Research
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2022
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IF 11.036
Yiqiu Fei,Shuobo Zhang,Shengyi Han,Bo Qiu,Yanmeng Lu,Weixing Huang,Fang Li,Deying Chen,Björn Berglund,Hang Xiao,Lanjuan Li,Mingfei Yao
Currently approved therapeutical strategies for inflammatory bowel diseases (IBD) suffer from variable efficacy and association with risk of serious side effects. Therefore, efforts have been made in searching for alternative therapeutics strategies utilizing gut microbiota manipulation. In this study, we show that the probiotic strain Ligilactobacillus salivarius Li01 (Li01) and the phytochemical prebiotic resveratrol (RSV) have synergistic effect in ameliorating colitis in mice. Oral coadministration of Li01 (10 9 CFU/d) and RSV (1.5 g/kg/d) promoted restoration of various inflammatory injuries and gut microbiota composition, exhibiting a favorable anti-inflammatory effect in DSS-induced colitis mice. The combination treatment was associated with reductions in the levels of proinflammatory cytokines IL-1 β and IL-6 and increases in the levels of the anti-inflammatory cytokine IL-17A in mouse serum. Moreover, the combination treatment was found to alter the composition and metabolism of the gut microbiota, especially influencing the production of short chain fatty acids and anti-inflammatory related molecules. The mechanism underlying the improved anti-inflammatory effect from the RSV and Li01 combination treatment was found to be associated with the environmental sensor mammalian aryl hydrocarbon receptor (AHR) and tryptophan metabolism pathway. Administration of RSV in combination with Li01 in different mouse model led to enhanced conversion of RSV into metabolites, including dihydroresveratrol (DHR), resveratrol-sulfate, and resveratrol-glucuronide. DHR was found to be the dominant metabolite of RSV in conventional and colitis mice. An increased DHR/RSV ratio was confirmed to activate AHR and contribute to an enhanced anti-inflammatory effect. DHR is considered as a potential AHR ligand. The DHR/RSV ratio also affected the serotonin pathway by controlling the expression of Tph1, SERT, and 5-HT 7 R leading to amelioration of colitis in mice. Our data suggest that treatment with a combination of Li01 and RSV has potential as a therapeutic strategy for IBD; further investigation of this combination in clinical settings is warranted.
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Phenomics
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2025
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IF 6.2
Hu Hongye,Wu Yanzhi,Hong Jingwei,Wang Huiying,Zhang Xiaohua,Huang Guanli,Zhu Xiaofang
Breast cancer (BC) remains the predominant form of cancer among women. Arsenic trioxide (ATO), an element in traditional Chinese medicine, has shown potential for treating BC, particularly when combined with resveratrol. However, the exact mechanisms of their combined action are not fully understood. This study aims to clarify their combined mechanisms through network pharmacology and experimental validation. In vitro experiments confirmed that compared with either agent alone, the combination of ATO and resveratrol more effectively inhibited the production of estrogen receptor 1 ( ESR1 ), tumor protein P53 ( TP53 ), and v-AKT murine thymoma viral oncogene homolog 1 ( AKT1 ) in MCF-7 cells. Our findings indicate that the combination of ATO and resveratrol significantly promotes cell apoptosis by suppressing ESR1 , TP53 , and AKT1 . Thus, ATO and resveratrol together may offer a promising strategy for BC treatment.
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PHYTOMEDICINE
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2026
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IF 11.3
Minghui Zhao,Hongfang Mu,Qian Ji,Jiale Song,Fuyixuan Zheng,Tianlong Liu,Wenbin Li,Rong Wang
Background The effects of persistent hypoxic conditions in high-altitude regions on metabolic disorders remain poorly understood and in-depth investigation into its underlying molecular mechanisms is notably insufficient. As a metabolism-associated liver disease, the pathogenesis of non-alcoholic fatty liver disease (NAFLD) under hypoxic conditions urgently requires clarification. Previous studies have demonstrated that resveratrol (Rsv) possesses significant anti-inflammatory, antioxidant, and lipid metabolism-modulating properties, and it can act as an inhibitor of ferroptosis. Yet its precise therapeutic efficacy and mechanism in hypoxic NAFLD remain to be further explored. Objective This study aims to explore the potential mechanism by which Rsv improves the deterioration of NAFLD under hypoxia exposure. Methods Herein, we performed concurrent interventions in both in vivo and in vitro models of NAFLD, comprehensively detecting biochemical indicators (inflammatory factors, oxidative stress markers, liver function), liver histopathological changes, and nucleic acid levels to assess the effects of Rsv. By introducing ferroptosis modulators, we measured core ferroptosis parameters (mitochondrial ultrastructure, Fe²⁺, 4-HNE, LPO levels, and key protein expressions) to define disease progression patterns. By HIF-1α silencing was employed to verify its regulatory roles in ferroptosis-related factors and NAFLD pathogenesis. Co-Immunoprecipitation assays and immunofluorescence co-localization were used to explore protein interactions among ACSL4, TfR1, and HIF-1α. Conclusion Our results demonstrated that high-altitude hypoxia exacerbates NAFLD via inducing ferroptosis; HIF-1α upregulates the expression of key ferroptosis mediators (ACSL4, TfR1), and HIF-1α silencing attenuates ferroptosis. Rsv exerts therapeutic effects against hypoxia-related NAFLD by targeting the HIF-1α-mediated ferroptosis pathway. This study elucidates the pivotal role of HIF-1α-dependent ferroptosis in hypoxia-aggravated NAFLD, identifies the therapeutic targets and mechanisms of Rsv, and provides novel theoretical foundations and potential intervention strategies for clinical management of hypoxia-related NAFLD in high-altitude areas.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2026
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IF 8.7
Ping Yang,Caiying Yang,Xiaoqian Xu,Jinyan Gao,Hongbing Chen,Ping Tong
Covalent modification of RES under heat stress reduced the allergenicity of OVA. • HOVA-RES enhanced the digestibility and cellular transport capacity of OVA in vitro. • HOVA-RES obviously decreased the levels of specific antibodies and mMCP-1 in mice. • HOVA-RES significantly reduced the secretion of Th2-type cytokines. • HOVA-RES modulated the composition and diversity of the intestinal flora of mice. Heat stress (H) and covalent modification with resveratrol (RES) can significantly change the conformation of ovalbumin (OVA) and improve its processing properties, however, whether HOVA-RES affects the immunological function of OVA is still unclear. In this study, the effect of HOVA-RES on the digestion, transport, immune cell responsiveness, and allergenicity of OVA were investigated using the in vitro and in vivo models. Results showed that HOVA-RES enhanced the digestion and cellular transporter capacity of OVA, and the transported productions inhibited histamine and β-HEX release in the degranulation reaction of KU812 cells. In addition, HOVA-RES significantly reduced the OVA-specific IgE, IgG, IgG1, and mMCP-1 levels in mice sera. It also resulted in decreased secretion of Th2-type cytokines (IL-4, IL-5, and, IL-13) and reduced intestinal tissue damage. Moreover, HOVA-RES modulated the composition and diversity of the intestinal flora in OVA-sensitized mice, altered the abundance of dominant genera, and improved the intestinal microecology. Therefore, HOVA-RES covalent conjugation can improve the in vivo and in vitro immunological functions of OVA, especially significantly reduce its allergenicity, which provides a new direction to develop hypoallergenic products. Download: Download high-res image (132KB) Download: Download full-size image
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FOOD CHEMISTRY
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2026
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IF 10.4
Qiufang Liang,Panpan Cao,Yunxia Du,Aosen Lu,Haile Ma,Mingming Zhong,Yufan Sun,Abdul Qayum,Xiaofeng Ren
A novel two-step ultrasound way constructs zein-resveratrol-pectin ternary complexes. • Resveratrol plays a dual role as bioactive compound and protein structural modifier. • Primary ultrasound boosts resveratrol encapsulation and nanoparticle uniformity. • Secondary ultrasound drives interfacial assembly into a dense, stable layer. • The Pickering emulsion exhibits superior stability to heat, pH, salt and oxidation. This study introduces a two-step ultrasonic strategy for fabricating zein-resveratrol-pectin ternary complexes as Pickering emulsion stabilizers. The novelty lies in two aspects. First, resveratrol serves as both a structural modulator and an antioxidant. Second, ultrasonication plays a distinct dual role, with primary ultrasonication optimizing nanoparticle assembly (encapsulation efficiency 86.0%, particle size ∼180 nm) and secondary ultrasonication activating interfacial complexation with pectin to yield complexes with superior emulsifying performance (emulsifying activity index 15.94 m 2 /g). The resulting emulsion exhibited solid-like gel behavior (storage modulus ∼100 Pa), minimal creaming (20.01%), and exceptional stability under thermal, pH, and ionic stresses, with minimal creaming even at 85 °C. Raman spectroscopy confirmed the formation of a dense interfacial layer, which underpinned the enhanced oxidative resistance (peroxide value 0.25 mmol/L after 5 days). This work demonstrates that integrating polyphenol modification with dual-stage ultrasonication offers a green and effective approach for developing high-performance, clean-label food colloids. Download: Download high-res image (176KB) Download: Download full-size image
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FOOD RESEARCH INTERNATIONAL
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2026
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IF 8.8
Cuiyun Zhu,Huibin Zhang,Zhengtao Dai,Zifeng Liao,Fang Tian,Shuhao Fan,Wei Li,Yu Li,Xianrui Zheng,Zongjun Yin,Xiaodong Zhang
Resveratrol (RSV) improve gut-ovarian metabolic inflammation, and this effect could be related to the remodeling of the gut microbiota. • RSV reverses the high-fat diet (HFD) induced ovary glycolytic switch and restores its mitochondrial energy homeostasis. • RSV is associated with downregulated expression of Il-6 , Lpl , and Fabbp4 , which helps alleviate the vicious cycle between lipotoxicity and inflammation in the ovaries. • RSV can promote the enrichment of Akkermansia and Lachnospiraceae , a change that may be associated with gut microbiota remodeling. Metabolic stress induced by a high-fat diet (HFD) is one of the key factors leading to ovarian dysfunction. In this study, a multi-omics approach was employed to investigate the protective effects of resveratrol (RSV) against HFD-induced ovarian dysfunction in rats. The results indicate that RSV not only significantly mitigated systemic metabolic imbalances, such as weight gain and dyslipidemia, but also restored ovarian homeostasis, as evidenced by normalized estrous cycles, improved ovarian morphology, and balanced hormone levels. Mechanistically, RSV normalized altered ovarian energy metabolism by enhancing the tricarboxylic acid (TCA) cycle and oxidative phosphorylation while inhibiting glycolysis, thereby increasing ATP production. Transcriptomic analysis further revealed significant upregulation of key pathways, including the PPAR signaling pathway and steroidogenesis, and identified Apob and Lpl as potential core regulatory genes. Notably, RSV intervention modulated the gut microbiota, increasing microbial diversity and enriching beneficial bacterial genera, suggesting a restorative effect on the gut-ovary axis. In summary, our findings demonstrate that RSV alleviates HFD-induced ovarian dysfunction partially alleviates through a multilevel network involving systemic metabolism, ovarian energy metabolism, and gut microbiota regulation. This demonstrates its potential as a functional food ingredient for protecting female reproductive health. Download: Download high-res image (104KB) Download: Download full-size image
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Pharmaceutics
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2026
·Vol. 18
·期 7
·872
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IF 6.9
Weinan Li,Sisi Yan,Yingying Gao,Yuhan Fu,Yutong Mei,Yanhong Wang,Zhixin Yang
Background: The highly heterogeneous and dynamically evolving tumor microenvironment leads to the development of drug resistance and recurrence in traditional therapies. Although immunotherapy demonstrates unique advantages, its clinical utility remains constrained by the suboptimal immunogenicity and the limited effect of monotherapy. Herein, a hybrid drug delivery system based on a spatiotemporal hierarchical controlled-release strategy was proposed to achieve dual immunotherapy with immune checkpoint blockade (ICB) and immunogenic cell death (ICD) to promote synergistic anti-tumor therapy.Methods: A liposome–micelle hybrid drug delivery system (RUT-RPP-LP) was constructed using a lipid bilayer composed of dioleoyl phosphatidylethanolamine/hemisuccinyl cholesterol to encapsulate rutin (RUT) and to form an inner cavity-encapsulated resveratrol micelle (RPP). RUT-RPP-LP was characterized, and its pH sensitivity and release behavior were investigated. Subsequently, a colon cancer tumor-bearing mouse model was constructed to evaluate the in vivo targeted anti-tumor effect and biological safety. On this basis, the combined mechanism of ICB and ICD was preliminarily explored.Results: RUT-RPP-LP possessed excellent formulation characteristics, stability, and biocompatibility, achieving graded controlled release of drugs via responding to the TME and lysosomal acidity, respectively. Obviously, RUT-RPP-LP could specifically target the tumor site, induce the occurrence of ICD, and simultaneously block the PD-1/PD-L1 immune checkpoint signaling pathway, thereby enhancing the function of T cells and inducing apoptosis of tumor cells.Conclusions: The RUT-RPP-LP based on the hierarchical controlled-release strategy exerted a spatiotemporally coordinated enhancement of anti-tumor immunity, and may provide a novel combinatorial approach to overcome the low response of immunotherapy in solid tumors.
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BMC BIOTECHNOLOGY
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2026
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IF 4.8
Chen Zhongxin,Cao Wei,Zhao Minghua,Wang Qing,Li Yujiang,Fu Rong,Gao Xinyu,Ke Zunqian,Xu Xinqing,Li Shengcun
Background Secondary injury after acute brain injury (ABI) involves interconnected oxidative, inflammatory, and apoptosis-associated cellular responses. Resveratrol (RSV) has antioxidant and anti-inflammatory activities, but its limited aqueous stability and rapid clearance restrict sustained biological activity. This study developed a pH-responsive RSV delivery platform consisting of chitosan-based nanoparticles embedded in gelatin methacryloyl (GelMA) and evaluated its physicochemical properties, release behavior, and effects on ABI-relevant cellular responses in vitro. Results RSV-loaded chitosan-based nanoparticles (RSV@PCCC) were prepared through electrostatic self-assembly and subsequently incorporated into GelMA hydrogel. The optimized nanoparticles maintained relatively stable hydrodynamic characteristics at pH 7.2 and exhibited increased RSV release under acidic conditions. After 72 h, cumulative RSV release from RSV@PCCC reached ~ 74% at pH 6.4 and ~ 50% at pH 7.2. Incorporation into GelMA (RSV@PCCC-Hydrogel) prolonged RSV release, resulting in cumulative release of ~ 58% and ~ 36% at pH 6.4 and pH 7.2, respectively. In LPS-stimulated neural and microglial cells, the RSV-containing formulations reduced intracellular reactive oxygen species. RSV@PCCC reduced IL-1β and TNF-α protein expression by ~ 60% and ~ 50% respectively. RSV@PCCC and RSV@PCCC-Hydrogel reduced the Bax to Bcl-2 ratio by ~ 50% and ~ 40% respectively. These results indicate attenuation of oxidative stress, inflammatory activation, and apoptosis-associated changes under the tested in vitro conditions. Conclusions The chitosan-based nanoparticle/GelMA platform enabled pH-responsive and sustained RSV release and attenuated LPS-induced oxidative, inflammatory, and apoptosis-associated changes in neural and microglial cells. These findings provide an in vitro proof-of-concept for modulating cellular processes associated with secondary injury after ABI and support further evaluation of this platform in physiologically relevant ABI models.
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PHYTOTHERAPY RESEARCH
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2026
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IF 8.1
Huimao Liu,Dan Yang,Hanyan Cheng,Lijuan Cao,Xu Song,Xun Zhou,Yuanfeng Zou,Lixia Li,Renyong Jia,Dongmei Zhang,Mingyue Li,Zhongqiong Yin
Resveratrol (RSV), a dietary polyphenol widely present in traditional medicinal plants and foods, exhibits antioxidant and anti-inflammatory properties that are relevant to ethnopharmacological strategies for protecting against environmental neurotoxicants. Given increasing real-world co-exposure to lead (Pb) and cadmium (Cd), elucidating RSV's capacity to preserve gut–brain axis (GBA) homeostasis has direct translational relevance for populations relying on phytochemical interventions. Sprague–Dawley rats were randomized into control, Pb–Cd model, and RSV treatment groups (10, 20, or 40 mg/kg). For 4 weeks, rats received Pb (300 mg/L) and Cd (50 mg/L) in drinking water with daily RSV. Cognitive function was assessed by Morris water maze; barrier integrity by Evans blue assay, histology, and Western blot for ZO-1/Occludin; synaptic ultrastructure by TEM; microbiota composition by 16S rRNA sequencing; and short-chain fatty acids (SCFAs) by GC-MS. Neurotransmitters (5-HT, GABA, SP, VIP) and cytokines (IL-6, IL-1β, TNF-α) were measured by ELISA. RSV improved spatial learning, reduced EB extravasation, preserved synaptic ultrastructure and proteins (BDNF, SYN, PSD-95), and restored intestinal architecture with increased ZO-1/Occludin. RSV attenuated cytokine release, normalized goblet cells, reversed dysbiosis by restoring Lactobacillaceae/Prevotellaceae, and increased acetate, propionate, and butyrate. It reinstated 5-HT and GABA while reducing SP and restoring VIP across serum, colon, and hippocampus. RSV attenuated Pb–Cd–associated neurotoxicity and was accompanied by improved intestinal and BBB-related readouts, partial normalization of gut microbiota features and SCFA levels, and preservation of synaptic and neurotransmitter-related markers, consistent with a link to gut–brain axis function. This study is among the first to test RSV in a Pb–Cd co-exposure model using a multi-dose regimen with integrated behavioral, barrier, microbial, and neurochemical endpoints.
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PSYCHOPHARMACOLOGY
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2026
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IF 3.3
Chen Shuting,Zhao Kexuan,Shi Zhidan,Zhang Chu,Wu Hao,Tian Meng,Sun Yi,He Ling
Rationale Tau protein hyperphosphorylation and neuroinflammation playimportant roles in the onset and progression of Alzheimer's disease (AD). SIRT1has been implicated in the regulation of synaptic plasticity, cognitive function, andmemory, and is associated with the modulation of autophagy-and inflammation-related signaling pathways, including AMPK/mTOR/ULK1 and NF-κB. Resveratrol(RSV) has been reported to ameliorate cognitive impairment in AD models,primarily in the context of Aβ–related pathology; however, its potential effects andunderlying mechanisms in Tau-driven pathology remain incompletely understood. Objectives To investigate the effect of RSV on cognitive impairment in mice withTau mutation-induced Alzheimer's disease, and to explore its effects on autophagyand neuroinflammation. Methods Tauopathy models were established using AAV-P301L-Tau. Cognitivefunction was assessed via behavioral tests; Hippocampal injury was evaluatedAccepted manuscriptACCEPTED MANUSCRIPTusing HE and Nissl staining, while autophagy was assessed byimmunofluorescence staining. Mechanisms were examined using Western blot,qRT-PCR, and CCK-8 assays. Results RSV treatment was associated with attenuation of neuronal damage,reduction of p-Tau accumulation, and improvement of cognitive impairment in ADmice. Consistent trends were observed in vitro, where RSV treatment wasassociated with increased cell viability and modulation of autophagy-relatedmarkers in AAV-P301L-Tau-induced BV2 cells. In addition, RSV administration wasaccompanied by coordinated changes in signaling components related to SIRT1,AMPK/mTOR/ULK1, and NF-κB pathways, along with reduced expression ofinflammatory mediators. Conclusions RSV treatment was associated with coordinated modulation ofsignaling components related to the AMPK/mTOR/ULK1 and NF-κB pathways,together with improvements in cognitive performance in AD mice. These findingssupport the potential therapeutic relevance of RSV in Tau-drivenneurodegenerative pathology, while further studies are required to clarify theunderlying mechanisms.
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Foods
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2022
·Vol. 11
·期 23
·3813
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IF 5.561
Jinhao Zou,Xueming Liu,Xuping Wang,Huaigu Yang,Jingrong Cheng,Yaosheng Lin,Daobang Tang
Chlorogenic acid (CA), gallic acid (GA), and resveratrol (RES) were added to a gelatin (GEL)-chitosan (CHI)-glycerol (GLY) edible coating, and their effects on the coating of fresh beef preservation were investigated. The results revealed that CA had the most significant improvement effect on fresh beef preservation. The combination of GEL-CHI-GLY-CA preserved the color of the beef better and delayed the increase of the total volatile base nitrogen, even though its total phenolic content decreased at a faster rate during beef preservation. GA also improved the preservation effect as on the 12th day of storage, the beef samples treated with GEL-CHI-GLY-GA had the lowest thiobarbituric acid reactive substances (0.76 mg Malondialdehyde (MDA)/kg) and total viable count (6.0 log cfu/g). On the whole, though RES showed an improvement on beef preservation, the improvement was not as good as the other two polyphenols. After 12 days of storage, the beef samples treated with GEL-CHI-GLY-RES had a higher pH value (6.25) than the other two polyphenol treatmed groups. Overall, the three polyphenol-added combinations increased the shelf life of beef by approximately 3–6 days compared to the control group (treated GEL-CHI-GLY with distilled water).Keywords:fresh beef;edible coating;polyphenols;meat quality
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Journal of Analytical Methods in Chemistry
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2022
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IF 2.594
Ying Xu,Song-xia Zhang,Jing Guo,Li-jie Chen,Yu-ligh Liou,Tai Rao,Jing-bo Peng,Ying Guo,Wei-hua Huang,Zhi-rong Tan,Dong-sheng Ou-yang,Hong-hao Zhou,Wei Zhang,Yao Chen
Mice are the most frequently used animals in pharmacokinetic studies; however, collecting series of blood samples from mice is difficult because of their small sizes and tiny vessels. In addition, due to the small sample size, it is problematic to perform high required quantification. Thus, present work aims to find an effective strategy for overcoming these challenges using trans-resveratrol as a tool drug. Based on the idea of a joint technology, the capillary microsampling (CMS) was chosen for blood sample collection from mice after delivery of trans-resveratrol (150 mg/kg) by gavage, and a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed for the determination of trans-resveratrol and its main metabolites. All the mouse blood samples were exactly collected by CMS without obvious deviation. This provided credible samples for subsequent quantitative analysis. The HPLC-MS/MS method was found to be sensitive, accurate, and repeatable, and the pharmacokinetic parameters for all analytes were comparable with those reported in previous studies. However, the present joint technology offers the advantages of less animal damage, easy for sample preparation, and improved reliability. It has overcome some of the major limitations revealed in previous pharmacokinetic studies in mice and therefore provides a more effective option for future studies.
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危险品化学品经营许可证（带存储）