Food & Function
·
2021
·Vol. 12
·期 12
·5524-5538
·
IF 5.396
Bo Li,Xinglishang He,Hai-Ying Jin,Hui-Ying Wang,Fu-Chen Zhou,Ning-Yu Zhang,Dong-Ying Jie,Lin-Zi Li,Jie Su,Xiang Zheng,Rong Luo,Gui-Yuan Lv,Ning-Hua Jiang,Qiao-Xian Yu,Su-Hong Chen
Given the increasing global trend toward unhealthy lifestyles and dietary decisions, such as “over-consumption of alcohol, and high sugar and fat diets” (ACHSFDs), it is not surprising that metabolic hypertension (MH) is now the most common type of hypertension. There is an urgent, global need for effective measures for the prevention and treatment of MH. Improper diet leads to decreased short-chain fatty acid (SCFA) production in the gut, leading to decreased gastrointestinal function, metabolism, and blood pressure as a result of signaling through G-protein-coupled receptors (GPCRs), ultimately causing MH. Previous studies have suggested that Dendrobium officinale (DO) may improve gastrointestinal function, lower blood pressure, and regulate metabolic abnormalities, but it is not clear whether it acts on MH by increasing SCFA and, if so, how. In this research, it was observed that Dendrobium officinale ultrafine powder (DOFP) could lower blood pressure and improve lipid abnormalities in ACHSFD-induced MH model rats. Moreover, DOFP was found to improve the intestinal flora and increased the SCFA level in feces and serum, as well as increased the expressions of GPCR43/41 and eNOS and the nitric oxide (NO) level. An experiment on isolated aorta rings revealed that DOFP improved the vascular endothelial relaxation function in MH rats, and this effect could be blocked by the eNOS inhibitor L-NAME. These experimental results suggest that DOFP improved the intestinal flora and increased the production, transportation, and utilization of SCFA, activated the intestinal-vascular axis SCFA-GPCR43/41 pathway, improved vascular endothelial function, and finally lowered blood pressure in MH model rats. This research provides a new focus for the mechanism of the effect of DOFP against MH by triggering the enteric-origin SCFA-GPCR43/41 pathway.
研究领域:
药理学
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营养学
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心血管科学
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胃肠病学
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产品关联
DOI
PubMed
高影响因子
Food Bioscience
·
2024
·
IF 4.8
Siyi Song,Shuqi He,Qianxia Lin,Huoxi Jin
Hypertension significantly contributes to adverse cardiovascular outcomes. Our investigation was designed to evaluate the effects of supplementation with collagen peptide (LR-7) and taurine (Tau) on cardiovascular impairment in hypertensive mice induced by an 8% high-salt (HS) diet. Compared to administration of LR-7 (200 μmol/kg) or Tau (200 μmol/kg) alone, the combined treatment of LR-7 (100 μmol/kg) and Tau (100 μmol/kg) exhibited the strongest inhibition of systolic blood pressure elevation, aortic intimal thickening, reduction in myocardial fiber density, and myocardial fibrosis in HS-induced hypertensive mice. Furthermore, the treatment with LR-7+Tau significantly ameliorated the levels of cardiac adhesion factor (intercellular adhesion molecule 1), antioxidant enzymes (catalase and glutathione peroxidase), and inflammatory markers (interleukin-6, interleukin-1β, and nuclear factor kappa-B) in hypertensive mice compared to either LR-7 or Tau alone. To uncover the underlying mechanisms, the calpain 1/junctophilin-2 (JP2) pathway in cardiac tissue was investigated. Our findings revealed that LR-7+Tau treatment reversed the abnormal expression of calpain 1 and JP2 proteins in cardiac tissue. Additionally, it upregulated the endothelial nitric oxide synthase (eNOS) and phosphorylated eNOS (p-eNOS) levels in the heart. In summary, LR-7 and Tau collectively exerted a cardiovascular protective effect in HS diet-induced hypertensive mice, demonstrating synergistic efficacy.
研究领域:
心脏病学
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药理学
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分子生物学
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产品关联
DOI
高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2021
·Vol. 25
·期 7
·3601-3609
·
IF 5.31
Meng Jiang,Shanya Huang,Wang Duan,Qiaoshu Liu,Minxiang Lei
Diabetic vascular complications are the leading causes of death and disability in patients with diabetes. Alpha-mangostin has been reported to have anti-diabetic capacity in recent years. Here, we investigated the protective function of alpha-mangostin on endothelium in vitro and in vivo experiments. We also observed that alpha-mangostin improved impaired endothelium-dependent vasodilation (EDV) of diabetic animals while it limited the aSMase/ceramide pathway and up-regulated eNOS/NO pathway in aortas from diabetic mice. Meanwhile, alpha-mangostin inhibited elevated aSMase/ceramide pathway and reversed impaired EDV induced by high glucose in isolated mouse aortas. In addition, alpha-mangostin increased phosphorylation of eNOS and NO production in high glucose-treated aortas. Alpha-mangostin normalized high glucose-induced activation of aSMase/ceramide pathway and improved eNOS/NO pathway in endothelial cells with high glucose. In conclusion, alpha-mangostin regulates eNOS/NO pathway and improves EDV in aortas of diabetic mice through inhibiting aSMase activity and endogenous ceramide accumulation.
研究领域:
药理学
·
内分泌学
·
心血管科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Bioscience
·
2025
·
IF 5.9
Jialing Cao,Rong Tsao,Cheng Yang,Yun Wang,Lianfu Zhang
Red ginseng has been used to ameliorate erectile dysfunction (ED), a common age-related male reproductive disorder, though the active constituents responsible for this effect remain unclear. Arginyl-fructosyl-glucose (AFG) and arginyl-fructose (FA), are two arginine-derived Amadori compounds formed via Maillard reaction during red ginseng processing. An optimized vacuum dehydration method yielded 64.58% and 87.95%, respectively for AFG and FA, a significant increase compared to previous reported best results. In D-galactose-induced aging ED rats, the prepared AFG and FA significantly improved erectile function by reducing fibrosis and alleviating oxidative stress in the penile corpus cavernosum (PCC), alongside up-regulation of the eNOS/NO/cGMP signaling pathway within PCC. AFG and FA co-administration with 20(S)-ginsenoside Rg3 further enhanced the efficacy. These findings identify AFG and FA as key bioactives mediating the ED-improving effects of red ginseng and provide novel insights for red ginseng-based functional food development.
研究领域:
生药学
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天然产物化学
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衰老研究
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泌尿学
·
功能食品
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Mengjuan Sun,Chang Liu,Ji Liu,Jing Wen,Tianjiao Hao,Daquan Chen,Yan Shen
Thrombus-induced cardiovascular diseases threaten human health. Current treatment strategies often rely on urokinase plasminogen activator (uPA) for its efficacy, yet it has such limiting factors as short half-life, lack of thrombus targeting, and systemic side effects leading to unintended bleeding. In addition, thrombolytic interventions can trigger inflammation-induced damage at thrombus sites, which affects endothelial function. To address these challenges, Fer-1/uPA@pep-CREKA-Lipo (Fu@pep-CLipo) has been developed. This system achieves precise and efficient thrombolysis while enhancing the thrombus microenvironment and mitigating ischemia-reperfusion injury, with exceptional thrombus targeting ability via the strong affinity of the Cys-Arg-Glu-Lys-Ala (CREKA) peptide for fibrin. The Cys-Nle-TPRSFL-DSPE (pep) could respond to the thrombus microenvironment and fixed-point cleavage. The uPA component linked to the liposome surface is strategically cleaved upon exposure to abundant thrombin at thrombus sites. Importantly, the inclusion of Fer-1 within Fu@pep-CLipo contributes to reactive oxygen species (ROS) scavenging and significantly improves the thrombus microenvironment. This innovative approach not only achieves highly efficient and precise thrombolysis but also positively influences the expression of eNOS protein while suppressing inflammatory factors like TNF-α and IL-6. This dual action contributes to improved thrombus inflammatory microenvironment and mitigated ischemia-reperfusion injury.
研究领域:
心血管疾病
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药学
·
纳米技术
·
治疗学
✓ 已验证
产品关联
DOI
PubMed
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
·
心血管疾病
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2026
·
IF 5.6
Yu Dun,Jinxi Xie,Jian Zhou,Hanbing Hu,Fuli Liu,Yiru Shao,Jie Shen
CD34/CD45-DSCs alleviate phosgene-induced acute lung injury (P-ALI) in rats. • CD34 + CD45 + cells reside in bone marrow, peripheral blood, and BALF with dynamic changes post-injury. • CD34/CD45-DSCs exhibit MSC-like properties with osteogenic, adipogenic, and chondrogenic potential in vitro. • CD34/CD45-DSCs showed prolonged lung retention perivascular engraftment, and PVSC-like phenotype acquisition without exacerbating fibrosis. • CD34/CD45-DSCs restore pulmonary vascular barrier via VEGF-PI3K/AKT/eNOS signaling pathway. Phosgene inhalation causes acute lung injury (ALI) with high mortality and no effective antidote, and stem cell therapy is limited by poor cell survival and low engraftment efficiency. Here, we identified a rare endogenous CD34 + CD45 + cell fraction that reside in bone marrow, peripheral blood, and bronchoalveolar lavage fluid (∼1% baseline), exhibits a “decrease-then-recovery” dynamic after phosgene injury, and displays MSC-like properties with trilineage (osteogenic, adipogenic, and chondrogenic) potential in vitro. Intravenous administration of expanded CD34 + CD45 + -derived stromal cells (CD34/CD45-DSCs) significantly alleviated pulmonary vascular leakage and inflammatory in a rat model of phosgene-induced ALI (P-ALI). In vivo bioluminescence imaging further revealed that CD34/CD45-DSCs exhibited prolonged pulmonary retention compared with BMSCs (11.3 days vs. 48 h), proliferated, engrafted around the pulmonary vasculature, and acquired a perivascular stromal cell (PVSC)-like phenotype expressing late-stage mesenchymal progenitor, pericyte, and fibroblast markers. In a bleomycin-induced pulmonary fibrosis model, CD34/CD45-DSCs did not exacerbate fibrotic changes at day 28. Mechanistically, VEGF knockdown or neutralization abolished the barrier-protective effect, which was rescued by an AKT agonist and blocked by an inhibitor. Moreover, CD34/CD45-DSCs upregulated tight junction proteins ZO-1 and Occludin in injured endothelial cells via VEGF-PI3K/AKT/eNOS signaling. Collectively, our study defines the origin, spatiotemporal dynamics, perivasucular engraftment, PVSC-like fate acquisition, and VEGF-PI3K/AKT/eNOS-dependent mechanism of CD34/CD45-DSCs, supporting their potential as a relatively safe, long-engrafting, and mechanistically transparent cell-based strategy for ALI.
✓ 已验证
DOI
PubMed
高影响因子
PROCESS BIOCHEMISTRY
·
2020
·
IF 2.952
Kai Lin,Zhao Ma,Mythili Ramachandran,Cristabelle De Souza,Xue Han,Lan-wei Zhang
The purpose of this study was to explore the effects of KYIPIQ, an angiotensin I-converting enzyme (ACE) inhibitory peptide found in yak milk casein, on the production of nitric oxide (NO) in human vascular endothelial cells (HUVECs). Additionally, we also sought to study the transport pathway of this peptide across monolayers of the human epithelial colorectal adenocarcinoma cell line (Caco-2). Treatment with peptide KYIPIQ increased NO synthesis and expression of phosphorylated endothelial nitric oxide synthase (eNOS) in HUVECs. Our results demonstrate that KYIPIQ-induced eNOS phosphorylation is dependent on the protein kinase B (Akt) activation pathway. Furthermore, our data indicate that the peptide KYIPIQ can be transported across the Caco-2 cell monolayer and that paracellular transport is the main transcellular mechanism. Thus, our studies suggest that KYIPIQ can be potentially used as a therapeutic agent for the treatment of hypertension.
研究领域:
药理学
·
细胞生物学
·
分子生物学
·
心血管科学
✓ 已验证
产品关联
DOI
高影响因子
TROPICAL JOURNAL OF PHARMACEUTICAL RESEARCH
·
2023
·Vol. 22
·期 1
·15-22
·
IF 0.6
Jingwen Gong,Yu Xie,Yinfen Tan,Hailong Li,Junqing Zhang
Purpose: To investigate the mechanism of action of galangin (GAL) against indomethacin (Indo)-induced gastric injury.
Methods: Ten micromolar GAL with 2 mM Indo or 0.5 mM L-NAME or 2 mM propargylglycine were co-administered to human gastric mucosal epithelial cells GES-1 for 24 h. Cell viability assay and reactive oxygen species (ROS) test were conducted with commercial kits. Protein expressions of constitutive and inducible nitric oxide synthase (cNOS and iNOS, respectively), and cystathionine-γ-lyase (CSE) in GSE-1 cells were investigated by western blot. After 100 - 300 mg/kg, GAL was daily administered to rats for 5 days, and 30 mg/kg Indo was administered to induce gastric injury. Protein expressions of endothelial NOS (eNOS), iNOS, CSE, nuclear factor (NF)-κB, PKC, Akt, phospho-eNOS (Ser-1177), and phospho-eNOS (Thr-495) were investigated by western blot.
Results: Galangin ameliorated the proliferative inhibitions of Indo, propargylglycine, and L-NAME on GSE-1 cells (p < 0.05), rapidly scavenged ROS, and increased cNOS protein expressions (p < 0.05). Galangin (300 mg/kg) inhibited protein expressions of iNOS (p < 0.01), NF-κB, Akt, and PKC (p < 0.05), inhibited the Ser-1177 and Thr 495 phosphorylation of eNOS, elevated eNOS and CSE protein expressions (p < 0.001).
Conclusion: Galangin protects gastric mucosa from Indo by scavenging ROS and inhibiting protein expressions of Akt and PKC. The inhibition leads to Ser-1177 and Thr 495 dephosphorylation of eNOS, thereby prolonging eNOS activity. Besides, GAL inhibits iNOS-produced NO by inhibiting NF-κB to ameliorate the inflammatory reaction induced by Indo.
研究领域:
药理学
·
胃肠病学
·
细胞生物学
·
分子生物学
✓ 已验证
DOI
高影响因子
EUROPEAN JOURNAL OF CELL BIOLOGY
·
2021
·
IF 4.492
Jian Zhao,Zhaoyu Liu,Zhihui Chang
Endothelial cell pyroptosis is a novel cause of endothelial dysfunction in sepsis. Reticulocalbin-2 (RCN2) is involved in regulating vascular inflammation and plays an important role in the cardiovascular system. However, the role of RCN2 in inflammation-induced endothelial cell pyroptosis remains to be explored. Here, we found that RCN2 was upregulated after lipopolysaccharide (LPS) treatment in a concentration‐ and time-dependent manner. RCN2 knockdown resulted in a significant decrease in pyroptosis, reduced LDH and IL-1β release and ROS production and inhibited the expression of pyroptosis‐related proteins (NLRP3, cleaved caspase-1, and cleaved GSDMD) (all p < 0.05). N‐acetyl‐L‐cysteine (NAC) counteracted the effects of RCN2 on pyroptosis (all p < 0.01). The silencing of RCN2 antagonized the inhibitory effect of LPS on the phosphorylation of eNOS (p < 0.05). We predicted and confirmed that specificity protein-1(SP1) could directly bind to the RCN2 promoter and regulate RCN2. RCN2 overexpression rescued the inhibitory effect of SP1 inhibitor on HUVEC pyroptosis induced by LPS (all p < 0.05). These findings suggested that the activation of the SP1/RCN2/ROS signaling pathway could promote LPS-induced endothelial cell pyroptosis.
研究领域:
免疫学
·
心血管生物学
·
细胞信号传导
·
炎症
✓ 已验证
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Jie Sheng,Ziyue Zu,Jianchen Qi,Yugang Zhang,Haoguang Wu,Zhicheng Wang,Yu Miao,Tao Zheng,Sheng Wang,Linlin Zhang,Guangming Lu,Longjiang Zhang
Atherosclerosis (AS), characterized by endothelial injury, progressive inflammation, and lipid deposition, can cause adverse cardiovascular events. However, effectively addressing all these pathological conditions simultaneously is challenging. To devise a comprehensive treatment strategy for AS, we developed a nanoparticle-based mild photothermal therapy (PTT) approach, which controlled the temperature within the range of 42–45 ℃, creating a unique 'hot spring' effect. The nanoparticles used in this therapy consist of a core made of zeolitic imidazolate framework-8 (ZIF-8) nanoparticles loaded with indocyanine green (IR820), and an outer shell made of L-arginine (LA)-modified polydopamine (PDA), which is further modified with hyaluronic acid (HA) to target plaques. In vitro studies have demonstrated that mild PTT can open the TRPV1 channel in foam cells and regulate lipid metabolic diseases by maintaining a controlled temperature range of 42–45 ℃. Furthermore, the LA-PDA shell has anti-inflammatory properties, decreasing NLRP3 expression. Moreover, the eNOS/NO pathway was activated by LA, promoting the healing of injured endothelial cells (ECs). Additionally, the increased temperature enhances HSP90 expression, thereby helping to maintain eNOS. In vivo studies further confirmed that the HLPIZ-guided ‘hot spring’ effect has impressive anti-atherosclerotic capability by scavenging lipids, reducing inflammation, and repairing injured ECs simultaneously. In conclusion, our study confirmed that HLPIZ-guided mild PTT can exhibit a ‘hot spring’ effect, effectively regulating three key pathophysiological processes of AS, being a novel, potentially effective strategy for anti-AS therapy.
研究领域:
心血管疾病
·
纳米技术
·
治疗策略
·
炎症
·
脂质代谢
✓ 已验证
产品关联
DOI
高影响因子
Bioactive Materials
·
2022
·
IF 16.874
Changhao Li,Cairong Xiao,Lizhen Zhan,Zhekun Zhang,Jun Xing,Jinxia Zhai,Zhengnan Zhou,Guoxin Tan,Jinhua Piao,Yahong Zhou,Suijian Qi,Zhengao Wang,Peng Yu,Chengyun Ning
Pathological angiogenesis frequently occurs in tumor tissue, limiting the efficiency of chemotherapeutic drug delivery and accelerating tumor progression. However, traditional vascular normalization strategies are not fully effective and limited by the development of resistance. Herein, inspired by the intervention of endogenous bioelectricity in vessel formation, we propose a wireless electrical stimulation therapeutic strategy, capable of breaking bioelectric homeostasis within cells, to achieve tumor vascular normalization. Polarized barium titanate nanoparticles with high mechano-electrical conversion performance were developed, which could generate pulsed open-circuit voltage under low-intensity pulsed ultrasound. We demonstrated that wireless electrical stimulation significantly inhibited endothelial cell migration and differentiation in vitro . Interestingly, we found that the angiogenesis-related eNOS/NO pathway was inhibited, which could be attributed to the destruction of the intracellular calcium ion gradient by wireless electrical stimulation. In vivo tumor-bearing mouse model indicated that wireless electrical stimulation normalized tumor vasculature by optimizing vascular structure, enhancing blood perfusion, reducing vascular leakage, and restoring local oxygenation. Ultimately, the anti-tumor efficacy of combination treatment was 1.8 times that of the single chemotherapeutic drug doxorubicin group. This work provides a wireless electrical stimulation strategy based on the mechano-electrical conversion performance of piezoelectric nanoparticles, which is expected to achieve safe and effective clinical adjuvant treatment of malignant tumors.
研究领域:
生物医学工程
·
肿瘤学
·
纳米技术
·
超声治疗
·
血管生物学
✓ 已验证
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）