FOOD AND CHEMICAL TOXICOLOGY
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2014
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IF 2.61
Jingze Duan,Yan Xie,Huilin Luo,Guowen Li,Tao Wu,Tong Zhang
Flavonoid isorhamnetin occurs in various plants and herbs, and demonstrates various biological effects in humans. This work will clarify the isorhamnetin absorption mechanism using the Caco-2 monolayer cell model. The isorhamnetin transport characteristics at different concentrations, pHs, temperatures, tight junctions and potential transporters were systemically investigated. Isorhamnetin was poorly absorbed by both passive diffusion and active transport mechanisms. Both trans- and paracellular pathways were involved during isorhamnetin transport. Active transport under an ATP-dependent transport mechanism was mediated by the organic anion transporting peptide (OATP); isorhamnetin’s permeability from the apical to the basolateral side significantly decreased after estrone-3-sulfate was added ( p < 0.01). Efflux transporters, P-glycoproteins (P-gp), breast cancer resistance proteins (BCRP) and multidrug resistance proteins (MRPs) participated in the isorhamnetin transport process. Among them, the MRPs (especially MRP2) were the main efflux transporters for isorhamnetin; transport from the apical to the basolateral side increased 10.8-fold after adding an MRP inhibitor (MK571). This study details isorhamnetin’s cellular transport and elaborates isorhamnetin’s absorption mechanisms to provide a foundation for further studies.
研究领域:
药理学
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生物化学
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PubMed
高影响因子
PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY
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2022
·
IF 3.915
Fengmao Zou,Honghui Zhao,Aijinxiu Ma,Danni Song,Xiangrong Zhang,Xu Zhao
To improve the solubility and anti-hyperuricemia activity of the insoluble natural flavonoid isorhamnetin (ISO), an isorhamnetin phospholipid complex (ISO-PC) was prepared. ISO-PC was prepared through solvent evaporation and its prescription process was optimized. The formation of ISO-PC was verified via multiple characterization methods. Parameters such as drug loading, solubility, octanol-water partition coefficient, stability, and in vivo anti-hyperuricemia activity of ISO-PC were investigated. The complexation efficiency of ISO-PC was 95.1% ± 0.56%. The characterization results confirmed that ISO-PC was bound by intermolecular interactions between ISO and phospholipids. Compared with ISO, the solubility of ISO-PC in water and 1-octanol increased by 122 and 16.5 times, respectively. In addition, the octanol-water partition coefficient decreased to 1.08. Pharmacodynamic studies have reported that ISO-PC has a more significant effect on reducing serum uric acid levels and renal protection. In conclusion, the findings of this study suggested that ISO-PC could be used as a promising formulation to improve the solubility and the anti-hyperuricemia activity of ISO.
研究领域:
药学
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生物化学
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DOI
PubMed
高影响因子
JOURNAL OF NANOPARTICLE RESEARCH
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2024
·Vol. 27
·期 1
·1-14
·
IF 2.1
Li Tingyuan,Li Jiaying,Wang Qilong,Gong Mingjie,Wang Xiaowen,Jiang Xia,Hua Qinyang,Ji Hao,Toreniyazov Elmurat,Yu Jiangnan,Cao Xia,Adu-Frimpong Michael,Xu Ximing
Isorhamnetin (ISO) is a kind of flavonoid widely found in sea buckthorn, ginkgo biloba, and other plants. It has many pharmacological activities, but poor solubility in aqueous media has limited its clinical application. In order to increase the bioavailability of ISO, we employed a thin film dispersion method to prepare ISO-loaded Soluplus-TPGS mixed polymer micelle (ISO-STM) and subsequently conducted appropriate characterizations. The micelles prepared in this work were spherical nanoparticles with uniform distribution with respective particle size (PS) and dispersion coefficient (PDI) of 81.62 ± 1.23 nm and 0.115 ± 0.020. Meanwhile, the encapsulation rate (EE) was 91.37% ± 0.82%, whereas the drug loading (DL) was 5.91% ± 0.06%. Compared to free ISO, the dissolution rate of mixed micelles (MM) significantly increased in three media. After oral administration, the oral bioavailability of MM was nearly 3 times higher than free ISO’s. In addition, the results of the zebrafish experiment showed that the anti-aging of zebrafish in the administration group was significantly better than that in the model control group. In summary, ISO-STM is a promising method with the potential to improve the solubility, and bioavailability and enhance the clinical application value of ISO.
研究领域:
药剂学
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药理学
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DOI
高影响因子
BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY
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2012
·Vol. 76
·期 6
·1091-1097
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IF 1.276
Yue-Xiu SI,Zhi-Jiang WANG,Daeui PARK,Hyoung Oh JEONG,Sen YE,Hae Young CHUNG,Jun-Mo YANG,Shang-Jun YIN,Guo-Ying QIAN
We studied the inhibitory effects of isorhamnetin on mushroom tyrosinase by inhibition kinetics and computational simulation. Isorhamnetin reversibly inhibited tyrosinase in a mixed-type manner at Ki=0.235 ± 0.013 mM. Measurements of intrinsic and 1-anilinonaphthalene-8-sulfonate(ANS)-binding fluorescence showed that isorhamnetin did not induce significant changes in the tertiary structure of tyrosinase. To gain insight into the inactivation process, the kinetics were computed via time-interval measurements and continuous substrate reactions. The results indicated that inactivation induced by isorhamnetin was a first-order reaction with biphasic processes. To gain further insight, we simulated docking between tyrosinase and isorhamnetin. Simulation was successful (binding energies for Dock6.3: −32.58 kcal/mol, for AutoDock4.2: −5.66 kcal/mol, and for Fred2.2: −48.86 kcal/mol), suggesting that isorhamnetin interacts with several residues, such as HIS244 and MET280. This strategy of predicting tyrosinase interaction in combination with kinetics based on a flavanone compound might prove useful in screening for potential natural tyrosinase inhibitors.
研究领域:
生物化学
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药理学
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PubMed
高影响因子
International Journal of Electrochemical Science
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2023
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IF 1.5
Li Sun,Buhong Gao,Weina Jiang,Li Xu,Wen Lu,Shilong Yang,Dong Jiang,Jichao Chen,Huayu Xue,Jiuzhou Shi
Isorhamnetin as a natural product has excellent biological activity, but there are few reports of it in electrochemical applications. In this paper, we developed a neoteric electrochemical sensor for sensitive detection of mercury ions (Hg 2+ ) for the first time using glassy carbon (GC) electrode which was modified with isorhamnetin (ISO) and graphene oxide (GO). The electrochemical behaviors of the fabricated GC electrode were characterized by cyclic voltammetry (CV) and differential pulse voltammetry (DPV). Under optimal conditions, the linear range to detect Hg 2+ with DPV was from 1.0×10 -6 to 1.0×10 -4 M with limit detection of 2.3×10 -8 M (S/N=3). In addition, it also showed excellent selectivity of Hg 2+ with comparison to several inorganic salt ions and other metal ions. We also report the application for Hg 2+ detection in real water samples with a good recovery (92.1-104.7%). In conclusion, isorhamnetin can be applied in the electrochemical field successfully with extraordinary results.
研究领域:
分析化学
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环境科学
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生物医学工程
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DOI
高影响因子
Journal of Spectroscopy
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2026
·Vol. 2026
·期 1
·5791311
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IF 1.7
Xue Zhang,Di Lian,Yuan Li,Yutong Du,Zihan Qu,YuXin Cui,Li Li
Studies indicated that some active flavonoids combined with acarbose could reduce the side effects of acarbose and enhance its efficacy. Isorhamnetin-3-O-rutinoside (IOR) is a flavonoid found in many edible herbs. In this work, the synergistic effects of IOR and acarbose on α -amylase/α-glucosidase (PA/AG) were evaluated using ZIP score analysis. In the presence of IOR, the binding constant K b values of acarbose with PA/AG were significantly improved, indicating that IOR exhibited synergistic effect with acarbose by increasing its K b values. Furthermore, in the presence of IOR, acarbose resulted in greater changes in microenvironment and secondary structure of PA/AG. The docking analysis confirmed that IOR and acarbose bound to the different sites of PA/AG. Compared with pure enzyme, the complexes formed by IOR/acarbose with two enzymes were more stable based on dynamics simulations. This study suggested that IOR might be used as a potential synergistic inhibitor of acarbose.
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高影响因子
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
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2026
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IF 3.3
Haiya Feng,Qianqian Li,Yangjun Lu,Hui Wang
Objective This study aimed to investigate the anti-tumor effects of the natural flavonoid Isorhamnetin (ISO) on BC and elucidate its underlying molecular mechanisms. Methods We integrated network pharmacology and bioinformatic analysis to predict the core targets and pathways between BC and ISO. In vitro functional assays were performed using the human BC cell line 5637. Cell viability, proliferation, apoptosis, migration, invasion, and adhesion were assessed via CCK-8, colony formation, flow cytometry, Transwell, and adhesion assays. Glycolytic function was evaluated by measuring extracellular acidification rate (ECAR), oxygen consumption rate (OCR), glucose uptake, and lactate production. Molecular docking and cellular thermal shift assays (CETSA) were used to validate ISO-SRC binding. Western blot and RT-qPCR analyses were conducted to examine protein and mRNA expression of key signaling and glycolytic components. For the rescue experiments, SRC was overexpressed along with treatment using the PI3K inhibitor LY294002. Results ISO significantly inhibited BC cell proliferation, migration, invasion, adhesion, and glycolysis while inducing G0/G1 phase arrest and apoptosis. Network pharmacology and molecular docking identified SRC as a direct target of ISO, with CETSA confirming their binding. ISO treatment downregulated phosphorylation of SRC and its downstream effectors (PI3K, Akt, mTOR), reduced the expression of glycolytic enzymes (HK2, GLUT1, PFKFB3), and decreased ECAR, OCR, glucose uptake, and lactate production. SRC overexpression reversed the anti-tumor and anti-glycolytic effects of ISO. Furthermore, administration of LY294002 on this basis counteracted the effects induced by SRC overexpression, confirming the critical role of the SRC/PI3K/Akt axis. Conclusion ISO inhibits the malignant progression of BC by directly targeting SRC to suppress glycolysis mediated by the PI3K/Akt signaling pathway. These findings provide a mechanistic basis for considering ISO as a potential metabolic-targeting agent for BC, warranting further preclinical evaluation.
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高影响因子
RSC Advances
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2026
·Vol. 16
·期 30
·27212-27222
·
IF 6.1
Yu Liu,Jian Lei,Ting Li,Aiyu Zhong,Zihan Zhu,Junxiao Lu,Zhipeng Wang,Panpan Zhao,Zhigang Wu
As two natural products, isorhamnetin and isoliquiritigenin have been demonstrated to have significant anticancer activity. However, various pharmaceutical defects, such as low solubility and poor bioavailability, impede their anticancer efficacy. To optimize the anticancer efficacy of isorhamnetin and isoliquiritigenin, a scientific cocrystal design was performed to obtain two newly prepared cocrystals in this study. Leveraging multiple analytical techniques including single-crystal X-ray diffraction, powder X-ray diffraction, Fourier transform infrared spectroscopy, differential scanning calorimetry and thermogravimetric analysis, the isorhamnetin-4,4′-bipyridine (2 : 3) and isoliquiritigenin-4,4′-bipyridine (1 : 1) cocrystals were systematically characterized. The results of a series of evaluations on their stabilities, dissolution and anticancer activities demonstrated that these two cocrystals could remain stable under three different extreme environments, and the isorhamnetin-4,4′-bipyridine (2 : 3) cocrystal achieved significant improvement in solubility, dissolution rate and anticancer efficacy compared to isorhamnetin. For the isoliquiritigenin-4,4′-bipyridine (1 : 1) cocrystal, there was no increase in its solubility and dissolution rate compared to isoliquiritigenin. Nevertheless, a slight increase in the anticancer activity of isoliquiritigenin was achieved by the formation of the cocrystal. This study was a meaningful investigation, which not only laid an innovative material foundation for the development of isorhamnetin and isoliquiritigenin but also provided a new strategy to optimize the pharmaceutical properties of natural products.
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高影响因子
Chinese Journal of Integrative Medicine
·
2024
·
IF 2.2
Liu Xiao-rong,Li Shuo-fu,Mei Wen-ya,Liu Xiang-dan,Zhou Ri-bao
Objective To investigate the effect of isorhamnetin on the pathology of rheumatoid arthritis (RA). Methods Tumor necrosis factor (TNF)- α -induced fibroblast-like synoviocytes (FLS) was exposed to additional isorhamnetin (10, 20 and 40 µ mol/L). Overexpression vectors for matrix metalloproteinase-2 (MMP2) or MMP9 or SRC were transfected to explore their roles in isorhamnetin-mediated RA-FLS function. RA-FLS viability, migration, and invasion were evaluated. Moreover, a collagen-induced arthritis (CIA) rat model was established. Rats were randomly divided to sham, CIA, low-, medium-, and high-dosage groups using a random number table ( n =5 in each group) and administed with normal saline or additional isorhamnetin [2, 10, and 20 mg/(kg·day)] for 4 weeks, respectively. Arthritis index was calculated and synovial tissue inflammation was determined in CIA rats. The levels of MMP2, MMP9, TNF-α, interleukin-6 (IL-6), and IL-1 β, as well as the phosphorylation levels of SRC, extracellular regulated kinase (ERK), and cyclic adenosine monophosphate response element-binding (CREB), were detected in RA-FLS and synovial tissue. Molecular docking was also used to analyze the binding of isorhamnetin to SRC. Results In in vitro studies, isorhamnetin inhibited RA-FLS viability, migration and invasion ( P <0.05). Isorhamnetin downregulated the levels of MMP2, MMP9, TNF-α, IL-6, and IL-1 β in RA-FLS ( P <0.05). The overexpression of either MMP2 or MMP9 reversed isorhamnetin-inhibited RA-FLS migration and invasion, as well as the levels of TNF-α, IL-6, and IL-1 β ( P <0.05). Furthermore, isorhamnetin bound to SRC and reduced the phosphorylation of SRC, ERK, and CREB ( P <0.05). SRC overexpression reversed the inhibitory effect of isorhamnetin on RA-FLS viability, migration and invasion, as well as the negative regulation of MMP2 and MMP9 ( P <0.05). In in vivo studies, isorhamnetin decreased arthritis index scores ( P <0.05) and alleviated synovial inflammation. Isorhamnetin reduced the levels of MMP2, MMP9, TNF-α, IL-6, and IL-1 β, as well as the phosphorylation of SRC, ERK, and CREB in synovial tissue ( P <0.05). Notably, the inhibitory effect of isorhamnetin was more pronounced at higher concentrations ( P <0.05). Conclusion Isorhamnetin exhibited anti-RA effects through modulating SRC/ERK/CREB and MMP2/MMP9 signaling pathways, suggesting that isorhamnetin may be a potential therapeutic agent for RA.
研究领域:
药理学
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免疫学
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风湿病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Biomedicines
·
2026
·Vol. 14
·期 5
·951
·
IF 4.5
Chengjing Shen,Taierpuke Maimaiti,Gulijikere Kuerban,Mireguli Abulimiti,Jialu Hu,Zilala Yalihong,Aikebaier Maimaiti
Background: Lung cancer remains the leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) accounting for approximately 85% of all cases. Isorhamnetin (ISO), a natural dietary flavonoid, has demonstrated potent anti-lung cancer activity in cell models. However, its precise mechanism of action within the complex landscape of NSCLC remains to be fully elucidated.Methods: The effects of ISO on NSCLC cell viability, apoptosis, and cell cycle distribution were assessed in A549 and H1650 cells using the MTT assay, Annexin V-FITC/PI staining, and flow cytometry. Wound healing and Transwell assays were employed to evaluate the isorhamnetin impact on cell migration, invasion, and adhesion. To investigate the underlying molecular mechanisms, RNA sequencing (RNA-seq) was performed, followed by validation of key target genes and proteins using qRT-PCR and Western blot analysis.Results: ISO treatment elicited a significant, dose- and time-dependent inhibition of NSCLC cell viability, which coincided with a marked induction of apoptosis. Cell cycle analysis revealed that ISO triggered an S-phase arrest. Transcriptomic profiling identifiedELFN1and TMEM186 as significantly upregulated genes, whileSETDB1was downregulated in a concentration-dependent manner; this was accompanied by a concomitant upregulation ofFGFBP1protein expression. Functionally, ISO effectively suppressed the migratory, invasive, and adhesive capabilities of both cell lines.Conclusions: Our findings demonstrate that ISO exerts a potent anti-proliferative and anti-metastatic effect on NSCLC cells. The underlying mechanism is multifaceted, involving the induction of apoptosis and cell cycle arrest, coupled with the modulation of a novel regulatory network centered onELFN1,TMEM186, SETDB1, andFGFBP1. These results provide new mechanistic insights into the anti-tumor pharmacology of isorhamnetin and highlight its potential as a therapeutic agent targeting both cancer cells and their supporting microenvironments.
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产品关联
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PubMed
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RSC Advances
·
2017
·Vol. 7
·期 58
·36728-36734
·
IF 3.108
Huaping Peng,Lingling Zhang,Zhili Cai,Yanhong Wu,Namin Chen,Chao Gu,Yuanzhong Chen,Xinhua Lin,Xinghua Xia,Ailin Liu
Isorhamnetin (ISO), a flavonol aglycone, plays an important role in human health, such as cardiovascular protection, anti-allergy activity, anti-inflammatory effects, and anticancer activity. Thus, the highly sensitive and rapid detection of ISO, and its pharmacokinetic study, has important clinical significance in the field of medicine. Herein, a simple, rapid, sensitive, and accurate method for the electrochemical determination of isorhamnetin (ISO) for pharmaceutical quality control and pharmacokinetic research was developed using an electrochemically reduced graphene oxide modified glassy carbon electrode (ERGO/GCE). The results indicated that the ERGO/GCE remarkably increased the peak currents of ISO oxidation. Under optimized conditions, using differential pulse voltammetry (DPV), the peak current had a linear dependence on the concentration of ISO in the range of 1.0 × 10−8 to 1.2 × 10−5 M with a low detection limit of 3.2 × 10−9 M. The present voltammetric method has been successfully applied to the detection of ISO in tablets and in plasma. Moreover, this assay has also been successfully applied in the pharmacokinetic study of ISO in vivo through intragastric administration of tablets to SD-rats. Therefore, this strategy opens up a new avenue for the application of an electrochemical method in the field of ISO pharmacokinetics.
研究领域:
分析化学
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药理学
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生物医学工程
·
纳米技术
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DOI
高影响因子
Asian Pacific Journal of Tropical Biomedicine
·
2026
·Vol. 16
·期 6
·225
·
IF 1.9
Zhang Rui,Zhou Yang,Xiao Ting,Gu Yan
Objective: To evaluate the effect of isorhamnetin on diabetic kidney disease and elucidate its underlying mechanisms. Methods: A high glucose-stimulated mouse podocyte (MPC-5) model was employed to evaluate the effects of isorhamnetin on podocyte injury, secretion of inflammatory cytokines, NLRP3 inflammasome activation, pyroptosis, mitochondrial function, cytosolic release of mtDNA, and activation of the cGAS-STING signaling pathway. Nigericin (an NLRP3 activator) and siRNA were used in combination to clarify the regulatory relationships between these pathways. Furthermore, a mouse model of diabetic kidney disease was established and treated with isorhamnetin via intragastric administration. Blood glucose and renal function parameters were measured, renal histopathological changes were examined, and alterations in podocyte marker proteins, inflammasome activation, pyroptosis, mitochondrial damage, and the cGAS-STING pathway in kidney tissues were analyzed. Results: Isorhamnetin alleviated high glucose-induced abnormalities in podocyte marker proteins and cellular injury. It also inhibited NLRP3 inflammasome activation, thereby attenuating pyroptosis. Furthermore, isorhamnetin stabilized mitochondrial membrane potential, decreased mitochondrial ROS production, suppressed excessive opening of the mitochondrial permeability transition pore, alleviated mitochondrial damage, and reduced cytosolic mtDNA release, which in turn suppressed activation of the cGAS-STING pathway. Knockdown of STING inhibited high glucose-induced NLRP3-dependent pyroptosis. Consistently, isorhamnetin improved renal function in mice with diabetic kidney disease, attenuated glomerulosclerosis and fibrosis, and markedly suppressed mitochondrial damage, mtDNA leakage, cGAS-STING activation, and NLRP3-mediated pyroptosis and inflammatory responses in renal tissues. Conclusions: Isorhamnetin treatment attenuates diabetic kidney disease by improving mitochondrial homeostasis and inhibiting the cGAS-STING/NLRP3 inflammasome pathway.
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