BRITISH JOURNAL OF PHARMACOLOGY
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2024
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IF 6.8
Chen Pan,Yuhao Xu,Zongsheng Jiang,Chengjiang Fan,Zhexi Chi,Yu Zhang,Mengmeng Miao,Yuxuan Ren,Ziyi Wu,Linbin Xu,Changqing Mei,Qingge Chen,Yang Xi,Xiaowei Chen
Background and Purpose Chemotherapy-induced peripheral neuropathy (CIPN) commonly causes neuropathic pain, but its pathogenesis remains unclear, and effective therapies are lacking. Naringenin, a natural dihydroflavonoid compound, has anti-inflammatory, anti-nociceptive and anti-tumour activities. However, the effects of naringenin on chemotherapy-induced pain and chemotherapy effectiveness remain unexplored. Experimental Approach Female and male mouse models of chemotherapy-induced pain were established using paclitaxel. Effects of naringenin were assessed on pain induced by paclitaxel or calcitonin gene-related peptide (CGRP) and on CGRP expression in dorsal root ganglia (DRG) and spinal cord tissue. Additionally, we examined peripheral macrophage infiltration, glial activation, c-fos expression, DRG neuron excitability, microglial M1/M2 polarization, and phosphorylation of spinal NF- κ B. Furthermore, we investigated the synergic effect and related mechanisms of naringenin and paclitaxel on cell survival of cancer cells in vitro. Key Results Systemic administration of naringenin attenuated paclitaxel-induced pain in both sexes. Naringenin reduced paclitaxel-enhanced CGRP expression in DRGs and the spinal cord, and alleviated CGRP-induced pain in naïve mice of both sexes. Naringenin mitigated macrophage infiltration and reversed paclitaxel-elevated c-fos expression and DRG neuron excitability. Naringenin decreased spinal glial activation and NF- κ B phosphorylation in both sexes but influenced microglial M1/M2 polarization only in females. Co-administration of naringenin with paclitaxel enhanced paclitaxel's anti-tumour effect, impeded by an apoptosis inhibitor. Conclusion and Implications Naringenin's anti-nociceptive mechanism involves CGRP signalling and neuroimmunoregulation. Furthermore, naringenin facilitates paclitaxel's anti-tumour action, possibly involving apoptosis. This study demonstrates naringenin's potential as a supplementary treatment in cancer therapy by mitigating side effects and potentiating efficacy of chemotherapy. Graphical ∎
研究领域:
药理学
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神经科学
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肿瘤学
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疼痛研究
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高影响因子
JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY
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2025
·
IF 3.1
Jiahui Sun,Luyao Shi,Fan Xu,Hanyan Sun,Yitong Liu,Jiangyun Sun,Qingxin Zhou
Colorectal cancer (CRC) is a worldwide health issue. It causes illness and death in millions of people each year. A positive correlation has been observed between the intake of dietary fat and the development of CRC. The composition of gut microbiota exhibits a significant correlation with pathophysiologic processes in intestine. Clinical treatment remains inadequate due to the complex pathogenic mechanisms of CRC triggered by a high-fat diet (HFD). Naringenin, a flavonoid from grapefruit, has anti-cancer activity. Our findings suggest that naringenin enhances gut microbiota diversity by increasing the abundance of beneficial bacterial species while reducing opportunistic pathogenic bacteria. The fecal microbiota transplantation assay (FMT) demonstrated that the anti-HFD-CRC activity of naringenin depended on the gut microbiota. Furthermore, naringenin antagonized the IL-6/STAT3 pathway. These results suggest that naringenin may be a potential treatment for HFD-CRC.
研究领域:
肿瘤学
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营养学
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微生物学
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PubMed
高影响因子
Food Bioscience
·
2026
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IF 6.2
Peijian Cai,Yingying Cao,Yifan Zhang,Yanqi Lin,Wenwen Feng,Yi Liu,Zhaozhi Zeng,Fansheng Kong
Although naringenin exhibits a wide range of biological activities, its practical use is limited by its poor water solubility and bioavailability. In this study, a pH-driven method utilizing sodium caseinate and carboxymethyl chitosan (CMCS) was employed to prepare protein-polysaccharide composite nanoparticles (N/NC NPs) for naringenin delivery. These nanoparticles were formed through hydrogen bonds, hydrophobic bonds, and weak electrostatic interactions. The physicochemical stability of nanoparticles improved after the surface modification of CMCS, compared to sodium caseinate nanoparticles loaded with naringenin (N/N NPs). The water solubility and bioactivities of naringenin, including its in vitro hypoglycemic and hypolipidemic effects, inhibition of erythrocyte oxidative hemolysis, and antimicrobial qualities, and its release rate (63.55%) during digestion were all greatly improved after encapsulation. When used as an active filler in starch gels (N/NC-SG), the nanoparticles softened the textural properties and conferred bioactivity to the gel. Moreover, the reticular structure within the gel encapsulated the nanoparticles, providing a physical barrier and effectively regulating the delivery of naringenin. The bioaccessibility of naringenin in N/NC-SG (53.49%), N/NC NPs (44.59%), and N/N NPs (42.80%) is significantly higher than that of free naringenin (23.05%). Consequently, N/NC NPs improved the usability of naringenin. The preparation of N/NC-SG broadens the application potential of N/NC NPs in the food industry, and the nanoparticle-starch gel composite could serve as a new and efficient bioactive substance delivery system.
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GENERAL PHYSIOLOGY AND BIOPHYSICS
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2024
·Vol. 43
·期 1
·13-23
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IF 1.3
Xiao Jin,Ling Jin,Bingxin Wu,Danping Xu
Myocardial ischemia/reperfusion (I/R) causes serious threats to human life. Naringenin, a polyphenolic compound naturally occurring in citrus fruit, has cardioprotective effects against myocardial I/R injury. Besides, miR-24-3p is also reported to have cardioprotective effects. We intended to explore whether the cardioprotective effects of naringenin relate to miR-24-3p and its underlying mechanism. In this study, we used an in vivo rat myocardial I/R model and an in vitro cardiomyocyte H9c2 hypoxia/reoxygenation (H/R) model. Myocardial injury was detected by hematoxylin-eosin staining and ELISA for creatine kinase (CK), malondialdehyde (MDA), and lactate dehydrogenase (LDH). miR-24-3p and cell death inducing p53 target 1 (Cdip1) mRNA expressions were examined by RT-PCR. We find that naringenin pretreatment significantly relieves myocardial I/R injury, reduces LDH, CD, and MDA levels, and increases miR-24-3p expression. Furthermore, miR-24-3p alleviates myocardial I/R injury partially through regulating Cdip1. Moreover, naringenin protects myocardial I/R injury partially by regulating miR-24-3p to inhibit Cdip1 expression. In conclusion, our data suggest naringenin protects myocardial I/R injury partially through miR-24-3p/Cdip1 axis.
研究领域:
心脏病学
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分子生物学
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药理学
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生物医学
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PubMed
高影响因子
Foods
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2023
·Vol. 12
·期 11
·2120
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IF 5.2
Jie Li,Bingyong Mao,Xin Tang,Qiuxiang Zhang,Jianxin Zhao,Hao Zhang,Shumao Cui
Naringenin and apigenin are common flavonoids derived from edible plants with the potential to alleviate inflammation and improve skin antioxidation. This study aimed to evaluate the effects of naringenin and apigenin on oleic acid-induced skin damage in mice and compare their underlying mechanisms of action. Triglycerides and non-esterified fatty acids were significantly decreased by naringenin and apigenin, while apigenin intervention resulted in a better recovery of skin lesions. Naringenin and apigenin improved the antioxidative abilities of the skin by increasing catalase and total antioxidant capacity levels and decreasing malondialdehyde and lipid peroxide levels. The release of skin proinflammatory cytokines, such as interleukin (IL)-6, IL-1β, and tumor necrosis factor α, was inhibited after naringenin and apigenin pretreatments, but naringenin only promoted the excretion of IL-10. Additionally, naringenin and apigenin regulated antioxidant defense and inflammatory response by activating nuclear factor erythroid-2 related factor 2-dependent mechanisms and suppressing the expression of nuclear factor-kappa B. In summary, naringenin and apigenin are prospective ingredients that contribute to the amelioration of skin damage by activating anti-inflammatory and antioxidative responses.Keywords:naringenin;apigenin;antioxidative system;inflammation;signaling pathway
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FOOD HYDROCOLLOIDS
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2024
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IF 11
Ying-Ying Chen,Qiang-Ming Li,Li-Hua Pan,Jian-Ping Luo,Xue-Ying Li,Xue-Qiang Zha
Naringenin (Nar) is a natural flavonoid with diverse health-promoting benefits. However, the bioavailability of Nar is significantly restricted due to its poor water-solubility, instability under physiological conditions, and limited absorption profile. In this study, a shellac-quinoa protein isolate (QPI) binary nanocomplex (SQP) was fabricated using the pH-shifting method for effectively delivering Nar. Isothermal titration calorimetry (ITC) and analysis of inner interactive forces revealed that the complexation between QPI and shellac was primarily driven by electrostatic and hydrophobic forces. Subsequently, Nar was successfully encapsulated within the stable and uniform SQP nanocomplex (Nar@SQP), achieving a high encapsulation capacity (94.52 % encapsulation efficiency and 14.68 % loading capacity). Meanwhile, the Nar@SQP nanoparticle exhibited excellent stability against pH, ionic strength, and long-term storage. Moreover, it also demonstrated sustained and slow-release characteristics during simulated gastrointestinal digestion. Compared to free Nar, the safe Nar@SQP nanoparticle effectively facilitated the cellular uptake of encapsulated Nar by Caco-2 cells, suggesting that Nar@SQP has a good potential to improve the bioavailability of Nar. Hence, these findings indicated that the developed Nar@SQP nanoparticle might hold significant promise as a nano-delivery system for hydrophobic bioactive nutrients, like Nar.
研究领域:
食品科学
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纳米技术
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药学
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生物技术
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高影响因子
Food Chemistry-X
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2024
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IF 6.5
Xiumei Chen,Yingying Sheng,Jinxin Che,Okwong Oketch Reymick,Nengguo Tao
Grapefruit ( Citrus × paradisi Macf.) peel, a by-product of the citrus-processing industry, possesses an important economic value due to the richness of bioactive compounds. In this study, boron-linked covalent organic frameworks integrated with molecularly imprinted polymers (CMIPs) were developed via a facile one-pot bulk polymerization approach for the selective extraction of naringenin from grapefruit peel extract. The obtained CMIPs possessed a three-dimensional network structure with uniform pore size distribution, large surface areas (476 m 2 /g), and high crystallinity. Benefiting from the hybrid functional monomer APTES-MAA, the acylamino group can coordinate with the boronate ligands of the boroxine-based framework to form B-N bands, facilitating the integration of imprinted cavities with the aromatic skeleton. The composite materials exhibited a high adsorption capacity of 153.65 mg/g, and a short adsorption equilibrium time of 30 min for naringenin, together with favorable selectivity towards other flavonoid analogues. Additionally, the CMIPs captured the template molecules through π–π* interaction and hydrogen bonding, as verified by FT-IR and XPS. Furthermore, they had good performance when employed to enrich naringenin in grapefruit peels extract compared with the common adsorbent materials including AB-8, D101, cationic exchange resin, and active carbon. This research highlights the potential of CMIPs composite materials as a promising alternative adsorbent for naringenin extraction from grapefruit peel.
研究领域:
食品科学
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材料科学
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PubMed
高影响因子
Frontiers in Pharmacology
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2024
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IF 4.4
Shi Yaning,Gao Zhixin,Xu Bing,Mao Junbing,Wang Yue,Liu Zongping,Wang Jicang
Cadmium (Cd) is a highly hazardous toxic substance that can cause serious harm to animals. Previous studies have indicated that cadmium chloride (CdCl2) can damage organs, such as the liver, ovaries, and testicles. Naringenin (Nar) represents a flavonoid with various properties that promote the alleviation of Cd-induced damage. In this experiment, 60 chickens were divided into the control group, 150 mg/kg CdCl2 treatment group, 250 mg/kg Nar treatment group, and 150 mg/kg CdCl2 + 250 mg/kg Nar co-treatment group, which were treated for 8 weeks. Kidney tissues samples were collected to investigate kidney function, including oxidative stress (OS), endoplasmic reticulum (ER) stress, and autophagy activity. Experimental results showed the decreased weight of chickens and increased relative weight of their kidneys after CdCl2 treatment. The increase in NAG, BUN, Cr, and UA activities, as well as the increase in MDA and GSH contents, and the decrease activities of T-AOC, SOD, and CAT in the kidney, manifested renal injury by OS in the chickens. TUNEL staining revealed that CdCl2 induced apoptosis in renal cells. CdCl2 upregulates the mRNA and protein expression levels of GRP78, PERK, eIF2α, ATF4, ATF6, CHOP, and LC3, and inhibited the mRNA and protein expression levels of P62 proteins, which leads to ER stress and autophagy. The CdCl2 + Nar co-treatment group exhibited alleviated CdCl2-induced kidney injury, OS, ER stress, and autophagy. Research has demonstrated that Nar reduces CdCl2-induced kidney injury through alleviation of OS, ER stress, and autophagy.
研究领域:
兽医学
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药理学
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毒理学
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高影响因子
ACS Applied Bio Materials
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2026
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IF 4.7
Yingying Du,Lin Wang,Yi Ouyang,Qun Chen,Ziwei Liu,Zhimei Liu
Quercetin (Que) and naringenin (Nar) are natural compounds with potent antioxidant and anti-inflammatory activities, showing promise for alleviating ultraviolet B (UVB)-induced skin photoaging. The presence or absence of a C═C bond in the C-ring defines whether the compound is a flavonol or a flavanone. To overcome poor water solubility and low bioavailability of the two flavonoids, we prepared inclusion complexes using β-cyclodextrin (β-CD), hydroxyethyl-β-cyclodextrin (HE-β-CD), and hydroxypropyl-β-CD (HP-β-CD). These complexes leverage the cyclodextrins’ hydrophilic exterior and hydrophobic interior to encapsulate Que and Nar, respectively. Through integrated analyses─including molecular docking, phase solubility studies, characterization (UV, Fourier-transform infrared (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM), and NMR), solubility tests, and antioxidant (2,2-diphenyl-1-picrylhydrazyl (DPPH)) assays─we systematically elucidated the structure–activity relationships of these flavonoid–cyclodextrin interactions. The therapeutic potential was further evaluated in a UVB-induced mouse model of skin photoaging. Results confirmed the spontaneous formation of stable 1:1 molar ratio inclusion complexes between the flavonoids and cyclodextrins. The enhancement of complex stability, water solubility, and antioxidant activity consistently followed the order: HP-β-CD > HE-β-CD > β-CD. Owing to Que’s conjugated planar structure, it exhibited weaker binding to β-CD than did Nar. However, Que formed more stable complexes with HE-β-CD and HP-β-CD than Nar did. In vivo, the Que/HP-β-CD complex demonstrated superior efficacy, most effectively reducing malondialdehyde (MDA) levels, alleviating epidermal hyperplasia, and increasing collagen fiber content. Furthermore, the inclusion complexes amplified the regulatory effects of Que and Nar on mitogen-activated protein kinase (MAPK) and TGF-β/Smad pathways: they enhanced the downregulation of p-p38 and MMP-1 to inhibit collagen degradation and promoted the upregulation of Smad2/3 and COL1A1 to stimulate collagen synthesis. In conclusion, the β-cyclodextrin inclusion complexes of flavonoids, designed based on structure–activity relationship studies, significantly improve the compounds’ solubility, stability, and bioactivity. This leads to enhanced protective efficacy against UVB-induced photodamage through the concurrent modulation of multiple signaling pathways.
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Aquaculture Reports
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2026
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IF 3.7
Dexiang Feng,Xiaotong Si,Wenxuan Liu,Pengwei Xun,Qianqian Huang,Mingzhu Liu,Ming Li
Naringenin (NGN), a flavonoid compound abundantly found in citrus fruits, exhibits anti-inflammatory, anti-oxidative activities, and hypolipidemic properties. However, nowadays, NGN is mainly used to inhibit the occurrence of viral diseases in aquatic animals by injection as an immunosuppressant, and its safety and other physiological effects as a feed additive have not been sufficiently investigated. This study elucidates how naringenin (NGN) mitigates the negative impacts exerted by a high-fat diet (HFD) on Largemouth bass ( Micropterus salmoides ) from hepatic and intestinal perspectives. After an 8-week feeding trial, the NGN groups had a significant effect on growth performance compared to the HFD group, and significantly decreased the lipid content of the whole body. Secondly, NGN significantly decreased the levels of triglycerides and total cholesterol in serum compared with the HFD group, down-regulated the lipogenesis-related genes, and significantly up-regulated the lipolysis-related genes. Furthermore, hepatic injury markers alanine transaminase and aspartate transaminase were also significantly decreased. Additionally, NGN significantly enhanced the antioxidant capacity of the liver, down-regulated the gene expression of pro-inflammatory factors, and up-regulated the anti-inflammatory factors. There were remarkable changes in the structure of the gut microbiota, where the biomarker of the Na1 group was Dyella , and the main ones in the Na2 group were Asinibacterium , Methylovirgula , Mesorhizobium, and Meiothermus . The function of the gut microbiota in the NGN was more enriched in the fatty acid biosynthesis pathway compared to the high-fat diet. To conclude, the supplementation of NGN to HFD can significantly reduce hepatic lipid deposition and alleviate liver damage, as well as improve gut health status. Among them, the addition of 0.007 % naringenin exhibited a better effect. The results of this study will be used to help reduce the negative effects of an HFD within the aquaculture sector and hold the potential to be regarded as a promising eco-friendly feed additive for aquaculture.
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ENVIRONMENTAL TOXICOLOGY
·
2022
·Vol. 37
·期 8
·1840-1852
·
IF 4.109
Huijie Chen,Yue Zhang,Mengmeng Zou,Xiaowei Sun,Xiaodan Huang,Shiwen Xu
Dibutyl phthalate (DBP) is a phthalic acid ester (PAE) that has posed a health hazard to the organisms. Naringenin (NRG) is a flavanone compound that has shown protection against several environmental chemicals through suppression of oxidative stress and activation of phosphatidylinositol 3-kinase/threonine kinase (PI3K/AKT) signaling pathway. Herein, swine testis (ST) cells were treated with 1.8 μM of DBP or/and 25.39 nM of NRG for 24 h, we described the discovery path of NRG inhibition on apoptosis in DBP-exposed ST cells through targeting phosphatase and tensin homologue deleted on chromosome 10 (PTEN). We first found that the anti-apoptosis effect of NRG is dependent on mitochondrial pathway through flow cytometry and related gene/protein expression, and then we detected PI3K/AKT pathway-related gene/protein expression, and established a computational docking assay between NRG and PTEN. We found that NRG specifically binds to three basic residues (His93, Lys125, Lys128) of P loop in PTEN, as well as phosphatase domains (Asp92, His93, Cys124, Lys125, Ala126, Lys128, and Arg130) in active dephosphorylation pockets, thereby reducing PTEN level and activating PI3K/AKT signaling pathway, and further inhibiting oxidative stress and mitochondrial pathway apoptosis. Taken together, our results push forward that NRG deserves further attention as a potential antagonistic therapy against DBP through targeting PTEN to inhibit oxidative stress and activate PI3K/AKT signaling pathway.
研究领域:
毒理学
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细胞生物学
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药理学
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高影响因子
FOOD AND CHEMICAL TOXICOLOGY
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2023
·
IF 4.3
Shuai Liu,Xintao Gao,Yulan Yin,Jing Wang,Kehong Dong,Dayong Shi,Xiaochen Wu,Chuanlong Guo
Silk fibroin (SF) has excellent biocompatibility and biodegradability as a biomaterial. The purity and molecular weight distribution of silk fibroin peptide (SFP) make it more suitable for medical application. In this study, SFP nanofibers (molecular weight ∼30kD) were prepared through CaCl 2 /H 2 O/C 2 H 5 OH solution decomposition and dialysis, and adsorbed naringenin (NGN) to obtain SFP/NGN NFs. In vitro results showed that SFP/NGN NFs increased the antioxidant activity of NGN and protected HK-2 cells from cisplatin-induced damage. In vivo results also showed that SFP/NGN NFs protected mice from cisplatin-induced acute kidney injury (AKI). The mechanism results showed that cisplatin induced mitochondrial damage, as well as increased mitophagy and mtDNA release, which activated the cGAS-STING pathway and induced the expression of inflammatory factors such as IL-6 and TNF-α. Interestingly, SFP/NGN NFs further activated mitophagy and inhibited mtDNA release and cGAS-STING pathway. Demonstrated that mitophagy-mtDNA-cGAS-STING signal axis was involved in the kidney protection mechanism of SFP/NGN NFs. In conclusion, our study confirmed that SFP/NGN NFs are candidates for protection of cisplatin-induced AKI, which is worthy of further study.
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