FITOTERAPIA
·
2024
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IF 2.5
Ling Jiang,Cai-Bo Tian,Rui-Han Ye,Nian Shi,Xing-Chao He,Yun-Li Zhao,Xiao-Dong Luo
Drug-induced liver injury caused acute hepatic failure and hepatitis frequently. In this investigation, kakuol and asarinin reduced the levels of serum alanine transaminase (ALT), aspartate transaminase (AST) and malondialdehyde (MDA) dramatically, and ameliorated the pathological damage of liver tissues in APAP-induced mice. Furthermore, both compounds increased the viabilities of APAP-induced L-O2 cells and extracellular glutathione (GSH) levels accompanied significantly by reducing the level of intracellular ROS in vitro . In addition, HSP90AA1/CDK2/mTOR signaling pathway and five target proteins (CDK2, HSP90AA1, HRAS, MMP1, mTOR) were proposed from network pharmacology and molecular docking prediction, and then the up-regulation of protein expression of CDK2, mTOR and down-regulation of HSP90AA1, HRAS, MMP1 by kakuol and asarinin in western blotting supported their mechanism.
研究领域:
药理学
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分子生物学
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毒理学
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肝病学
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产品关联
DOI
PubMed
高影响因子
Chinese Herbal Medicines
·
2019
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IF 0
Ya-yun Liu,Jiao-jiao You,Wei Xu,Ting Zhai,Chun-yuan Du,Yong Chen,Feng-mei Han
Objective The present work was to investigate the protective effects of the aqueous extract of Gynura procumbens (GPAE) against nonalcoholic steatohepatitis (NASH) in mice and NCTC-1469 cells. Methods C57BL/6J mice were fed with methionine and choline-deficient (MCD) diet and administered simultaneously with GPAE (500 and 1000 mg/kg/d, respectively) by gavage for six weeks. The biomarkers of NASH in serum and liver were determined. NCTC-1469 cells were pretreated with 0.25 mmol/L palmitic acid (PA) plus 0.5 mmol/L oleic acid (OA) for 24 h or treated with adenovirus expressing short-hairpin RNA against CFLAR (Ad-shCFLAR) for 24 h and then treated with GPAE (80 and 160 µg/mL, respectively) for 24 h, and the content of cellular biomarkers of NASH was detected. Results In mice treated with MCD , GPAE could decrease the levels of serum ALT , AST, the content of hepatic TG , TC and MDA , repress the activities and protein expression of CYP2E1 and CYP4A and the phosphorylation of JNK, increase the activities of HO-1, CAT and GSH-Px, up-regulate the mRNA expression of PPARα, FABP5, CPT1α, ACOX, SCD-1, mGPAT, MTTP and the protein expression of CFLAR and NRF2. In NCTC-1469 cells treated with PA and OA, GPAE could decrease the content of cellular TG and ROS , promote the uptake of 2-NBDG, up-regulate the protein expression of CFLAR and NRF2. In NCTC-1469 cells treated with Ad-sh CFLAR , GPAE up-regulated the mRNA and protein expression of CFLAR, down-regulated the phosphorylation of JNK, and increased the protein expression of NRF2 and pIRS1 . Conclusion These results indicated that the activation on CFLAR-JNK pathway might be the main anti-NASH mechanism of GPAE, which on the one hand promote the β-oxidation and efflux of fatty acids in liver, and finally reduce hepatic lipid accumulation , on the other hand increase the activities of anti-oxidant enzymes and inhibit the activities of ROS generation enzymes by activating NRF2, and therefore attenuates hepatic oxidative stress damage.
研究领域:
药理学
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肝病学
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分子生物学
✓ 已验证
产品关联
DOI
Reproductive Biology
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2022
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IF 2.089
Juan Zhao,Yong Tan,Zhe Feng,Yahong Zhou,Feihong Wang,Ge Zhou,Jing Yan,Xiaowei Nie
Oxidative stress plays a central role in polycystic ovary syndrome (PCOS). Catalpol (CAT) is the active ingredient of Rehmannia glutinosa Libosch which has therapeutic effect on PCOS. However, little is known about the mechanism of CAT in PCOS. PCOS rats were induced by subcutaneous injection of dehydroepiandrosteronec for four weeks and then were treated with CAT (50 mg/kg) or carboxyl methyl cellulose (the solvent of CAT) or normal saline for another 4 weeks. Histopathological observation of ovarian tissues, the levels of testosterone, estradiol and progesterone in rat plasma samples, the oxidative stress related-indexes and the expressions of NF-κB pathway-related proteins were determined. KGN cell (human ovarian granulosa cell line) was used as PCOS cell model and was transfected with siSIRT1 in the presence of CAT. The viability, proliferation and apoptosis of cells and the levels of SIRT1 and NF-κB pathway-related proteins were measured. CAT lessened the anthropometric indices and improved ovarian damage in PCOS model rats, and reduced the levels of testosterone, estradiol, progesterone and MDA , increased GSH content, and elevated the activities of catalase, GSH-Px and SOD in ovarian tissues of PCOS model rats. CAT up-regulated SIRT1 level and inhibited the activation of NF-κB signaling pathway in PCOS rat model and KGN cells. Silencing SIRT1 increased the viability and proliferation, whilst decreased the apoptosis of CAT-treated KGN cells. Silencing SIRT1 counteracted the effect of CAT on the level of oxidative stress-related factors and NF-κB signaling pathway in KGN cells. CAT attenuated PCOS by regulating SIRT1 mediated NF-κB signaling pathway.
研究领域:
药理学
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内分泌学
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细胞生物学
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分子生物学
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生殖医学
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产品关联
DOI
PubMed
高影响因子
Journal of Inflammation Research
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2022
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IF 4.631
Ling Li,Yaoyao Du,Yang Wang,Ning He,Bing Wang,Tong Zhang
Background Gastric ulcer (GU) is the most common multifactor gastrointestinal disorder affecting millions of people worldwide. There is evidence that gut microbiota is closely related to the development of GU. Atractylone (ATR) has been reported to possess potential biological activities, but research on ATR alleviating GU injury is unprecedented.Methods Helicobacter pylori (H. pylori)-induced GU model in zebrafish and ethanol-induced acute GU model in rat were established to evaluate the anti-inflammatory and ulcer inhibitory effects of ATR. Then, 16S rRNA sequencing and metabolomics analysis were performed to investigate the effect of ATR on the microbiota and metabolites in rat feces and their correlation.Results Therapeutically, ATR inhibited H. pylori-induced gastric mucosal injury in zebrafish. In the ulceration model of rat, ATR mitigated the gastric lesions damage caused by ethanol, decreased the ulcer area, and reduced the production of inflammatory factors. Additionally, ATR alleviated the gastric oxidative stress injury by increasing the activity of superoxide dismutase (SOD) and decreasing the level of malondialdehyde (MDA). Furthermore, ATR played a positive role in relieving ulcer through reshaping gut microbiota composition including Parabacteroides and Bacteroides and regulating the levels of metabolites including amino acids, short-chain fatty acids (SCFAs), and bile acids.Conclusion Our work sheded light on the mechanism of ATR treating GU from the perspective of the gut microbiota and explored the correlation between gut microbiota, metabolites, and host phenotype.
研究领域:
药理学
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胃肠病学
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微生物学
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代谢组学
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动物模型
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2023
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IF 5.4
Gao-shang Chai,Juan Gong,Jia-jun Wu,Rui-kun Ma,Jun Zhu,Dong-dong Jia,Yu-qi Zhang,Xiao-run Zhai,Hong-xu Sun,Yun juan Nie,Peng Zhao,Yi-liang Xu,Hai tao Yu
Ethnopharmacological relevance Danggui Buxue decoction (DBD) is a classic herbal decoction consisting of Astragali Radix (AR) and Angelica Sinensis Radix (ASR) with a 5:1 wt ratio, which can supplement ‘blood’ and ‘qi’ (vital energy) for the treatment of clinical diseases. According to Traditional Chinese Medicine (TCM) theory, dementia is induced by Blood deficiency and Qi weakness, which causes a decline in cognition. However, the underlying mechanisms of DBD improving cognition deficits in neurodegenerative disease are no clear. Aim of the study This study aims at revealing the underlying mechanisms of DBD plays a protective role in the cognitive deficits and pathology process of Alzheimer's disease (AD). Materials and methods The APP/PS1 (Mo/HuAPP695swe/PS1-dE9) double transgenic mice were adopted as an experimental model of AD. Qualitative and quantitative analysis of 3 compounds in DBT was analyzed by HPLC. Morris water maze test, Golgi staining and electrophysiology assays were used to evaluate the effects of DBD on cognitive function and synaptic plasticity in APP/PS1 mice. Western blot , immunofluorescence and Thioflavin S staining were used for the pathological evaluation of AD. Monitoring the level of ATP, mitochondrial membrane potential, SOD and MDA to evaluate the mitochondrial function, and with the usage of qPCR and CHIP for the changes of histone post-translational modification. Results In the current study, we found that DBD could effectively attenuate memory impairments and enhance long-term potentiation (LTP) with concurrent increased expression of memory-associated proteins. DBD markedly decreased Aβ accumulation in APP/PS1 mice by decreasing the phosphorylation of APP at the Thr668 level but not APP, PS1 or BACE1 . Further studies demonstrated that DBD restored mitochondrial biogenesis deficits and mitochondrial dysfunction. Finally, the restored mitochondrial biogenesis and cognitive deficits are under HADC2-mediated histone H4 lysine 12 (H4K12) acetylation at the peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α) and N-methyl-D-aspartate receptor type 2B (GluN2B) promoters. Conclusions These findings reveal that DBD could ameliorate mitochondrial biogenesis and cognitive deficits by improving H4K12 acetylation. DBD might be a promising complementary drug candidate for AD treatment.
研究领域:
药理学
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神经科学
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中医
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分子生物学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2013
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IF 5.008
Tianbin Ren,Wei Wu,Menghong Jia,Haiqing Dong,Yongyong Li,Zhouluo Ou
In the treatment of cancer, multidrug resistance (MDR) has been the major obstacle to the success of chemotherapy. The underlying mechanism relies on the overexpression of drug-efflux transporters that prevent the intracellular transport of the drug. In this study, reduction-cleavable vesicles were designed and developed with efficient glutathione-mediated drug-release behavior for reversing drug resistance. Polymeric vesicles were self-assembled from triblock copolymers with disulfide-bond-linked poly(ethylene glycol) (PEG) and poly(ε-benzyloxycarbonyl-l-lysine) (PzLL). Observations from transmission electron microscopy (TEM) and confocal laser scanning microscopy (CLSM) outline an obvious hollow structure surrounded by a thin outer layer, indicating the successful formation of the vesicles. Using fluorescently detectable doxorubicin hydrochloride (DOX·HCl) as the model drug, a significant acceleration of drug release regulated by glutathione (GSH) was found (>3-fold difference). Upon incubation of the DOX·HCl-loaded polymeric vesicles with the HeLa cervical cancer cell line exposed to glutathione, an enhanced nuclear accumulation of DOX·HCl was observed, elicited by the preferred disassembly of the vesicle structure under reducing conditions. Importantly, by using the gemcitabine hydrochloride (GC·HCl)-resistant breast cancer cell line MDA-MB-231, it was found that cell viability was significantly reduced after treatment with GC·HCl-loaded polymeric vesicles, indicating that these vesicles can help to reverse the drug resistance.
研究领域:
药理学
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癌症研究
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聚合物化学
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药物递送系统
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DOI
PubMed
高影响因子
POLYMER TESTING
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2020
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IF 3.275
Alberto García-Peñas,Yu Wang,Irene Mena-Palomo,Eduardo López-Collazo,Diana Díaz-García,Santiago Gómez-Ruiz,Florian J. Stadler
Recent advances focused on smart polymers have demonstrated the numerous advantages regarding other structures because they can adapt the behavior depending on physicochemical properties. In this way, functionalized thermoresponsive polymers with organometallic complexes were profoundly analyzed. Consequently, novel catalytic systems or biomedical devices could be developed. This publication focuses on the facile preparation of poly( N -isopropylacrylamide- co -dopamine methacrylamide) copolymers functionalized with triphenyltin chloride by protonolysis through the –OH of catechol groups. The presence of hydrophobic organotin(IV) derivatives could modify the solubility, thermoresponsive behavior, and other properties regarding pure copolymers. Also, sensitive analysis of the microstructure could help to understand the changes associated with the lower critical solution temperature by rheology, UV–vis spectroscopy, and calorimetry. In addition, a preliminary biological study against MDA-MB-231 cancer cells and peripheral blood mononuclear cells showed that the functionalized copolymers could be a potential platform to be explored in the future in the fight against cancer.
研究领域:
聚合物化学
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材料科学
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生物医学工程
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癌症研究
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产品关联
DOI
高影响因子
BIOMATERIALS
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2016
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IF 8.387
Leyong Zeng,Yuanwei Pan,Ruifen Zou,Jinchao Zhang,Ying Tian,Zhaogang Teng,Shouju Wang,Wenzhi Ren,Xueshan Xiao,Jichao Zhang,Lili Zhang,Aiguo Li,Guangming Lu,Aiguo Wu
To avoid the overheating effect of excitation light and improve the efficacy of photodynamic therapy (PDT) of upconversion nanoplatform, a novel nanoprobe based on 808 nm-excited upconversion nanocomposites ( [email protected] @mSiO 2 ) with low heating effect and deep penetration has been successfully constructed for targeted upconversion luminescence , magnetic resonance imaging (MRI) and high-efficacy PDT in HER2-overexpressed breast cancer. In this nanocomposite, photosensitizers (Ce6) were covalently conjugated inside of mesoporous silica to enhance the PDT efficacy by shortening the distance of fluorescence resonance energy transfer and to decrease the cytotoxicity by preventing the undesired leakage of Ce6 . Compared with [email protected] 2 @Ce6, [email protected] @mSiO 2 greatly promoted the singlet oxygen generation and amplified the PDT efficacy under the excitation of 808 nm laser . Importantly, the designed nanoprobe can greatly improve the uptake of HER2-positive cells and tumors by modifying the site-specific peptide, and the in vivo experiments showed excellent MRI and PDT via intravenous injection by modeling MDA-MB-435 tumor-bearing nude mice . Our strategy may provide an effective solution for overcoming the heating effect and improving the PDT efficacy of upconversion nanoprobes, and has potential application in visualized theranostics of HER2-overexpressed breast cancer.
研究领域:
纳米技术
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癌症研究
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治疗诊断学
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生物医学工程
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2023
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IF 9.5
Shan Xiao,Lu Guo,Chen Ai,Mengmeng Shang,Dandan Shi,Dong Meng,Xiao Sun,Xiaoxuan Wang,Rui Liu,Yading Zhao,Jie Li
Multiple drug resistance (MDR) exists in divergent cancers including triple negative breast cancer (TNBC) and partly results in the resistance to many first-line anti-cancer agents, bringing a big challenge to TNBC management. To develop novel TNBC therapeutics, in our study, a hyaluronic acid (HA)–carboxymethyl chitosan (CMC) conjugate linked via a disulfide-bond (HA-SS-CMC, HSC) was synthesized to fabricate nanodroplets (NDs). The NDs encapsulating doxorubicin (DOX) and perfluorohexane (DOX-HSC-NDs) were prepared via a homogenization/emulsification strategy and exhibited not only high biocompatibility but also noticeable tumor cell targeting ability and dual pH/redox responsiveness. Besides, DOX-HSC-NDs can be used as a contrast-enhanced ultrasound imaging agent for specific tumor imaging. DOX-HSC-NDs in combination with ultrasound targeted microbubble destruction could improve intracellular drug aggregation and retention of MDR cells and work against multiple mechanisms of drug resistance through synergistic strategies, including up-regulating the reactive oxygen species (ROS) level, promoting apoptosis, and scavenging glutathione, while reducing the expression levels of P-glycoprotein and inhibiting the epithelial–mesenchymal transition. This combination strategy showed protective effects against TNBC in both MDA-MB-231/ADR cells and tumor-bearing mice. Our study for the first time developed and reported the ultrasound-augmented HSC-NDs as the DOX nanocarrier and provided scientific evidence to support the future application of DOX-HSC-NDs as a potential TNBC therapy.
研究领域:
癌症治疗
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纳米技术
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药学
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生物医学工程
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
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2022
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IF 3.682
Limin Zhu,Shuangyan Wang
Mesoporous silica nanoparticle (MSN), sodium hyaluronate (SH), silk fibroin (SS), and oxidized sodium carboxymethyl cellulose (O-CMC) hybrids were used to develop an intelligent drug delivery platform that may be employed for pH and redox-responsive bi-drug administration. The first drug, cytarabine (Cyt), was loaded with amino-functionalized mesoporous silica (MSN-NH2) encased by the hydrogel of cystamine (Cys) and SH cross-linked by amide bonds. Hydrophobic doxorubicin (DOX) was co-loaded with Cyt/MSN-NH2/SA in the hydrogel of SS and O-CMC in the Cyt- loaded hydrogel. Dual-responsive drug delivery may be achieved by encapsulating SS and O-CMC in a hydrogel, including Cyt/MSN-NH2/SA/DOX/SS/O-CMC, which has acyl hydrazone bonds (-HC = N) and disulfide bond (-S-S-) exchange reaction with glutathione (GSH). Compared to hydrogels encapsulating only one drug (Cyt or DOX), cell survival analysis revealed that the newly fabricated hydrogels have significantly greater chemotherapeutic efficacy. The cell proliferation of the fabricated nanoparticles was examined in MCF-7 and MDA-MB-231 cells, which indicates that the nanoparticles effectively kill the cancer cells without affecting non-cancerous cells. Further, we effectively investigated the morphological changes, and various biochemical staining methods examined nuclear fragmentation/condensation. Furthermore, the biosafety of the nanoparticles was investigated by the in vivo animal model, which reveals that they remarkably enhanced the safety profile in various organs. These outcomes demonstrated that this nanoparticle platform was a promising beneficial agent for improving breast cancer treatment.
研究领域:
纳米技术
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药学
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癌症研究
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材料科学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food & Function
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2022
·Vol. 13
·期 16
·8593-8604
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IF 6.317
Yanfang Yu,Yuhuan Chen,Xuping Shi,Chuan Ye,Junwen Wang,Jinzhi Huang,Bing Zhang,Zeyuan Deng
This study investigated the hepatoprotective effects of various mulberry (Morus alba L.) leaf extracts (MLEs), including mulberry ethanol extract (MEE), aqueous extract (MAE) and a combination extract (MCE) against D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced acute liver injury in rats. It aimed to explore the possible molecular mechanism of the liver-protecting function of mulberry leaves and provide a reference for choosing the appropriate extraction method. The results showed that the three extracts contained different amounts of phenolic compounds, 1-deoxynojirimycin (DNJ) and polysaccharides. MLEs markedly improved the pathological status of rat liver tissue, decreased the levels of AST, ALT, TNF-α, IL-1β, IL-6 and MDA, while increased the levels of GSH, SOD and CAT in the D-GalN/LPS-treated rats at the same time. MEE, with the highest amount of total phenolics, exhibited the highest antioxidant activity corresponding to the protein expression level of Nrf2 and HO-1. MCE significantly suppressed the expression of apoptosis-related dot-like protein (ASC) and Caspase-1 and inhibited the phosphorylation of p38 MAPK and ERK1/2, thereby showing high anti-inflammatory activity. These results indicated that the active components from mulberry leaves protected rats against acute liver injury, attributed to a reduction in both oxidative stress and inflammatory response. The protective effect may be implicated in regulating the Nrf2, NLRP3 and MAPK signaling pathways.
研究领域:
药理学
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肝病学
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生物化学
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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 DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2024
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IF 4.5
Yuman Zhang,Yao Yu,Qi Wang,Wenjun Shi,Hanying Hu,Danqing Hou,Zhi Li
Non-alcoholic fatty liver disease (NAFLD) was a pathological syndrome characterized by excessive lipid deposition in the liver. Excessive lipid in the liver produced reactive oxygen species (ROS), the occurrence of oxidative stress and lipid peroxidation was accelerated, which aggravated liver function damage. Based on these, resveratrol, a natural antioxidan, was encapsulated in liposoluble interior by amphiphilic phosphatidylserine, and then self-assembled with chitosan oligosaccharide complexed with zinc ions to form Zn-Cos/Res@Ps nanoparticles. The size of the Zn-Cos/Res@Ps was about 168.57 ± 4.35 nm, and the zeta potential was about 17.45 ± 1.79 mV. Furthermore, Zn-Cos/Res@Ps could significantly inhibition of lipid deposition, decreased the contents of reactive oxygen species (ROS) and synergistically decreased the levels of malondialdehyde (MDA) in HepG2 cells. Zn-Cos/Res@Ps could also reduce the content of serum total cholesterol (TC), triglyceride (TG), aspartate aminotransferase (AST) and alanine aminotransferase (ALT), improved the liver injury and reduced the degree of liver fibrosis in mice. The Zn-Cos/Res@Ps group showed better results than the single-drug nanoparticle group. In conclusion, Zn-Cos/Res@Ps nanoparticles could effectively alleviate the disease progression by inhibiting oxidative stress and lipid peroxidation, promoted fatty acid catabolism, and effectively reverse and prevent the progress of nonalcoholic steatohepatitis.
研究领域:
纳米技术
·
药理学
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肝病学
·
分子生物学
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）