Journal of Taibah University for Science
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2024
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IF 2.8
Lingyu Wang,Ruolan Li,Meiyan Li,Jiayi Sun,Jia Liu,Min Xie,Yunhui Chen,Songqi Tang
This study aimed to investigate the inhibitory effect of Zuojin Pill (ZJP) on KYSE 150 cells and xenograft tumours of the digestive tract cancer – esophageal cancer (EC) and its underlying mechanism. Initially, in vivo research demonstrated that oral administration of ZJP effectively inhibited the growth of EC tumours, and in vitro studies revealed that ZJP suppressed the proliferation, migration, and invasion of cells. Then, network pharmacology prediction identified the core target, active ingredient, and involvement of the PI3K-Akt signalling pathway in ZJP treatment of EC. Cell studies validated that ZJP affected the expression of core targets, and its active ingredients inhibited the proliferation of cells. Additionally, ZJP was shown to induce cell apoptosis, decrease mitochondrial membrane potential, and increase the level of intracellular oxidative stress. Further experimental verifications suggested that the inhibitory effects of ZJP on EC might be attributed to the modulation of PI3 K/Akt signalling pathways.
研究领域:
肿瘤学
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药理学
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分子生物学
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DOI
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2025
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IF 6.2
Yi Wu,Yilin Ling,Yuqi Yang,Haoxing Long,Linghao Kong,Peiyang Song,Yujie Lu,Wanqiu Zhao,Wei Wang,Jingrong Zhu,Nan Wang
Obesity is a growing global health concern associated with severe metabolic disorders, necessitating the development of safer and more effective therapeutic strategies. Soybean sprout peptides (SSPs), derived from germinated soybeans, are bioactive compounds with potential antiobesity effects. This study aimed to investigate the molecular mechanisms of SSPs through an integrated approach combining network pharmacology, molecular docking, and in vivo experiments. SSP sequences were identified using UPLC-Orbitrap-MS/MS, and their bioactivity was predicted using PeptideRanker. Network pharmacology identified key SSP targets, including AKT1, SRC, STAT3, ESR1, FOS, and NFKB1, which are implicated in the PI3K-Akt and JAK-STAT pathways. Molecular docking validated strong interactions between SSPs and these targets. In vivo, SSP administration significantly reduced body weight gain, abdominal fat accumulation, and serum lipid abnormalities in high-fat-diet-induced obese mice while modulating gut microbiota composition by restoring the Firmicutes-to-Bacteroidetes ratio and reducing pathogenic taxa. Fecal metabolomics revealed that SSP alleviated oxidative stress and improved amino acid metabolism, contributing to its antiobesity effects. These findings suggest that SSP holds promise as a functional food ingredient or nutraceutical for obesity prevention and management.
研究领域:
营养学
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分子生物学
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药理学
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DOI
PubMed
高影响因子
CURRENT ISSUES IN MOLECULAR BIOLOGY
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2024
·Vol. 46
·期 10
·11359-11374
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IF 2.8
Xin Li,Kai Zheng,Hao Chen,Wei Li
While Ginsenoside Re has been shown to protect the central nervous system, reports of its effects on memory in the model of scopolamine-induced memory impairment are rare. The aim of this study was to investigate the effects of Ginsenoside Re on scopolamine (SCOP)-induced memory damage and the mechanism of action. Male ICR mice were treated with SCOP (3 mg/kg) for 7 days and with or without Ginsenoside Re for 14 days. As evidenced by behavioral studies (escape latency and cross platform position), brain tissue morphology, and oxidative stress indicators after Ginsenoside Re treatment, the memory damage caused by SCOP was significantly ameliorated. Further mechanism research indicated that Ginsenoside Re inhibited cell apoptosis by regulating the PI3K/Akt/Nrf2 pathway, thereby exerting a cognitive impairment improvement effect. This research suggests that Ginsenoside Re could protect against SCOP-induced memory defects possibly through inhibiting oxidative stress and cell apoptosis.
研究领域:
神经科学
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药理学
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氧化应激
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PubMed
高影响因子
CURRENT MEDICINAL CHEMISTRY
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2024
·Vol. 32
·期 33
·7357-7376
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IF 3.5
Jinna Di,Wei Bo,Chun Wang,Chunying Liu
IntroductionThe effectiveness of therapy is strongly impacted by the resistance of lung cancer cells to cisplatin. The objective of this research is to characterize the impact of ailanthone on cisplatin resistance in non-small cell lung cancer (NSCLC) and examine any potential in vivo and in vitro molecular pathways.MethodsFollowing treatment of A549/DDP cells with ailanthone and cisplatin, cell survival and apoptosis were measured using flow cytometry and Cell Counting Kit-8 (CCK8) assays, respectively. mRFP-GFP-LC3 adenovirus transfection was used to track autophagy, and protein expression levels were analyzed by western blotting. Hematoxylin and eosin (H&E) staining was used after the organs of the mice were removed for in vivo investigations. In A549/DDP cells, ailanthone and cisplatin together induced autophagy and apoptosis in a dose and time-dependent manner (p< 0.05). After receiving combined treatment with ailanthone and cisplatin, the expression levels of cleaved caspase-3, Bcl-2, cleaved PARP, Beclin 1, LC3B-II were considerably elevated by inhibiting the PI3K/AKT/mTOR signaling pathway.ResultsOur findings show that ailanthone, without causing adverse effects in vivo, greatly suppressed the growth of A549/DDP-grafted tumors and improved the anti-tumor efficaciousness of cisplatin.ConclusionAccording to this study, ailanthone may increase sensitivity to cisplatin and promote autophagy and death in NSCLC A549/DDP cells through the signaling pathway of PI3K/AKT/mTOR.
研究领域:
肿瘤学
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分子生物学
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药理学
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转化医学
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细胞信号转导
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DOI
高影响因子
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
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2025
·Vol. 136
·期 6
·e70045
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IF 3.3
Dong Yan,Yuanwei Fu,Jie Mei,Junhong Wang,Ayijiang Jiamaliding,Ying Liu,Zanmei Zhao,Qingbian Ma
Phosgene, used in large‐scale industrial production, is highly toxic and irritant. Accidental exposure can lead to varying degrees of injuries, with severe cases potentially resulting in acute lung injury or acute respiratory distress syndrome, resulting in a mortality rate of 40%–50%. The indirect damages of phosgene (inflammation and oxidative stress) are considered important factors in phosgene‐induced acute lung injury (P‐ALI). The expression of Liver X Receptor α (LXRα) significantly reduces during periods of inflammation. LXRs were initially discovered to be highly expressed in the liver, whereas LXRs are expressed in immune cells and vascular endothelial cells, playing a significant role in anti‐inflammatory and antioxidant responses. LXRα may have pulmonary protection in P‐ALI. However, evidence to verify this association is still lacking. In this study, rats were divided into six groups to explore the potential role of LXRα in P‐ALI. This study found that GW3965 effectively activated LXRα, upregulated its expression and downregulated the levels of proinflammatory cytokines, inhibited malondialdehyde activity while enhancing superoxide dismutase activity, suppressed apoptosis and ameliorated the pathological processes of P‐ALI, ultimately exerting pulmonary protection in P‐ALI. Further validation revealed that the pulmonary protective effect of LXRα may be associated with the PI3K/Akt and NF‐kB signalling pathways.
研究领域:
药理学
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呼吸病学
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2025
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IF 5.4
Yuewei Lin,Qi He,Baihao Chen,Zuang Li,Chuyi Chen,Wei Deng,Haishan Li,Jiamin Yang,Bin Mai,Zhen Zhang,Dongping Wang,Huizhi Guo,Yongchao Tang,Kai Yuan,Guoye Mo,Liangliang Xu,Yongxian Li,Haibin Wang,Shuncong Zhang
Ethnopharmacological relevance Zuogui Pill (ZGP) is a classic herbal formula in Traditional Chinese Medicine, primarily used to tonify the kidney and replenish essence, and is widely applied in treating various kidney deficiency-related conditions. Over time, ZGP has demonstrated significant efficacy in addressing symptoms such as fatigue, weakness, and soreness of the lower back and knees, which are often caused by kidney deficiency. According to Traditional Chinese Medicine theory, the kidneys govern the bones, meaning that sufficient kidney essence is closely related to bone strength. By nourishing the kidneys and replenishing essence, ZGP helps to increase bone density and improve bone microstructure, making it an important therapeutic option for osteoporosis. Aim of the study To investigate the protective effects of ZGP in iron overload-induced osteoporosis and elucidate its molecular mechanisms through the activation of the Phosphoinositide 3-Kinase (PI3K)/Protein Kinase B (AKT) and Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2)/Heme Oxygenase-1 (HO-1) pathways, which reduce oxidative stress, inhibit osteoblast apoptosis, and promote osteoblast differentiation and mineralization. Materials and methods An in vivo mouse model of iron overload-induced osteoporosis and an in vitro MC3T3-E1 osteoblast model were used. In vitro experiments involved the use of ZGP containing-serum, along with transcriptomic analysis, Western blot, flow cytometry, TUNEL staining, and immunofluorescence, to assess the effects on oxidative stress, mitochondrial function, and apoptosis. In vivo experiments evaluated the effects of ZGP on bone mass, oxidative stress, and apoptosis using Micro-computed tomography (micro-CT), Hematoxylin and eosin staining (H&E), TUNEL staining, and immunohistochemistry. Results The study found that ZGP containing-serum significantly enhanced the viability of osteoblasts induced by iron overload and reduced apoptosis through the reactive oxygen species (ROS)-mediated Phosphoinositide 3-Kinase (PI3K) / Protein Kinase B (AKT) pathway while mitigating mitochondrial damage. In vivo , micro-computed tomography results showed that ZGP improved bone mass, and decreased ROS and apoptosis, consistent with the in vitro findings. Conclusion ZGP demonstrates significant antioxidant and anti-apoptotic effects in iron overload-induced osteoporosis, primarily through the ROS-mediated PI3K/AKT pathway and by reducing mitochondrial damage. These findings suggest that ZGP may be a promising therapeutic agent for treating osteoporosis associated with iron overload.
研究领域:
民族药理学
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分子生物学
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医学
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
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2025
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IF 4.7
Shengli Quan,Jinhua Li,Shuxian Ding,Xingjie Zhuo,Yuanxiao Yang,Qin Li
Background Parkinson's disease is a progressive neurodegenerative disorder of the brain, that commonly leads to motor dysfunction and dementia. Artemether is a semi - synthetic derivative of artemisinin, which is extracted from the traditional Chinese herb Artemisia annua. And it is widely used in the treatment of malaria. Recent studies have shown that it exhibits significant neuroprotective effects and holds potential for the treatment of neurodegenerative diseases. However, its effects and mechanisms in the context of Parkinson 's disease remain unclear. Objective To explore Artemether's neuroprotective effects and mechanisms in 6-OHDA-induced PD models. Methods Network pharmacology and molecular docking were used to predict potential pathways and targets of Artemether against Parkinson's disease. PD models were established using 6-OHDA-induced PC12 cells and C57BL/6 mice to assess Artemether's effects and mechanisms. Results Through network pharmacological analysis and molecular docking verification, it was found that Artemether against Parkinson 's disease was related to apoptosis-related signaling pathways, and Artemether had good spontaneous binding activity with key targets PI3K, Akt, GSK-3β, and Bcl-2. Furthermore, the related experimental results showed that Artemether could increase the cell viability of PC12 cells induced by 6-OHDA, reduce intracellular ROS level, increase mitochondrial membrane potential and decrease apoptosis. In addition, Artemether improved motor dysfunction and cognitive dysfunction in Parkinson 's disease mice, and increased the expression of dopamine neurons in both the Substantia Nigra and Striatum. Conclusion Artemether exerted neuroprotective effects in Parkinson 's disease models in vitro and in vivo induced by 6-OHDA through the PI3K/Akt/GSK-3β signaling pathway.
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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PubMed
高影响因子
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
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2025
·Vol. 66
·期 5
·21-21
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IF 4.7
Xianyang Liu,Hangjia Zuo,Chao Wu,Na Li,Qian Zhou,Fan Cao,Baorui Chu,Shuhao Zeng,Hui Feng,Yakun Wang,Fengyang Lei,Ke Hu,Shengping Hou
Purpose:Uveitis is an immune-mediated ocular disorder that poses a significant threat to vision, particularly among young and middle-aged adults. The treatment of uveitis is complicated by the presence of the blood-retinal barrier (BRB), which restricts the passage of large molecular drugs into the eye, thus limiting effective therapeutic options. The primary objective of this study is to identify a novel therapeutic agent capable of treating uveitis and explore its underlying mechanism.Methods:In this study, we used a mouse model of experimental autoimmune uveitis (EAU) induced by interphotoreceptor retinoid-binding protein (IRBP) and lipopolysaccharide (LPS) and interferon-gamma (IFN-γ)-induced inflammatory BV2 cells. Evans blue and fundus fluorescein angiography (FFA) experiments were performed to evaluate the destruction of BRB. Silt lamp and hematoxylin and eosin (H&E) staining were conducted to evaluate the inflammatory response. In vivo proteomics and Western blot were carried to investigate the underlying mechanisms.Results:Our study reveals that Muscone significantly alleviates EAU and restores the integrity of BRB. Moreover, Muscone treatment markedly downregulated inflammatory factors within the retinas and BV2 cells. In vivo proteomic combined with liquid chromatography-mass spectrometry (LC-MS) has elucidated that Muscone exerts its anti-inflammatory effects by modulating the PI3K-AKT signaling pathway. Moreover, by using LY294002 to specifically inhibit PI3K, we observed a marked decrease in inflammatory phenotype and BRB destruction of EAU.Conclusions:In summary, this study establishes the protective efficacy of Muscone against the progression of EAU and provides insights into the molecular mechanisms responsible for its therapeutic action.
研究领域:
免疫学
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眼科学
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药理学
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分子生物学
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神经炎症
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DOI
PubMed
高影响因子
Chemical Biology & Drug Design
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2022
·Vol. 101
·期 1
·24-39
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IF 2.873
Donglin Zhang,Aiqin Pan,Jianke Gu,Renfeng Liao,Xueyu Chen,Zhaozhu Xu
MicroRNAs (miRs) are implicated in heart failure (HF). Thereby, we aim to uncover the role of miR-144-3p in HF. Doxorubicin (Dox)-induced HF model was constructed in rats and cardiomyocytes H9C2, and the cardiac function was determined using ultrasound cardiogram. Morphology of cardiac tissue was observed using hematoxylin–eosin (H&E) staining. The viability and apoptosis of Dox-treated and transfected cardiomyocytes were determined using Cell Counting Kit-8 (CCK-8) assay and flow cytometry. Relative expressions of the HF-associated miRs (including miR-144-3p), suppressor of cytokine signaling 2 (SOCS2), apoptosis- and phosphoinositide 3-kinase (PI3K)/AKT pathway-related factors (B-cell lymphoma 2, Bcl-2; Bcl-2 associated X protein, Bax; cleaved [C] capsase-3; phosphoinositide 3-kinase, PI3K; phosphorylated-PI3K, p-PI3K; p-AKT; AKT) were measured with quantitative real-time polymerase chain reaction or Western blot. Target gene of miR-144-3p was predicted by Starbase and TargetScan and confirmed with dual-luciferase reporter assay. Dox caused rat cardiac dysfunction, aggravated cardiac injury, decreased cardiomyocytes viability, and the expression of miR-144-3p, Bcl-2, and phosphorylation of both PI3K and AKT yet the upregulated those of Bax and C caspase-3, which was reversed by upregulating miR-144-3p, whereas downregulating miR-144-3p did oppositely. SOCS2 was the target gene of miR-144-3p, Dox promoted SOCS2 expression, which was reversed by upregulating miR-144-3p, while downregulating miR-144-3p did conversely. In addition, silencing SOCS2 reversed the effects of miR-144-3p downregulation in Dox-treated cardiomyocytes. Upregulating miR-144-3p alleviated Dox-induced cardiac dysfunction and cell apoptosis via targeting SOCS2, providing a novel evidence of miR-144-3p in HF.
研究领域:
心脏病学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
Bioengineered
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2021
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IF 3.269
Yingnan Dai,Yeping Chen,Guoqian Wei,Li Zha,Xueqi Li
Ivabradine (Iva), a heart rate reducing agent that specifically inhibits the pacemaker I(f) ionic current, has been demonstrated to be cardioprotective in many cardiovascular diseases. Autophagy is an evolutionarily conserved metabolic process that regulates cardiac homeostasis. This study is aimed to explore whether autophagy is functionally involved in the cardioprotective effect of Iva in a rat model of myocardial infarction (MI). We observed that Iva treatment (po, 10 mg/kg/day) showed significant recovery on the hemodynamics parameters in MI rats, including left ventricular systolic pressure, left ventricular end diastolic pressure, and maximal ascending/descending rate of left ventricular pressure. Also, Iva treatment dramatically decreased infarct size, inhibited myocardial apoptosis, and reduced the levels of pro-inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 in MI rats. Moreover, Iva treatment enhanced autophagy and inhibited PI3K/AKT/mTOR/p70S6K pathway in MI rats. Simultaneously, we observed that autophagy enhancer rapamycin (ip, 10 mg/kg/day) showed similar cardioprotective effects with Iva. Furthermore, we observed that addition of autophagy inhibitor 3-methyladenine (ip, 10 mg/kg/day) counteracted the therapeutic effect of Iva, addressing that Iva attenuated post-MI cardiac injury by enhancing autophagy. In summary, these findings demonstrated that Iva attenuated MI in rats by enhancing autophagy, and PI3K/AKT/mTOR/p70S6K pathway might be involved in the process. Autophagy activation by Iva may be a potential therapeutic strategy for the treatment of MI.
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
PSYCHOPHARMACOLOGY
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2022
·Vol. 239
·期 11
·3579-3593
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IF 4.415
Mou Chen-Ye,Xie Yan-Fei,Wei Jia-Xin,Wang Qi-Yao,Le Jing-Yang,Bao Yong-Jie,Zhang Pan-Pan,Mao Yue-Chun,Huang Xing-Han,Pan Han-Bo,Naman C. Benjamin,Liu Lin,Liang Hong-Ze,Wu Xiang,Xu Jia,Cui Wei
Rationale
Tau hyperphosphorylation and aggregation is considered as a main pathological mechanism underlying Alzheimer’s disease (AD). Rose Bengal (RB) is a synthetic dye used for disease diagnosis, which was reported to inhibit tau toxicity via inhibiting tau aggregation in Drosophila . However, it was unknown if RB could produce anti-AD effects in rodents. Objectives The research aimed to investigate if and how RB could prevent β-amyloid (Aβ) oligomers-induced tau hyperphosphorylation in rodents. Methods and results RB was tested in vitro (0.3–1 μM) and prevented Aβ oligomers-induced tau hyperphosphorylation in PC12 cells. Moreover, RB (10–30 mg/kg, i.p. ) effectively attenuated cognitive impairments induced by Aβ oligomers in mice. Western blotting analysis demonstrated that RB significantly increased the expression of pSer473-Akt, pSer9-glycogen synthase kinase-3β (GSK3β) and reduced the expression of cyclin-dependent kinase 5 (CDK5) both in vitro and in vivo. Molecular docking analysis suggested that RB might directly interact with GSK3β and CDK5 by acting on ATP binding sites. Gene Ontology enrichment analysis indicated that RB might act on protein phosphorylation pathways to inhibit tau hyperphosphorylation. Conclusions RB was shown to inhibit tau neurotoxicity at least partially via inhibiting the activity of GSK3β and CDK5, which is a novel neuroprotective mechanism besides the inhibition of tau aggregation. As tau hyperphosphorylation is an important target for AD therapy, this study also provided support for investigating the drug repurposing of RB as an anti-AD drug candidate.
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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病理学
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产品关联
DOI
PubMed
高影响因子
American Journal of Translational Research
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2021
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IF 4.06
Lingli Huang,Di Xiao,Tianyu Wu,Xin Hu,Jun Deng,Xinjian Yan,Jingtao Wu,Simeng Xu,Xiaoping Yang,Gaofeng Li
Sorafenib is a first-line drug to treat advanced hepatocellular carcinoma (HCC), which can prolong the median overall survival of patients by approximately 3 months. Phenformin is a biguanide derivative that has been shown to exhibit antitumor activity superior to that of metformin. We herein explored the ability of phenformin to enhance the anti-cancer activity of sorafenib against HCC and the mechanisms underlying such synergy. The Hep-G2 and SMMC-7721 HCC cell lines were treated with sorafenib and/or phenformin, after which the proliferation of these cells was evaluated via MTT and colony formation assays, while invasion and apoptotic cell death were evaluated via Transwell and flow cytometry assays, respectively. In addition, protein levels were assessed by Western blotting, drug synergy was assessed with the CompuSyn software, and xenograft models were established by implanting Hep-G2 cells into nude mice and then assessing drug antitumor efficacy. Sorafenib and phenformin exhibited a synergistic ability to suppress HCC cell proliferation, migration, and survival. Phenformin further bolstered the ability of sorafenib to inhibit the CRAF/ERK and PI3K/AKT/mTOR pathways. Strikingly, the combination of these two drugs achieved better in vivo efficacy in a murine model system, without causing significant weight loss or hepatorenal toxicity. Sorafenib and phenformin can synergistically suppress CRAF/ERK and PI3K/AKT/mTOR pathway activation in HCC cells, and may thus represent a promising approach to treating this deadly cancer.
研究领域:
肿瘤学
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分子生物学
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药理学
✓ 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）