INTERNATIONAL DAIRY JOURNAL
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2025
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IF 3.4
Ruikai Zhu,Hong Zhang,Yulong Wu,Huanhuan Li,Honggang Tang,Xianrong Xu,Ke Zhao
Hypertension poses a significant threat to human health, and the efficient exploration of food-derived ACEI peptides as milder and safer alternatives to ACEI drugs has garnered increasing attention. Therefore, a combined in silico and in vitro study was performed to investigate novel ACEI peptides from goat milk proteins. First, the papain plus proteinase K was identified as the best enzymatic combination for generating ACEI peptides using BIOPEP. Then the enzymatic conditions of the papain/proteinase, the input order of the enzymes, and the molecular weight (MW) of the hydrolysate were further optimized to obtain the hydrolysate with the highest ACEI activity. Under the optimized condition described, 698 peptides (<25 AA) were successfully identified from the milk hydrolysate of goat (MW < 3 KDa). Among them, six potential novel ACEI peptides were efficiently screened virtually. Verification studies using synthesized peptides partially confirmed the in silico results, with four out of the six selected peptides (FKF, FRY, RWL, and WKP) exhibiting ACEI activity. Additionally, the blood pressure-lowering effects of the top two ACEI peptides (FRY and FKF) were further validated in spontaneously hypertensive rats (SHRs), and FRY treatment significantly lowered the blood pressure of SHRs. To summarize, this study established a rapid enzymatic hydrolysis system for screening novel ACEI peptides and identified a novel antihypertensive peptide, FRY, which provides a new method for research on bioactive peptides research and high-value utilization of goat milk.
研究领域:
食品科学
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分子生物学
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医学
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DOI
高影响因子
JOURNAL OF MOLECULAR HISTOLOGY
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2025
·Vol. 56
·期 3
·1-15
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IF 2.2
Bai Jing,Yang Yujuan
The Hippo/YAP signaling pathway is closely related to the occurrence and development of cardiovascular diseases. However, it’s still unclear whether this pathway plays a certain role in hypertension. In this study, aortic morphology and function in spontaneously hypertensive rats (SHR) were comprehensively evaluated using Wistar-Kyoto rats (WKY) as controls. Results indicated that the aorta of SHRs have distinct changes in pathological structure. Furthermore, the proliferative activity of vascular smooth muscle cells (VSMCs) was enhanced, with vascular fibrosis being aggravated. Immunohistochemical analysis revealed that SHRs exhibited high expression of Yes-Associated Protein (YAP). Western Blot analysis showed that cytoplasmic YAP and TAZ expression decreased in hypertensive rats, indicating that YAP/TAZ nuclear transfer increased and Hippo/YAP signaling pathway had been activated. The cell function experiments of VSMCs extracted from rat aorta showed that the cell viability and proliferation ability of VSMCs in SHRs were enhanced, the expression of Fibronectin and collagen I was increased, and vascular fibrosis was aggravated. siRNA-YAP (si-YAP) can reverse the above phenomenon in VSMCs. Knockdown of YAP can inhibit Foxm1 expression. As an inhibitor of large tumor suppressor kinases LAST1/2, GA-107 can inhibit the phosphorylation level of YAP, increase blood pressure, aggravate aortic pathomorphological changes, promote VSMCs proliferation and vascular fibrosis, and thus aggravate hypertension symptoms in SHRs. However, these effects of GA-107 can be antagonized by inhibiting Foxm1 with thiosulfathiazole (Thio). Conclusively, Hippo/YAP signaling pathway promotes vascular remodeling through the regulation of Foxm1 and causes hypertension.
研究领域:
心血管疾病
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分子生物学
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病理学
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产品关联
DOI
PubMed
高影响因子
Nano Energy
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2024
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IF 16.8
Zhongrong Chen,Yulin Lai,Siyu Xu,Mengfei Zhu,Yue Sun,Yue Cheng,Gang Zhao
Hypertensive emergency is a clinical syndrome characterized by abrupt and substantial elevation of blood pressure in hypertensive patients due to specific triggers, leading to potentially life-threatening consequences. Intravenous injection of sodium nitroprusside is commonly used to rapidly lower blood pressure. However, its specialized nature limits its applicability for first aid or self-help in emergency situations. To address this issue, we have developed a self-powered and controllable microneedle drug delivery system that is easy to use and effective for lowering blood pressure. The system mainly consists of two parts: a piezoelectric thin film self-powered module made of polyvinylidene fluoride and carbon nanotubes, and a drug delivery module composed of polylactic acid-Au microneedles and polylactic acid-Au-polypyrrole microneedles. The results show that different pressures applied to the self-powered module generate different voltages, thereby controlling the drug release efficiency of the microneedles. Compared with conventional active devices, it exhibits a higher drug release rate and effectiveness. Furthermore, the system was successfully utilized to reduce and control blood pressure in spontaneously hypertensive rats. Compared with the injection of sodium nitroprusside, this system can more effectively lower and control blood pressure levels, and its biological safety has been verified. This study presents a controllable and user-friendly rapid blood pressure lowering system suitable for hypertensive emergencies, which has important clinical application prospects.
研究领域:
医学工程
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药理学
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生物医学材料
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DOI
高影响因子
DRUG METABOLISM AND DISPOSITION
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2025
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IF 4
Dafa Yi,Jiazong Ye,Zebei Lu,Leilei Lu,Tengfei Qi,Tong Luo,Xiuyun Peng,Abdullah Al Mamun,Quan Zhou,Daqing Chen,Shuanghu Wang
This study investigates the potential drug-drug interactions between commonly prescribed anti-hypertensive drugs and mobocertinib in clinical practice to provide the scientific basis for the appropriate therapeutic application of drugs. The study used UPLC-MS/MS to detect the essential metabolites of mobocertinib in rat liver microsomes. Moreover, several anti-hypertensive drugs were used as inhibitors and the IC 50 values were determined for calcium channel blockers, angiotensin II receptor blockers and α and β receptor blockers against mobocertinib. The inhibitory mechanism of mobocertinib was further investigated for nicardipine, irbesartan, telmisartan, carvedilol, prazosin hydrochloride and spironolactone. Twenty-five Sprague Dawley ( SD) rats were randomly divided into five groups: benidipine, nicardipine, telmisartan, irbesartan and blank control groups. The drugs were administered over a period of 7 days. Mobocertinib was administered once by gavage to five groups and then blood samples were collected for further analysis. UPLC-MS/MS was performed to analyze the concentration of mobocertinib and its metabolites in rat plasma. Most anti-hypertensive drugs were found to inhibit the metabolism of mobocertinib in vitro. Several anti-hypertensive drugs were also found to increase the plasma concentration and decrease the metabolic rate of mobocertinib when administered multiple times. More importantly, we found that benidipine, nicardipine, telmisartan and irbesartan inhibited the metabolism of mobocertinib in vitro and in vivo . In summary, our data reveal that anti-hypertensive drugs interact with mobocertinib and additional attention is needed when co-administering the two drugs.
研究领域:
药理学
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临床医学
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产品关联
DOI
PubMed
高影响因子
Journal of Translational Medicine
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2024
·Vol. 22
·期 1
·1-13
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IF 6.1
Li Jing,Wang Xiaochen,Bai Jie,Wei Huangzhao,Wang Wenbo,Wang Shuai
Background Hypertension influences the inflammatory pathological changes in the retina. The function of the inflammasomes is significant. To see if Sirtuin 1 (SIRT1) regulates angiotensin II (Ang II)-induced hypertensive retinopathy and inflammation by modulating NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome activation and the potential protective effects of fucoidan (FO) in mouse retinal vascular endothelial cells (mRECs) and mice retina. Methods The diagnosis of hypertensive retinopathy was made after three weeks of Ang II infusion (3000 ng/kg/min). One day prior to the commencement of Ang II infusion, the mice were treatment with NLRP3 inhibitor MCC950 (10 mg/kg/day, intraperitoneal injections) or FO (300 mg/kg/day, oral gavage). A blood pressure was recorded. Hematoxylin and eosin (H&E) staining was used to conduct pathological alterations, dihydroethidium bromide (DHE) was utilized to assess oxidative stress damage in the retina, and fluorescence angiography was used to identify vascular disorders in the eye. Using immunohistochemical labeling, NLRP3 expression was found. Reactive protein and mRNA expression levels in mouse retina and cells were assessed using Western blot and real-time quantitative polymerase chain reaction (RT-qPCR). Results NLRP3 inflammasome activation and SIRT1 decrease were brought about by Ang II infusion. Retinopathy and dysfunction were lessened by MCC950 target-induced NLRP3 inflammasome activation, while overexpression of SIRT1 had the opposite impact on NLRP3 inflammasome activation, indicating that SIRT1 functions as an upstream regulator of NLRP3 activity. FO may improve SIRT1 expression and decrease NLRP3 activation in retinopathy and dysfunction brought on by Ang II, and the effects were consistent across both in vivo and in vitro models. Conclusions SIRT1 adversely regulates the NLRP3 inflammasome pathway, which in turn increases Ang II-induced inflammation and hypertensive retinopathy. FO may mitigate Ang II-induced retinopathy and dysfunction via modulating the expression of SIRT1/NLRP3. This implies practical approaches to the management of hypertensive retinopathy.
研究领域:
医学
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分子生物学
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药理学
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DOI
PubMed
高影响因子
Translational and Clinical Pharmacology
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2021
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IF 0
Hyeon-Cheol Jeong,Yo-Han Seo,Namyi Gu,Moo Yong Rhee,Kwang-Hee Shin
Candesartan and olmesartan are angiotensin II receptor blockers (ARBs) used for the treatment of hypertension and heart failure. Quantitation methods for candesartan and olmesartan were developed using ultra-high performance liquid chromatography-tandem mass spectrometry following protein precipitation. Candesartan was separated using 5 mM ammonium formate (A) and 100% acetonitrile (B) and olmesartan was separated using 2 mM ammonium formate with 0.1% formic acid (A) and 100% acetonitrile (B). Separation was performed using an isocratic method with a Thermo hypersil GOLD C18 column. Electrospray ionization was used for analyte ionization and detection of candesartan, olmesartan, and the internal standards by multiple reaction monitoring. Developed method showed excellent linearity ( r > 0.99) in the concentration range of 2–500 ng/mL for candesartan and 5–2,500 ng/mL for olmesartan. Accuracies were 86.70–108.8% for candesartan and 87.87–112.6% for olmesartan. These methods were able to successfully measure plasma candesartan or olmesartan concentrations in hypertensive patients. This study can be used for pharmacokinetic studies of candesartan or olmesartan in humans.
研究领域:
药理学
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分析化学
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DOI
PubMed
TALANTA
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2025
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IF 6.1
Jiameng Pei,Lina Tang,Chenyang Kang,Fan Shi,Fengxia Liang,Yutao Li,Guo-Jun Zhang
Acupuncture therapy reduces blood pressure in hypertensive patients by stimulating acupoints located at specific anatomical positions with needles. Hydrogen sulfide (H 2 S) release and accumulation in the paraventricular nucleus (PVN) might be a pivotal step for triggering blood pressure reduction. But to date, the dynamics of H 2 S in the PVN during acupuncture treatment remain unclear. In this work, a multiple-nanomaterial-functionalized microneedle sensor is prepared for real-time monitoring of H 2 S in the PVN of rat while stimulated by electroacupuncture. Gold nanoparticles (AuNPs), molybdenum disulfide (MoS 2 ) and Ag 2 S were sequentially layered on the needle surface. The excellent electrical conductivity of AuNPs, the high carrier mobility of MoS 2 and the high catalytic performance of Ag 2 S ensure sensitive and specific detection of H 2 S in the range of 1 μM–100 μM with detection limit down to 95 nM. The microneedle sensor also demonstrates exceptional stability, remaining effective at room temperature for up to two weeks. Based on this, the microneedle sensor is used to monitor H 2 S release in vivo before and after acupuncture treatment. Our research indicates that acupuncture effectively increases H 2 S levels in the PVN of hypertensive rats, contributing to blood pressure reduction. This microneedle sensor provides a reliable method for monitoring H 2 S release in vivo, offering valuable insights into the role of H 2 S in the neurophysiology of hypertension and the mechanism of acupuncture in its treatment.
研究领域:
神经生理学
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生物传感技术
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中医药学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR LIQUIDS
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2018
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IF 4.513
Canghao Ni,Changqing Sun,Zhaofeng Zhou,Yongli Huang,Xinjuan Liu
Overdosing of Na(Cl, C 5 H 8 NO 4 ) can raise one's blood pressure but moderately intaking of C 6 H 8 O 6 ascorbic and C 2 H 4 O 2 acetic acids effects contrastingly with mechanisms yet to be clear. From the perspective of hydrogen bond (O:H O or HB with “:” being electron lone pairs of oxygen) cooperativity, we show phonon-spectrometrically that solvation of the Na-based doses raises their solution surface tension by ionic polarization, but solvation of the organic acids performs contrastingly by dipolar fragilization. The Na-based doses dissolve into Na + cations and anions that serve each as a charge center to cluster, stretch, and polarize the solvent O:H O bonds, raising the viscosity of the solution. However, the acidic dipoles break the solvation network into small fragments, helping to the blood flowing. Findings could offer workable mechanisms for hypertension medication and prevention.
研究领域:
生物物理学
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医学
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产品关联
DOI
高影响因子
JOURNAL OF MOLECULAR MEDICINE-JMM
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2025
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IF 4.2
Wen Xin,Peng Yuefeng,Yang Wenqing,Zhu Yuzhong,Yu Fan,Geng Li,Wang Xianfeng,Wang Xiaoyan,Zhang Xiaodong,Tang Yi,Feng Lei,Zhou Tingting,Jia Hongliang,Yang Liu
Transient receptor potential canonical 1 (TRPC1) channel, a Ca 2+ -permeable ion channel widely expressed in vasculature, has been reported to be involved in various cardiovascular disorders. However, the pathophysiological function of vascular smooth muscle cell (VSMC)-derived TRPC1 in hypertension and hypertensive cardiovascular remodeling remains to be defined. In this study, we found increased TRPC1 expression in both angiotensin II (AngII)-treated VSMCs and aortas from AngII-infused mice. VSMC-specific TRPC1 deficiency strikingly attenuated AngII-induced vasoconstriction, hypertension, vascular remodeling, and cardiac hypertrophy. Mechanistically, AngII activated enhancer of zeste homolog 2 (EZH2) to stimulate TRPC1 expression, induced calcium influx and phosphorylation of mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK-ERK), which in turn triggered VSMC proliferation and migration and exacerbated hypertension and cardiovascular remodeling. Treatment with EZH2 inhibitor reduced VSMC proliferation and migration and alleviated vasoconstriction and hypertension in AngII-infused mice. Together, we revealed the pathogenic role of the EZH2-TRPC1-MEK/ERK pathway in AngII-induced hypertension and cardiovascular damage. TRPC1 or EZH2 inhibition may represent a desirable therapeutic target for the treatment of hypertension. Key messages
AngII activates AT1R-EZH2-TRPC1 pathway in VSMCs and aortas of hypertensive mice.
TRPC1 promotes VSMC proliferation and migration via MEK/ERK signaling.
Inhibition of TRPC1 or EZH2 alleviates hypertension and cardiovascular remodeling.
研究领域:
心血管病学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
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2025
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IF 4.7
Meizhu Wu,Yuting Zhou,Zhi Guo,Dawei Lian,Hong Chen,Renfeng Li,Jing Lin,Farman Ali,Aling Shen,Jun Peng
Isoliensinine, a bioactive alkaloid derived from Nelumbo nucifera Gaertn , has antihypertension effects. This study investigated its antihypertensive effect and molecular mechanism. Spontaneously hypertensive rats (SHRs) and Wistar Kyoto rats (n=6 per group) were treated with 2.5, 5 or 10 mg/kg isoliensinine or 7 mg/kg valsartan for 10 weeks. Ultrasonography, histology, immunohistochemistry, RNA-sequencing analysis, vascular tension, calcium imaging, and virtual docking were performed. Isoliensinine effectively attenuated the elevation of blood pressure, pulse wave velocity, and medial thickness of the abdominal aortas in SHRs. It reversed 253-upregulated and 161-downregulated differentially expressed transcripts in the abdominal aorta of SHRs, with enrichment in vascular smooth muscle contraction and calcium signaling pathways. Isoliensinine significantly attenuated the vasoconstriction induced by angiotensin II (Ang II), norepinephrine (NE), or potassium chloride (KCl) and maintained its inhibitory effects across increasing calcium concentrations. It promotes vasodilation in the abdominal aorta rings induced by NE or KCl independent of the endothelium and potassium ion channels but is associated with the modulation of L-type calcium channels. Isoliensinine also suppressed calcium release in vascular smooth muscle cells after KCl, Ang II, or NE stimulation. Isoliensinine upregulated the expression of MLCP but downregulated that of p-MLC2 in the abdominal aorta of SHRs. Virtual docking analysis revealed lower binding energy values for isoliensinine with MLCP, suggesting a potential interaction. Isoliensinine lowers blood pressure by regulating vascular smooth muscle contraction and relaxation, and its effects are potentially mediated by regulating calcium signaling pathways.
研究领域:
药理学
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心血管生物学
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产品关联
DOI
PubMed
高影响因子
Science China-Life Sciences
·
2024
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IF 8
Zhang Zhen,Huang Weijun,Zhang Xiaoran,Wang Zhecun,Xie Manting,Xie Bingbing,Wang Yiling,Chen Xiaoyong,Xiang Andy Peng,Xiang Qiuling
Despite substantial advancements in modern medicine, the management of hypertension remains a major challenge. Stem cell-based therapies have recently demonstrated remarkable efficacy in treating cardiovascular diseases, including hypertension. However, the antihypertensive mechanism of mesenchymal stem cells (MSCs) has not been extensively explored. This study aimed to investigate the role of injected MSCs in regulating blood pressure homeostasis. Our previous study demonstrated that human induced pluripotent stem cell-derived mesenchymal stem cells (hiPSC-MSCs) are functional and homogeneous sources for MSC-based therapy. After the injection of hiPSC-MSCs, a significant reduction in blood pressure and end target organ inflammation were observed in spontaneously hypertensive rats (SHRs). Cell tracking assays demonstrated that the injected hiPSC-MSCs accumulated in the spleens of the SHRs. The injected hiPSC-MSCs accumulated adjacent to the splenic nerve, potentially contributing to the antihypertensive effects. Furthermore, the hiPSC-MSCs released abundant glutamate, which acts as a neuromodulator to activate the splenic sympathetic nerve. After inhibition of glutamate synthesis by siRNA, the ability of hiPSC-MSCs to activate sympathetic nerves was significantly diminished. In addition, the antihypertensive effects of hiPSC-MSCs were eliminated after splenic nerve denervation (SND), underscoring the critical role of the splenic nerve. Moreover, activation of the splenic nerve resulted in increased release of norepinephrine (NE), which increased the number of choline acetyltransferase-positive (ChAT + ) cells in the spleen and peripheral blood. Consequently, the acetylcholine (ACh) produced by elevated ChAT + cells could act as a vasodilator, lowering blood pressure and mitigating inflammation in end target organs. In summary, our findings indicate that hiPSC-MSCs effectively lower blood pressure in hypertension by influencing the splenic nerves and regulating ChAT + cells. The connection between blood pressure regulation and the splenic nerve may offer new insights into the treatment of hypertension.
研究领域:
干细胞治疗
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心血管疾病
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高血压
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神经科学
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药理学
✓ 已验证
DOI
PubMed
高影响因子
Journal of Inflammation Research
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2021
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IF 6.922
Tiantian Wang,Lei Gao,Zejun Yang,Feifei Wang,Yuexin Guo,Boya Wang,Rongxuan Hua,Hongwei Shang,Jingdong Xu
Purpose Hypertension (HTN) is a major risk factor for cardiovascular disease. In recent years, there were numerous studies on the function of stress in HTN. However, the gut dysbiosis linked to hypertension in animal models under stress is still incompletely understood. Purpose of this study is to use multiple determination method to determine the juvenile stage intestinal bacteria, cytokines and changes in hormone levels. Methods Four groups of juvenile male spontaneously hypertensive rats (SHRs) and age-matched male Wistar-Kyoto (WKY) rats were randomly selected as control and experimental groups. Rats in the two stress groups were exposed to restraint stress for 3 hours per day for 7 consecutive days. In one day three times in the method of non-invasive type tail-cuff monitoring blood pressure. The detailed mechanism was illuminated based on the intestinal change using immunohistochemical and immunofluorescence staining and the stress-related hormone and inflammation factors were analyzed via ELISA method. The integrity of the epithelial barrier was assessed using FITC/HRP and the expression levels of proteins associated with the tight junction was detected by Western blot. The alteration of stress-related intestinal flora from ileocecal junction and distal colon were also analyzed using its 16S rDNA sequencing. Results The results indicate that acute stress rapidly increases mean arterial pressure which is positive correlation to hormone concentration, especially in SHR-stress group. Meanwhile, stress promoted the enhancement of epithelial permeability accompanied with a reduced expression of the tight junction-related protein and the macrophages (Mφ) aggregation to the lamina propria. There were remarkable significant increase of stress-related hormones and pro-inflammatory factor interleukin (IL)-6 along with a decrease in the diversity of intestinal flora and an imbalance in the F/B ratio. Conclusion Our results reveal that stress accompanied with HTN could significantly disrupt the domino effect between intestinal flora and homeostasis.
研究领域:
心血管疾病
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药理学
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免疫学
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微生物学
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病理生理学
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DOI
PubMed
高影响因子
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