Journal of Functional Foods
·
2018
·
IF 3.47
Hong Ding,Xiaofei Li,Jian Li,Zhike Li,Yunhui Niu,Wanying Ren,Jianyang Tan,Shanye Yin
The present study examined the effects of procyanidin B2 (PB2) on L-NAME (nitric oxide synthase inhibitor)-induced hypertensive nephropathy. After 4 weeks of treatment with daily PB2 supplementation, lower blood pressure levels were observed in rats. The potential mechanisms were combined with amelioration of renal function impairment. The L-NAME–induced renal histological damage were reduced by PB2 treatment, which showed similar protective tendency in kidney injury molecule–1, nephrin, fibronectin and α–smooth muscle actin protein expression. This appears to be due to PB2 inducing a less pronounced generation of renal reactive oxygen species and inflammatory mediators than in the model group. Downregulation of Ang II type 1 receptor and NADPH oxidase subunit (NOX4, gp91phox and p47phox) played a critical role in the effect of PB2 reducing oxidative stress production. These activities could further support the use of PB2 commercially in food for the prevention of hypertension and its complications.
研究领域:
药理学
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肾病学
·
高血压研究
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分子生物学
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DOI
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2023
·
IF 5
Meng Chen,Qilan Hu,Shengquan Wang,Ling Tao,Xiaoxia Hu,Xiangchun Shen
Our previous data confirmed that 1,8-Cineole had an antihypertensive effect in animal models. However, it is unclear whether antihypertension is dependent on the protective effect of 1,8-Cineole on endothelial function and structure. At present, the purpose was to investigate the protective effects of 1,8-Cineole on vascular endothelial tissue in hypertensive rats and human umbilical vein endothelial cells (HUVECs). Our results showed that 1,8-Cineole significantly reduced the blood pressure and improved the vascular endothelial lesion , attenuated vascular oxidative stress and inflammation induced by Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME) in rats. Pretreatment with 1,8-Cineole was able to inhibit the increase in malondialdehyde (MDA) and reactive oxygen species (ROS) induced by L-NAME, and increased the release and expression of superoxide dismutase (SOD) and nitric oxide (NO). In addition, 1,8-Cineole also reversed the increase of autophagy-associated protein LC3Ⅱ/LC3Ⅰ and the decrease of P62 in vivo and in vitro respectively. There was a synergistic effect between PI3K agonists and drugs, while PI3K inhibitors blocked the efficacy of 1,8-Cineole. The addition of autophagy inhibitor chloroquine increases the expression of eNOS. Taken together, our results indicate that 1,8-Cineole has potential beneficial promising antihypertension depending on the integrity of vascular endothelial structure and function induced by L-NAME, and the mechanism involves ameliorating autophagy by regulating of PI3K/mTOR.
研究领域:
药理学
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心血管疾病
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
Acta Pharmaceutica Sinica B
·
2025
·
IF 14.6
Jiahui Chen,Liping Zhang,Ting Xie,Xiao Zhang,Congcong Pan,Fangli Sun,Wenfeng Li,Zhijie Sun,Deli Dong
The clinical antiprotozoal drug nitazoxanide has been demonstrated to improve the experimental diabetes mellitus, lipid metabolism disorders, atherosclerosis and inhibit inflammation. Since the pathogenesis of heart failure with preserved ejection (HFpEF) is multifactorial and closely associated with the aforementioned diseases, we aim to study the effect of nitazoxanide on high-fat diet (HFD) plus L-NAME (N ω -nitro-L-arginine methyl ester)-induced HFpEF and metabolic syndrome in mice. We found that oral nitazoxanide improved cardiac hypertrophy, cardiac fibrosis, cardiac diastolic dysfunction, increased blood pressure, impaired exercise tolerance, impaired glucose handling, serum lipid disorders, hepatic steatosis, increased weight of white adipose tissues and kidney fibrosis in HFD+L-NAME-treated mice. In the established HFD+L-NAME-induced HFpEF and metabolic syndrome mouse model, therapeutic treatment with nitazoxanide rescued HFD+L-NAME-induced pathological phenotypes as mentioned above. The in vitro experiments revealed that tizoxanide, the active metabolite of nitazoxanide, increased the basal mitochondria metabolism of cardiomyocytes, inhibited cardiomyocyte hypertrophy and collagen secretion from cardiac fibroblasts, and relaxed phenylephrine- and U46619-induced constriction of rat mesenteric arteries, indicating that the direct effect of tizoxanide might partly contribute to the protective effect of nitazoxanide against HFpEF in vivo . The present study suggests that nitazoxanide might be a potential drug for HFpEF and metabolic syndrome therapy.
研究领域:
心脏病学
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药理学
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代谢性疾病
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分子生物学
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DOI
PubMed
高影响因子
Food & Function
·
2016
·Vol. 7
·期 5
·2398-2408
·
IF 2.686
Xiaofei Li,Jian Li,Zhike Li,Ying Sang,Yunhui Niu,Qianying Zhang,Hong Ding,Shanye Yin
Despite major scientific advances in its prevention, treatment and care, hypertension remains a serious condition that might lead to long-term complications such as heart disease and stroke. The great majority of forms of hypertension eventually result from an increased vasomotor tone activity that is regulated by endothelial NOS (eNOS) in vascular endothelium. Here, we examined the effect of fucoidan on eNOS activation in human umbilical vein endothelial cells (HUVECs). We also examined the effects of functional components of Undaria pinnatifida fucoidan on blood pressure and vascular function in eNOS inhibition-induced hypertensive rats in vivo. Our results suggest that fucoidan increased nitric oxide production by activating eNOS and Akt phosphorylation, which could be impaired by Akt or eNOS inhibitors. In the hypertensive rat model, treatment of fucoidan resulted in potent and persistent reduction of high blood pressure (BP) even after drug withdrawal. Our results showed that the mechanisms might involve protection against vascular structure damage, enhanced endothelium-independent vascular function and inhibition of abnormal proliferation of smooth muscle cells, which are mediated by the Akt–eNOS signaling pathway. Moreover, fucoidan treatment reduced the vascular inflammation and oxidative stress control caused by iNOS expression. Together, these results support a putative role of fucoidan in hypertension prevention and treatment.
研究领域:
药理学
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心血管疾病
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分子生物学
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营养保健品
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DOI
PubMed
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
·
2023
·
IF 5.1
Xuan Zhang,Lei Sun
Preeclampsia (PE) is a complex disease of pregnancy, and an important cause of this disease is insufficient trophoblast invasion and migration. However, the underlying mechanism of PE remains largely unknown. Here, transcriptome sequencing analysis found the high expression of hepatocyte nuclear factor 4 alpha (HNF4A) in PE placentas. Meanwhile, we found that HNF4A expression was up-regulated in the placentas of PE patients. Thus, we assumed that HNF4A might be involved in PE progression. To validate our hypothesis, l -arginine methyl ester ( l -NAME) or lipopolysaccharide (LPS)-treated rats were used to mimic the pathological status of PE in vivo . Consistently, HTR8/SVneo cells were treated with hypoxia/reoxygenation (H/R) or LPS to simulate PE progression in vitro . The results observed an increase in elevated urine protein levels, systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP), which indicated that the PE-like rat model was successfully established. Meanwhile, the expression of pro-inflammatory cytokines interleukin (IL)-6 and IL-1β was increased in PE placentas. HTR8/SVneo cells were used to further explore the underlying mechanism of PE in vitro . H/R conditions up-regulated the acetylation level of HNF4A. Further analysis showed that HNF4A overexpression inhibited trophoblast invasion and migration, while HNF4A knockdown promoted the progression. Additionally, inhibiting HNF4A was found to reduce the levels of IL-6 and IL-1β secretion in HTR8/SVneo cells following H/R or LPS exposure. Conclusively, these findings suggest that inhibiting HNF4A suppresses inflammation whilst promoting trophoblast invasion and migration in PE, providing a promising target for the treatment of PE.
研究领域:
妇产科学
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分子生物学
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病理生理学
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DOI
PubMed
高影响因子
EXPERIMENTAL CELL RESEARCH
·
2025
·
IF 3.5
Xiaodan Chu,Xuan Chen,Man Guo,Xinyue Li,Zhihai Qu,Peiling Li
Insufficient trophoblast cell infiltration is implicated in the progression of preeclampsia (PE). The immunoglobulin superfamily member 8 (IGSF8) has been shown to promote cell migration, invasion, and epithelial mesenchymal transition (EMT). However, the specific impact of IGSF8 on trophoblast cells in PE has not been definitively demonstrated. To address this, placental tissues from PE patients and normal subjects was collected. A PE-like rat model was established by administering L-NAME (60 mg/kg) intragastrically to pregnant rats from the 10th to the 19th day of gestation. Knockdown and overexpression plasmids of IGSF8 were transfected into JEG-3 cells for further experiments. Clinical samples indicated impaired spiral artery remodeling, and high IGSF8 expression in the placental tissues of PE patients. PE rats exhibited increased mean arterial pressure, elevated 24-h urine protein levels, higher abortion rates, and decreased placental and fetal weight compared to rats of sham group. Failure of physiological transformation of spiral arteries was observed in PE rats, along with increased IGSF8 expression. IGSF8 overexpression inhibited JEG-3 cell migration, invasion and EMT, as well as reduced release of VEGF in JEG-3 cells, impairing HUVEC tube formation. mRNA-sequencing analysis of JEG-3 cells transfected with shIGSF8 showed differentially expressed genes related to angiogenesis, and mesenchymal cell differentiation, with IGSF8 knockdown being associated with the activation of pathways involved in blood vessel development and cell migration. Overall, this study suggests that IGSF8 plays a role in the development of PE and provides new insights for potential treatments.
研究领域:
妇产科学
·
分子生物学
·
细胞生物学
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病理生理学
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产品关联
DOI
PubMed
高影响因子
iScience
·
2025
·Vol. 28
·期 8
·112744
·
IF 4.1
Ke Li,Xiaoyan Jia,Dawei Guo,Haiming Wang,Haonan Shui,Hongbo Qi,Hua Zhang
Placenta-targeting nano-drugs have emerged as a safe and effective treatment option for preeclampsia (PE). Downregulation of peroxisome proliferator-activated receptor γ (PPARγ) induces dysfunctional placental trophoblasts and facilitates placental reactive oxygen species, which weakens the PGC1α/UCP2 oxidative stress pathway, causing PE symptoms. Herein, rosiglitazone (RGZ), as an effective PPARγ agonist, exhibited great potential in PE treatment. However, low solubility and nonspecific effect limit the clinical application. Therefore, this study presents CGKRK-modified and RGZ-loaded lipid nanoparticles (CRNPs), based on the specific binding of CGKRK to calreticulin highly expressed in human and mouse trophoblasts. CRNP alleviates excessive oxidative stress and improves placental development and fetal growth in L-NAME-induced PE mice. However, it does not cause maternal side effects or fetal malformation in pregnant mice injected with a high dose of CRNP through the tail vein. Consequently, the safe and effective delivery of CRNP optimizes the placental-targeting therapeutic strategy. Natural sciences; Nanoparticles; Biological sciences; Female reproductive endocrinology
研究领域:
纳米医学
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妇产科学
·
药理学
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分子生物学
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生殖生物学
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生物科学
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自然科学
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DOI
PubMed
高影响因子
BRAIN RESEARCH
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2025
·
IF 2.6
Naizhu Wang,Jingkun Wu,Zhaofei Song,Hongbin Wang,Yan Zhao
Hypertension in the brain may lead to hypertensive intracerebral hemorrhage (HICH), a devastating disease. This study, grounded on bioinformatics insights, aims to investigate the functions of Selectin E (SELE) and forkhead box P1 (FOXP1) in the progression of HICH. Increased SELE expression was detected in the striatum of a mouse model of HICH generated via angiotensin II and L-NAME treatments. Knockdown of SELE alleviated hemorrhage, neutrophil infiltration, and blood–brain barrier (BBB) rupture in the mouse brain. FOXP1, poorly expressed in the HICH mice, was found to repress SELE transcription by binding to its promoter region. Overexpression of FOXP1 resulted in analogous alleviating effects in the HICH mice; however, the effects were abrogated by the additional SELE overexpression. In vitro , human brain microvascular endothelial cells (HBMECs) were treated with thrombin to generate a cellular model of ICH, followed by co-culture with HL-60 cell-derived neutrophils. The FOXP1 overexpression reduced the adhesion of neutrophils, and it alleviated HBMEC apoptosis and permeability while enhancing angiogenesis. Still, these effects were counteracted by the SELE upregulation. In conclusion, this study demonstrates that SELE upregulation upon FOXP1 loss is associated with neutrophil infiltration and BBB rupture in HICH.
研究领域:
神经病学
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分子生物学
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心血管疾病
·
免疫学
·
生物信息学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
MOLECULAR BIOTECHNOLOGY
·
2023
·
IF 2.6
Chang Ruijing,Su Yuan,Kong Hongfang,Wang Fang,Xing Ying,Jiang Lei,Xin Hong
Disturbance of extravillous trophoblast infiltration is associated with preeclampsia (PE), a severe condition of pregnancy characterized by hypertension and proteinuria. Senescence-associated epithelial membrane protein 1 (SEMP1), an integral membrane protein, is a vital component of tight junction strands in epithelial or endothelial cells, with no clear function reported in PE. Gene Expression Omnibus (GEO) datasets showed that SEMP1 expression was downregulated in the placental tissues of PE patients, which was confirmed by assessing SEMP1 levels in placental samples collected in our hospital. Furthermore, less SEMP1 was detected in cytokeratin 7 positive trophoblast cells in the spiral arteries of rat placentas post L-arginine methyl ester hydrochloride (L-NAME) treatment. Trophoblast cells acquired robust ability of proliferation, migration, and invasion when SEMP1 was overexpressed. Such capability was weakened in SEMP1-silenced cells. Trophoblast cells overexpressing SEMP1 secreted more vascular endothelial growth factor A (VEGFA), which facilitated the tube formation of human umbilical vein endothelial cells. Blockade of PI3K/AKT signaling transduction with LY294002 dampened the effects of SEMP1 on trophoblast cells. Collectively, we firstly indicated that SEMP1 inhibition is a potential driver for PE, which may be associated with the deactivation of the PI3K/AKT pathway. Graphical Abstract SEMP1 was involved in PE progression by regulating cell growth, migration, invasion, and tube formation via PI3K/AKT signaling pathway in trophoblast cells and endothelial cells.
研究领域:
妇产科学
·
分子生物学
·
细胞生物学
·
病理生理学
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产品关联
DOI
PubMed
高影响因子
FREE RADICAL RESEARCH
·
2024
·
IF 3.6
Xue Peng,Xi Tan,Li Dai,Wei Xia,Zhao Wu
This research investigates the interplay between Reactive Oxygen Species (ROS) and Apelin (APLN) in regulating autophagy, with implications for placental cell senescence and apoptosis in pre-eclampsia (PE). We manipulated APLN expression using sgRNA to study its effects on ROS levels and subsequent cellular responses. Our findings reveal that APLN overexpression elevates ROS production, accelerating cellular senescence and apoptosis. In contrast, silencing APLN enhances autophagy, thereby diminishing cellular aging and apoptosis. These outcomes were confirmed in vitro and in vivo experiments, establishing a causative relationship between ROS-mediated APLN modulation and altered placental cell dynamics in PE. The results suggest potential therapeutic targets within the ROS and APLN pathways to alleviate detrimental changes in the placenta, offering new strategies for the clinical management of PE. This study emphasizes the crucial role of autophagy in placental health and sets the stage for future investigations into therapeutic interventions for pregnancy-related complications.
研究领域:
妇产科学
·
分子生物学
·
细胞生物学
·
药理学
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DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Miao Tang,Yu Xin,Yunchun Zhao,Xiao Zhang,Meng Zhang,Dongli Sun,Xiaojun Zhu,Yao Yao,Weidong Fei,Caihong Zheng
Physiological or pathological hypoperfusion of the placenta is one of the main causes of intrauterine growth restriction (IUGR) which poses a significant risk to the health of the fetus and newborn. Tadalafil, a 5-type phosphodiesterase inhibitor, has previously been found to improve the symptoms of IUGR in various clinical studies. Unfortunately, its clinical utility is hindered by its limited water solubility, rapid metabolism, and lack of specific distribution in target tissues rendering tadalafil unable to maintain long-term placental perfusion. In this study, iRGD-modified tadalafil-loaded liposomes (iRGD-lipo@Tad) featuring a size of approximately 480 nm were designed to rectify the shortcomings of tadalafil. The prepared iRGD-lipo@Tad exhibited superior stability, sustained drug release capacity, and low cytotoxicity. The fluorescence study, tissue slice study, and drug biodistribution study together demonstrated the placenta-anchored ability of iRGD-modified liposomes. This was achieved by a dual approach consisting of the iRGD-mediated placenta-targeting effect and special particle size-mediated placenta resident effect. The pharmacokinetic study revealed a significant improvement in the in vivo process of tadalafil encapsulated by the iRGD-modified liposomes. In comparison to the tadalafil solution, the peak plasma concentration of iRGD-lipo@Tad was significantly increased, and the area under the curve was increased by about 7.88 times. In the pharmacodynamic study, iRGD-lipo@Tad achieved a continuous and efficient improvement of placental blood perfusion. This was achieved by decreasing the ratio of plasma soluble fms-like tyrosine kinase to placental growth factor and increasing the levels of cyclic guanosine monophosphate and nitric oxide. Consequently, iRGD-lipo@Tad resulted in a significant increase in embryo weight and a reduction in the miscarriage rate of N-Nitro-L-arginine methyl ester-induced IUGR pregnant mice without detectable toxicity. In summary, the nanotechnology-assisted therapy strategy presented here not only overcomes the limitations of tadalafil in the clinical treatment of IUGR but also offers new avenues to address the treatment of other placenta-originated diseases.
研究领域:
药理学
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妇产科学
·
纳米技术
·
生物医学工程
·
生殖医学
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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2026
·
IF 6.5
Wen-jie Bu,Si-si Li,Yi Yu,Chao-run Dong,Dong Lu,Dong-jie Zheng,Zhe-yu Fan,Guang Lian,Wei Zhang,Yun-long Bai
Obesity and cigarette smoking are two major cardiovascular risk factors that frequently coexist, yet their combined impact on vascular function and the underlying mechanisms remains insufficiently defined. Here, we show that short-term cigarette smoke (CS) exposure induces persistent endothelial dysfunction exclusively in obese mice, while having minimal vascular effects in lean mice. Obese mice exposed to CS exhibited severely impaired acetylcholine-induced vasodilation, elevated blood pressure, sustained vascular oxidative stress, and accelerated endothelial senescence. Integrated metabolomic and transcriptomic analyses revealed that CS superimposed on obesity drives a distinct metabolic and transcriptional reprogramming characterized by disrupted redox homeostasis and inflammatory signaling. Mechanistically, CS selectively suppressed endothelial GTP cyclohydrolase 1 (GTPCH1) expression in obese mice, resulting in tetrahydrobiopterin (BH4) depletion, endothelial nitric oxide synthase (eNOS) uncoupling, reduced nitric oxide bioavailability, and increased superoxide production. Endothelial-specific restoration of GTPCH1 expression or pharmacological treatment with sepiapterin restored eNOS coupling, normalized endothelial redox balance, and rescued vascular function. In summary, we demonstrate that CS leads to sustained endothelial dysfunction in the setting of obesity, a phenomenon that is associated with disruption of the GTPCH1/BH4/eNOS axis. This provides a mechanistic explanation for the heightened cardiovascular risk in obese smokers and identifies actionable molecular targets for intervention
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PubMed
高影响因子
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