EUROPEAN JOURNAL OF PHARMACOLOGY
·
2025
·
IF 4.7
Linfang Wu,Jing Wang,Yonghuan Yan,Lu Wang,Qi Huang,Jinyong Peng,Lili Li
Endometritis is a prevalent condition of the reproductive system that leads to significant tissue damage in the uterus, thereby seriously impacting the health and quality of life of these patients. Hesperidin (HES), a natural flavonoid glycoside, displays various biological activities. Nonetheless, the protective effect of HES treatment against endometritis remains uncertain. In this study, we examined the protective effects of HES on endometritis induced by lipopolysaccharide (LPS) both in vivo and in vitro . In vitro experimental results showed that HES reduced the levels of inflammatory factors, improved mitochondrial morphology, increased mitochondrial activity and inhibited ROS levels; moreover, it activated the AMPK/PGC-1 α signalling pathway in LPS-induced human endometrial endothelial cells (HEECs). AMPK served as a potential target of HES, which was further validated using molecular docking, molecular dynamic simulation, CETSA and SPR. Moreover, in vivo experimental results indicated that HES significantly mitigated the histopathological alterations in the uterus caused by LPS, as well as reduced the levels of inflammatory factors, MPO activity, the expression levels of CD38, and CD138 and activated the AMPK/PGC-1α signalling pathway. Overall, HES mitigated mitochondrial oxidative stress and inflammatory response primarily through activation of the AMPK/PGC-1α signalling pathway, thereby exerting protective effects against endometritis.
研究领域:
药理学
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免疫学
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细胞生物学
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分子生物学
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妇产科学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Yongshuai Jing,Mingsong Li,Yingqi Li,Teng Ma,Ying Qu,Beibei Hu,Yinghua Xie,Zhiwei Li
This study aimed to characterize the structure of polysaccharide ZOPA extracted from Zingiber officinale and its purified form (ZOPA-1), and to investigate their anti-fatigue mechanisms based on the gut-muscle axis. The study found that the backbone of ZOPA-1 is primarily composed of →3,4)-α-Glcp-1→ and →4,6)-α-Glcp-(1→ linkages, with →4)-α-Glcp(1→ serving as its side chain. In exhaustive swimming experiments with mice, both crude ZOPA and purified ZOPA-1 demonstrated significant anti-fatigue effects, including enhanced glycogen storage, improved antioxidant capacity, reduced accumulation of metabolic waste products, and regulated energy metabolism in the gastrocnemius muscles. These effects may be mediated through the activation of the Keap1-Nrf2/ARE and AMPK/PGC-1α signaling pathways. Furthermore, ZOPA and ZOPA-1 modulated the intestinal flora of mice, increasing diversity, altering abundance, and regulating short-chain fatty acid concentrations, suggesting a potential role of the gut-muscle axis in mediating the anti-fatigue effects. This study provides valuable insights into the complex interplay between polysaccharides, the gut-muscle axis, and exercise-induced fatigue.
研究领域:
食品科学
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运动医学
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营养学
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2022
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IF 5.195
Xiaohui Jin,Leilei Zhu,Shuaifei Lu,Caiyin Li,Ming Bai,Erping Xu,Jiduo Shen,Yucheng Li
Mitochondrial dysfunction has been reported to be involved in the pathogenesis of depression, and mitophagy is a key pathway for mitochondrial quality control. This study aimed to investigate the effect of baicalin on mitophagy in the hippocampus of mice exposed to chronic unpredictable mild stress (CUMS) and explore its potential mechanism. After exposure to CUMS for 6 weeks, mice were given baicalin (20 mg/kg) or fluoxetine (20 mg/kg) by oral gavage for 4 weeks, and HT22 cells were injured by corticosterone (CORT) in vitro. Depression-like behaviors were assessed by sucrose preference test and tail suspension test . The mitochondrial structure was observed by transmission electron microscopy . Detection of mitophagy and mitophagy-related protein by mitophagy kit and Western blot . The results showed that baicalin improved depressive-like behaviors in CUMS mice, and ameliorated mitochondrial structural impairment in the hippocampus neuron. Baicalin significantly down-regulated light chain 3(LC3)II/I, protein sequestosome 1 (P62), and translocase of the outer membrane 20 (TOM20), and up-regulated Nip-like protein (NIX), Adenylate activated protein kinase (AMPK), and Peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1α. Furthermore, molecular docking showed that baicalin interacts with AMPK through hydrogen bonding. Baicalin increased NIX and AMPK, and improved mitophagy level and mitochondrial function in HT22 cells. Treatment with Phorbol 12-Myristate 13-acetate demonstrated that up-regulation of NIX ameliorated CORT-induced mitochondrial dysfunction in HT22 cells. In conclusion, the present study suggested that the antidepressant effect of baicalin may be related to the enhancement of NIX-mediated mitophagy through activating the AMPK/PGC-1α pathway by directly binding to AMPK.
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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产品关联
DOI
PubMed
高影响因子
Biology-Basel
·
2026
·Vol. 15
·期 13
·999
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IF 4.3
Xiang Li,Bo Tian,Yuxin Chen,Huili Tong,Xiaoming Chen,Zhifeng Cheng
Simple SummaryType 2 diabetes (T2DM) often leads to skeletal muscle loss and weakness, a condition called sarcopenia, which worsens human health. This study explored whether carnosine, a natural dipeptide found in meat and present in human muscle, can help protect against muscle wasting. Using a T2DM sarcopenia mouse model and a high-glucose-treated C2C12 myotube in vitro model, the researchers found that carnosine levels were reduced in T2DM sarcopenia muscles. Oral carnosine supplementation in the mice helped alleviate skeletal muscle atrophy. Carnosine works by activating a cellular signaling pathway that boosts the number of mitochondria (the energy powerhouses of cells) and shifts muscle fibers toward a more oxidative type, leading to stronger and healthier muscles in T2DM sarcopenia mice. These findings suggest that carnosine supplementation could be a simple and promising nutritional strategy to help manage skeletal muscle loss in people with type 2 diabetes, though further studies in humans are needed to confirm its effectiveness.Type 2 diabetes mellitus (T2DM) accounts for over 90% of diabetes cases, and T2DM-related sarcopenia is a growing concern. Carnosine, abundant in human skeletal muscle, helps maintain muscle quality and function. This study investigated whether carnosine deficiency contributes to T2DM-related sarcopenia and whether exogenous carnosine supplementation alleviates muscle atrophy. A mouse model of T2DM sarcopenia was established using streptozotocin combined with a high-fat diet. LC-MS metabolomics revealed a significant reduction in carnosine content in the gastrocnemius muscle of model mice. A C2C12 myotube atrophy model was induced by high-glucose (HG), and qRT-PCR showed altered expression of carnosine metabolism-related enzymes, suggesting disrupted carnosine homeostasis under T2DM conditions. Mechanistic investigations using immunofluorescence, Western blotting, transcriptome sequencing, mitochondrial staining, and molecular docking indicated that carnosine may alleviate high-glucose-induced myotube atrophy through the PI3K/AMPK/PGC-1α signaling pathway. In vivo, carnosine supplementation increased the number of mitochondria and the proportion of slow muscle fibers in gastrocnemius muscle, ameliorating the atrophic phenotype. These findings suggest that carnosine has potential as a candidate for intervention in T2DM-related sarcopenia, though further validation of its direct molecular targets is required.
✓ 已验证
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
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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
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DOI
高影响因子
Food Bioscience
·
2024
·
IF 4.8
Meimei Shan,Xingrui Xu,Chuanqi Chu,He Wang,Chengting Zhang,Shengbao Cai
Fatigue is an intricate physiological phenomenon, causing serious secondary concerns and bioregulation disorders. The objective of this research was to look into the anti-fatigue effect and potential mechanisms of natural ingredients in methanol extract of edible oil from Rhus chinensis Mill. fruits (PMRO). Results showed that a total of 18 fatty acids and 9 anacardic acids were identified by GC-MS and UHPLC-ESI-HCES/MS in PMRO. PMRO significantly increased the weight-bearing swimming time. Further investigations showed that PMRO significantly improved physiological indexes related to fatigue and regulated the oxidative stress (Keap1/Nrf2) and energy metabolism (AMPK/PGC-1α)-related proteins expression to exert anti-fatigue effects. The 16S rRNA sequence analysis indicated that a potential role of PMRO in modulating the abundance of gut bacteria and influencing the short-chain fatty acids content, thereby exerting an anti-fatigue effect. Therefore, the natural ingredients in PMRO may hold promise as a dietary supplement capable of delaying body fatigue.
研究领域:
营养学
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药理学
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微生物学
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生物化学
✓ 已验证
产品关联
DOI
高影响因子
Advanced Science
·
2024
·
IF 14.3
Junpeng Xu,Peng Dai,Chen Zhang,Na Dong,Caiyan Li,Chonghui Tang,Zhihao Jin,Shih-Ho Lin,Luyang Ye,Tianmiao Sun,Yukai Jin,Fenzan Wu,Lihua Luo,Ping Wu,Shengcun Li,Xiaokun Li,Shan-hui Hsu,Dawei Jiang,Zhouguang Wang
Parkinson's disease (PD) is one of the most common long-term neurodegenerative disorders, with multiple comorbid psychiatric and behavioral abnormalities. The combination of clinical drugs targeting different symptoms with smart hydrogels to achieve asynchronous releases is highly translational and challenging. Here, a hierarchical bioactive hydrogel (OACDP) is designed with asynchronous release based on PD pathology. The hydrogel with caffeic acid-grafted polymer main chain is crosslinked using a micellar nanocrosslinker, with sufficient modulus (≈167 Pa), antioxidant activity (> 50%), injectability (30-gauge syringe needle), and shape-adaptability. Each of the three drugs (caffeic acid, fibroblast growth factor 21, and Edaravone) is separately engaged in different micro- or nanostructures of the hydrogel and released with asynchronous kinetics of first-order release, zero-order release, or matching Korsmeyer–Peppas model. The triple-loaded hydrogel is injected into the brains of PD rats, showing behavioral improvement. Histological analysis revealed that the triple-loaded OACDP hydrogels are effective in achieving immediate neuroprotection, i.e., reduction the loss of tyrosine hydroxylase in substantia nigra compacta and striatum (retained ≈10-fold versus control), decreasing oxidative stress, reducing astrocyte and microglia activation, and stimulating the AMPK/PGC-1α axis to regulate the mitochondrial function, providing a multi-dimensional PD therapy. The asynchronous release of OACDP hydrogel provides a new conception for PD treatment and other neurodegenerative diseases.
研究领域:
神经科学
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药学
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生物材料
·
神经退行性疾病
✓ 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）