Scientific Reports
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2025
·Vol. 15
·期 1
·1-14
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IF 3.9
Sun Jinzhou,Chen Qianqian,Zhuang Chumeng,Li Xiaohong,Yu Li,Jin Weifeng
Develop a novel coupled PK-PD model and apply it to quantitatively evaluate the synergistic effects of Hydroxysafflor Yellow A (HSYA) combined with Calycosin (CA) in the treatment of ischemic stroke. A total of 6 rats were modelled for middle cerebral artery occlusion (MCAO). Plasma was collected from the submandibular venous plexus of rats after the administration of HSYA and CA, and was detected and analyzed by LC-MS method. The plasma expression levels of Caspase-9, IL-1β and SOD in rats were also determined by ELISA kit. Meanwhile, a coupled PK-PD model was proposed, incorporating interaction terms between drugs and coupling of pharmacodynamic effects, to quantitatively reveal their interactions. Moreover, a numerical solution technique based on optimization methods was proposed, enabling the model to be effectively applied to experimental data. Based on the coupled PK model, HSYA and CA significantly increased each other’s metabolic rates. The model also showed that CA had a larger apparent volume of distribution and clearance in rats, while HSYA had a shorter mean retention time and elimination half-life. The coupled PK-PD model indicated a synergistic effect between HSYA and CA on all three pharmacodynamic markers, with HSYA contributing more significantly. Despite individual variability among the six rats, the parameter interpretations remained consistent. The proposed coupled PK-PD model and its numerical solution algorithm successfully revealed the synergistic effects of HSYA and CA in the treatment of ischemic stroke. This model lays the foundation for future models with more complex interactions and effects.
研究领域:
药理学
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生物医学工程
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神经科学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2017
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IF 3.649
Bingxiang Zhao,Sufang Gu,Yong Du,Minjie Shen,Xiangrui Liu,Youqing Shen
Hydroxysafflor yellow A (HSYA) is the main bioactive flavonoid extracted from the flower of Carthamus tinctorius L ., which is widely used in traditional Chinese medicine for the treatment of myocardial ischemia and cerebral ischemia . HSYA has high water solubility but poor intestinal membrane permeability, resulting in low oral bioavailability. Currently, only HSYA sodium chloride injection has been approved for clinical use and oral formulations are urgently needed. In this study, HSYA solid lipid nanoparticles (SLNs) with the structure of w/o/w were prepared by a warm microemulsion process using approved drug excipients for oral delivery to increase the oral absorption of HSYA. The optimized HSYA SLNs are spherical with an average size of 214 nm and the encapsulation efficiency is 55%. HSYA SLNs exhibited little cytotoxicity in Caco-2 and Hela cells, but increased the oral absorption of HSYA about 3.97-fold in rats, compared to HSYA water solution. In addition, cycloheximide pretreatment significantly decreased the oral absorption of HSYA delivered by SLNs. Importantly, the pharmacodynamics evaluation demonstrated that SLNs further decreased the infarct areas in rats. In conclude, SLNs could be a promising delivery system to enhance the oral absorption and pharmacological activities of HSYA.
研究领域:
药剂学
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药物递送
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中医药学
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药理学
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DOI
PubMed
高影响因子
Pharmaceuticals
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2022
·Vol. 15
·期 11
·1394
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IF 5.215
Tingting Li,Dong Han,Zhongxian Li,Mengqi Qiu,Yuting Zhu,Kai Li,Jiawei Xiang,Huizhen Sun,Yahong Shi,Tun Yan,Xiaoli Shi,Qiang Zhang
Idiopathic pulmonary fibrosis is a fatal interstitial disease characterized by fibroblast proliferation and differentiation and abnormal accumulation of extracellular matrix, with high mortality and an increasing annual incidence. Since few drugs are available for the treatment of pulmonary fibrosis, there is an urgent need for high-efficiency therapeutic drugs and treatment methods to reduce the mortality associated with pulmonary fibrosis. The interstitium, a highly efficient transportation system that pervades the body, plays an important role in the occurrence and development of disease, and can be used as a new route for disease diagnosis and treatment. In this study, we evaluated the administration of hydroxysafflor yellow A phytosomes via intervaginal space injection (ISI) as an anti-pulmonary fibrosis treatment. Our results show that this therapeutic strategy blocked the activation of p38 protein in the MAPK-p38 signaling pathway and inhibited the expression of Smad3 protein in the TGF-β/Smad signaling pathway, thereby reducing secretion of related inflammatory factors, deposition of collagen in the lungs of mice, and destruction of the alveolar structure. Use of ISI in the treatment of pulmonary fibrosis provides a potential novel therapeutic modality for the disease.Keywords:intervaginal space injection;pulmonary fibrosis;hydroxysafflor yellow A;phytosome;interstitial treatment
研究领域:
药理学
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肺科学
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分子生物学
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DOI
PubMed
高影响因子
MATERIALS & DESIGN
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2023
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IF 8.4
Yulin Li,Anning Yang,Yue Sun,Dayue Liu,Peidong You,Yaling Zeng,Shangkun Quan,Hongwen Zhang,Huiping Zhang,Shengchao Ma,Yinju Hao,Jiantuan Xiong,Bin Liu,Guizhong Li,Yideng Jiang
Cardiovascular disease (CVD) caused by atherosclerosis has become a main threaten for human health. As an independent risk factor, hyperhomocysteinemia (HHcy) played an important role in the pathogenesis of atherosclerosis by regulating DNA methylation modification and autophagy of macrophages. In this study, we constructed a new kind of macro-liposome nanoparticle by hybridizing liposome with macrophages membranes (Møm) to encapsulate hydroxysafflower yellow A (HSYA). Assertion of Hyaluronic acid (HA) on the macro-liposome NPs was adopted to endow nanodrug targeting ability. In vitro results showed that the prepared macro-liposome nanoparticles can significantly inhibit Atg13 DNA methylation, while enhance autophagy of macrophages to promote cholesterol efflux, as well. In vivo studies have shown that the HA modification made the macro-liposome NPs an ideal decoy for targeting plaques. Thus, the macro-liposome NPs with prolonged blood circulation time, and improved targeting ability can achieve optimal HSYA accumulation at the region of atherosclerotic plaques to obtain high efficacy. According to our point, the nano-drug delivery system with high immune escape capability provided a feasible therapeutic strategy for efficient atherosclerosis therapy.
研究领域:
心血管疾病
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药学
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纳米技术
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分子生物学
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产品关联
DOI
高影响因子
FOOD CHEMISTRY
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2024
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IF 8.5
Taiwei Ye,Dongyun Tang,Chunxiao Tao,Xiuping Chen,Xinhong Wang,Yan Xie
Carthamus tinctorius L. (Safflower) is extensively used as a functional food and herbal medicine , with its application closely associated with hydroxysafflor yellow A (HSYA). However, the low oral bioavailability of HSYA in safflower extract (SFE) limits its health benefits and application. Our study found that co-administration of 250, 330, and 400 mg/kg peach kernel oil (PKO) increased the oral bioavailability of HSYA in SFE by 1.99-, 2.11-, and 2.49-fold, respectively. The enhanced bioavailability is attributed to improved lipid solubility and intestinal permeability of HSYA in SFE due to PKO. PKO is believed to modify membrane fluidity and tight junctions, increase paracellular penetration, and inhibit the expression and function of P-glycoprotein, enhancing the transcellular transport of substrates. These mechanisms suggest that PKO is an effective absorption enhancer. Our findings provide valuable insights for developing functional foods with improved bioavailability.
研究领域:
药理学
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功能性食品研究
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中药学
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产品关联
DOI
PubMed
高影响因子
MedComm
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2023
·Vol. 4
·期 5
·e352
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IF 9.9
Jing Chen,Can Ren,Chong Yao,Mirko Baruscotti,Yi Wang,Lu Zhao
Enhanced P53 signaling may lead to hematopoietic disorders, yet an effective therapeutic strategy is still lacking. Our study, along with previous research, suggests that P53 overactivation and hematopoietic defects are major consequences of zinc deficiency. However, the relationship between these two pathological processes remains unclear. In this study, we observed a severe reduction in the number of hematopoietic stem cells (HSCs) and multi-lineage progenitor cells in zebrafish treated with the zinc chelator N , N , N ′, N ′-tetrakis(2-pyridylmethyl)ethylenediamine and showed the indispensable role of P53 signaling in the process. Next, we took advantage of HSCs-labeled transgenic zebrafish and conducted a highly efficient phenotypic screening for small molecules against P53-dependent hematopoietic disorders. Hydroxysafflor yellow A (HSYA), a natural chalcone glycoside, exhibited potent protection against hematopoietic failure in zinc-deficient zebrafish and strongly inhibited the P53 pathway. We confirmed the protective effect of HSYA in zinc-deficient mice bone marrow nucleated cells, which showed a significant suppression of P53 signaling and oxidative stress. Furthermore, the hematopoietic-protective activity of HSYA was validated using a mice model of myelotoxicity induced by 5-FU. In summary, our work provides an effective phenotypic screening strategy for identifying hematopoietic-protective agents and reveals the novel role of HSYA as a promising lead compound in rescuing hematopoietic disorders associated with P53 overactivation.
研究领域:
血液学
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分子生物学
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药理学
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发育生物学
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DOI
PubMed
高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
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2023
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IF 3.8
Jiaxi Chen,Mengyue Pan,Jingjie Wang,Mengling Zhang,Mingmei Feng,Xiaoming Chai,Qi Zhang,Yang Sun
Hydroxysafflor yellow A (HSYA), a chalcone glycoside, is a component of Carthamus tinctorius L. and exerts anti-inflammatory and antioxidative effects. However, the therapeutic effect and the underlying mechanism of HSYA on ulcerative colitis is unclear. This study aimed to investigate the unexplored protective effects and underlying mechanisms of HSYA on UC. In vitro analyses showed that HSYA reduced the secretion of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and IL-6 and inhibited nucleotide-binding and oligomerization domain-like receptor protein 3 (NLRP3)/gasdermin D (GSDMD)-mediated pyroptosis in lipopolysaccharide/ adenosine-5′-triphosphate (LPS/ATP)-stimulated macrophages. Gas chromatography–mass spectrometry (GC–MS) profiling of intracellular metabolites showed that HSYA reduced the increased levels of glucose, glucose 6-phosphate, and lactic acid, and inhibited the increased hexokinase 1 (HK1) expression caused by LPS/ATP stimulation. HK1 shRNA transfection further confirmed that HSYA inhibited the NLRP3/GSDMD-mediated pyroptosis via HK1 downregulation. In vivo analyses showed that HSYA drastically attenuated UC symptoms by relieving body weight loss, a decline in colon length, and inflammatory infiltration in colonic tissues induced by dextran sulfate sodium (DSS). HSYA also reduced the secretion of pro-inflammatory cytokines including IL-1β, IL-6, TNF-α, and IL-18. Moreover, HSYA inhibited HK1/NLRP3/GSDMD-mediated pyroptosis in DSS-induced colitis mice. Finally, 16S rRNA sequencing analyses of gut microbiota revealed that HSYA reversed gut microbiota dysbiosis by reducing the abundance of Proteobacteria and increasing that of Bacteroidetes. This study demonstrated that HSYA not only exerted anti-inflammatory effects by inhibiting HK1/NLRP3/GSDMD and suppressing pyroptosis but also regulated gut microbiota in mice with DSS-induced colitis. Our findings provide new experimental evidence that HSYA might be a potential candidate for treating inflammatory bowel diseases.
研究领域:
药理学
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免疫学
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微生物学
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胃肠病学
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产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2022
·
IF 7.419
Qianqian Chen,Jiayang Wan,Yangyang Zhang,Yu He,Yida Bao,Li Yu,Jiehong Yang
Objective Astragalus and Safflower are commonly used in the treatment of stroke. Studies have shown that their two active components, hydroxysafflor yellow A (HSYA) and calycosin (CA), have protective effects on cerebral ischemia-reperfusion injury (I/R). However, the pharmacokinetic-pharmacodynamic (PK-PD) modeling study of the combination of the two components has not been reported in rats. The study aimed to perform combined PK-PD modeling of HSYA and CA in normal and cerebral ischemia model rats to explain quantitatively their time-concentration-effect relationship. Methods To make the middle cerebral artery occlusion (MCAO) model. SD rats were randomly divided into normal treated group (NTG) ( n = 6), model group (MDG) ( n = 6) and model treated group (MTG) ( n = 6). Plasma was collected from the mandibular vein after 0, 2, 5, 10, 15, 20, 30, 45, 60, 75, 90, 120, 180, and 240 min after intravenous administration. Rats in NTG and MTG were administered the same dose of HSYA (5 mg/kg) and CA (8 mg/kg) by tail vein injection. HPLC-VWD method was used for detection and analysis. Simultaneously, ELISA was performed to detect the levels of IL-1β and caspase-9 in rat plasma at different time points. The improvement in the above indicators was compared after administration. Lastly, after combining the pharmacokinetic parameters and pharmacodynamic indicators in vivo , DAS 3.2.6 software was used to fit the PK-PD model. Results The MCAO model was successfully established. Compared to NTG, there was a significant difference ( P < 0.05) in t 1/2α , t 1/2β , V 1 , V 2 , CL 1 , CL 2 , AUC (0−t) , AUC (0-∞) , and K 12 of MTG for HSYA, and there was a significant difference ( P < 0.05) in t 1/2α , V 1 , CL 1 , AUC (0−t) , AUC (0-∞) , and K 10 of MTG for CA . Compared to NTG, the PK parameters of t 1/2α , V 1 , V 2 , CL 1 , and K 10 were higher for HSYA in MTG, while AUC (0−t) , AUC (0-∞) , K 12 , and K 21 were lower; the PK parameters of t 1/2α , V 1 , V 2 , AUC (0−t) , and AUC (0-∞) were higher for CA in MTG, while CL 1 , CL 2 , K 10 , K 12 , and K 21 were lower. Also, the results of PD showed extremely significant differences in the levels of caspase-9 and IL-1β at the different time points in MTG ( P < 0.01) compared with 0 min. The levels of caspase-9 and IL-1β in NTG rats showed little fluctuation and were relatively stable; however, their levels in MTG showed a downward trend with time. There were highly significant differences in the levels of each of the pharmacodynamic indicators at every time point between NTG and MTG ( P < 0.01). Conclusion The PK-PD model of the combined administration of HSYA and CA was successfully established in rats, and the differences in pharmacodynamic and pharmacokinetic properties between the normal and cerebral ischemic rats were evaluated. Based on comprehensive data analysis, we found that the combination of HSYA and CA may exert protective effects against I/R injury in rats via anti-apoptotic and anti-inflammatory pathways. The study provided additional insights into the development of drugs for ischemic stroke as well as the design of appropriate dosing regimens.
研究领域:
药理学
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神经科学
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药学
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产品关联
DOI
PubMed
高影响因子
Polymers
·
2025
·Vol. 17
·期 14
·1900
·
IF 4.9
Guoying Zhou,Yujia Yan,Linh Nguyen,Jiangkai Fan,Xiao Zhang,Li Gan,Tingzi Yan,Haitong Wan
Traumatic brain injury (TBI) leads to severe neurological dysfunction, disability, and even death. Surgical intervention and neurorehabilitation represent the current clinical management methods, yet there remains no effective treatment for recovery after TBI. Post-traumatic hyperinflammation and vascular injury are the key therapeutic challenges. Therefore, a novel-designed multifunctional HT/SAA/HSYA hydrogel based on hyaluronic acid (HA) co-loaded with salvianolic acid A (SAA) and hydroxysafflor yellow A (HSYA) was developed in order to simultaneously target inflammation and vascular injury, addressing key pathological processes in TBI. The HT hydrogel was formed through covalent cross-linking of tyramine-modified HA catalyzed by horseradish peroxidase (HRP). Results demonstrated that the HT hydrogel possesses a porous structure, sustained release capabilities of loaded drugs, suitable biodegradability, and excellent biocompatibility both in vitro and in vivo. WB, immunofluorescence staining, and PCR results revealed that SAA and HSYA significantly reduced the expression level of pro-inflammatory cytokines (IL-1β and TNF-α) and inhibited M1 macrophage polarization through the suppression of the TLR4/NF-κB inflammatory pathway. In vivo experiments confirmed that the HT/SAA/HSYA hydrogel exhibited remarkable pro-angiogenic effects, as evidenced by increased expression of CD31 and α-SMA. Finally, H&E staining showed that the HT/SAA/HSYA hydrogel effectively reduced the lesion volume in a mouse TBI model, and demonstrated more pronounced effects in promoting brain repair at the injury site, compared to the control and single-drug-loaded hydrogel groups. In conclusion, the HT hydrogel co-loaded with SAA and HSYA demonstrates excellent anti-inflammatory and pro-angiogenic effects, offering a promising therapeutic approach for brain repair following TBI.
研究领域:
神经外科学
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生物材料学
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免疫学
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药理学
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再生医学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）