voltammetry delivered linear ranges of 0.006–65.0 μM (rutin), 0.05–70.0 μM (quercetin), and 0.02–50.0 μM (baicalin), with detection limits of 3.7, 17.3, and 6.3 nM, respectively. The sensor maintained consistent responses over 15 days and exhibited reliable selectivity against common interferents. Recovery studies in Sophora japonica, onion, and Scutellaria baicalensis extracts correlated with UV–Vis reference data, illustrating how coupling conducting polymers with redox-active nanoparticles can modulate interfacial electron-transfer pathways for targeted electrochemical sensing. Download: Download high-res image (354KB) Download: Download full-size image
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CHEMISTRY & BIODIVERSITY
·
2022
·Vol. 19
·期 8
·e202200471
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IF 2.745
Qiang-Ming Li,Xiu-Rong Yang,Xue-Qiang Zha,Li-Hua Pan,Dan-Dan Zang,Feng-Yun Zhang,Jian-Ping Luo
Dendrobium huoshanense flowers have been widely used for liver protection in China. This work was aimed to discover the natural products with activity of mitigating alcoholic hepatocyte injury from Dendrobium huoshanense flowers via bioactivity-guided isolation, and to clarify the underlying mechanisms of these natural products. As a result, three flavonoids, 3′- O- methylquercetin-3- O-β -D-galactopyranoside ( 1 ), 3′- O- methylquercetin-3- O-β -D-glucopyranoside ( 2 ) and quercetin-3- O-β -D-glucopyranoside ( 3 ), were firstly isolated from D. huoshanense flowers. Results exhibited that flavonoids 1 – 3 could enhance the cell viability, decrease the expression of ALT and AST, inhibit the cell apoptosis, alleviate the oxidative stress, and mitigate the inflammatory response of alcohol-induced L02 cells. Mechanism study exhibited that flavonoids 1 – 3 could increase the expression of Nrf2 as well as its downstream antioxidation genes of alcohol-induced L02 cells, while ML-385 (Nrf2 inhibitor) could abolish the inhibitory effects of 1 – 3 on alcohol-induced hepatocyte injury. Flavonoids 1 – 3 could also reduce the phosphorylation levels of I κ B α and NF- κ B p65 of alcohol-induced L02 cells, while SC75741 (NF- κ B inhibitor) could not enhance the inhibitory effects of 1 – 3 on alcohol-induced L02 cells injury. The data above indicated that flavonoids 1 – 3 could inhibit alcohol-induced hepatocyte injury, which might be attributed to alleviating oxidative stress and mitigating inflammatory response by activating Nrf2 and inhibiting NF- κ B pathways.
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INTERNATIONAL IMMUNOPHARMACOLOGY
·
2021
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IF 4.932
Lu Wang,Xiaohui Wang,Lina Kong,Shuyuan Wang,Kai Huang,Jingjing Wu,Changyuan Wang,Huijun Sun,Kexin Liu,Qiang Meng
Acute liver failure (ALF) is a dramatic liver disease characterized by large areas of inflammation. However, there are no available effective targeted drugs for ALF treatment. In the study, serum biochemical index and H&E were used to explore the amelioration of the liver histopathological changes. The oxidative stress kits, quantitative real-time PCR, western blot, immunohistochemistry, immunofluorescence staining, reactive oxygen species (ROS), and siRNA were used to elucidate the mechanisms underlying isoliquiritigenin (ISL) protection. The results showed that ISL significantly improved the liver pathological changes. Furthermore, ISL reduced oxidative stress by altering the expression of PGC-1α, Nrf2, HO-1, NQO1, Keap1, GCLC, and GCLM in damaged hepatocytes. Moreover, the levels of inflammation-related genes including NLRP3 inflammasome, IL-1β, IL-6, TNF-α, iNOS, and Mip-2 were repressed by ISL. In addition, ISL alleviated LPS/D-GalN-induced hepatocytes apoptosis by increasing the Bcl-2/Bax ratio and suppressing the expression of cleaved caspase-3. Further in vivo and in vitro evidence proved the involvement of the PGC-1α/Nrf2 signaling pathway in ISL protection. In conclusion, ISL improves the ability of anti-oxidative stress, alleviates inflammatory reaction, apoptosis, and inhibits NLRP3 inflammasome to protect lipopolysaccharide/D-galactosamine (LPS/D-GalN)-induced ALF through activating the PGC-1α/Nrf2 pathway, which provides the possibility for the treatment of ALF.
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PHYTOMEDICINE
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2021
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IF 5.34
Xiaohui Wang,Lu Wang,Renchao Dong,Kai Huang,Changyuan Wang,Jiangning Gu,Haifeng Luo,Kexin Liu,Jingjing Wu,Huijun Sun,Qiang Meng
Background Chemical liver injury is one of the main causes of acute liver failure and death. To date, however, treatment strategies for acute liver injury have been limited. Therefore, there is an urgent need to find new therapeutic targets and effective drugs. NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome is a complex of multiple proteins that has been shown to induce cell death under inflammatory and stress pathologic conditions and is thought to provide new targets for the treatment of a variety of diseases. Purpose The purpose of this study was to investigate whether luteolin has a protective effect on the liver and further elucidate whether it is realized through the thioredoxin interacting protein (TXNIP)-NLRP3 axis. Study design Acute hepatic injury in mice caused by intraperitoneal injection of lipopolysaccharide (LPS) was treated with or without luteolin. Methods Male C57BL/6 mice and mouse primary hepatocytes were selected. TXNIP protein knockdown was achieved by siRNA , qPCR and Western blot were performed to explore the mechanism of luteolin in alleviating acute liver injury. Results The results indicated that luteolin had a markedly protective effect on acute liver injury induced by LPS in mice by inhibiting the TXNIP-NLRP3 axis. Luteolin inhibits NLRP3 inflammasome activation by suppressing TXNIP, apoptosis associated speck-like protein containing a CARD domain (ASC), caspase-1, interleukin-1β (IL-1β) and IL-18 to reduce liver injury. In addition, luteolin inhibits LPS-induced liver inflammation by inhibiting the production of inflammation-related gene tumor necrosis factor-α (TNF-α), IL-10, and IL-6. What's more, luteolin alleviated LPS-induced hepatocyte injury by inhibiting oxidative stress and regulating MDA , SOD , and GSH levels. However, the protective effect of luteolin on acute LPS-induced liver injury in mice was blocked by si-TXNIP in vitro . Conclusions These combined data showed that luteolin may alleviate LPS-induced liver injury through the TXNIP-NLPR3 axis, providing new therapeutic targets and therapeutic drugs for subsequent studies.
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JOURNAL OF CONTROLLED RELEASE
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2020
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IF 7.727
Meirong Huo,Honglan Wang,Ying Zhang,Han Cai,Pan Zhang,Lingchao Li,Jianping Zhou,Tingjie Yin
Modulation of tumor microenvironment (TME) has been indicated as an approach to improve efficacy of cancer therapy. Here, we proposed a nano co-delivery based combination therapy of paclitaxel (PTX) and silybin (SB) which can employ the synergistic effects through chemotherapy sensitization and microenvironment modulation. A dextran-based amphiphilic polymer (Dex-DOCA) was successfully developed for in vivo co-delivery and thus “synchronizing” the biodistribution , transport and release of PTX and SB. Resultantly, Dex-DOCA exhibited an excellent encapsulating efficiency for both PTX and SB with adjustable loading ratio for an optimal synergistic antitumor activity . Moreover, the co-loaded nanoparticles efficiently discharged the two drugs at the prospective dosage ratio specifically in acid endo/lysosome mimic environments. The results of in vitro cytotoxicity and cell apoptosis assays further confirmed the SB sensitized PTX potency. Finally, in vivo investigation demonstrated that the co-loaded nanoparticles could effectively accumulate in tumor sites by passive targeting, and inhibit tumor growth through an enhanced intratumoral penetration (resulted from stromal components eradication and tumor vessels normalization associated TME modulation), as well as a sensitization effect of SB on PTX cytotoxic chemotherapy .
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Nutrients
·
2023
·Vol. 15
·期 19
·4176
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IF 5.9
Yuxu Chen,Zhiye Zhao,Shancheng Guo,Yaxian Li,Haiaolong Yin,Lei Tian,Guiguang Cheng,Ye Li
Alcoholic liver disease (ALD), leading to the most common chronic liver diseases, is increasingly emerging as a global health problem, which is intensifying the need to develop novel treatments. Herein, our work aimed to estimate the therapeutic efficacy of red rice (Oryza sativaL.) seed coat on ALD and further uncover the underlying mechanisms. Red rice seed coat extract (RRA) was obtained with citric acid–ethanol and analyzed via a widely targeted components approach. The potential targets of RRA to ALD were predicted by bioinformatics analysis. Drunken behavior, histopathological examination, liver function, gut microbiota composition and intestinal barrier integrity were used to assess the effects of RRA (RRAH, 600 mg/kg·body weight; RRAL, 200 mg/kg·body weight) on ALD. Oxidative stress, inflammation, apoptosis associated factors and signaling pathways were measured by corresponding kits, Western blot and immunofluorescence staining. In ALD model mice, RRA treatment increased sphingosine kinase 2 (SPHK2) and sphingosine-1-phosphate (S1P) levels, improved gut microbiota composition, restored intestinal barrier, decreased lipopolysaccharide (LPS) levels in plasma and the liver, cut down Toll-like receptor 4 (TLR4)/Nuclear factor kappa B (NF-κB) pathways, alleviated liver pathological injury and oxidative stress, attenuated inflammation and apoptosis and enhanced liver function. To sum up, RRA targeting SPHK2 can ameliorate ALD by repairing intestinal barrier damage and reducing liver LPS level via the TLR4/NF-κB pathway and intestinal microbiota, revealing that red rice seed coat holds potential as a functional food for the prevention and treatment of ALD.Keywords:red rice seed coat;alcoholic liver disease;SPHK2;gut microbiota;intestinal barrier
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ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY
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2023
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IF 4.3
Guanglu Wang,Yue Xin,Kaixin Ping,Xuhui Xu,Ying Sun,Xing Li,Xinying Guan,Jingquan Dong
Avermectins, as a new type of environmental pollutant, have received significant attention in recent years. Previous research has shown that acute exposure to avermectins can induce oxidative stress and inflammation in non-target fish species, such as carp. Flavonoid lignans, particularly Silybin, have demonstrated promising biological activities, including regulation of non-alcoholic fatty liver and cerebral ischemia-reperfusion injury. This study aims to investigate the impact of dietary supplementation with Silybin on the intestinal damage in carp caused by chronic exposure to avermectins and to improve the health status and production of carp in aquaculture. Silybin was used as a dietary supplement by adding it to the experimental feed, and an animal experimental model was utilized to assess its effects on oxidative stress, inflammation, and cell apoptosis in carp intestine. Additionally, intestinal barrier integrity, digestive capacity, and fish growth were evaluated. The results indicated that dietary supplementation with Silybin effectively alleviated the oxidative stress induced by chronic exposure to avermectins in carp intestine. Furthermore, Silybin improved intestinal barrier integrity and digestive capacity by modulating the Nrf2/Keap1 pathway. This study demonstrates that dietary supplementation with Silybin can effectively mitigate the intestinal damage caused by chronic exposure to avermectins in carp, providing a sustainable solution for the aquaculture industry to enhance the overall health and production of cultured fish. The research expands our understanding of avermectin environmental pollution and offers a potential remediation approach.
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FISH PHYSIOLOGY AND BIOCHEMISTRY
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2023
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IF 2.9
Pan En-Zhuang,Xin Yue,Li Xue-Qing,Wu Xin-Yu,Tan Xue-Lian,Dong Jing-Quan
The aim of this study was to investigate the splenic tissue damage of environmental biological drug avermectin to freshwater cultured carp and to evaluate the effect of silybin on the splenic tissue damage of carp induced by avermectin. A total of 60 carp were divided into 4 groups with 15 carp in each group, including the control group fed with basic diet, experimental group fed with basal diet and exposed to avermectin (avermectin group), experimental group fed with basal diet supplement silybin (silybin group), and experimental group fed with basal diet supplement silybin and exposed to avermectin (silybin + avermectin group). The whole test period lasted for 30 days, and spleen tissue was collected for analysis. In this study, H&E staining, mitochondrial purification and membrane potential detection, ATP detection, DHE staining, biochemical tests, qPCR, immunohistochemistry, and apoptosis staining were used to evaluate the biological processes of spleen tissue injury, mitochondrial function, oxidative stress, apoptosis, and endoplasmic reticulum stress. The results show that silybin protected carp splenic tissue damage caused by chronic avermectin exposure, decreased mitochondrial membrane potential, decreased ATP content, ROS accumulation, oxidative stress, apoptosis, and endoplasmic reticulum stress. Silybin may ameliorate the splenic tissue damage of cultured freshwater carp caused by environmental biopesticide avermectin by alleviating mitochondrial dysfunction and inhibiting PERK-ATF4-CHOP-driven mitochondrial apoptosis. Adding silybin into the diet becomes a feasible strategy to resist the pollution of avermectin and provides a theoretical basis for creating a good living environment for freshwater carp. Graphical Abstract
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JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
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2023
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IF 4.1
Zheyuan Ren,Yang Yu,Zhongyao Ji,Huitao Li,Xiaoheng Li,Han Lin,Renshan Ge,Qiqi Zhu
The potential inhibitory effects of flavonoids on gonadal steroid biosynthesis have gained attention due to their widespread presence in natural plant sources. Specifically, our study focused on evaluating the inhibitory efficacy of these compounds on human 3β-hydroxysteroid dehydrogenase 2 (h3β-HSD2) and rat homolog r3β-HSD1, enzymes responsible for the conversion of pregnenolone to progesterone . Through our investigations, we observed that the potency of flavonoids was silymarin (IC 50 , 1.31 μM) > luteolin (4.63 μM) > tectorigenin > (5.86 μM), and rutin (44.12 μM) in inhibiting human KGN cell microsomal h3β-HSD2. Similarly, the potency of flavonoids was silymarin (9.50 μM) > luteolin (11.49 μM) > tectorigenin (14.06 μM), and rutin (145.71 μM) in inhibiting rat testicular r3β-HSD1. Silymarin, luteolin, and tectorigenin acted as mixed inhibitors of both human and rat 3β-HSDs. Luteolin and tectorigenin were able to penetrate human KGN cells to inhibit progesterone secretion . Furthermore, docking analysis and structure-activity relationship analysis highlighted the importance of hydrogen bond formation for the inhibitory efficacy of these compounds against h3β-HSD2 and r3β-HSD1. Overall, this study demonstrates that silymarin exhibits the most potent inhibition of human and rat gonadal 3β-HSDs, and significant SAR differences exist among the tested compounds.
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