PHYTOTHERAPY RESEARCH
·
2025
·
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
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Regenerative Biomaterials
·
2023
·
IF 6.7
Hua Xi,Hou Mingzhuang,Deng Lei,Lv Nanning,Xu Yong,Zhu Xuesong,Yang Huilin,Shi Qin,Liu Hao,He Fan
The scarcity of native periosteum poses a significant clinical barrier in the repair of critical-sized bone defects. The challenge of enhancing regenerative potential in bone healing is further compounded by oxidative stress at the fracture site. However, the introduction of artificial periosteum has demonstrated its ability to promote bone regeneration through the provision of appropriate mechanical support and controlled release of pro-osteogenic factors. In this study, a polylactic acid (PLLA)/hyaluronic acid (HA)-based nanofibrous membrane was fabricated using the coaxial electrospinning technique. The incorporation of irisin into the core-shell structure of PLLA/HA nanofibers (PLLA/HA@Irisin) achieved its sustained release. In vitro experiments demonstrated that the PLLA/HA@Irisin membranes exhibited favorable biocompatibility. The osteogenic differentiation of bone marrow mesenchymal stem cells (BMMSCs) was improved by PLLA/HA@Irisin, as evidenced by a significant increase in alkaline phosphatase (ALP) activity and matrix mineralization. Mechanistically, PLLA/HA@Irisin significantly enhanced the mitochondrial function of BMMSCs via the activation of the sirtuin 3 antioxidant pathway. To assess the therapeutic effectiveness, PLLA/HA@Irisin membranes were implanted in situ into critical-sized calvarial defects in rats. The results at four and eight weeks post-surgery indicated that the implantation of PLLA/HA@Irisin exhibited superior efficacy in promoting vascularized bone formation, as demonstrated by the enhancement of bone matrix synthesis and the development of new blood vessels. The results of our study indicate that the electrospun PLLA/HA@Irisin nanofibers possess characteristics of a biomimetic periosteum, showing potential for effectively treating critical-sized bone defects by improving the mitochondrial function and maintaining redox homeostasis of BMMSCs.
研究领域:
组织工程
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再生医学
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生物材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2025
·
IF 4.8
Hongtao Zhang,Yi Huang,Songhong Yang,Feipeng Gong,Yuncheng Gu,Qin Xie,Yanrong Ye,Xingmei Lu,Lingyun Zhong
Introduction: Sand-fired aconite slices (SFAS) demonstrate anti-heart failure effects, but the mechanism remains unclear. This study investigated myocardial mitochondrial energy metabolism as a therapeutic mechanism of SFAS in doxorubicin-induced chronic heart failure (CHF) rats.Methods: The CHF rat model was established via the intraperitoneal injection of doxorubicin (DOX). Following successful model production, rats were randomly assigned to nine groups. After drug administration, their cardiac function was assessed, and their cardiac tissue morphology and myocardial mitochondria were examined. Atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), norepinephrine (NE), malondialdehyde (MDA), superoxide dismutase (SOD), free fatty acid (FFA), sodium-potassium-ATPase (Na+-k+-ATPase), calcium-magnesium-ATPase (Ca2+-Mg2+-ATPase), and adenosine triphosphate (ATP) levels were quantified using enzyme-linked immunosorbent assays (ELISAs). Fatty acid translocase (CD36), carnitine palmitoyl transferase 1 (CPT1), adenosine 5′-monophosphate-activated protein kinase (AMPK), phosphorylated adenosine monophosphate-activated protein kinase (p-AMPK), peroxisome proliferator-activated receptor γ coactivator 1 alpha (PGC-1α), and Sirtuin 3 (SIRT3) protein expression levels were assessed by Western blot.Results: SFAS significantly improved cardiac function in CHF rats. It increased the left ventricular ejection fraction (LVEF) (from 34.22% ± 2.03%–83.68% ± 2.34%; P < 0.001) and left ventricular shortening fraction (LVFS) (from 17.06% ± 1.08%–53.86% ± 2.82%; P < 0.001) and decreased ANP (from 551.29 ± 14.63 pg/mL to 291.96 ± 11.28 pg/mL; P < 0.05), BNP (from 743.15 ± 18.03 pg/mL to 478.75 ± 10.57 pg/mL; P < 0.001), and NE levels (from 1,105.36 ± 21.79 pg/mL to 672.67 ± 6.70 pg/mL; P < 0.001). Additionally, it decreased MDA production (from 8.89 ± 0.36 nmol/mL to 5.11 ± 0.35 nmol/mL; P < 0.05) and increased SOD activity (from 264.82 ± 4.26 pg/mL to 529.64 ± 10.27 pg/mL; P < 0.001), Na+-K+-ATPase levels (from 7.19 ± 0.65 μmol/mL to 14.08 ± 0.28 μmol/mL; P < 0.001), Ca2+-Mg2+-ATPase levels (from 0.86 ± 0.03 μmol/mL to 1.40 ± 0.02 μmol/mL; P < 0.05), CD36 levels (P < 0.05), and CPT1 levels (P < 0.01). Moreover, it improved mitochondrial structural damage and reduced the level of oxidative stress in cardiomyocytes. Furthermore, SFAS promoted FFA oxidation (from 1,477.49 ± 7.60 μmol/mL to 768.87 ± 82.53 μmol/mL; P < 0.05) and ATP production (from 2,869.85 ± 298.26 nmol/mL to 5,483.17 ± 120.03 nmol/mL; P < 0.001) and increased p-AMPK, PGC-1α, and SIRT3 levels (P < 0.05 and P < 0.01).Conclusion: By activating the AMPK/PGC-1α/SIRT3 signaling pathway, SFAS ameliorated the impaired fatty acid oxidation pathway and enhanced mitochondrial function and antioxidant capacity in cardiomyocytes, ultimately reducing myocardial damage and restoring cardiac function in CHF rats.
研究领域:
心血管药理学
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中医药学
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线粒体生物学
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代谢紊乱
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2023
·
IF 15.1
Bao-Feng Zhao,Fan Wang,Jia-Chen Sun,Jin-Peng Gao,Li-Juan Zhao,Zhao-Liang Shen,Zhi-Peng Li,Yi-Xuan Wang,Yuan Wang,Dan Li,Xi-Fan Mei
Spinal cord injury (SCI) inflicts devastating consequences for health. While drugs have been employed to alleviate SCI symptoms, their complex synthesis procedures and the need for specialized drug delivery raise concerns regarding administration. Herein, we utilize a green synthesis protocol to produce polymer quantum dots (Pdots) from polyvinylpyrrolidone precursors, empowered by the catalytic prowess of copper. These Copper-catalyzed Pdots (CPdots) not only offer enhanced improved fluorescence properties but also exhibit remarkable antioxidant, anti-inflammatory, and mitochondrial function repair effects. An intriguing finding emerged from our research as CPdots were observed to activate the AMPK/PGC-1α/Sirt3 pathway-a distinctive molecular mechanism that combats mitochondrial dysfunction, and mitigates calcium overload associated with acute SCI. Furthermore, the rapid metabolism and exceptional biocompatibility of our CPdots reinforce their safety and efficacy.
研究领域:
神经科学
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材料科学
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生物医学工程
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药理学
✓ 已验证
DOI
高影响因子
Science Advances
·
2024
·Vol. 10
·期 42
·
IF 11.7
Xulong Liu,Shangtong Jiang,Ting Jiang,Ziyang Lan,Xin Zhang,Zhenyu Zhong,Xiaodan Wu,Cunjing Xu,Yingying Du,Shengmin Zhang
Cartilage regeneration relies on adequate and continuous bioenergy supply to facilitate cellular differentiation and extracellular matrix synthesis. Chondrocytes frequently undergo energy stress under pathological conditions, characterized by disrupted cellular metabolism and reduced adenosine triphosphate (ATP) levels. However, there has limited progress in modulating energy metabolism for cartilage regeneration thus far. Here, we developed bioenergetic-active exosomes (Suc-EXO) to promote cartilage regeneration and homeostasis maintenance. Suc-EXO exhibited a 5.42-fold increase in ATP content, enabling the manipulation of cellular energy metabolism by fueling the TCA cycle. With continuous energy supply, Suc-EXO promoted BMSC chondrogenic differentiation via the P2X7-mediated PI3K-AKT pathway. Moreover, Suc-EXO improved chondrocyte anabolism and mitochondrial homeostasis via the P2X7-mediated SIRT3 pathway. In a rabbit cartilage defect model, the Suc-EXO–encapsulated hydrogel notably promoted cartilage regeneration and maintained neocartilage homeostasis, leading to 2.26 and 1.53 times increase in Col2 and ACAN abundance, respectively. These findings make a remarkable breakthrough in modulating energy metabolism for cartilage regeneration, offering immense potential for clinical translation.
研究领域:
再生医学
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细胞代谢
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组织工程
·
生物医学工程
✓ 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）