JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
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2019
·Vol. 23
·期 3
·2174-2183
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IF 4.658
Haiman Mu,Haiwen Liu,Jiayi Zhang,Jianhua Huang,Chen Zhu,Yue Lu,Yueping Shi,Yi Wang
In addition to the known antitumour effects of ursolic acid (UA), increasing evidence indicates that this molecule plays a role in cardiac protection. In this study, the effects of ursolic acid on the heart in mice treated with doxorubicin (DOX) were assessed. The results showed that ursolic acid improved left ventrical fractional shortening (LVFS) and left ventrical ejection fraction (LVEF) of the heart, increased nitrogen oxide (NO) levels, inhibited reactive oxygen species (ROS) production and decreased cardiac apoptosis in mice treated with doxorubicin. Mechanistically, ursolic acid increased AKT and endothelial nitric-oxide synthase (eNOS) phosphorylation levels, and enhanced eNOS expression, while inhibiting doxorubicin induced eNOS uncoupling through NADPH oxidase 4 (NOX4) down-regulation. These effects of ursolic acid resulted in heart protection from doxorubicin-induced injury. Therefore, ursolic acid may be considered a potential therapeutic agent for doxorubicin-associated cardiac toxicity in clinical practice.
研究领域:
药理学
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心脏病学
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分子生物学
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DOI
PubMed
高影响因子
Molecular Medicine Reports
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2017
·Vol. 16
·期 6
·9361-9366
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IF 1.692
Weixin Zhu,Weihong Qiu,Ailan Lu
Cerebral stroke is a kind of acute cerebrovascular disease with high incidence, morbidity and disability. Treatments against various types of cerebral stroke are limited at preventive measurements due to the lack of effective therapeutic method. The present study aimed to investigate the protective effect of cryptotanshinone (CPT) on cerebral stroke, and investigate the possible mechanism involved in order to develop a novel therapy against stoke. The phosphoinositide 3‑kinase membrane translocation of cerebral stroke rats pretreated with CPT at various concentrations were measured, as well as the phosphorylation of protein kinase B (AKT) and endothelial nitric oxide synthase (eNOS). Additionally, the expression level of B‑cell lymphoma 2 (Bcl‑2), Bcl‑2‑associated X protein (Bax) and vascular endothelial growth factor were also assessed using western blotting and reverse transcription‑quantitative polymerase chain reaction. Furthermore, biochemical tests were used to measure the activity of superoxide dismutase (SOD), malondialdehyde (MDA) and nitric oxide (NO) in both the cerebral cortex and peripheral blood. As a result, CPT‑pretreated rats presented declined phosphoinositide 3‑kinase (PI3K) and AKT expression levels, indicating that the PI3K/AKT signaling pathway was inhibited. Increased Bcl‑2 and NO levels in both the cerebral cortex and peripheral blood demonstrated the anti‑apoptosis and blood vessel protection effect of CPT. Furthermore, increased SOD activity and declined MDA levels demonstrated suppressed lipid peroxidation. In conclusion, CPT exhibited a protective effect against cerebral stroke through inhibition of the PI3K/AKT‑eNOS signaling pathway. These results suggested the potential of CPT as a promising agent in the treatment of cerebral stroke.
研究领域:
神经科学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2023
·
IF 5.6
Tingxiang Chen,Hongyu Chen,Yuedong Fu,Xuao Liu,Haosheng Huang,Zhijie Li,Shi Li
In reconstructive and plastic surgery, random skin flaps are commonly utilized to treat skin abnormalities produced by a variety of factors. Flap delay procedure is commonly used to reduce flap necrosis. Due to the limitations of various conditions, the traditional surgical improvement can’t effectively alleviate the skin flap necrosis. And leonurine (Leo) has antioxidant and anti-inflammatory effects. In this study, we researched the mechanism underlying the influences of varied Leo concentrations on the survival rate of random skin flaps. Our results showed that after Leo treatment, tissue edema and necrosis of the flap were significantly reduced, while angiogenesis and flap perfusion were significantly increased. Through immunohistochemistry and Western blot, we proved that Leo treatment can upregulate the level of angiogenesis, while Leo treatment significantly reduced the expression levels of oxidative stress, apoptosis and inflammation. As a result, it can significantly improve the overall viability of the random skin flaps through the increase of angiogenesis, restriction of inflammation, attenuation of oxidative stress, and reduction of apoptosis. And this protective function was inhibited by LY294002 (a broad-spectrum inhibitor of PI3K) and L-NAME (NG- nitro-L-arginine methyl ester, a non-selective NOS inhibitor). All in all, Leo is an effective drug that can activate the eNOS via the PI3K/Akt pathway. By encouraging angiogenesis, preventing inflammation, minimizing oxidative stress, and lowering apoptosis, Leo can raise the survival rate of random skin flaps. The recommended concentration of Leo in this study was 30 mg/kg.
研究领域:
整形与重建外科
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药理学
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分子生物学
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DOI
PubMed
高影响因子
Bio-Design and Manufacturing
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2020
·Vol. 4
·期 1
·72-86
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IF 4.095
Xing Zheng,Zhao Chen,Zhang Chunchen,Fan Yubo,Liu Haifeng
For the surgical treatment of cardiovascular disease (CVD), there is a clear and unmet need in developing small-diameter (diameter < 6 mm) vascular grafts. In our previous work, sulfated silk fibroin (SF) was successfully fabricated as a potential candidate for preparing vascular grafts due to the great cytocompatibility and hemocompatibility. However, vascular graft with single layer is difficult to adapt to the complex internal environment. In this work, polycaprolactone (PCL) and sulfated SF were used to fabricate bilayer vascular graft (BLVG) to mimic the structure of natural blood vessels. To enhance the biological activity of BLVG, nicorandil (NIC), an FDA-approved drug with multi-bioactivity, was loaded in the BLVG to fabricate NIC-loaded BLVG. The morphology, chemical composition and mechanical properties of NIC-loaded BLVG were assessed. The results showed that the bilayer structure of NIC-loaded BLVG endowed the graft with a biphasic drug release behavior. The in vitro studies indicated that NIC-loaded BLVG could significantly increase the proliferation, migration and antioxidation capability of endothelial cells (ECs). Moreover, we found that the potential biological mechanism was the activation of PI3K/AKT/eNOS signaling pathway. Overall, the results effectively demonstrated that NIC-loaded BLVG had a promising in vitro performance as a functional small-diameter vascular graft.
研究领域:
生物医学工程
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心血管疾病
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组织工程
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产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
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IF 8.5
Meng-xiao Wang,Ke-ke Luo,Meng-yao Tian,Wen-ya Gao,Shan Jiang,Yan Zhang,Jian Yang,Nan Si,Shi-lan Ding,Xiao-lu Wei,Yu-yang Liu,Bao-lin Bian,Yan-yan Zhou,Hong-jie Wang
The diagnosis and treatment of chronic glomerulonephritis (CGN) during childhood pose distinct challenges. Acteoside (ACT) is the primary active ingredient extracted from the leaves of Rehmannia glutinosa by our research group, accounting for 2.15 %, which possess multiple biological activities, especially for nephropathy treatment. However, its mechanism intervention on CGN in children remains obscure. In this study, we established a model of purinomycin aminonucleoside (PAN)-induced CGN in childhood rats to assess the potential therapeutic effect and underlying mechanisms of ACT. Leveraging network pharmacology and multi-omics technology, we delved into the effects and mechanisms of ACT intervention on CGN. And these findings were further corroborated through qRT-PCR, western blot and targeted metabolomics. Our results demonstrated that ACT had significantly efficient in the treatment of CGN in childhood rats by improving the key indicators and pathological changes. Further, ACT could significantly regulate differences in endogenous small molecules and genes based on non-target metabolomics and transcriptomics. Meanwhile, target capture analysis found the crucial targets of ACT treatment in CGN. Integrated analysis of multi-omics study indicated that PI3K/Akt signaling pathway and its downstream amino acid metabolism were significantly enriched, hinting at the essential regulatory pathway for ACT in treating of CGN. Finally, through qRT-PCR, western blot and targeted metabolomics, it was verified that ACT could ameliorate CGN through Cxcr4-PI3K-Akt-eNOS signaling pathway, thereby regulating amino acid metabolism. The collective results were consistent with those of multi-omics analysis. Our study illuminated that ACT had notable curative effect on CGN rats, and preliminarily elucidated its mechanism of action. Our research will provide solid basis for the treatment of chronic glomerulonephritis in children with ACT and developing it into innovative traditional Chinese medicine.
研究领域:
药理学
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分子生物学
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肾脏病学
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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
Ming Luo,Yawei Du,Xuanchen Liu,Shuwen Zhang,Wenwen Zhu,Kaipeng Liu,Xiubao Ren,Ningning Zhang
Background Portal hypertension (PHT) is a severe complication of liver cirrhosis, with limited therapeutic options. Despite emerging evidence linking gut microbiota dysbiosis to PHT progression, the mechanisms by which microbial metabolites modulate liver sinusoidal endothelial cells (LSECs) dysfunction and the therapeutic efficacy of fecal microbiota transplantation (FMT) remain poorly understood. This study investigated the potential of FMT to alleviate PHT in cirrhotic rats, exploring the underlying mechanisms involving butyrate-mediated HDAC3 inhibition and PI3K/Akt/eNOS signaling regulation in LSECs. Methods Cirrhosis with PHT was induced in Sprague-Dawley rats via intraperitoneal carbon tetrachloride injection, followed by FMT or butyrate supplementation via oral gavage. Analyses included portal hemodynamic measurements, gut microbiota sequencing, serum SCFA metabolomics profiling, HDAC3 activity assays, NO level quantification, and assessments of liver fibrosis, liver function, and LSEC ultrastructure. LSECs were isolated for PI3K/Akt/eNOS signaling analysis via qRT-PCR, Western blotting, and immunofluorescence staining. Results A two-week FMT intervention in cirrhotic rats with PHT enriched butyrate-producing bacteria and increased serum butyrate levels, which were associated with reduced portal pressure and intrahepatic vascular resistance, without affecting liver fibrosis, function, or LSEC ultrastructure. FMT reduced HDAC3 activity by 2.17-fold and increased Akt and eNOS phosphorylation in primary LSECs by 1.69-fold and 1.25-fold, respectively, elevating plasma NO levels by 1.66-fold compared to untreated controls. In vitro experiments with primary LSECs confirmed these butyrate-mediated effects. Conclusion FMT alleviates cirrhotic PHT through butyrate-mediated HDAC3 inhibition and subsequent PI3K/Akt/eNOS signaling activation in LSECs, highlighting the therapeutic potential of targeting the gut-liver axis via microbial metabolites for PHT management.
研究领域:
医学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Journal of Diabetes
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2023
·
IF 4.5
Guangwei Yang,Zitian Liu,Shuohui Dong,Xiang Zhao,Zheng Ge,Zhiqiang Cheng,Xiang Zhang,Kexin Wang
Background Diabetic cardiomyopathy is a serious complication of obesity with type 2 diabetes and is a major cause of mortality. Metabolic surgery, such as duodenal-jejunal bypass (DJB), can effectively improve diabetic cardiomyopathy; however, the underlying mechanisms remain elusive. Oxidative stress is one of the pivotal mechanisms of diabetic cardiomyopathy. Our objective was to investigate the effect and potential mechanisms of DJB on oxidative stress in the heart of diabetic cardiomyopathy rats. Methods High-fat diet combined with intraperitoneal injection of streptozotocin was used to establish diabetic cardiomyopathy rats. DJB was performed on diabetic cardiomyopathy rats, and high glucose and palmitate were used to simulate diabetic cardiomyopathy in H9C2 cells in vitro. Sera from different groups of rats were used for experiments in vivo and in vitro. Results DJB effectively improved oxidative stress and activated the adenosine monophosphate (AMP)-activated protein kinase (AMPK) pathway to increase endothelial nitric oxide synthase (eNOS) phosphorylation level and the expression of antioxidative system-related proteins and genes in the heart of diabetic cardiomyopathy rats. AMPK agonists and serum from DJB rats activated the AMPK pathway to increase eNOS phosphorylation level and the expression of antioxidative system-related proteins and genes and decreased the content of reactive oxygen species in H9C2 cells, but this improvement was almost eliminated by the addition of AMPK inhibitors. Conclusions DJB activates eNOS and enhances the antioxidant system by activating the AMPK pathway—and not solely by improving blood glucose—to improve oxidative stress in the heart of diabetic cardiomyopathy rats.
研究领域:
外科手术
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糖尿病
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心脏病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Food & Function
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2016
·Vol. 7
·期 5
·2398-2408
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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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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2020
·
IF 4.225
Zhao Yixiu,Zhu Jiuxin,Liang Hangfei,Yang Shuang,Zhang Yannan,Han Weina,Chen Chao,Cao Na,Aruhan,Liang Peiqiang,Du Xing,Huang Jian,Wang Jinhui,Zhang Yan,Yang Baofeng
Hypertension is a major risk factor for stroke and cardiovascular events in clinic, which is accompanied by the abnormality of vascular tone and endothelial dysfunction of small artery. Here we report that Kang Le Xin (KLX), a novel anthraquinones compound, could reduce blood pressure and the underlying mechanisms involves that KLX induces endothelium-dependent vasodilation. KLX significantly decreases the arterial blood pressure of spontaneous hypertensive rats (SHR), decreases the contractile reactivity of superior mesenteric artery to phenylephrine and increases the vasodilatory reactivity of superior mesenteric artery to carbachol in a dose-dependent manner. Besides, KLX reduces vascular tension of endothelium-intact mesenteric artery pre-constricted with phenylephrine in a dose-dependent manner, while this effect is inhibited by depriving vascular endothelium or pretreating vascular rings with L-NAME (endothelial nitric oxide synthase inhibitor) or compound C (AMP-activated protein kinase inhibitor). Moreover, KLX increases nitric oxide (NO) generation, endothelial nitric oxide synthase (eNOS), AKT and AMP-activated protein kinase (AMPK) phosphorylation in cultured human umbilical vein endothelial cells (HUVECs), while these effects are inhibited by pretreating cells with compound C. In conclusion, KLX is a new compound with the pharmacological action of reducing arterial blood pressure. The underlying mechanism involves KLX induces endothelium-dependent vasodilation through activating AMPK-AKT-eNOS signaling pathway.
研究领域:
药理学
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心血管科学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Food Bioscience
·
2024
·
IF 4.8
Zishan Dou,Yang Xu,Jingli Liu,Wei Chen
LVLPGE is an angiotensin-converting enzyme (ACE) inhibitory peptide extracted from broccoli protein hydrolysates. The antihypertensive mechanism of LVLPGE was explored in the present study. The results indicated that the IC 50 value of LVLPGE was 19.49 μM, and its binding to ACE occurred via a static fluorescence quenching involving the secondary structure changes of ACE. In addition, LVLPGE competitively bound to the active site of ACE through hydrogen bonding. Furthermore, LVLPGE markedly enhanced the levels of the vasodilator nitric oxide (NO) in the Ang I-induced HUVECs model, suppressed the expression of vasoconstrictor endothelin-1 (ET-1), and increased the phosphorylation of eNOS. Moreover, LVLPGE was found to enhance the production of cyclic guanosine monophosphate (cGMP), which leading to a subsequent decrease in intracellular calcium concentration, ultimately facilitating the relaxation of vascular smooth muscles and lowering the blood pressure. These results demonstrated that LVLPGE achieves the antihypertensive effects by inhibiting ACE activity and activating the eNOS/NO/cGMP signaling pathway. This study provides new insights into the antihypertensive mechanism of LVLPGE and contributes to the high-value utilization of broccoli resources.
研究领域:
药理学
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心血管科学
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功能性食品
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生物化学
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DOI
高影响因子
APOPTOSIS
·
2017
·Vol. 22
·期 5
·672-680
·
IF 3.833
Liu Shumin,Sun Zhengwu,Chu Peng,Li Hailong,Ahsan Anil,Zhou Ziru,Zhang Zonghui,Sun Bin,Wu Jingjun,Xi Yalin,Han Guozhu,Lin Yuan,Peng Jinyong,Tang Zeyao
Homocysteine (Hcy) induced vascular endothelial injury leads to the progression of endothelial dysfunction in atherosclerosis. Epigallocatechin gallate (EGCG), a natural dietary antioxidant, has been applied to protect against atherosclerosis. However, the underlying protective mechanism of EGCG has not been clarified. The present study investigated the mechanism of EGCG protected against Hcy-induced human umbilical vein endothelial cells (HUVECs) apoptosis. Methyl thiazolyl tetrazolium assay (MTT), transmission electron microscope, fluorescent staining, flow cytometry, western blot were used in this study. The study has demonstrated that EGCG suppressed Hcy-induced endothelial cell morphological changes and reactive oxygen species (ROS) generation. Moreover, EGCG dose-dependently prevented Hcy-induced HUVECs cytotoxicity and apoptotic biochemical changes such as reducing mitochondrial membrane potential (MMP), decreasing Bcl-2/Bax protein ratio and activating caspase-9 and 3. In addition, EGCG enhanced the protein ratio of p-Akt/Akt, endothelial nitric oxide synthase (eNOS) activation and nitric oxide (NO) formation in injured cells. In conclusion, the present study shows that EGCG prevents Hcy-induced HUVECs apoptosis via modulating mitochondrial apoptotic and PI3K/Akt/eNOS signaling pathways. Furthermore, the results indicate that EGCG is likely to represent a potential therapeutic strategy for atherosclerosis associated with Hyperhomocysteinemia (HHcy).
研究领域:
心血管疾病
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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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产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2021
·
IF 6.291
Jinsong Zhang,Jie Cui,Xinying Li,Xiaohui Hao,Lingli Guo,Hongli Wang,Heliang Liu
Silicosis, a type of lung inflammation and fibrosis caused by long-term inhalation of SiO 2 particles, lacks effective treatment currently. Based on the results of our previous animal experiments, in lungs of SiO 2 -induced silicosis rats, a large number of lymphatic vessels are generated in the early stage of inflammation, which is of great significance for the removal of dust and inflammatory mediators. Here, the molecular mechanism of lymphangiogenesis is further studied. Vascular endothelial growth factor (VEGF-C) is a key pro-lymphangiogenic factor, and its elevated expression is closely related to lymphangiogenesis. In this investigation, we demonstrated that the protein level of VEGF-C was differentially expressed in bronchoalveolar lavage fluid (BALF) and alveolar macrophages (AM) in silicosis patients and healthy controls. We further stimulated human monocyte-macrophage line U937 with SiO 2 , collected the culture supernatants as conditioned medium (CM) for culturing lymphatic endothelial cells (LECs) in vitro, and observed the expression of VEGF-C in the supernatant and its effect on LEC tube formation. The results showed that both CM and single VEGF-C recombinant protein stimulation significantly enhanced LEC proliferation [(1.80 ± 0.18), (1.73 ± 0.16)], chemotaxis [chemotactic cell number (101.40 ± 13.83), (93.40 ± 9.61)], and tube formation [tube number (32.20 ± 7.26), (25.00 ± 6.25); branch number (77.20 ± 6.80), (84.60 ± 7.90)], whereas CM treated with VEGF-CmAb inhibited the proliferation (1.37 ± 0.17), chemotaxis [chemotactic cell number (57.40 ± 8.62)], and tube formation [tube number (7.40 ± 1.85); branch number (47.20 ± 13.44)] of LECs. In addition, CM and VEGF-C can promote the expression of vascular endothelial growth factor receptor 3 (VEGFR-3) and lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) in LECs, which may further mediate lymphangiogenesis by up-regulating the Src/eNOS downstream signaling molecular pathway. This study is the first to clarify the molecular mechanism of pulmonary lymphangiogenesis in silicosis and may point in the direction of eventual treatments, surveillance, and regulation at a molecular level.
研究领域:
呼吸科
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分子生物学
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免疫学
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DOI
PubMed
高影响因子
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