INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2024
·
IF 5.3
Qin Chen,Fen-Sheng Qiu,Wei Xie,Wen-Ying Yu,Zhao-An Su,Guang-Ming Qin,You-Kun Kang,Song-Lin Jiang,Chen-Huan Yu
Diabetic retinopathy (DR) is one of the chronic microvascular complications of type 2 diabetes mellitus (T2DM), which will cause retinal detachment and blindness without ideal therapies. Gypenoside A (GPA) are the main bioactive compound from Gynostemma pentaphyllum , and have various pharmacological effects. However, it suffered from poor bioavailability and potential cardiotoxicity in the clinical application. To overcome those limitations, in this study, nearly spherical nanoparticles (GPA-NP) with a mean particle size of 140.6 ± 22.4 nm were prepared by encapsulating GPA into mPEG-PLGA. This encapsulation efficiency was 84.4 ± 6.9 %, and the drug load was 4.02 %±0.35 %. The results showed that GPA-NP displayed more prolonged GPA release and higher bioavailability in vitro than GPA. GPA-NP obviously reduced the levels of oxidative stress markers and inflammatory cytokines in both retinal tissues of DR mice and high glucose-exposed HRMEC better than GPA alone. Mechanismly, GPA blocked the Nrf2-Keap1 interaction by binding with Kelch domain of Keap1 via alkyl and hydrogen bonds. Therefore, GPA-NP exerted more potent protectivity effects against high glucose-induced retinal microvascular endothelial ferroptosis in vitro and in vivo by activating Nrf2/HO-1/GPX4 pathway. It could be a promising therapeutic agent for preventing DR.
研究领域:
药理学
·
纳米技术
·
糖尿病
·
眼科学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TOXICOLOGY
·
2021
·
IF 4.221
Peipei Qiao,Yingbing Zhang,Ying Yang,Ru Meng,Zhiming Xu,Xianlei Jiang,Yong Zhang,Chengtu Zhang,Jianmin Su
Isoniazid (INH), a synthetic first-line tuberculosis antibiotic, has been widely used in clinical treatment. It has been reported to cause toxic effects at multiple tissue sites and also increases the incidence of adverse pregnancy outcomes; but the mechanism of action of INH on the reproductive system of female mammals remains unclear. Here, we demonstrate that oral INH (40 mg/kg/day every other day for 28 days) severely affects oocyte maturation and fertilization, late blastocyst development and fertility. We found that INH could disrupt standard spindle assembly, chromosome arrangement, and actin filament dynamics, which compromised meiotic progression of mouse oocytes. INH treatment increased the level of reactive oxygen species (ROS) and activated the oxidative stress response pathway, Keap1-Nrf2. It also caused apoptosis of oocytes and mitochondrial dysfunction. Our findings demonstrate that oral INH reduces fertility and damages the mammalian reproductive system by altering cytoskeletal dynamics and Juno expression, inducing oxidative stress and apoptosis, and activating the Keap1-Nrf2 signaling pathway in mouse oocytes.
研究领域:
药理学
·
生殖生物学
·
毒理学
✓ 已验证
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Lei Xu,Jiahe Hu,Xiuwei Yan,Hongtao Zhao,Mo Geng,Jiheng Zhang,Chunxiao Zhou,Zhihui Liu,Bo Li,Shaoshan Hu
Photodynamic therapy (PDT) is an effective treatment for glioblastoma (GBM) that activates photosensitizers to produce reactive oxygen species (ROS) while minimizing harm to normal tissues. However, the therapeutic outcomes of PDT are often unsatisfactory. This limitation arises partly from the challenges posed by the blood–brain barrier (BBB) in transporting photosensitizers and partly from the excessive levels of glutathione (GSH) in the tumor microenvironment (TME), which can neutralize ROS. Hypericin (HYP) has emerged as a promising photosensitizer for PDT due to its excellent photosensitizing properties and antitumor activity. Dysregulated iron metabolism is a hallmark of numerous cancers, including GBM. In this study, biodegradable tetra-sulfide-bound dendritic mesoporous organosilicas nanocomposite (NCs) modified with bovine serum albumin (BSA) were synthesized. NCs penetrates the BBB and selectively targets GBM by binding to secreted acidic protein acidic and rich in cysteine (SPARC), an albumin-binding receptor that is prominently expressed in both the BBB and GBM. Upon degradation in response to high GSH concentrations in the TME, the NCs release their payload while concurrently depleting GSH. Under laser irradiation, the ROS-generating agent HYP, loaded within the NCs, is combined with the ferroptosis inducer erastin to achieve a synergistic anti-GBM effect via PDT/ferroptosis. Additionally, the NCs induces oxeiptosis by regulating KEAP1/PGAM5/AIFM1 pathway. Consequently, NC inhibits GBM growth by inducing ferroptosis and oxeiptosis through excessive ROS production. This study demonstrates the potential of NCs to enhance the effectiveness of PDT, offering a promising therapeutic strategy for GBM patients.
研究领域:
肿瘤学
·
纳米技术
·
治疗学
·
神经科学
✓ 已验证
产品关联
DOI
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Wanting Xue,Weihan Zheng,Huihui Zhang,Jiaxin Yang,Wenfeng Deng,Zhenning Dai,Ke Liu,Yunyun Chen,Xinyi Yun,Jiaying Li,Shiyu Li,Wenhua Huang
Reperfusion therapy for acute myocardial infarction is limited by myocardial ischemia-reperfusion injury (MIRI). MIRI is primarily mediated by oxidative stress in cardiomyocytes, exacerbated by M1 macrophages in the inflammatory microenvironment. Synergistic therapies targeting cardiomyocytes with antioxidants and M1 macrophages with anti-inflammatories have shown significant potential. Mitochondrial dysfunction is a unifying target for both cell types in MIRI; however, current nanoplatforms cannot simultaneously target them. Mito Q@MMNv is designed as a dual-targeting nanovesicle for cardiomyocytes and macrophages. It scavenges reactive oxygen species in cardiomyocytes while restoring oxidative phosphorylation in M1 macrophages through cell-selective metabolic reprogramming. In vivo, Mito Q@MMNv improves cardiac function and the inflammatory microenvironment: left ventricular ejection fraction increases by 62%, and the M1/M2 ratio shifts (delta cells increase 1.9-fold). Synergistic activation of Keap1 and inhibition of NF-κB attenuate inflammatory cascades while enhancing endogenous antioxidant defenses. Thus, this nano-engineered platform offers an immunomodulatory therapy for inflammation control and tissue repair in MIRI, providing new insights into cardiovascular nanomedicine.
研究领域:
心血管纳米医学
·
免疫调节治疗
·
代谢工程
·
活性氧清除
·
炎症调控
✓ 已验证
产品关联
DOI
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Anwei Zhang,Zhiwei Liu,Ling Zou,Lu Yang,Yonghui Wu,Xinxing Wang,Daigui Cao,Junli Liu,Xiaochao Yang,Shengli Zhang
Osteoporosis induced by the long-term administration of glucocorticoids is a common clinical problem. Current anti-osteoporosis therapies mainly focus on bone resorption inhibition or bone formation promotion unilaterally. However, the imbalance between bone formation and resorption often leads to suboptimal therapeutic outcomes. This study confirms the pathways through which dexamethasone (DEX), a typical glucocorticoid, triggers GIO, and explores both the therapeutic potential and underlying mechanisms of ceria nanoparticles (CNPs) in mitigating GIO. Our results demonstrate that DEX-induced bone homeostasis imbalance is the primary mechanism underlying GIO development in mice. Specifically, DEX inhibits pre-osteoblast proliferation and differentiation by inducing apoptosis and ferroptosis. Concurrently, DEX promotes osteoclast precursor proliferation and differentiation, significantly accelerating bone resorption. Administration of CNPs significantly mitigates DEX-induced disruption of bone homeostasis by ameliorating intracellular reactive oxygen species (ROS) accumulation via regulation of the Keap1/Nrf2 signaling pathway. Regarding osteogenesis, CNPs are capable of alleviating DEX-induced pre-osteoblast apoptosis and ferroptosis through the regulation of GPX4/ACSL4 signaling pathway. In terms of bone resorption, CNPs inhibit the RANKL-dependent osteoclast formation pathway. These findings validate the potential application of inorganic nanoparticles in GIO prevention.
研究领域:
纳米医学
·
骨骼生物学
·
药理学
·
分子生物学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Bioscience
·
2024
·
IF 4.8
Qianxia Lin,Siyi Song,Jinfeng Pei,Leifang Zhang,Xiaoe Chen,Huoxi Jin
Cysteine (Cys) plays a significant role in the stability and antioxidant capacity of peptide. This study was to prepare Cys-rich collagen peptide and evaluate its preventive effect on microparticle (MPs)-induced HK-2 cell damage. The results showed that the Cys-rich peptides (AMP-C) were successfully prepared from collagen hydrolysate by plastein reaction in the presence of exogenous Cys. The scavenging activities of 2,2-Diphenyl-1-picrylhydrazyl and hydroxyl radical of AMP-C were significantly higher than those of original peptides without Cys. The fraction with molecular weight <3 kDa (AMP-CA) significantly improved MPs-induced damage and apoptosis of HK-2 cells. Compared with the same fractions lacking Cys (AMP-A), AMP-CA showed better performance in reducing reactive oxygen species and increasing the total superoxide dismutase and glutathione peroxidase levels, which may be related to its down-regulation of Kelch-like ECH-associated protein 1 (Keap1) expression. In addition, AMP-CA showed strong effects on inhibiting interleukin-6, tumor necrosis factor-α, monocyte chemoattractant protein-1, kidney injury molecule-1, and nuclear factor kappa-B levels. Finally, 330 Cys-containing peptides were isolated from AMP-CA, among which Leucine-Glycine-Asparagine-Glycine-Cysteine-Proline (LGNGCP) showed the lowest binding energy with Keap1 protein. In conclusion, the Cys-rich collagen peptide with higher antioxidant activity was successfully prepared by plastein reaction, which alleviated the HK-2 cells damage induced by MPs through antioxidant and anti-inflammatory. Our findings suggested that Cys-rich collagen peptide might be used as a functional food to mitigate health hazards associated with MPs accumulation.
研究领域:
生物技术
·
毒理学
·
细胞生物学
·
药学
·
环境科学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2015
·
IF 2.912
Chuanyang Su,Xiaomin Xia,Qiong Shi,Xiufang Song,Juanli Fu,Congxue Xiao,Hongjun Chen,Bin Lu,Zhiyin Sun,Shanmei Wu,Siyu Yang,Xuegang Li,Xiaoli Ye,Erqun Song,Yang Song
Neohesperidin dihydrochalcone (NHDC), a sweetener derived from citrus, belongs to the family of bycyclic flavonoids dihydrochalcones. NHDC has been reported to act against CCl4-induced hepatic injury, but its mechanism is still unclear. We first discovered that NHDC showed a strong ability to scavenge free radicals. In addition, NHDC induces the phase II antioxidant enzymes heme oxygenase 1 (HO-1) and NAD(P)H/quinone oxidoreductase 1 (NQO1) through the activation of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/antioxidant response element (ARE) signaling. Further assays demonstrated that NHDC induces accumulation of Nrf2 in the nucleus and augmented Nrf2-ARE binding activity. Moreover, NHDC inhibits the ubiquitination of Nrf2 and suggests the modification of Kelch-like ECH-associated protein 1 (Keap1) and the disruption of the Keap1/Nrf2 complex. c-Jun N-terminal kinase (JNK) and p38 but not extracellular signal-regulated protein kinase (ERK) phosphorylations were up-regulated by NHDC treatment. Taken together, NHDC showed its protective antioxidant effect against CCl4-induced oxidative damage via the direct free radical scavenging and indirect Nrf2/ARE signaling pathway.
研究领域:
药理学
·
毒理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PROCESS BIOCHEMISTRY
·
2024
·
IF 3.7
Yidan Zhang,Hui Lian,Linhui Yang,Lingling Tong,Yang Wu,Suxing Jin,Dongsheng Guo
Ophiocordyceps gracilis is a type of fungus commonly utilized in both health food and Chinese medicine. Herein, we prepared antioxidant hydrolysate from O. gracilis , and isolated and purified the prepared hydrolysate to obtain O. gracilis peptides-4-3-1 (OGP-4-3-1) grade with the highest scavenging activity on DPPH, ABTS and hydroxyl radicals. Three new peptides with high antioxidant capacity were identified as LFNHF, PLDRHPF and YPFLRPL, respectively. The three peptides can reduce the proportion of senescent cells conveying positive expression of senescence-associated-β-galactosidase (SA-β-Gal) and increase survival pace of H 2 O 2 -induced human hepatocellular carcinomas (HepG2 cells), and the protective effects on cellular against senescence might be related to their increase in the activities of antioxidant enzymes, as well as the decrease in the concentration of malondialdehyde (MDA) and reactive oxygen species (ROS). The molecular docking results indicated that they could form durable hydrophobic and hydrogen bonds with critical amino acid residues of the Kelch-like ECH-associated protein 1 (Keap1), which could potentially modulate pathway of nuclear factor erythroid 2-related factor 2 (Nrf2) in conjunction with Keap1. In conclusion, the current research offers a theoretical foundation for the further development of the anti-aging effect of OGP, which has a broad application prospect in the fields of functional food and cosmetics.
研究领域:
生物化学
·
药理学
·
细胞生物学
·
食品科学
·
化妆品学
✓ 已验证
产品关联
DOI
高影响因子
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
·
2023
·
IF 6.7
Yang Wang,Ruiqi Su,Jianwen Chen,Xuan Liu,Jingning Luo,Yaoqiang Lao,Ping Huang,Jinguo Shi,Caibao Jiang,Liping Liao,Jingxia Zhang
Acute ischemic stroke (AIS) is a serious cardiovascular and cerebrovascular disease; Oxidative stress and neuroinflammation are important factors which destroy blood-brain barrier (BBB) in AIS. In the study, a series of 1,3,5-triphenyl-1,2,4-triazole derivatives were designed and synthesized; the optimal compound 9 was obtained by screening their anti-oxidant and anti-inflammatory effects; the neuroprotection effect of compound 9 was evaluated with a rat middle cerebral artery occlusion (MCAO) model. Subsequently, the mechanism of neuroprotection were explored via Western blot. The results prompt compound 9 maybe exert anti-AIS neuroprotection by inhibiting oxidative stress and neuroinflammation inhibition by inhibiting Keap1, COX-2 and iNOS. At the same time, it can protect BBB by reducing glycocalyx degradation and matrix metallopeptidase-9 levels. Its LD 50 > 1000 mg/kg on mice and hERG channel inhibition IC 50 > 30 μM, which lower acute toxicity and hERG channel inhibition would make compound 9 a promising stroke treatment candidate.
研究领域:
药理学
·
神经科学
·
心血管疾病
·
药物发现
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2019
·
IF 3.571
Ya-Nan Jia,Ya-Lin Peng,Yi-Ping Zhao,Xi-Fei Cheng,You Zhou,Chun-Li Chai,Ling-Shu Zeng,Min-Hui Pan,Li Xu
The purpose of this study was to compare the hepatoprotective effects of Oxy (oxyresveratrol), Res (resveratrol), and MulA (mulberroside A) (80 mg/kg body weight/d, i.g.) on acute liver injury (ALI) induced by lipopolysaccharide (LPS)/d-galactosamine (d-GalN) in mice. After 7 h of LPS (50 μg/kg body weight, i.p.) and d-GalN (500 mg/kg body weight, i.p.) exposure, the activities of serum transaminases and antioxidant enzymes were determined. The expressions of the Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2) signal pathway, the nuclear factor-kappa B (NF-κB) signal pathway, and the mitogen-activated protein kinase (MAPK) signal pathway related proteins were evaluated by Western blot assays. Histopathological analysis was performed by hematoxylin-eosin (H&E) staining on the separated livers of mice. The results showed that treatment with Oxy, Res, and MulA could significantly decreases the levels of alanine transaminase (ALT) and aspartate transaminase (AST) (P < 0.01). MulA was the most effective ingredient among the three, and the ALT and AST levels were reduced at 90.3 ± 1.3% and 93.9 ± 1.1% compared with the LPS/D-GalN treated group (P < 0.01). Meanwhile, the stilbenes curbed the expression of inflammatory factors, NF-κB pathway activation, and MAPKs phosphorylation and upregulated antioxidant enzymes, Nrf2, NAD (P) H:quinone oxidoreductase (NQO1), and heme oxygenase-1 (HO-1) expression levels. Stilbenes might protect the ALI caused by LPS/d-GalN through inhibiting the negative effectiveness of oxidation stress and inflammation. The protective performance of MulA was better than those of Oxy and Res, and we hypothesize that it might be due to the mediation of the specific metabolic pathway of the MulA in vivo. All of these results implied that stilbenes in mulberry twigs might be promising as natural additives.
研究领域:
药理学
·
肝病学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Bioscience
·
2024
·
IF 4.8
Zixuan Hu,Chunfeng Liu,Chengtuo Niu,Jinjing Wang,Feiyun Zheng,Qi Li
Brewer's spent grain (BSG) and brewer's spent yeast (BSY) are two major brewing by-products, which are low-cost raw materials with high yields and nutritional value. In this study, the antioxidant peptides from brewing by-products were separated, purified and identified by UF, GFC or HIC, semi-preparative RP-HPLC, and nano-HPLC-MS/MS. Thereafter, in silico analysis was applied to predict the bioactivity, toxicity, and bioavailability of the identified peptides, and a total of 23 potential novel peptides with antioxidant activity and bioavailability were excavated. Furthermore, molecular docking results revealed the potential antioxidant peptides had stable binding ability to Keap1, and Tyr334, Arg380, Arg415, Arg483, and Tyr525 residues contributed enormously to docking, all of which were located in the binding sites of Keap1-Nrf2 interaction. Peptides with the lowest binding energy (i.e. AGRLPW, DRLW, KPW, PLWWRHPR, RVWNPFR, and ANLPWLGK) were further synthesized and validated in vitro and at the cellular level to be bioactive. Western blot results showed that KPW, RVWNPFR, and ANLPWLGK could protect HaCaT cells from H 2 O 2 -induced oxidative damage by activating Keap1-Nrf2 pathway. These findings provided insights into the high value-added utilization of brewing by-products.
研究领域:
食品科学
·
生物化学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-26
·
IF 10.6
Zhao Xinxin,Zhang Yuchen,Wang Pengchong,Liu Kailai,Zheng Yunhe,Wen Jinpeng,Wang Ke,Wen Xiaopeng
Natural compound-based treatments provide innovative ways for ulcerative colitis therapy. However, poor targeting and rapid degradation curtail its application, which needs to be addressed. Inspired by biomacromolecule-based materials, we have developed an orally administrated nanoparticle (GBP@HA NPs) using bovine serum albumin as a carrier for polyphenol delivery. The system synergizes galactosylated bovine serum albumin with two polyphenols, epigallocatechin gallate and tannic acid, which is then encased in “nanoarmor” of ε-Polylysine and hyaluronic acid to boost its stability and targeting. Remarkably, the nanoarmor demonstrated profound therapeutic effects in both acute and chronic mouse models of ulcerative colitis, mitigating disease symptoms via multiple mechanisms, regulating inflammation related factors and exerting a modulatory impact on gut microbiota. Further mechanistic investigations indicate that GBP@HA NPs may act through several pathways, including modulation of Keap1-Nrf2 and NF-κB signaling, as well as Caspase-1-dependent pyroptosis. Consequently, this novel armored nanotherapy promotes the way for enhanced polyphenol utilization in ulcerative colitis treatment research.
研究领域:
纳米技术
·
药学
·
胃肠病学
·
免疫学
·
微生物学
✓ 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）