JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
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2024
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IF 4.3
Xiaoyang Zhou,Kai Lian,Junjie Jia,Xue Zhao,Peng Duan,Jiaolong Huang,Yihua Shi
Epimedium is thought to enhance the integrity of tendons and bones, ease joint discomfort and rigidity and enhance kidney function. Although glucocorticoids are commonly used in clinical practice, the mechanism by which the active compound Epimedin C (EC) alleviates glucocorticoid‐induced osteoporosis (GIOP) is not well understood. The therapeutic potential of EC in treating GIOP was evaluated using alizarin red S staining, calcein immersion and fluorescence imaging, and bone mineralization, bone mass accumulation and bone density in zebrafish larvae were determined. Using the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, the key signalling pathways related to bone development were identified. A protein–protein interaction network (PPIN) was constructed to identify osteoclast characteristic genes and the findings were verified using real‐time quantitative PCR (RT‐qPCR). The bone tissue damage caused by prednisolone was reduced by EC. It also altered physiological processes, improved bone density, boosted mineralization and increased bone mass and activity. Subsequent empirical investigations showed that EC impacted the major signalling pathways involved in bone development, such as osteoclast differentiation, oestrogen, MAPK, insulin resistance, PPAR and AMPK signalling pathways. It also decreased the expression of genes typical of osteoclasts. The results of our study uncover a previously unknown function of EC in controlling bone formation and emphasize the potential of EC as a therapeutic target. The osteoprotective effect of EC indicates its potential as a cost‐effective strategy for treating GIOP.
研究领域:
药理学
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生物学
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基因组学
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分子生物学
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生物信息学
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DOI
PubMed
高影响因子
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY
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2023
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IF 3.9
Liwang Xu,Xiaole Yang,Ying He,Qinglian Hu,Zhengwei Fu
In aquatic environment, engineered materials may inevitably interact with the coexisted organic pollutants, which affect their bioavailability and toxicity. In this contribution, the combined impacts of tetracycline (TC) and titanium dioxide nanoparticles (TiO 2 NPs) on the neurodevelopment of zebrafish larvae were investigated, and the underlying mechanisms were further elucidated. Firstly, it was confirmed that the co-existence of TC would increase the size and decrease the zeta potential of TiO 2 NPs. Following, developmental indicators and motor behaviors were investigated. Our results indicated that co-exposure to TC and TiO 2 NPs exhibited enhanced embryonic malformation rates and abnormal nervous system development in zebrafish embryos. Meanwhile, the locomotor behavior was increased upon treatment of TC and TiO 2 NP. Further, pathway enrichment analyses of transcriptomic sequencing provided detailed information that either lipid metabolism or PPAR signaling pathway were significantly affected in the co-exposure group. Also, TC + TiO 2 NP exposure significantly changed the mRNA expression of neural development-related genes and up-regulated the expression levels of neurotransmitters like 5-hydroxytryptamine, dopamine, acetylcholinesterase , and γ-aminobutyric acid. Taken together, our results demonstrated that the co-exposure of TC and TiO 2 NPs had the potential to cause neurotoxicity in zebrafish embryos.
研究领域:
环境科学
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毒理学
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神经科学
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产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2024
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IF 6.9
Jaili Li,Ting Luo,Yao Zhao,Dou Wang,Yuanxiang Jin,Zufang Wu,Guiling Yang,Xingjiang Qi
Doxorubicin (DOX) is a commonly used anthracycline in cancer chemotherapy. The clinical application of DOX is constrained by its cardiotoxicity. Myricetin (MYR) is a natural flavonoid widely present in many plants with antioxidant and anti-inflammatory properties. However, MYR's beneficial effects and mechanisms in alleviating DOX-induced cardiotoxicity (DIC) remain unknown. C57BL/6 mice were injected with 15 mg/kg of DOX to establish the DIC, and MYR solutions were administrated by gavage to investigate its cardioprotective potentials. Histopathological analysis, physiological indicators assessment, transcriptomics analysis, and RT-qPCR were used to elucidate the potential mechanism of MYR in DIC treatment. MYR reduced cardiac injury produced by DOX, decreased levels of cTnI, AST, LDH, and BNP, and improved myocardial injury and fibrosis. MYR effectively prevented DOX-induced oxidative stress, such as lowered MDA levels and elevated SOD, CAT, and GSH activities. MYR effectively suppressed NLRP3 and ASC gene expression levels to inhibit pyroptosis while regulating Caspase1 and Bax levels to reduce cardiac cell apoptosis. According to the transcriptomic analysis, glucose and fatty acid metabolism were associated with differential gene expression. KEGG pathway analysis revealed differential gene enrichment in PPAR and AMPK pathways, among others. Following validation, MYR was found to alleviate DIC by regulating glycolipid metabolism and AMPK pathway-related genes. Our findings demonstrated that MYR could mitigate DIC by regulating the processes of oxidative stress, apoptosis, and pyroptosis. MYR is critical in improving DOX-induced myocardial energy metabolism abnormalities mediated by the AMPK signaling pathway. In conclusion, MYR holds promise as a therapeutic strategy for DIC.
研究领域:
药理学
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毒理学
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分子生物学
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心脏病学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2025
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IF 11.5
Danlei Hu,Dongmei Chen,Aoxue Zhang,Kuiyu Meng,Min Chen,Raja Mubbashar,Wei Qu,Shuyu Xie
Current IBD therapies face limitations such as systemic toxicity, off-target effects, and microbiota dysbiosis. We developed an oral multifunctional gel bead integrating three innovations: (1) a butyrate–apigenin synergy that inhibits NF-κB via CK2/p65 phosphorylation suppression, activates a PPAR-γ-mediated metabolic shift to β-oxidation, and modulates the microbiota by enhancing Bacteroidetes/suppressing Enterobacteriaceae; (2) an apigenin–butyrate ester prodrug overcoming organoleptic issues while enabling CK2 targeting; and (3) a pH/enzyme–responsive delivery system using the FDA-approved ascorbyl palmitate/alginate, achieving gastric protection, charge–mediated colitis targeting, and esterase–triggered release. In colitis model mice, gel beads restore clinical parameters, intestinal integrity, and microbial balance, outperforming apigenin-butyrate ester and 5-ASA at half-doses with extended intervals. It significantly downregulated colon CK2 expression (4.07-fold) and the phospho-P65/total P65 ratio (3.04-fold). This integrated strategy combining multimodal drug actions and precision delivery establishes a new paradigm for efficient and alternative IBD therapeutics with reduced dosing requirements.
研究领域:
药学
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胃肠病学
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药物递送
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分子医学
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微生物组研究
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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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2022
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IF 5.895
Bei Yan,Lei Chen,Yanhui Wang,Jiacheng Zhang,Hui Zhao,Qinglian Hua,Shengjie Pei,Zihang Yue,Hui Liang,Huaqi Zhang
In this work, the protective effect of apple polyphenol extract (APE) on hepatic steatosis was investigated. Thirty-two C57BL/6J mice were assigned randomly to control group, hepatic steatosis group, lovastatin group, and APE group. After 8 weeks of intervention, APE supplementation markedly decreased the body weight gain, liver weight, liver index, epididymal adipose weight, epididymal adipose index, serum, and hepatic lipid levels. Hematoxylin and eosin staining revealed that APE supplementation alleviated histopathological changes of hepatic steatosis. Western blot revealed that APE downregulated the protein levels of GRP78, IRE1α, p-IRE1α, XBP1, PERK, p-PERK, p-eIF2α, ATF6, PPAR-γ, SREBP-1c, FAS, and ACC1. In conclusion, this study found that APE inhibited IRE1α-XBP1, PERK-eIF2α, and ATF6 signaling pathways to alleviate endoplasmic reticulum stress, thereby improving HFD-induced hepatic steatosis.
研究领域:
药理学
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营养学
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分子生物学
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病理学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Genetics
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2022
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IF 4.772
Zhang Yuying,Guo Kaimin,Zhang Pengfei,Zhang Mengying,Li Xiaoqiang,Zhou Shuiping,Sun He,Wang Wenjia,Wang Hui,Hu Yunhui
It is clinical reported that YangXue QingNao Wan (YXQNW) combined with donepezil can significantly improve the cognitive function of AD patients. However, the mechanism is not clear. A network pharmacology approach was employed to predict the protein targets and affected pathways of YXQNW in the treatment of AD. Based on random walk evaluation, the correlation between YXQNW and AD was calculated; while a variety of AD clinical approved Western drugs were compared. The targets of YXQNW were enriched and analyzed by using the TSEA platform and MetaCore. We proved that the overall correlation between YXQNW and AD is equivalent to clinical Western drugs, but the mechanism of action is very different. Firstly, YXQNW may promote cerebral blood flow velocity by regulating platelet aggregation and the vasoconstriction/relaxation signal pathway, which has been verified by clinical meta-analysis. Secondly, YXQNW may promote Aβ degradation in the liver by modulating the abnormal glucose and lipid metabolisms via the adiponectin-dependent pathway, RXR/PPAR-dependent lipid metabolism signal pathway, and fatty acid synthase activity signal pathway. We also verified whether YXQNW indeed promoted Aβ degradation in hepatic stellate cells. This work provides a novel scientific basis for the mechanism of YXQNW in the treatment of AD.
研究领域:
药理学
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神经病学
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临床研究
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2017
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IF 3.154
Jiarui Nie,Yaning Chang,Yujia Li,Yingjun Zhou,Jiawen Qin,Zhen Sun,Haibin Li
Caffeic acid phenethyl ester (CAPE), extracted from propolis, was evaluated for the ameliorative effects on insulin resistance and the mechanisms were identified, using non-insulin-dependent diabetes mellitus (NIDDM) model mice and insulin resistance (IR) model cells. After 5 weeks of CAPE supplementation, insulin sensitivity, hyperlipidemia, and peroxisome proliferator-activated receptor-α (PPAR-α) levels were improved in mice. Proinflammatory cytokines in serum and the expressions of tumor necrosis factor-alpha (TNF-α) mRNA in tissues were markedly downregulated from CAPE-treated mice. In vitro, CAPE supplement significantly improved glucose consumption, glucose uptake, glycogen content, and oxidative stress and decreased expression of glucose-6-phosphatase (G6Pase) mRNA in cells. Both in vivo and in vitro, CAPE enhanced p-Akt (Ser473) and p-insulin receptor substrate (IRS)-1 (Tyr612), but inhibited p-JNK (Thr183/Tyr185), p-NF-κB p65 (Ser536), and nuclear translocation of p-NF-κB p65 (Ser536). In summary, CAPE can ameliorate insulin resistance through modulation of JNK and NF-κB signaling pathway in mice and HepG2 cells.
研究领域:
药理学
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内分泌学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2022
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IF 5.195
Yangyang Wang,Yanping Sun,Bingyou Yang,Qiuhong Wang,Haixue Kuang
Ethnopharmacological relevance The ‘cold’ property herbs are commonly applied in heat syndrome. Unfortunately, the underlying mechanisms of the ‘cold’ property herbs on heat syndrome has not been investigated. Aim of the study The study aimed to probe the activities of the four typical ‘cold’ property herbs on hyperthyroidism . Materials and methods Firstly, the four typical ‘heat’ property herbs were set as contrasting experiment. Then. the physical sign, thyroid function and metabolism profile (multivariate statistical analysis) were assessing the difference between the four typical ‘cod’ property herbs and the four typical ‘heat’ property herbs. H&E staining were used to confirmed the influence of the typical ‘cold’ property herbs on hyperthyroidism. A metabolomics approach combine with network pharmacology were explored the effected mechanism of the typical ‘cold’ property herbs on hyperthyroidism. the gene expression of UCP-1 was detected by RT-PCR. The metabolites pathway and target-associated metabolites were verified Na + /K + -ATP enzyme and GSH, as well IL6, IL17, MAPK and PPAR-γ, which detected by commercial kits and Western blot . Results It is proved that the four typical ‘cold’ property herbs effectively ameliorate the physical sign, thyroid function and metabolism profile in hyperthyroidism rats, but the four typical ‘heat’ property herbs showed no benefit. Moreover, the four typical ‘cold’ property herbs regulated energy metabolism, glutathione metabolism, taurine hypotaurine metabolism, thyroid hormone synthesis, arachidonic acid metabolism and linoleic acid metabolism and the inflammation mediated by inflammatory factor (IL6, IL17), Ca 2+ and MAPK signaling pathway. And the levels of UCP-1, Na + /K + -ATP enzyme, GSH, and the targets protein of IL6, IL17, MAPK and PPAR-γ were ameliorated by the four typical ‘cold’ property herbs. Conclusion The four typical ‘cold’ property herbs could alleviate hyperthyroidism by ameliorate thyroid hormone synthesis, restraining inflammation and oxidative stress via regulating energy metabolism, glutathione metabolism, taurine hypotaurine metabolism, arachidonic acid metabolism and linoleic acid metabolism and Ca 2+ /MAPK signaling pathway, which might be a useful strategy for treating hyperthyroidism.
研究领域:
民族药理学
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代谢组学
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药理学
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内分泌学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHARMACOLOGICAL RESEARCH
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2019
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IF 5.574
Rinkiko Suguro,Xiao-cong Pang,Zhong-wen Yuan,Si-yao Chen,Yi-Zhun Zhu,Ying Xie
Silybin (SB) is widely used to treat chronic liver diseases , especially this compound is much efficient for the treatments of alcoholic and non-alcoholic steatohepatitis (NASH). However, low bioavailability seriously limits wide-application of SB in biomedical niche. Prior to this study, we found that tangeretin (TG) could remarkably increase the bioavailability of SB by the inhibition of efflux transporters, which encourges us to therapeutical discovery of SB and TG combitional use against NASH. Here, we revealed that TG is capable of improving hepatic-protective activity of SB in mice with NASH by interfering liver oxidative stress, inflammation, and lipid accumulation. In addition, TG was observed to enhance the exposural level of SB in the plasma and liver of mice. Our metabolome assay confirmed that amino acid metabolism and lipid biosynthesis mostly accounted for combitional use of SB and TG to teat NASH in mice, basically biosynthesis of unsaturated fatty acids was mostly affected. Notably, significant inhibitions in fatty acid generating and transporting proteins such as G6PD, FABP4, LPL and CD36/FAT, and cholesterol metabolism enzyme CYP27A1 as well as nuclear transcription factors FXR , PPAR-γ, and LXR were illustrated to decipher therapeutic mechanisms of SB and TG against experimental NASH . Taken together, the strategy based combitional use of SB and TG has a potential-capacity to treat NASH.
研究领域:
肝病学
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药理学
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代谢组学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Nutrition
·
2023
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IF 5
Cao Feiwei,Ding Qinchao,Zhuge Hui,Lai Shanglei,Chang Kaixin,Le Chunyan,Yang Guorong,Valencak Teresa G.,Li Songtao,Ren Daxi
This present study was designed to explore the protective role of Lactobacillus plantarum ZJUIDS14 against Non-alcoholic Fatty Liver Disease (NAFLD) in a high-fat-diet (HFD)-induced C57BL/6 mice model. The probiotic (109 CFU/every other day) was administered by oral gavage for 12 weeks. We found that L. plantarum ZJUIDS14 intervention significantly alleviated HFD related hepatic steatosis, liver damage, insulin resistance, and increased hepatic expression of peroxisome proliferator activated receptor α (PPAR-α) while stimulating the activation of AMP-activated protein kinase (AMPK). Furthermore, L. plantarum ZJUIDS14 improved mitochondrial function as reflected by an increase in dynamin related protein 1 (DRP1) and a decrease of proteins associated with oxidative phosphorylation (OXPHOS) after the treatment. Additionally, mice from the L. plantarum ZJUIDS14 group had a restored intestinal flora and homeostasis involving Coprostanoligenes group, Ruminococcaceae UCG-014, Allobaculum, Ruminiclostridium 1, and Roseburia. Meanwhile, these five genera exhibited a significant (negative or positive) association with ileum inflammation mRNA levels and SCFA contents, by Spearman’s correlation analysis. In general, our data demonstrated that L. plantarum ZJUIDS14 mitigates hepatic steatosis and liver damage induced by HFD. Specifically, they strengthened the integrity of the intestinal barrier, regulated gut microbiota, and improved mitochondrial function. Our data provide an experimental basis for L. plantarum ZJUIDS14 as a promising candidate to prevent NAFLD.
研究领域:
微生物学
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营养学
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分子生物学
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胃肠病学
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代谢学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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