INFLAMMOPHARMACOLOGY
·
2024
·
IF 4.6
Li Ming-Jie,Xu Jing-Yi,Zhang Hua-Yue,Guo Min,Lan Meng-Ning,Kong Jie,Liu Shi-Wei,Zheng Hua-Jun
Alzheimer’s disease (AD) is a neurodegenerative disorder frequently accompanied by neuroinflammation and oxidative stress. The medicine and food homology (MFH) has shown potential for treating neuroinflammation and oxidative stress. This study aimed to provide a safe and efficient therapy for AD based on MFH. In this study, we develop a MFH formula consisting of egg yolk oil, perilla seed oil, raphani seed oil, cinnamon oil, and noni puree (EPRCN). To evaluate the ameliorative effects of EPRCN on AD-related symptoms, a mouse model of AD was constructed using intraperitoneal injection of scopolamine in ICR mice. Experimental results demonstrated that EPRCN supplement restored behavioral deficits and suppressed neuroinflammation and oxidative stress in the hippocampus of scopolamine-induced mice. An in vitro study was then performed using induction of Aβ (25–35) in glial (BV–2 and SW–1783) and neuron (SH–SY5Y) cell lines to examine the improvement mechanism of EPRCN on cognitive deficits. Multi-omics and in vitro studies demonstrated that these changes were driven by the anandamide (AEA)-Trpv1-Nrf2 pathway, which was inhibited by AM404 (an AEA inhibitor), AMG9810 (a Trpv1 inhibitor), and BT (an Nrf2 inhibitor). Consequently, EPRCN is an effective therapy on preventing cognitive deficits in mouse models of AD. In contrast to donepezil, EPRCN exhibits a novel modes action for ameliorating neuroinflammation. The mechanism of EPRCN on preventing cognitive deficits is mediated by improving neuroinflammation and oxidative stress via activating the AEA–Trpv1–Nrf2 pathway.
研究领域:
神经科学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2024
·Vol. 29
·期 10
·2306
·
IF 4.2
Danyang Zhang,Xiaoshi He,Ting Wang,Yan Xing,Zhilong Xiu,Yongming Bao,Yuesheng Dong
Methylglyoxal-induced ROS elevation is the primary cause of neuronal damage. Metformin is a traditional hypoglycemic drug that has been reported to be beneficial to the nervous system. In this study, flavonoids were found to enhance the protective effect of metformin when added at a molar concentration of 0.5%. The structure–activity relationship (SAR) analysis indicated that ortho- substitution in the B ring, and the absence of double bonds between the 2 and 3 position combined with the gallate substitution with R configuration at the 3 position in the C ring played crucial roles in the synergistic effects, which could be beneficial for designing a combination of the compounds. Additionally, the mechanism study revealed that a typical flavonoid, EGCG, enhanced ROS scavenging and anti-apoptotic ability via the BCL2/Bax/Cyto C/Caspase-3 pathway, and synergistically inhibited the expression of GSK-3β, BACE-1, and APP in PC-12 cells when used in combination with metformin. The dose of metformin used in the combination was only 1/4 of the conventional dose when used alone. These results suggested that ROS-mediated apoptosis and the pathways related to amyloid plaques (Aβ) formation can be the targets for the synergistic neuroprotective effects of flavonoids and metformin.
研究领域:
药理学
·
神经科学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Yutong Chen,Ji-an Wei,Liqiang Wang,Qianyu Cai,Fang Yang,Li Zhang,Jie Liu,Yanan Liu
Mitochondrial damage induced by reactive oxygen species and mitochondrial autophagy dysfunction are closely related to the pathogenesis of Alzheimer's disease (AD). Therefore, the recovery of mitochondrial autophagy disorder is crucial in maintaining mitochondrial homeostasis, protecting neurons, and improving AD. Herein, Ruthenium dioxide nanoparticles (RuO 2 ) have multi-enzyme activities, such as superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD). And the multi-enzyme activity depends on the size, oxygen vacancy, morphology and specific surface area of the nanoparticles. The ultrasmall Ruthenium dioxide showed excellent antioxidant activity in the enzyme activity experiment. The results of in vitro experiments show that RuO 2 can restore damaged neurons by clearing Aβ and H 2 O 2 -induced reactive oxygen species (ROS). It maintains mitochondrial function, restores mitochondrial autophagy and normalizes mitochondrial dysfunction, thereby restoring injured neuronal cells. At the same time, it also showed the ability to regulate microglia polarization, inhibit microglia overactivation, and relieve neuroinflammation. After screening the results of enzyme activity experiment and in vitro experiment, sRuO 2 with small particle size and good enzyme activity was selected for in vivo experiment. sRuO 2 can inhibit oxidative stress in vivo , reduce the burden of Aβ, regulate the neuroprotective function of microglia and improve neuroinflammation. It ultimately improve memory decline and cognitive impairment in Aβ mice. These results suggest that sRuO 2 nanoenzymes with antioxidant activity have great potential in the treatment of AD. The multi-target strategy also offers a promising treatment option for AD.
研究领域:
神经科学
·
纳米技术
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2024
·
IF 5.7
Kun Hu,Shaojun Wu,Jiaxin Xu,Yongzhen Zhang,Yanan Zhang,Xinyuan Wu,Jie Miao,Yongxu Yao,Susu Zhu,Guangtong Chen,Jie Ren
Alzheimer’s disease (AD), one of the neurodegenerative disorders, is highly correlated with the abnormal hyperphosphorylation of Tau and aggregation of β-amyloid (Aβ). Oxidative stress, neuroinflammation, and abnormal autophagy are key drivers of AD and how they contribute to neuropathology remains largely unknown. The flavonoid compound pongamol is reported to possess a variety of pharmacological activities, such as antioxidant, antibacterial, and anti-inflammatory. This study investigated the neuroprotective effect and its mechanisms of pongamol in lipopolysaccharide (LPS)-induced BV2 cells, d-galactose/sodium nitrite/aluminum chloride (d-gal/NaNO2/AlCl3)-induced AD mice, and Caenorhabditis elegans models. Our research revealed that pongamol reduced the release of inflammatory factors IL-1β, TNF-α, COX-2, and iNOS in LPS-induced BV2 cells. Pongamol also protected neurons and significantly restored memory function, inhibited Tau phosphorylation, downregulated Aβ aggregation, and increased oxidoreductase activity in the hippocampus of AD mice. In addition, pongamol reversed the nuclear transfer of NF-κB and increased the levels of Beclin 1 and LC3 II/LC3 I. Most importantly, the anti-inflammatory and promoter autophagy effects of pongamol may be related to the regulation of the Akt/mTOR signaling pathway. In summary, these results showed that pongamol has a potential neuroprotective effect, which greatly enriched the research on the pharmacological activity of pongamol for improving AD.
研究领域:
神经科学
·
药理学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-19
·
IF 10.6
Zhang Liding,Cao Kai,Xie Jun,Liang Xiaohan,Gong Hui,Luo Qingming,Luo Haiming
Amyloid-β (Aβ) readily misfolds into neurotoxic aggregates, generating high levels of reactive oxygen species (ROS), leading to progressive oxidative damage and ultimately cell death. Therefore, simultaneous inhibition of Aβ aggregation and scavenging of ROS may be a promising therapeutic strategy to alleviate Alzheimer’s disease pathology. Based on the previously developed antibody 1F12 that targets all forms of Aβ 42 , we developed an Aβ 42 and ROS dual-targeting nanocomposite using biodegradable mesoporous silica nanoparticles as carriers to load ultra-small cerium oxide nanocrystals (bMSNs@Ce-1F12). By modifying the brain-targeted rabies virus glycoprotein 29 (RVG29-bMSNs@Ce-1F12), this intelligent nanocomposite can efficiently target brain Aβ-rich regions. Combined with peripheral and central nervous system treatments, RVG29-bMSNs@Ce-1F12 can significantly alleviate AD symptoms by inhibiting Aβ 42 misfolding, accelerating Aβ 42 clearance, and scavenging ROS. Furthermore, this synergistic effect of ROS scavenging and Aβ clearance exhibited by this Aβ 42 and ROS dual-targeted strategy also reduced the burden of hyperphosphorylated tau, alleviated glial cell activation, and ultimately improved cognitive function in APP/PS1 mice. Our findings indicate that RVG29-bMSNs@Ce-1F12 is a promising nanodrug that can facilitate multi-target treatment of AD.
研究领域:
神经科学
·
纳米技术
·
药学
·
分子生物学
·
治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2024
·
IF 9.4
Jichun Liu,Mingyuan Chi,Lianxin Li,Yuewen Zhang,Meng Xie
Mitochondrial dysfunction and metal ion imbalance are recognized as pathological hallmarks of Alzheimer's Disease (AD), leading to deposition of β-amyloid (Aβ) thereby and inducing neurotoxicity, activating apoptosis, eliciting oxidative stress, and ultimately leading to cognitive impairment. In this study, the red blood cell membrane (RBC) was used as a vehicle for encapsulating carbon quantum dots (CQD) and polydopamine (PDA), creating a nanocomposite (PDA-CQD/RBC). This nanocomposite was combined with near-infrared light (NIR) for AD treatment. The RBC offers anti-immunorecognition properties to evade immune clearance, PDA exhibits enzyme-mimicking activity to mitigate oxidative stress damage, and CQD acts as a chelating agent for metal ions (Cu 2+ ), effectively preventing Cu 2+ -mediated aggregation of Aβ. Furthermore, the local heating induced by near-infrared laser irradiation can dismantle the formed Aβ fibers and enhance the blood–brain barrier's permeability. Both in vitro and animal experiments have shown that PDA-CQD/RBC, in combination with NIR, mitigates neuroinflammation, and ameliorates behavioral deficits in mice. This approach targets multiple pathological pathways, surpassing the limitations of single-target treatments and enhancing therapeutic efficacy while decelerating disease progression.
研究领域:
神经科学
·
纳米技术
·
药学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR LIQUIDS
·
2024
·
IF 5.3
Wan-Yi Ge,Wen-Pu Shi,Xue-Ting Wang,Huan Liang,Xu-Dong Deng,Liang-Liang Chen,Xiao-Qian Jin,Wei-Hong Guo,Da-Chuan Yin
Protein liquid–liquid phase separation (LLPS) is a significant process in biology and material sciences. Finding suitable conditions for protein LLPS is essential for its in-depth and systematic study. Here, we provide a mixed solution screening kit based on biomacromolecule crowding agents to find protein LLPS conditions. The screening kit consists of 96 chemical formulations, in which the biomacromolecule crowding agents are used as the key components. The aqueous solution of the target protein is mixed with each chemical agent in the kit and then placed in an incubator for some time. The LLPS conditions for the target protein can be found by examining the LLPS phenomena in the droplets. We used nine proteins as model target proteins—lysozyme, bovine serum albumin, bovine hemoglobin, ovalbumin, catalase, FUS, Aβ, Tau, and α-Synuclein—to evaluate the performance of the screening kit. We found that utilization of the screening kit is efficient and useful to find different conditions for LLPS of proteins. The screening results reveal two types of conditions: those that promote and those that inhibit LLPS. Both conditions are extremely valuable because those that promote LLPS can be used to do extensive studies on the LLPS processes of the proteins of interest, whereas those that inhibit LLPS can be utilized as leads for developing novel medications to treat LLPS-related disorders. Furthermore, novel applications for the kit were investigated by utilizing the screening products.
研究领域:
生物学
·
材料科学
·
生物物理学
·
药学
✓ 已验证
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Binbin Dong,Zong Hou,Zhong Zheng,Junpeng Xing,Ningning Zhao,Zhiqiang Liu,Shu Liu
The abundant ginseng neutral polysaccharide (GPN) has been neglected due to its lower activity compared to acidic polysaccharide in ginseng. Herein, the composite enzymes were used to modify the GPN and obtained the enzymatic-degradation-GPN (EGPN). The structural changes were further characterized by GPC, FT-IR, Congo red, XRD, zeta potential, TG, cryo-SEM and AFM. The antioxidant activity of GPNs in vitro was investigated by in vitro chemical experiments and oxidative stress-related indicators on PC12 cells damaged by Aβ 25 – 35 , and EGPN showed favorable antioxidant activity. In addition, EGPN metabolized by intestinal microbiota also significantly increased the viability of injured PC12 cells. Furthermore, in vitro fermentation model was used to investigate the differences of physicochemical properties of GPNs and their regulatory effects on the microbiota. EGPN enhanced the diversity of the microbiota and increased the concentration of short-chain fatty acids (SCFAs). Importantly, EGPN demonstrated a significant reduction in the presence of detrimental bacteria such as Enterococcus and Allobaculum , while simultaneously promoting the growth of beneficial microorganisms including Lactobacillus , Prevotella , and Ruminococcu . This study highlights the potential use of EGPN prepared by composite enzymatic degradation in antioxidant, neuroprotection and restoration of intestinal homeostasis.
研究领域:
药理学
·
生物化学
·
微生物学
·
神经科学
·
生物技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Microbiology
·
2024
·
IF 4
Song Zhenyan,He Jiawei,Yu Wenjing,He Chunxiang,Yang Miao,Li Ping,Li Ze,Jian Gonghui,Cheng Shaowu
Background: Schisanlactone E, also known as XueTongSu (XTS), is an active compound extracted from the traditional Tujia medicine Kadsura heteroclita (“XueTong”). Recent studies highlight its anti-inflammatory and antioxidant properties, yet the mechanisms of XTS’s therapeutic effects on Alzheimer’s disease (AD) are unclear. This study aims to elucidate the therapeutic efficacy and mechanisms of XTS in AD.Methods: Ten C57BL/6 mice were assigned to the control group (NC), and twenty APP/PS1 transgenic mice were randomly divided into the model group (M) (10 mice) and the XTS treatment group (Tre) (10 mice). After an acclimatization period of 7 days, intraperitoneal injections were administered over a 60-day treatment period. The NC and M groups received saline, while the Tre group received XTS at 2 mg/kg. Learning and memory abilities were assessed using the Morris Water Maze (MWM) test. Histopathological changes were evaluated using hematoxylin and eosin (HE) and Nissl staining, and immunofluorescence was used to assess pathological products and glial cell activation. Cytokine levels (IL-1β, IL-6, TNF-α) in the hippocampus were quantified by qPCR. 16S rDNA sequencing analyzed gut microbiota metabolic alterations, and metabolomic analysis was performed on cortical samples. The KEGG database was used to analyze the regulatory mechanisms of XTS in AD treatment.Results: XTS significantly improved learning and spatial memory in APP/PS1 mice and ameliorated histopathological changes, reducing Aβ plaque aggregation and glial cell activation. XTS decreased the expression of inflammatory cytokines IL-1β, IL-6, and TNF-α. It also enhanced gut microbiota diversity, notably increasing Akkermansia species, and modulated levels of metabolites such as isosakuranetin, 5-KETE, 4-methylcatechol, and sphinganine. Pathway analysis indicated that XTS regulated carbohydrate metabolism, neuroactive ligand-receptor interactions, and alanine, aspartate, and glutamate metabolism, mitigating gut microbiota dysbiosis and metabolic disturbances.Conclusion: XTS ameliorates cognitive deficits, pathological changes, and inflammatory responses in APP/PS1 mice. It significantly modulates the gut microbiota, particularly increasing Akkermansia abundance, and influences levels of key metabolites in both the gut and brain. These findings suggest that XTS exerts anti-AD effects through the microbial-gut-brain axis (MGBA).
研究领域:
神经科学
·
药理学
·
分子生物学
·
微生物学
·
代谢组学
✓ 已验证
DOI
高影响因子
PSYCHOPHARMACOLOGY
·
2024
·
IF 3.5
Liu Xin,Jin Yongzeng,Cheng Xinyi,Song Qinghua,Wang Yanan,He Ling,Chen Tong
Rationale The plasma ceramide levels in Alzheimer’s disease (AD) patients are found abnormally elevated, which is related to cognitive decline. Objectives This research was aimed to investigate the mechanisms of aberrant elevated ceramides in the pathogenesis of AD. Results The ICR mice intracerebroventricularly injected with Aβ 1-42 and APP/PS1 transgenic mice were employed as AD mice. The cognitive deficiency, impaired episodic and spatial memory were observed without altered spontaneous ability. The serum levels of p-tau and ceramide were evidently elevated. The modified expressions and activities of glycogen synthase kinase-3β (GSK-3β) and protein phosphatase 2A (PP2A) influenced the serum content of p-tau. The levels of ceramide synthesis-related genes including sptlc1, sptlc2, cers2, and cers6 in the liver of AD mice were increased, while the ceramide degradation-related gene asah2 did not significantly change. The regulations of these genes were conducted by activated nuclear factor kappa-B (NF-κB) signaling. NF-κB, promoted by free fatty acid (FFA), also increased the hepatic concentrations of proinflammatory cytokines. The FFA amount was modulated by fatty acid synthesis-related genes acc1 and srebp-1c. Besides, the decreased levels of pre-proopiomelanocortin (pomc) mRNA and increased agouti-related protein (agrp) mRNA were found in the hypothalamus without significant alteration of melanocortin receptor 4 (MC4R) mRNA. The bioinformatic analyses proved the results using GEO datasets and AlzData. Conclusions Ceramide was positively related to the increased p-tau and impaired cognitive function. The increased generation of ceramide and endoplasmic reticulum stress in the hypothalamus was positively related to fatty acid synthesis and NF-κB signaling via brain–liver axis.
研究领域:
神经科学
·
药理学
·
分子生物学
·
病理学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）