International Journal of Nanomedicine
·
2016
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IF 4.32
Shan Jiang,Rongrong Zhu,Xiaolie He,Jiao Wang,Mei Wang,Yechang Qian,Shilong Wang
Curcumin (Cur) is a promising photosensitizer that could be used in photodynamic therapy. However, its poor solubility and hydrolytic instability limit its clinical use. The aim of the present study was to encapsulate Cur into solid lipid nanoparticles (SLNs) in order to improve its therapeutic activity. The Cur-loaded SLNs (Cur-SLNs) were prepared using an emulsification and low-temperature solidification method. The functions of Cur and Cur-SLNs were studied on the non-small cell lung cancer A549 cells for photodynamic therapy. The results revealed that Cur-SLNs induced ~2.27-fold toxicity higher than free Cur at a low concentration of 15 μM under light excitation, stocking more cell cycle at G2/M phase. Cur-SLNs could act as an efficient drug delivery system to increase the intracellular concentration of Cur and its accumulation in mitochondria; meanwhile, the hydrolytic stability of free Cur could be improved. Furthermore, Cur-SLNs exposed to 430 nm light could produce more reactive oxygen species to induce the disruption of mitochondrial membrane potential. Western blot analysis revealed that Cur-SLNs increased the expression of caspase-3, caspase-9 proteins and promoted the ratio of Bax/Bcl-2. Overall, the results from these studies demonstrated that the SLNs could enhance the phototoxic effects of Cur.
研究领域:
药学
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纳米技术
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
MOLECULAR NUTRITION & FOOD RESEARCH
·
2019
·Vol. 63
·期 14
·1801432
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IF 4.653
Lele Yang,Jinchao Wei,Feiya Sheng,Peng Li
Scope Saturated free fatty acids (FFAs) induce hepatocyte lipotoxicity, wherein oxidative stress–associated mitochondrial dysfunction is mechanistically involved. Chlorogenic acid (CGA), a potent antioxidant and anti-inflammatory compound, protects against high-fat-diet-induced oxidative stress and mitochondrial dysfunction in liver. This study investigates whether CGA protects against FFA-induced hepatocyte lipotoxicity via the regulation of mitochondrial fission/fusion and elucidates its underlying mechanisms. Methods and results AML12 cell, a non-transformed hepatocyte cell line, is treated with palmitate. Here, it is shown that CGA prevents palmitate-induced lipotoxicity by activation of SIRT1 regulated mitochondrial morphology. CGA treatment mitigates oxidative stress and mitochondrial dysfunction, as evidenced by a decrease in reactive oxygen species (ROS) production, and an increase in mitochondrial mass and mitochondrial membrane potential. CGA also significantly decreases Bax expression and thereby reduces mitochondria-mediated caspase-dependent apoptosis. Mechanistically, CGA attenuates ROS-induced mitochondrial fragmentation by inhibiting dynamin-related protein 1 (Drp1) and enhancing Mfn2 expression. In contrast, the inhibitory effects of CGA on the generation of mitochondrial ROS and Drp1 are blocked by siRNA knockdown of SIRT1. Conclusion Collectively, these findings show that supplementation with CGA protects hepatocytes from FFA-induced lipotoxicity through activation of SIRT1, which reverses the oxidative stress and dysfunction of mitochondrial biogenesis directly.
研究领域:
药理学
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细胞生物学
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分子生物学
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肝病学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2019
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IF 3.845
Wei Xia,Zhu Qingfen,Liu Na,Xu Lihua,Wei Sheng,Fan Zhiyun,Sun Changhua,Zhao Yan,Qiao Mingqi,Wu Jibiao,Hu Defu,Wang Yang,Sun Peng
Zhenlong Xingnao Capsule (ZXC) is a Tibetan medicine used to treat ischemic stroke. In this study, we determined the in vitro and in vivo effects of ZXC on reactive oxygen species (ROS) in a mouse BV-2 microglial cell hypoxia-reoxygenation and rat middle cerebral artery occlusion infarction models. We aimed to clarify the role of ZXC in cerebral ischemia protection; reveal amino acid neurotransmitter changes in the frontal cortex after drug intervention; determine mRNA and protein expression changes in Bcl-2, Bax, caspase-3, P38, and nuclear factor (NF)-кB in the frontal cortex and changes in antioxidant indices in the brain; and elucidate the mechanisms underlying ZXC action. After hypoxia-reoxygenation, ROS levels were significantly increased in BV-2 cells, and their levels decreased after treatment with ZXC. ZXC had protective effects on ischemic/anoxic injury in vitro and in vivo by downregulating the expressions of caspase-3 and NF-кB mRNA during ischemia and reperfusion and that of p38 and caspase-3 during acute ischemia and reperfusion as well as the steady-state levels of excitatory amino acids/inhibitory amino acids and by improving the total antioxidant capacity and total superoxide dismutase activities during ischemia. These findings provide new molecular evidence for the mechanisms underlying ZXC action.
研究领域:
药理学
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神经科学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
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2019
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IF 4.315
JiaJia Wang,YanJun Li,Ke Lai,QiMei Zhong,Konstantin A. Demin,Allan V. Kalueff,Cai Song
Neuroinflammation and metabolic deficits contribute to the etiology of human affective disorders, such as anxiety and depression. The zebrafish ( Danio rerio ) has recently emerged as a powerful new model organism in CNS disease modeling. Here, we exposed zebrafish to 2% glucose and 10% cholesterol for 19 days to experimentally induce type 2 diabetes (DM) and to assess stress responses, microglia , inflammation and apoptosis . We analyzed zebrafish anxiety-like behavior in the novel tank and light-dark box (Days 15–16) tests, as well as examined their biochemical and genomic biomarkers (Day 19). Confirming DM-like state in zebrafish, we found higher whole-body glucose, triglyceride , total cholesterol, low-density lipoprotein levels and glucagon mRNA expression, and lower high-density lipoprotein levels. DM zebrafish also showed anxiety-like behavior, elevated whole-body cortisol and cytokines IFN-γ and IL-4, as well as higher brain mRNA expression of the glucocorticoid receptor , CD11b (a microglial biomarker), pro-inflammatory cytokines IL-6 and TNF-α (but not IL-1β or anti-inflammatory cytokines IL-4 and IL-10), GFAP (an astrocytal biomarker), neurotrophin BDNF , its receptors p75 and TrkB, as well as apoptotic Bax and Caspase-3 (but not BCl-2 ) genes. Collectively, this supports the overlapping nature of DM-related affective pathogenesis and emphasizes the role of peripheral and central inflammation and apoptosis in DM-related affective and neuroendocrine deficits in zebrafish.
研究领域:
神经科学
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代谢紊乱
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行为科学
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炎症研究
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
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2021
·Vol. 25
·期 15
·7472-7484
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IF 5.31
Pengfei Zhu,Zhengchao Wang,Zhenxing Sun,Bokai Liao,Yu Cai
Osteoarthritis (OA) is a common joint disease that mainly affects the diarthrodial joints. Treatments for OA include non-pharmacological interventions, topical and oral therapies, intra-articular therapies and joint surgery. However, all the treatments mentioned above mainly aim to control the symptoms instead of improving or reversing the joint condition. In this research, we observed the effect of recombinant platelet-derived growth factor (PDGF)-BB on OA in a monosodium iodoacetate (MIA)–induced rat model and revealed the possible mechanisms. In vitro, the level of inflammation in the chondrocytes was gradually alleviated, and the apoptosis rate was gradually decreased by PDGF-BB at increasing concentrations. The levels of p-p38, Bax and caspase-3 decreased, and the level of p-Erk increased with increasing PDGF-BB concentration. In vivo, PDGF-BB could significantly reverse chondrocyte and matrix loss. Furthermore, high concentrations of PDGF-BB could alleviate cartilage hyperplasia to remodel the tissue. The level of collagen II was up-regulated, and the levels of collagen X and apoptosis were down-regulated by increasing concentrations of PDGF-BB. In conclusion, recombinant PDGF-BB alleviated OA by down-regulating caspase-3-dependent apoptosis. The effects of PDGF-BB on OA mainly include inhibiting chondrocyte loss, reducing cartilage hyperplasia and osteophyte formation, and regulating collagen anabolism.
研究领域:
骨科
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分子生物学
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细胞生物学
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药理学
✓ 已验证
DOI
PubMed
高影响因子
ACS Omega
·
2024
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IF 3.7
Xiaotong Duan,Jingwen Ao,Ming Yu,Sali Li,Xiaofei Li,Jianyong Zhang
Cantharidin (CTD) is a compound of mylabris with antitumor activity, and CTD can potentially cause toxicity, especially hepatotoxicity. The classical Traditional Chinese Medicine prescription Shuganning injection (SGNI) exerts notable anti-inflammatory and hepatoprotective effects. However, the protective property and mechanism of SGNI against CTD-induced liver injury (CTD-DILI) have not yet been elucidated. To investigate the effective compounds, potential targets, and molecular mechanism of SGNI against CTD-DILI, network pharmacology combined with experiments were performed. This study found that SGNI could act with 62 core therapeutic targets, regulate multiple biological processes such as apoptosis, and oxidative stress, and influence apoptotic and p53 signaling pathways to treat CTD-DILI. Subsequently, HepaRG cell experiments demonstrated that SGNI pretreatment significantly increased the levels of GSH-Px and SOD, inhibiting the apoptosis induced by CTD. In vivo, according to H&E staining, SGNI can reduce the degeneration of hepatocytes and cytoplasmic vacuolation in mice exposed to CTD. Western blot analysis results indicated that SGNI pretreatment significantly suppressed the expressions of Caspase-3 and Bax while increasing the expression of Bcl-2. In conclusion, SGNI acted as a protective agent against CTD-DILI by inhibiting apoptosis.
研究领域:
药理学
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毒理学
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中药学
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细胞生物学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
npj Parkinsons Disease
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2025
·Vol. 11
·期 1
·1-16
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IF 8.2
Chen Wen,Wang Haobo,Ye Xiang,Hao Xingkai,Yan Fujie,Wu Jian,Li Danyang,Wang Yan,Xu Lizhou
Plant-derived extracellular vesicles (EVs) show health benefits. Gardenia jasminoides Ellis, known for its neuroprotective properties, lacks therapeutic investigation on gardenia-derived extracellular vesicles (GDEVs). This study investigated the value of GDEVs in Parkinson’s disease (PD) using rotenone (Rot)-induced Parkinsonism models in dopaminergic PC12 neuron cells and Caenorhabditis elegans . PD features apoptosis in dopaminergic neurons, while GDEVs alleviate PD by mitigating mitochondrial-mediated apoptosis. Specifically, GDEVs improve Rot-induced mitochondrial dysfunction to reduce cytochrome C release and apoptosis. Consequently, GDEVs reduce the risk of PD by lowering α-synuclein levels and regulating dopamine release. RNA sequencing and subsequent studies showed that GDEVs reduce p38 MAPK and p53 phosphorylation levels, and increase the Bcl-2/Bax ratio to prevent apoptosis in PC12 cells. In Caenorhabditis elegans , we verified that GDEVs reduce PD progression by increasing dopaminergic neurons using BZ555 mutants, and enhance dopamine release and motility. This study highlights the therapeutic potential of GDEVs in preventing neurodegenerative diseases.
研究领域:
神经科学
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植物学
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药理学
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细胞生物学
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分子生物学
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神经退行性疾病
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生物医学研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2025
·
IF 14.1
Yanan Wang,Xutao Ma,Xinyuan Wang,Liru Liu,Xue Zhang,Qiuyue Wang,Yingfei Zhu,Huanhua Xu,Liangmin Yu,Zhiyu He
The scarcity of effective neuroprotective agents and the presence of blood-brain barrier (BBB)-mediated extremely inefficient intracerebral drug delivery are predominant obstacles to the treatment of cerebral ischemic stroke (CIS). Herein, ROS-responsive borneol-based amphiphilic polymeric NPs are constructed by using traditional Chinese medicine borneol as functional blocks that served as surface brain-targeting ligand, inner hydrophobic core for efficient drug loading of membrane-permeable calcium chelator BAPTA-AM, and neuroprotective structural component. In MCAO mice, the nanoformulation (polymer: 3.2 mg·kg −1 , BAPTA-AM: 400 µg·kg −1 ) reversibly opened the BBB and achieved high brain biodistribution up to 12.7%ID/g of the total administered dose after 3 h post single injection, effectively restoring intracellular Ca 2+ and redox homeostasis, improving cerebral histopathology, and inhibiting mitochondrial PI3K/Akt/Bcl-2/Bax/Cyto-C/Caspase-3,9 apoptosis pathway for rescuing dying neurons (reduced apoptosis cell from 59.5% to 7.9%). It also remodeled the inflammatory microenvironment in cerebral ischemic penumbra by inhibiting astrocyte over-activation, reprogramming microglia polarization toward an anti-inflammatory phenotype, and blocking NF-κB/TNF- α /IL-6 signaling pathways. These interventions eventually reduced the cerebral infarction area by 96.3%, significantly improved neurological function, and restored blood flow reperfusion from 66.2% to ≈100%, all while facilitating BBB repair and avoiding brain edema. This provides a potentially effective multiple-stage sequential treatment strategy for clinical CIS.
研究领域:
药学
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神经科学
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药物递送系统
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传统中药
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中风治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Enjuan Shi,Xiaoqin Wang,Huili Jing,Yayuan Xu,Lei Feng,Fatao He,Dajing Li,Zhuqing Dai
In this study, N -Methyl-N-nitrosourea (MNU) was intraperitoneally injected to construct a mouse retinitis pigmentosa (RP) model to evaluate the protective effect of chitosan and β-carotene on RP. The results demonstrated that chitosan synergized with β-carotene significantly reduced retinal histopathological structural damage in RP mice. The co-treatment group of β-carotene and chitosan restored the retinal thickness and outer nuclear layer thickness better than the group treated with the two alone, and the thickness reached the normal level. The content of β-carotene and retinoids in the liver of chitosan and β-carotene co-treated group increased by 46.75 % and 20.69 %, respectively, compared to the β-carotene group. Chitosan and β-carotene supplement suppressed the expressions of Bax, Calpain2, Caspase3, NF-κB, TNF-α, IL-6, and IL-1β, and promoted the up-regulation of Bcl2. Chitosan and β-carotene interventions remarkably contributed to the content of SCFAs and enhanced the abundance of Ruminococcaceae , Rikenellaceae , Odoribacteraceae and Helicobacteraceae . Correlation analysis demonstrated a strong association between gut microbiota and improvement in retinitis pigmentosa. This study will provide a reference for the study of the gut-eye axis.
研究领域:
眼科学
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药理学
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分子生物学
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微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ARCHIV DER PHARMAZIE
·
2024
·
IF 4.3
Jiahong Su,Xingyue Wang,Sha Li,Xu Wu,Mingxing Li,Fukuan Du,Shuai Deng,Jing Shen,Yueshui Zhao,Zhangang Xiao,Yu Chen
Glycyrrhetinic acid (GA) is a naturally occurring triterpene compound. The aim of this study was to employ the pharmacophore hybrid strategy to merge GA with various dithiocarbamates and obtain novel compounds with better antitumor activities. We present a two-step synthetic protocol wherein the GA derivative underwent reaction with carbon disulfide and various secondary amines in a one-pot manner under mild conditions, facilitating the preparation of a series of structurally novel GA-dithiocarbamate derivatives. Bioassay screening revealed that the representative compound 3c demonstrated the capacity to reduce the mitochondrial membrane potential in Hep3B and Huh-7 cells, induce nuclear apoptosis, inhibit invasion and migration, and prompt both early and late apoptosis. Furthermore, our research findings indicated that this apoptotic phenomenon may be associated with the expression of Bcl-2, Bax, Bak, PARP, and cleaved-PARP proteins. Utilizing network pharmacology for predicting core targets and signaling pathways of compound 3c for hepatocellular carcinoma (HCC) treatment involved employing molecular docking models to demonstrate high affinity between compound and target protein. In conjunction with Western blot analysis, compound 3c may impact HCC through the PI3K-AKT-mTOR pathway.
研究领域:
药理学
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肿瘤学
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药物化学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY
·
2015
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IF 2.084
Shimei Qi,Xianjuan Kou,Jun Lv,Zhilin Qi,Liang Yan
Our results showed that ampelopsin significantly inhibited cell viability of hepatoma HepG2 cells using MTT assay. We further investigated the mechanism of anticancer activity by ampelopsin, it showed that ampelopsin induced apoptosis of HepG2 cells using DAPI assay and flow cytometry, which was confirmed by activation of PARP. Next, activation of the caspase cascades were demonstrated, including caspase-8, -9 and -3. We also found that ampelopsin increased the levels of death receptor 4 (DR4), death receptor 5 (DR5) and decreased the expression of Bcl-2 protein, which led to an increase of the Bax/Bcl-2 ratio. Meanwhile, the release of cytochrome c from mitochondria was observed. Ampelopsin decreased the levels of iNOS and COX-2 but had no impact on the level of reactive oxygen species (ROS). In addition, ampelopsin activated ERK1/2 and P38, but little JNK1/2 activation was detected. Further investigation showed that suppression of P38 activation by SB203580 increased the cell viability and also prevented cleavage of caspase-3 and PARP, inhibition of ERK1/2 with U0126 had the opposite action. In conclusion, our results indicated that ampelopsin mainly elicited apoptosis through extrinsic and intrinsic pathway and that ERK1/2 and P38 had opponent effects on the apoptosis.
研究领域:
癌症生物学
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分子生物学
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细胞生物学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
LIFE SCIENCES
·
2017
·
IF 2.936
En-Xia Wang,Bo-Yang Zou,Lei Shi,Lin-Ying Du,Yan-Yan Zhu,Ya-Meng Jiang,Xiao-Dong Ma,Xiao-Hui Kang,Chang-Yuan Wang,Yu-Hong Zhen,Li-Dan Sun
Aims To investigate the antitumor effects of 7- O -geranylquercetin (GQ), a novel O -alkylated derivative of quercetin, against non-small cell lung cancer (NSCLC) cell lines A549 and NCI-H1975 and the corresponding mechanisms. Main methods Cell viability was assessed using MTT assay. The expression of proteins involved in apoptosis and autophagy was measured using western blotting. Besides, apoptosis was determined with DAPI staining, Annexin V-PI staining and transmission electron microscopy (TEM) assay, and autophagy was observed with TEM assay. Cell cycle and reactive oxygen species (ROS) level were detected using flow cytometry. Key findings GQ inhibited viability of A549 and NCI-H1975 cells in a dose- and time-dependent manner without apparent cytotoxicity to normal human lung fibroblast cells. GQ down-regulated the expression of apoptosis-related proteins pro-caspase 3 and Bcl-2, and up-regulated the expression of cleaved-PARP and Bax in A549 and NCI-H1975 cells. Meanwhile, GQ-induced cell apoptosis could be attenuated by caspase inhibitor Z-VAD-FMK. Besides, GQ induced autophagosome formation in A549 and NCI-H1975 cells, promoted the expression of autophagy-related proteins LC3-II and Beclin 1, and suppressed the expression of p62. Autophagy inhibition with chloroquine or Beclin 1 siRNA could effectively inhibit GQ-induced apoptosis. Furthermore, GQ treatment increased the generation of ROS, and ROS inhibitor N -acetylcysteine could reverse GQ-induced autophagy and apoptosis. Taken together, GQ could induce apoptosis and autophagy via ROS generation in A549 and NCI-H1975 cells, and GQ-induced autophagy contributed to apoptosis. Significance Our findings highlight that GQ is a promising anticancer agent for the treatment of lung cancer.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
✓ 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）