Journal of Ginseng Research
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2025
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IF 5.6
Weimin Wang,Kaixuan Zhou,Zengshuai Fu,Yucheng Huang,Jianjun Deng,Daidi Fan,Haixia Yang
Background Alcohol-induced liver injury contributes to various liver diseases, with dietary interventions of ginsenosides being a promising solution. Ginsenosides, the major active compounds of Panax ginseng Meyer , are divided into protopanaxadiol (PPD) and protopanaxatriol (PPT) based on C-3 or C-6 glycosylation, which have anti-inflammatory and antioxidant effects, but structure-activity relationships remain unclear. Methods Using C57BL/C mice with alcohol-induced liver injury, we evaluated Rg5 and F4 effects on liver function, inflammation, lipid deposition, apoptosis, alcohol metabolism, and lipid synthesis. Results Rg5 (60 mg/kg) demonstrated significantly superior efficacy to F4 in alleviating alcohol-induced liver injury, reducing lipid deposition through 33.9% and 25.8% decreases in serum triglyceride (TG) and total cholesterol (TC) levels versus the F4 group. Additionally, Rg5 attenuated hepatic apoptosis by reducing BAX and cleaved-CASPASE-3 protein expression by 26.3% and 28.4% compared to F4. Rg5 enhanced alcohol metabolism through activation of alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH), thereby restoring AMP-activated protein kinase (AMPK) phosphorylation by 26.1% while reducing sterol regulatory element-binding protein 1 (SREBP-1) expression by 27.8% (compared to F4), with efficacy approaching that of positive control silymarin. Molecular docking revealed that the C-6 sugar moiety of F4 induced hydrogen bond donor repulsion, increasing hydrogen bond length and weakening binding stability with ADH, ALDH and AMPK, providing a structural basis for Rg5's superior hepatoprotective activity. Conclusion These findings highlight the critical influence of glycosylation position on hepatoprotective activity of ginsenosides, and provide insights into the structural modification of ginsenosides, which could contribute to the treatment of alcohol-related liver disease.
研究领域:
药理学
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生物化学
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药物化学
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分子生物学
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营养学
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产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL POLLUTION
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2022
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IF 9.988
Zhiying Miao,Zhiruo Miao,Xiaohua Teng,Shiwen Xu
As a widespread aquatic environmental contaminant, Lead (Pb) can provoke hepatic injury in various animals. Melatonin (MT) plays a crucial role in the regulation of inflammatory response. Accumulating evidence elucidates exogenous toxins can elicit hepatic lipid metabolic disorders by influencing the gut microbiome. Nevertheless, the effects of Pb on gut microbiota and hepatic lipid metabolism of the common carps, and whether MT can prevent and cure Pb-induced toxicity via regulating microbiome remains unknown. Here, metagenomic and transcriptomic analysis were subsequently implemented to identify the Pb exposure-triggered prominent alternation of gut-liver signal. In the present study the severe intestinal injury and fatty liver formation caused by Pb in common carp were preliminarily determined. Metagenomic analysis confirmed that the gut microbiome dominant phyla, family and genus of the common carps were Fusobacteria , Fusobacteriaceae and Cetobacterium . Meanwhile, lipopolysaccharide (LPS) biosynthesis pathway was regarded as one of the main responsible for Pb exposure. Subsequently, LPS was demonstrated as the Pb-triggered microbial-derived signal of the common carps by ELISA analysis, and involves in the hepatic metabolic disorders via deteriorating the intestinal barrier. Additionally, it confirmed that hepatocytes ferroptosis associated with Pb-evoked fatty liver of the common carps, and the aggravation of lysosomal dyshomeostasis as well as inhibition of AMPK phosphorylation were referred to lipid metabolic disorders. The results of the present study demonstrated microbial-derived signal induced by aquatic Pb contaminant cause fatty liver formation in the common carps, and the protective effects of MT on Pb toxicity were performed by receding LPS over-synthesis, restraining microbiota-sourced LPS transport, along with attenuation of hepatocytes ferroptosis.
研究领域:
环境毒理学
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水生生物学
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分子生物学
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微生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
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2025
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IF 19
Yanzhi Zhao,Weixian Hu,Shengming Zhang,Yuheng Liao,Kangkang Zha,Chenyan Yu,Zhenhe Zhang,Wenqian Zhang,Bobin Mi,Faqi Cao,Guohui Liu,Wu Zhou
Impaired fracture healing in diabetic patients poses a persistent clinical challenge, with underlying mechanisms that remain to be fully elucidated. These findings reveal that high glucose microenvironments generate excessive reactive oxygen species in bone marrow mesenchymal stem cells (BMSCs) and bone marrow-derived macrophages (BMDMs), leading to mitochondrial dysfunction and metabolic impairment. These pathophysiological disruptions suppress osteogenic differentiation in BMSCs while driving pro-inflammatory polarization in BMDMs, processes closely tied to high-glucose-induced inhibition of Adenosine 5′-monophosphate-activated protein kinase (AMPK) phosphorylation. Restoration of AMPK phosphorylation emerges as a pivotal strategy to mitigate oxidative stress and restore cellular function. To address this, a dual-targeted therapeutic system (DLNPs@HA hydrogel) is developed that combines anti-CD105-antibody-modified nanoliposomes and phosphatidylserine-modified nanoliposomes, both encapsulating the specific AMPK activator α-lipoic acid. This hydrogel facilitates sustained nanoparticle release, enabling precise and effective delivery to BMSCs and BMDMs. In vitro, DLNPs@HA hydrogel successfully enhances osteogenic activity and suppresses inflammatory responses. In vivo, it accelerates fracture healing in diabetic mice. By precisely targeting BMSCs and BMDMs and reversing bicellular oxidative stress, this integrative medical-engineering strategy provides a promising and translatable solution for diabetic fracture repair, seamlessly bridging mechanistic insights with therapeutic innovation.
研究领域:
生物医学工程
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内分泌学
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创伤骨科
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细胞生物学
✓ 已验证
产品关联
DOI
高影响因子
Acta Pharmaceutica Sinica B
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2024
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IF 14.7
Zaigang Zhou,Wenjuan Luo,Chunjuan Zheng,Haoxiang Wang,Rui Hu,Hui Deng,Jianliang Shen
Currently, the efficacy of albumin-bound paclitaxel (PTX@Alb) is still limited due to the impaired PTX@Alb accumulation in tumors partly mediated by the dense collagen distribution. Meanwhile, acquired immune resistance always occurs due to the enhanced programmed cell death-ligand 1 (PD-L1) expression after PTX@Alb treatment, which then leads to immune tolerance. To fill these gaps, we newly revealed that tamoxifen (TAM), a clinically widely used adjuvant therapy for breast cancer with mitochondrial metabolism blockade capacity, could also be used as a novel effective PD-L1 and TGF- β dual-inhibitor via inducing the phosphorylation of adenosine 5ʹ-monophosphate-activated protein kinase (AMPK) protein. Following this, to obtain a more significant effect, TPP-TAM was prepared by conjugating mitochondria-targeted triphenylphosphine (TPP) with TAM, which then further self-assembled with albumin (Alb) to form TPP-TAM@Alb nanoparticles. By doing this, TPP-TAM@Alb nanoparticles effectively decreased the expression of collagen in vitro , which then led to the enhanced accumulation of PTX@Alb in 4T1 tumors. Besides, TPP-TAM@Alb also effectively decreased the expression of PD-L1 and TGF- β in tumors to better sensitize PTX@Alb-mediated chemo-immunotherapy by enhancing T cell infiltration. All in all, we newly put forward a novel mitochondrial metabolism blockade strategy to inhibit PTX@Alb-resistant tumors, further supporting its better clinical application.
研究领域:
肿瘤学
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药理学
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免疫学
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纳米技术
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2018
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IF 3.412
Rui Chen,Yang Cui,Xuelian Zhang,Yanghai Zhang,Mingyue Chen,Tong Zhou,Xianyong Lan,Wuzi Dong,Chuanying Pan
Chlorpyrifos (CPF) is the most frequently applied insecticide. Aside from effects on the neuronal cholinergic system, previous studies suggested a potential relationship between CPF exposure and male infertility; however, the molecular mechanism remains elusive. The aim of this study was to investigate the toxic effect of CPF on testicular cells and the potential mechanism via in vitro and in vivo experiments. The cytotoxic effects of CPF on mouse-derived spermatogonial cell lines (GC-1), Sertoli cell lines (TM4) and Leydig cell lines (TM3) were assessed by a CCK-8 assay, flow cytometry, a TUNEL assay, quantitative RT-PCR, and Western blotting. Exposure to CPF (10–50 μM) for 12 or 24 h resulted in significant death in all three testicular cell lines. The number of TUNEL-positive apoptotic cells were dose-dependent and increased with raised CPF concentrations. Further investigation indicated that CPF induced cell-cycle arrest and then promoted cell apoptosis. Additionally, CPF increased reactive-oxygen-species (ROS) production and lipid peroxidation (MDA) and reduced mitochondrial-membrane potential. The mechanism of cell apoptosis induced by CPF involved an increase in phosphorylated-AMP-activated-protein-kinase (p-AMPK) levels in the tested cells. In vivo, the expression of steroid-hormone-biosynthesis-related genes in testis, spleen, and lung in F0 and F1 mice were downregulated when there was intraperitoneal injection or dietary supplementation of CPF. This study provides a potential molecular mechanism of CPF-induced toxicity in testicular cells and a theoretical basis for future treatment of male infertility.
研究领域:
毒理学
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生殖生物学
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细胞生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
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2024
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IF 3.8
Shuwei Ke,Siyu Zhang,Dongsheng Liu,Tengjiao Zhao,Xiayan Lou,Sunying Cheng,Tingheng Zhu,Hanbing Li
Ectopic olfactory receptors, such as OR1A1, are involved in the regulation of lipid metabolism homeostasis. In this study, we investigated the effects of three monoterpenes, (+)-limonene, (−)-carvone and thymol, upon hepatic lipid deposition. Oral administration of (+)-limonene, (−)-carvone and thymol for 8 weeks in high-fat-diet (HFD)-fed mice significantly lowered the levels of fasting blood glucose, improved glucose intolerance, serum lipid parameters, adiposity, and hepatic steatosis. In LO2 cells, (+)-limonene, (−)-carvone and thymol increased the cyclic adenosine monophosphate (cAMP), induced protein kinase A (PKA) activity and phosphorylation of AMPK, downregulated the expression of SREBP-1 and FASN, and eventually led to a reduction in hepatic lipid deposition. Meanwhile, these beneficial effects in cultured LO2 cells were negated by OR1A1 knockdown and the adenylyl cyclase inhibitor SQ22536, respectively, indicating that they can ameliorate disorders of lipid metabolism through activating OR1A1 and subsequent AMPK/SREBP-1/FASN pathway, indicating OR1A1 as a potential target for counteracting hepatic steatosis.
研究领域:
药理学
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代谢学
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肝病学
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分子生物学
✓ 已验证
DOI
高影响因子
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