FITOTERAPIA
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2014
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IF 2.216
Yan Xie,Huilin Luo,Jingze Duan,Chao Hong,Ping Ma,Guowen Li,Tong Zhang,Tao Wu,Guang Ji
Aim Total flavones of Hippophae rhamnoides L. (TFH) have a clinical use in the treatment of cardiac disease. The pharmacological effects of TFH are attributed to its major flavonoid components, isorhamnetin , kaempferol , and quercetin . However, poor oral bioavailability of these flavonoids limits the clinical applications of TFH. This study explores phytic acid (IP 6 ) enhancement of the oral absorption in rats of isorhamnetin, kaempferol, and quercetin in TFH. Methods In vitro Caco-2 cell experiments and in vivo pharmacokinetic studies were performed to investigate the effects of IP 6 . The aqueous solubility and lipophilicity of isorhamnetin, quercetin, and kaempferol were determined with and without IP 6 , and mucosal epithelial damage resulting from IP 6 addition was evaluated by MTT assays and morphology observations. Results The P app of isorhamnetin, kaempferol, and quercetin was improved 2.03-, 1.69-, and 2.11-fold in the presence of 333 μg/mL of IP 6 , respectively. Water solubility was increased 22.75-, 15.15-, and 12.86-fold for isorhamnetin, kaempferol, and quercetin, respectively, in the presence of 20 mg/mL IP 6 . The lipophilicity of the three flavonoids was slightly decreased, but their hydrophilicity was increased after the addition of IP 6 in the water phase as the logP values of isorhamnetin, kaempferol, and quercetin decreased from 2.38 ± 0.12 to 1.64 ± 0.02, from 2.57 ± 0.20 to 2.01 ± 0.04, and from 2.39 ± 0.12 to 1.15 ± 0.01, respectively. The absorption enhancement ratios were 3.21 for isorhamnetin, 2.98 for kaempferol, and 1.64 for quercetin with co-administration of IP 6 (200 mg/kg) in rats. In addition, IP 6 (200 mg/kg, oral) caused neither significant irritation to the rat intestines nor cytotoxicity (400 μg/mL) in Caco-2 cells. Conclusions The oral bioavailability of isorhamnetin, kaempferol, and quercetin in TFH was enhanced by the co-administration of IP 6 . The main mechanisms are related to their enhanced aqueous solubility and permeability in the presence of IP 6 . In summary, IP 6 is a potential absorption enhancer for pharmaceutical formulations that is both effective and safe.
研究领域:
药理学
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药剂学
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营养保健品
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DOI
PubMed
高影响因子
CHEMISTRY & BIODIVERSITY
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2021
·Vol. 18
·期 11
·e2100301
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IF 2.408
Zhuojin Yang,Yi Zheng,Nafisa Tursumamat,Mingyan Zhu
Isorhamnetin is a natural flavonoid which shows a variety of biological activities such as antioxidant, anti-inflammatory and antitumor. In order to identify the cellular binding protein of isorhamnetin as potential anti-cancer target, we first synthesized 3′- O -substituted quercetin as isorhamnetin homologues and evaluated the growth inhibitory activity of these derivatives on breast, colon and prostate cancer cell lines. The preliminary results showed that the 3′- O modification did not affect the cytotoxic activity of the scaffold. Analysis of the co-crystal structure and the docking pose of isorhamnetin with reported binding protein of isorhamnetin or quercetin indicated the 3′- O -substitution groups located outside of the binding pocket, which is in accordance with activity of 3′- O derivatives. Then a biotin conjugate of isorhamnetin with a tetraethylene glycol (PEG) 4 linker at the 3′ position was synthesized and the resulting probe retained the anti-proliferative activity on cancer cell lines, while the cellular fluorescence analysis showed the distribution of probe inside the cells which indicated the probe had limited cell permeability. Finally, pull down assay both in situ inside cells and in the cell lysates indicated the isorhamnetin biotin probe was capable of protein labeling in cell lysates. These findings provide the isorhamnetin 3′- O -biotin probe as a tool to reveal the target proteins of isorhamnetin. Graphical
研究领域:
药理学
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癌症研究
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化学
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分子生物学
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PubMed
高影响因子
Food & Function
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2025
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IF 5.4
Xiaoran Kong,Li Zhao,He Huang,Qiaozhen Kang,Jike Lu,Jia-Qing Zhu
Hyperuricemia is chronic metabolic disease with a high incidence, and it has become the “fourth highest” health risk in modern times. Isorhamnetin is a natural flavonoid found in a variety of plants, especially fruits such as buckthorn. In vivo hyperuricemia ameliorating effect of isorhamnetin and the specific molecular mechanism were profoundly investigated through a hyperuricemia mice model in the present study. The results demonstrated that isorhamnetin showed a significant uric acid-lowering effect in mice. Isorhamnetin was able to reduce uric acid production by inhibiting XOD activity. On the other hand, it reduced the expression of GLUT9 to inhibit uric acid reabsorption and enhanced the expression of ABCG2, OAT1, and OAT3 to promote uric acid excretion. Metabolomics analysis revealed that isorhamnetin gavage restored the purine metabolism and riboflavin metabolism disorders, and thus significantly alleviated the hyperuricemia in mice. Further, the alleviating effect of isorhamnetin on hyperuricemia-induced renal inflammation and its specific mechanism were explored through network pharmacology and molecular validation experiments. Network pharmacology predicted that seven targets were enriched in the PI3K/AKT pathway (CDK6, SYK, KDR, RELA, PIK3CG, IGF1R, MCL1) and four targets were enriched in the NF-κB pathway (SYK, PARP1, PTGS2, RELA). Western blot validated that isorhamnetin inhibited the phosphorylation of PI3K and AKT and down-regulated the expression of NF-κB p65. It indicated that isorhamnetin could inhibit the PI3K/AKT/NF-κB signaling pathway to reduce the levels of renal inflammatory factors (TNF-α, IL-β and IL-6) and ultimately ameliorate the hyperuricemia-induced renal inflammation in mice. This study will provide comprehensive and penetrating theoretical basis for the application of isorhamnetin in the field of functional foods or dietary supplements to improve hyperuricemia.
研究领域:
药理学
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代谢生物学
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分子生物学
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PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
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2025
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IF 3.1
Xiangjun Chen,Yue Wang,Pinzheng Li,Jianbiao Yao,Yuanzheng Song,Huidi Jiang,Su Zeng,Lingfang Chen,Hui Zhou
The total flavone of Abelmoschi Corolla (TFA) has diverse pharmacological effects, including anti-inflammatory and antioxidant properties, and improving insulin resistance. Clinically, TFA has been utilized for a substantial duration for managing various renal diseases. Phase II metabolites, such as sulfated and glucuronidated conjugates, are the primary in vivo forms of flavonoids and may mediate the pharmacological effects of TFA. However, the direct quantification of conjugated metabolites is limited by the lack of reference standards. To address this, β-glucuronidase/sulfatase hydrolysis can be used to cleave these conjugates, releasing aglycones and enabling the indirect quantification of total flavonoids. In this study, a reliable and sensitive ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the quantification of gossypetin, myricetin, quercetin, and isorhamnetin in mouse plasma following enzymatic hydrolysis. Chromatographic separation was performed using a Waters ACQUITY UPLC HSS-T3 column with gradient elution. The mobile phase consisted of acetonitrile and water (both containing 0.1 % formic acid) at a flow rate of 0.35 mL/min. The method was validated for plasma analysis and successfully applied to a pharmacokinetic study in mice following oral administration of TFA. The results showed that the analyzed aglycones rapidly attained maximum plasma concentrations. The area under the curve for each compound demonstrated a positive correlation with the administered dose in the range of 100–400 mg/kg. Moreover, the isorhamnetin concentration increased significantly following 7-day repeated gavage compared to that with a single 200 mg/kg TFA dose. These pharmacokinetic findings may inform future drug development and clinical applications of TFA-derived substances.
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PubMed
高影响因子
INFLAMMATION
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2021
·Vol. 44
·期 5
·1993-2005
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IF 4.092
Wu Yuqin,Fan Lin,Wang Yun,Ding Jing,Wang Rongfu
This study is aimed at exploring the potential of isorhamnetin in protection against diabetes-exacerbated ischemia/reperfusion-induced brain injury and elucidating its action mechanism. After establishment of the model of high glucose (HG)-aggravated oxygen-glucose deprivation and reoxygenation (OGD/R), HT22 cell viability was detected by CCK-8. Lactate dehydrogenase (LDH) activity, casapase-3 activity, and oxidative stress-related markers in HT22 cells were detected by corresponding commercial kits. The apoptosis of HG-treated HT22 cells following OGD/R was observed with TUNEL staining. The level of pro-inflammatory cytokines was examined by ELISA. The expression of Akt/SIRT1/Nrf2/HO-1 signaling-related proteins was assayed by Western blot. The results showed that HG noticeably worsened the OGD/R-induced apoptosis of HT22 cells. Isorhamnetin relieved the HG-aggravated OGD/R-induced apoptosis, inflammatory response, and oxidative stress of HT22 cells. Isorhamnetin alleviated the HG-aggravated OGD/R injury in HT22 cells through Akt/SIRT1/Nrf2/HO-1 signaling pathway. Meanwhile, treatment with Akt inhibitor LY294002 reversed the protective effects of isorhamnetin against HG-aggravated OGD/R injury in HT22 cells. In a conclusion, Isorhamnetin alleviates HG-aggravated OGD/R in HT22 hippocampal neurons through Akt/SIRT1/Nrf2/HO-1 signaling pathway.
研究领域:
神经科学
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药理学
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细胞生物学
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分子生物学
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PubMed
高影响因子
ANALYTICAL LETTERS
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2021
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IF 2.329
Ping-Rong Zhou,Zhang-Feng Tang,Ke-Su Wei,Ya Wan,Yu-Meng Gao,Yan-Mei Liang,Xiu-Fang Yan,Jun Bin,Chao Kang
Ultraviolet-visible absorption spectrometry is used for the determination of many inorganic, organic, and biological species. However, poor selectivity limits its applications for quantitative analysis in complex mixtures. In this work, its mathematical selectivity was explored using trilinear decomposition on spectral-pH measurements for the selective determination of two flavonoids in three Chinese herbal medicines. Through introducing a pH mode, second-order spectral pH data were constructed per sample. By using trilinear decomposition on the calibration and prediction samples, the rutin signals were extracted from lonicerae japonicae flos, perillae folium, and perillae fructus samples, respectively. Novel second-order calibration was developed for interference-free determination of rutin in these medicines followed by univariate regression of the decomposed intensity versus concentration. The predicted 95% confidence intervals for the concentration of rutin in these samples were 5.19 ± 0.16, 5.81 ± 0.10, and 7.00 ± 0.36 μg mL−1, respectively. These results were validated by high performance liquid chromatography (HPLC). Similarly, interference-free determination of isorhamnetin was achieved in these materials. By increasing the selectivity of ultraviolet-visible spectroscopy with trilinear decomposition, the requirements for sample preparation and chemical separation are reduced. The developed spectral pH second-order calibration allows direct analysis of complex samples by ultraviolet-visible absorption spectrometry due to the mathematical selectivity.
研究领域:
分析化学
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药物分析
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光谱学
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高影响因子
危险品化学品经营许可证（带存储）