Nutrients
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2023
·Vol. 15
·期 6
·1340
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IF 5.9
Yu Li,Bo He,Chao Zhang,Yanji He,Tianyang Xia,Chunyu Zeng
Cardiac hypertrophy is accompanied by increased myocardial oxidative stress, and whether naringenin, a natural antioxidant, is effective in the therapy of cardiac hypertrophy remains unknown. In the present study, different dosage regimens (25, 50, and 100 mg/kg/d for three weeks) of naringenin (NAR) were orally gavaged in an isoprenaline (ISO) (7.5mg/kg)-induced cardiac hypertrophic C57BL/6J mouse model. The administration of ISO led to significant cardiac hypertrophy, which was alleviated by pretreatment with naringenin in both in vivo and in vitro experiments. Naringenin inhibited ISO-induced oxidative stress, as demonstrated by the increased SOD activity, decreased MDA level and NOX2 expression, and inhibited MAPK signaling. Meanwhile, after the pretreatment with compound C (a selective AMPK inhibitor), the anti-hypertrophic and anti-oxidative stress effects of naringenin were blocked, suggesting the protective effect of naringenin on cardiac hypertrophy. Our present study indicated that naringenin attenuated ISO-induced cardiac hypertrophy by regulating the AMPK/NOX2/MAPK signaling pathway.Keywords:naringenin;cardiac hypertrophy;oxidative stress;AMPK;NOX2
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
Heliyon
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2024
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IF 3.4
Ruisha Li,Keyin Zhang,Zhenjun Xu,Yanrong Yu,Dongjin Wang,Kai Li,Wenxue Liu,Jun Pan
Recent studies have underscored the cardioprotective properties of liraglutide. This research explores its impact on cardiac hypertrophy and heart failure following transverse aortic constriction (TAC). We found that liraglutide administration markedly ameliorated cardiac hypertrophy, fibrosis, and function. These benefits correlated with increased ANP expression and reduced activity in the calcineurin A/NFATc3 signaling pathway. Moreover, liraglutide mitigated ER stress and cardiomyocyte apoptosis, and enhanced autophagy. Notably, the positive effects of liraglutide diminished when co-administered with A71915, an ANP inhibitor, suggesting that ANP upregulation is critical to its cardioprotective mechanism.
研究领域:
心血管病学
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分子生物学
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DOI
PubMed
高影响因子
PHYTOTHERAPY RESEARCH
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2025
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IF 6.3
Shushu Jiang,Cheng Wang,Yin Dong,Long Chen,Menghao Shi,Fengxiao Zhang,Zhaohui Wang,Minglu Liang
Numerous studies have documented erucin's anticancer and vasodilatory properties, yet its impact on pathological cardiac hypertrophy remains to be fully understood. This study aimed to explore the therapeutic potential of erucin in cardiac hypertrophy induced by pressure overload. Cardiac hypertrophy was induced in mice by transverse aortic constriction (TAC) surgery, and in neonatal rat cardiomyocytes via phenylephrine (PE) treatment. Cardiac function and remodeling were evaluated using echocardiography, histological assessment, and molecular analyses. Mitochondrial function was assessed by measuring mitochondrial respiration, ATP concentration, the NAD+/NADH ratio, and reactive oxygen species (ROS) levels. Molecular docking was performed to identify erucin's downstream effector. Nrf2 and Sirt3 were silenced using siRNAs, and their activities were inhibited with ML385 and 3-TYP, respectively. Here, we found that erucin improved cardiac function and remodeling in TAC-induced hypertrophic mice, mitigated PE-induced cell hypertrophy, and restored mitochondrial function. Molecular docking analysis identified Nrf2 as a target protein of erucin. Erucin increased Nrf2 protein levels and activated the Nrf2 signaling pathway, which in turn promoted Sirt3 transcription. This effect was blocked by silencing Nrf2 or using ML385. Additionally, silencing Nrf2 and Sirt3 or using ML385 and 3-TYP abolished erucin's protective effects. This study is the first to demonstrate that erucin protects against cardiac hypertrophy by improving mitochondrial function through the activation of the Nrf2-Sirt3 pathway. Erucin may emerge as a promising therapeutic candidate for treating cardiac hypertrophy.
研究领域:
心血管生物学
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药理学
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DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2025
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IF 4.7
Longwei Yang,Wenhao Ge,Xi Lin,Ning Yu,Xiaodong Xu,Jianfa Zhang
Allergic asthma is an inflammatory airway disease in which mast cells play a key role in its pathogenesis. Riclinoctaose (Rios), an octasaccharide composed of glucose and galactose, has been reported to modulate macrophage polarization in renal ischemia-reperfusion injury. This study investigates the effects of nebulized Rios in an ovalbumin (OVA)-induced allergic asthma model. Nebulized Rios significantly reduced airway hyperresponsiveness (AHR), inflammatory cell infiltration, pulmonary fibrosis, and mucus production in OVA-treated mice. Additionally, Rios suppressed lung inflammatory cytokine production and protected against OVA-induced oxidative injury. In bronchoalveolar lavage fluid (BALF), Rios decreased the number of neutrophils and macrophages, as well as serum immunoglobulin E (IgE) and interleukin-4 (IL-4) levels. Metabolomics analysis using 1 H NMR showed significant changes in the lung metabolic profile of OVA-induced asthma mice, which were partially reversed by Rios treatment. Confocal laser microscopy (CLM) revealed that fluorescently labeled Rios specifically binds to mast cell membranes. In vitro, Rios reduced degranulation and inflammatory responses in mast cells RBL-2H3 following anti-Dinitrophenyl-Immunoglobulin E (anti-DNP-IgE) sensitization and anti-Dinitrophenyl-Bovine Serum Albumin (anti-DNP-BSA) stimulation. These results suggest that Rios has therapeutic potential for allergic asthma, likely through the modulation of mast cell degranulation and mediator release.
研究领域:
免疫学
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呼吸病学
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药理学
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DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2022
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IF 7.419
Cheng Wang,Yajing Hou,Shuai Ge,Jiayu Lu,Xiangjun Wang,Yuexin Lv,Nan Wang,Huaizhen He
Anaphylaxis is a severe systemic allergic reaction that exhibits multiple clinical symptoms. The Mas-related G protein-coupled receptor X2 (MRGPRX2) is recognized as a key cell receptor mediating allergic diseases and drug-induced anaphylactoid reactions. Thus, it has been a promising target for preventing and treating these reactions. Based on the potential activity of imperatorin and active structural feature of MRGPRX2, we first demonstrated that the synthetic imperatorin derivatives (IDs) could significantly inhibit MRGPRX2 agonist-induced degranulation and cytokine release in LAD2 cells, as well as alleviate local and systemic anaphylaxis in mice. The IC 50 value of the most promising compound is an order of magnitude lower than that of imperatorin. IDs were further identified to display anti-pseudo-allergic activity by binding MRGPRX2 with the tertiary nitrogen substructures, just liking the reported MRGPRX2-ligand. These results would propose evidence for discovery of agents for treating MCs-dependent allergic disorders.
研究领域:
免疫学
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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
PHYTOMEDICINE
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2020
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IF 4.268
Rui Guo,Ningning Liu,Hao Liu,Junhua Zhang,Han Zhang,Yingchao Wang,Mirko Baruscotti,Lu Zhao,Yi Wang
Background : Cardiac hypertrophy is a prominent feature of heart remodeling, which may eventually lead to heart failure. Tongmaiyangxin (TMYX) pills are a clinically used botanical drug for treating multiple cardiovascular diseases including chronic heart failure. The aim of the current study was to identify the bioactive compounds in Tongmaiyangxin pills that attenuate cardiomyocytes hypertrophy, and to investigate the underlying mechanism of action. Methods and Results : The anti-hypertrophy effect of TMYX was validated in isoproterenol-induced cardiac hypertrophy model in C57BL/6 mice. After TMYX treatment for 2 weeks, the heart ejection fraction and fractional shortening of the mice model was increased by approximately 20% and 15%, respectively, ( p < 0.05). Besides, TMYX dose-dependently reduced the cross section area of cardiomyocytes in the angiotensin-II induced hypertrophy H9c2 model ( p < 0.01). Combining high content screening and liquid chromatography mass spectrometry, four compounds with anti-cardiac hypertrophy effects were identified from TMYX, which includes emodin, licoisoflavone A, licoricone and glyasperin A. Licoisoflavone A is one of the compounds with most significant protective effect and we continued to investigate the mechanism. Primary cultures of neonatal rat cardiomyocytes were treated with a hypertrophic agonist phenylephrine (PE) in the presence or absence of licoisoflavone A. After 48 h of treatment, cells were harvested and mitochondrial acetylation was analyzed by western blotting and Image analysis. Interestingly, the results suggested that the anti-hypertrophic effects of licoisoflavone A depend on the activation of the deacetylase Sirt3 ( p < 0.01). Finally, we showed that licoisoflavone A-treatment was able to decrease relative ANF and BNP levels in the hypertrophic cardiac cells ( p < 0.01), but not in cells co-treated with Sirt3 inhibitors (3-TYP) ( p > 0.05). Conclusion : TMYX exerts its anti-hypertrophy effect possibly through upregulating Sirt3 expression. Four compounds were identified from TMYX which may be responsible for the anti-hypertrophy effect. Among these compounds, licoisoflavone A was demonstrated to block the hypertrophic response of cardiomyocytes, which required its positive regulation on the expression of Sirt3. These results suggested that licoisoflavone A is a potential Sirt3 activator with therapeutic effect on cardiac hypertrophy.
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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中医
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
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2023
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IF 7.9
Yi Cai,Shisheng Jiang,Chaoming Huang,Ao Shen,Xuan Zhang,Wanling Yang,Yichuan Xiao,Shuhan Gao,Rong Du,Guodong Zheng,Tingdong Yan,Chunpeng (Craig) Wan
Background The conserved sirtuin protein sirtuin 3 (SIRT3) is a vital protective protein for cardiac hypertrophy. Inhibition of SIRT3 accelerated the development of heart hypertrophy. On the other hand, myocardial hypertrophy was prevented by overexpressing SIRT3. SIRT3 has been proposed as a potential therapeutic target for managing or averting heart hypertrophy. Baicalin, a flavonoid extracted from the Scutellaria baicalensis plant, has anti-cardiovascular properties, including protection against cardiac hypertrophy. However, the molecular mechanism of the anti-hypertrophic effect of baicalin is not well known. Purpose In this study, we aim to investigate the effect of baicalin on cardiac hypertrophy and explored its underlying molecular mechanisms. Study-design/methods Abdominal aortic constriction (AAC)-induced mouse cardiac hypertrophy and angiotensin II (Ang II)-induced cardiomyocyte hypertrophy models were established. After baicalin treatment, cardiac hypertrophy was monitored by detecting the expression of hypertrophic genes and cell surface area. Echocardiogram was performed to check the heart function in vivo . Moreover, the protein expression of the SIRT3-dependent pathway was detected by Western blotting. Results In this work, we demonstrated that baicalin might suppress the cell surface area and the expression of the Ang II -induced myosin heavy chain β (β-MHC), brain natriuretic polypeptide (BNP), and atrial natriuretic factor (ANF). Additionally, it reduced the AAC rats' hypertrophic impact. We also found that baicalin prevents cardiac hypertrophy by regulating SIRT3/LKB1/AMPK signaling pathway. Moreover, we showed that baicalin upregulated the SIRT3 protein expression by inhibiting proteasome and by the activation of 20 S proteasome subunit beta type-5 (PSMB5). Conclusion These results offer the first proof that baicalin inhibits cardiac hypertrophy due to its effect on the SIRT3-dependent signaling pathway, indicating its potential for treating cardiac hypertrophy and heart failure. The present study provides a preliminary experimental basis for the clinical application of baicalin and baicalin-like compounds.
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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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2023
·Vol. 24
·期 13
·10839
·
IF 5.6
Mingkang Zhang,Ruirui Cui,Yan Zhou,Yanrong Ma,Yongwen Jin,Lina Wang,Wen Kou,Xin’an Wu
Renal fibrosis is relentlessly progressive and irreversible, and a life-threatening risk. With the continuous intake of a high-purine diet, hyperuricemia has become a health risk factor in addition to hyperglycemia, hypertension, and hyperlipidemia. Hyperuricemia is also an independent risk factor for renal interstitial fibrosis. Numerous studies have reported that increased mast cells (MCs) are closely associated with kidney injury induced by different triggering factors. This study investigated the effect of MCs on renal injury in rats caused by hyperuricemia and the relationship between MCs and renal fibrosis. Our results reveal that hyperuricemia contributes to renal injury, with a significant increase in renal MCs, leading to renal fibrosis, mitochondrial structural disorders, and oxidative stress damage. The administration of the MCs membrane stabilizer, sodium cromoglycate (SCG), decreased the expression of SCF/c-kit, reduced the expression of α-SMA, MMP2, and inhibited the TGF-β1/Smad2/3 pathway, thereby alleviating renal fibrosis. Additionally, SCG reduced renal oxidative stress and mitigated mitochondrial structural damage by inhibiting Ang II production and increasing renal GSH, GSH-Px, and GR levels. Collectively, the recruitment of MCs, activation of the TGF-β1/Smad2/3 pathway, and Ang II production drive renal oxidative stress, ultimately promoting the progression of renal fibrosis in hyperuricemic rats.Keywords:hyperuricemia;renal fibrosis;mast cells;TGF-β1/Smad2/3 pathway;oxidative stress
研究领域:
肾病学
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病理生理学
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药理学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2023
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IF 5.6
Yuanyuan Ding,Tianyou Ma,Yonghui Zhang,Chenrui Zhao,Chao Wang,Zhao Wang
Background Allergic contact dermatitis (ACD) is one of the most common dermatoses, which has high disease burden and quality of life impairment. Anti-histamine is not effective in a part of the ACD patients. Thus, the discovery of novel antipruritic therapy is of highly demand. Objective In this study, we investigated the anti-pruritic effects of rosmarinic acid (RA) and explored the underlying mechanism. Method SPF Balb/c mice were randomly divided into control group, ACD model group, RA group (1.0 mg/kg) and loratadine (LORA) group (1.5 mg/kg). Back epidermal thickness was recorded. H&E staining was used for pathological observation. Mast cell degranulation was assessed by toluidine blue staining. ELISA assay was employed to detect cytokines levels. Cortistatin-14 (CST-14) and Mas-related G protein-coupled receptor X2 (MRGPRX2) expression was detetcted by RT-PCR and western blot. Molecular docking assay was used to predict the affinity of RA and MRGPRX2. Surface plasmon resonance (SPR) assay was used to verify structure affinity of RA and MRGPRX2. Results RA treatment significantly decreased epidermal keratinization and inflammatory cell infiltration in ACD mouse model. Administration of RA significantly reduced secretion of histamine, IL-13, and mRNA expression of CST-14. Furthermore, RA treatment increased mRNA expression of MRGPRX2. In addition, Molecular docking results predict that RA has a good affinity with MRGPRX2. RA displayed a structure affinity ( K D = 8.89 × 10 -4 ) with MRGPRX2 by SPR. RA inhibited CST-14 and Compound 48/80 (C48/80)-induced mast cell activation via MRGPRX2-PLCγ1-PKC-NF-κB signaling pathway. Conclusion RA exhibits anti-pruritic and anti-inflammatory effects in ACD mice by inhibiting MRGPRX2-PLCγ1-PKC-NF-κB signaling pathway. RA might emerge as a potential drug for the treatment of pruritus and skin inflammation in the setting of ACD.
研究领域:
皮肤科
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免疫学
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药理学
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产品关联
DOI
PubMed
高影响因子
PeerJ
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2023
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IF 2.7
Linlin Sun,Miao Ding,Fuhua Chen,Dingyu Zhu,Xinmiao Xie
Background Diabetic nephropathy (DN) is a frequent microvascular complication of diabetes. Glomerular mesangial cell (MC) hypertrophy occurs at the initial phase of DN and plays a critical role in the pathogenesis of DN. Given the role of long non coding RNA (lncRNA) in regulating MC hypertrophy and extracellular matrix (ECM) accumulation, our aim was to identify functional lncRNAs during MC hypertrophy. Methods Here, an lncRNA, C920021L13Rik (L13Rik for short), was identified to be up-regulated in DN progression. The expression of L13Rik in DN patients and diabetic mice was assessed using quantitative real-time PCR (qRT-PCR), and the function of L13Rik in regulating HG-induced MC hypertrophy and ECM accumulation was assessed through flow cytometry and western blotting analysis. Results The L13Rik levels were significantly increased while the miR-2861 levels were decreased in the peripheral blood of DN patients, the renal tissues of diabetic mice, and HG-treated MCs. Functionally, both L13Rik depletion and miR-2861 overexpression effectively reduced HG-induced cell hypertrophy and ECM accumulation. Mechanistically, L13Rik functioned as a competing endogenous RNA (ceRNA) to sponge miR-2861, resulting in the de-repression of cyclin-dependent kinase inhibitor 1B (CDKN1B), a gene known to regulate cell cycle and MC hypertrophy. Conclusions Collectively, the current results demonstrate that up-regulated L13Rik is correlated with DN and may be a hopeful therapeutic target for DN.
研究领域:
分子生物学
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医学
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肾脏病学
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DOI
PubMed
高影响因子
ANTIOXIDANTS & REDOX SIGNALING
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2024
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IF 5.9
Siyu Lu,Yiming Zhou,Mincong Liu,Lijun Gong,Li Liu,Zhigui Duan,Keke Chen,Frank J. Gonzalez,Fang Wei,Rong Xiang,Guolin Li
Aims: Redox signaling plays a key role in skeletal muscle remodeling induced by exercise and prolonged inactivity, but it is unclear which oxidant triggers myofiber hypertrophy due to the lack of strategies to precisely regulate individual oxidants in vivo. In this study, we used tetrathiomolybdate (TM) to dissociate the link between superoxide (O2•−) and hydrogen peroxide and thereby to specifically explore the role of O2•− in muscle hypertrophy in C2C12 cells and mice.Results: TM can linearly regulate intracellular O2•− levels by inhibition of superoxide dismutase 1 (SOD1). A 70% increase in O2•− levels in C2C12 myoblast cells and mice is necessary and sufficient for triggering hypertrophy of differentiated myotubes and can enhance exercise performance by more than 50% in mice. SOD1 knockout blocks TM-induced O2•− increments and thereby prevents hypertrophy, whereas SOD1 restoration rescues all these effects. Scavenging O2•− with antioxidants abolishes TM-induced hypertrophy and the enhancement of exercise performance, whereas the restoration of O2•− levels with a O2•− generator promotes muscle hypertrophy independent of SOD1 activity.Innovation and Conclusion: These findings suggest that O2•− is an endogenous initiator of myofiber hypertrophy and that TM may be used to treat muscle wasting diseases. Our work not only suggests a novel druggable mechanism to increase muscle mass but also provides a tool for precisely regulating O2•− levels in vivo.
研究领域:
生理学
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药理学
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运动科学
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DOI
PubMed
高影响因子
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
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2025
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IF 3.3
Zhixin Zhang,Linli Zhao,Jiahui Wang,Hao Chen,Yan Lin,Fangbin Wang,Lu Wang,Juan Chen,Jian Liu,Xian Zhang
In beige adipocytes, UCP1-dependent thermogenesis can be driven by intracellular reactive oxygen species (ROS) generation. While ROS elevation also induces mast cell activation, serotonin synthesis and release from mast cells inhibits beige progenitor cell proliferation and browning. As a natural antioxidant and mast cell stabilizer, luteolin promotes adipocyte thermogenesis and inhibits mast cell activation. Thus, to activate adipocyte thermogenesis, how luteolin regulates ROS level in beige adipocytes and mast cells needs to be further investigated. In this study, mouse subcutaneous stromal vascular fraction (SVF) cells are induced to differentiate into beige adipocytes, and mouse bone marrow-derived mast cells (BMMCs) are activated with hydrogen peroxide (H 2 O 2 ). Intracellular ROS level is augmented in differentiated beige adipocytes and H 2 O 2 -activated BMMCs, and H 2 O 2 -activated BMMCs inhibited brown differentiation of SVF cells and thermogenesis of beige adipocytes. In beige adipocytes, unlike synthetic antioxidant N -acetylcysteine (NAC), luteolin elevates the expression of thermogenic and beige-selective marker genes and intracellular ROS generation. Contrarily, luteolin inhibits H 2 O 2 -induced mast cell activation and ROS generation. Further, luteolin partially reverses the inhibitory effects of H 2 O 2 -activated BMMCs on the brown differentiation of SVF cells and the thermogenesis of beige adipocytes. Molecular mechanistic studies demonstrate that luteolin regulates intracellular ROS level in beige adipocytes and mast cells via the nuclear factor erythroid 2-related factor 2 (Nrf2)/Catalase pathway. Altogether, as a ROS regulator, luteolin contrarily affects intracellular ROS generation in beige adipocytes and mast cells, and hence elevates adipocyte browning.
研究领域:
分子生物学
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代谢研究
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药理学
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DOI
PubMed
高影响因子
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