MOLECULAR NEUROBIOLOGY
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2024
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IF 4.6
Chen Jinglin,Wei Yumeng,Li Nong,Pi Chao,Zhao Wenmei,Zhong Yueting,Li Wen,Shen Hongping,Yang Yan,Zheng Wenwu,Jiang Jun,Liu Zerong,Liu Kezhi,Zhao Ling
The aim of this study was to develop a novel antidepressant with high activity. Based on the findings of molecular docking, eight novel curcumin analogues were evaluated in vitro to check for antidepressant efficacy. Among them, CACN136 had the strongest antidepressant effect. Firstly, CACN136 had a stronger 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonate) radical ion scavenging ability (IC 50 : 17.500 ± 0.267 μg/mL) compared to ascorbic acid (IC 50 : 38.858 ± 0.263 μg/mL) and curcumin (27.189 ± 0.192 μg/mL). Secondly, only CACN136 demonstrated clear protective effects on cells damaged by glutamate and oxidative stress at all concentrations. Finally, only CACN136 showed ASP + inhibition and was more effective than fluoxetine hydrochloride (FLU) at low concentrations. To further confirm the antidepressant effect of CACN136 in vivo, the CUMS model was established. Following 28 days of oral administration of CUMS mice, CACN136 increased the central area residence time in the open-field test, significantly increased the sucrose preference rate in the sucrose preference test ( P < 0.001) and significantly reduced the immobility period in the tail suspension test ( P < 0.0001), all of which were more effective than those of FLU. Subsequent research indicated that the antidepressant properties of CACN136 were linked to a decrease in the metabolism of 5-HT and the modulation of oxidative stress levels in vivo. In particular, the activation of the Keap1-Nrf2/BDNF-TrkB signaling pathway by CACN136 resulted in elevated levels of antioxidant enzymes, enhancing the antioxidant capability in mice subjected to CUMS. In conclusion, CACN136 has the potential to treat depression and could be an effective antidepressant. Graphical Abstract
研究领域:
药理学
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神经科学
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分子生物学
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DOI
PubMed
高影响因子
Food Bioscience
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2024
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IF 4.8
Jiayu Zheng,Fengjiao Fan,Wenqian Tang,Nanlong Li,Xiaoyi Jiang,Yong Fang
The TSeMMM and SeMDPGQQ, two selenium-containing peptides derived from Se-enriched rice protein hydrolysates, have previously been demonstrated to show neuroprotective properties against high-dose lead exposure. However, the potential toxicological effects of these functional peptides on low-dose lead-induced neurotoxicity remain poorly understood. The present study aimed to investigate the protective mechanism of two selenium-containing peptides in mitigating low-dose Pb 2+ -induced damage in HT22 cells. Results showed that treatment with 40 μmol/L Pb 2+ significantly reduced cell viability and increased apoptosis, both of which were alleviated by 40 μmol/L TSeMMM and SeMDPGQQ treatment. Furthermore, two peptides exhibited antioxidant potentials by reducing reactive oxygen species levels to 32.19% and 79.29% of the model group, respectively. They also enhanced antioxidant enzyme activities and mitigated oxidative stress through activation of the Keap1/Nrf2 pathway. Additionally, two peptides improved mitochondrial function by elevating mitochondrial membrane potential, ATP production while dramatically reducing reactive oxygen species levels. Interestingly, TSeMMM exhibited superior neurointerventional effects compared to SeMDPGQQ. The RNA sequencing analysis revealed that TSeMMM modulated gene expressions related to oxidative stress and neuroprotective function. The study provides insights into the protective mechanism underlying selenium-containing peptides for mitigating neuronal damage.
研究领域:
神经毒理学
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药理学
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分子生物学
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细胞生物学
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DOI
高影响因子
Scientific Reports
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2024
·Vol. 14
·期 1
·1-15
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IF 3.8
Wang Yan,Wang Shasha,Ma Chenchen,Qi Weiwei,Lv Jing,Zhang Mengqi,Wang Shibo,Wang Rui,Lu Yangyang,Qiu Wensheng
Gastric cancer (GC) is the most common malignant tumor of the gastrointestinal tract and currently has a poor clinical outcome. Turmeric’s rhizome contains a polyphenolic component called curcumin (Cur), which has been demonstrated to inhibit a variety of tumor cells, such as pancreatic, colon, lung and gastric cancers. However, it remains to be elucidated how Cur functions in GC and what molecular processes underlie it. Here, Cur showed a stronger inhibitory effect on GC cells AGS and HGC27. In addition, Cur’s inhibition of GC cells growth was accompanied by increased ROS production, triggering of the Keap1-Nrf2 signaling pathway, and increased transcription of its downstream antioxidant genes HO-1, GCLM, and NQO1. However, when a ROS scavenger NAC was used, the inhibitory effect of Cur on GC cells was reversed. Nuclear factor erythroid 2-related factor 2 (Nrf2) is overexpressed or activated in cancers to shield cancer cells from oxidative damage by responding to oxidative stress (OS). Cur has been found to act as an activator of Nrf2. Notably, compared with Nrf2 knockdown and Cur alone, the combination of the two dramatically increased Cur-induced ROS overaccumulation and inhibition of GC cells proliferation, migration, and invasive abilities. Consistent with in vitro experiments, Cur combined with Nrf2 knockdown significantly inhibited tumor growth in nude mice transplanted with AGS cells. Therefore, we concluded that Nrf2 depletion enhanced Cur therapy effect in GC by inducing the excessive accumulation of ROS, indicating that this is a promising treatment strategy.
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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癌症治疗
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DOI
PubMed
高影响因子
Antioxidants
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2020
·Vol. 9
·期 8
·745
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IF 5.014
Shuoqi Jiang,Zhuangwei Zhang,FangFang Huang,Zuisu Yang,Fangmiao Yu,Yunping Tang,Guofang Ding
The major component of theSolenocera crassicornishead protein hydrolysates-fraction 1 (SCHPs-F1) are low molecular weight peptides (MW < 1 kDa). In this study, we investigated the potential renoprotective effects of SCHPs-F1 in a cyclophosphamide (CTX) toxicity mouse model. In brief, 40 male mice were randomly divided into 5 groups and received either saline or 80 mg/kg body weight (BW) CTX by intraperitoneal injection for 5 days, followed by either saline or SCHPs-F1 (100, 200, and 400 mg/kg BW) by intragastric administration for 15 days. SCHPs-F1 treatment significantly reversed the CTX-induced decreases in the levels of blood urea nitrogen (BUN), creatinine (CRE), and cytochrome P450 (CYP450), as well as the renal histological lesions. Furthermore, the results indicated that SCHPs-F1 potentially alleviated CTX-induced nephrotoxicity through mitigating inflammatory responses, oxidative stress, and apoptosis status of the kidneys, as evidenced by decreased levels of malondialdehyde (MDA), interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ and increased levels of total antioxidant capacity (T-AOC), catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Moreover, overexpression of pro-apoptotic proteins pair B-cell lymphoma-2 (Bcl-2)-associated X (Bax)/Bcl-2, cysteinyl aspartate specific proteinase (caspase)-3 and caspase-9 in renal tissues were suppressed by treatment with SCHPs-F1. In addition, the protein levels of the antioxidant factor nuclear factor erythroid-2 related factor 2 (Nrf2) and the expression levels of its downstream target genes heme-oxygenase (HO-1), glutamate-cysteine ligase modifier subunit (GCLM) and NAD(P)H dehydrogenase (quinone) 1 (NQO-1) were stimulated by treatment with SCHPs-F1 in the CTX-induced renal injury model. Taken together, our data suggested that SCHPs-F1 could provide a novel potential strategy in mitigating the nephrotoxicity caused by CTX.Keywords:apoptosis;cyclophosphamide;inflammation;oxidative stress;peptides;Solenocera crassicornis
研究领域:
药理学
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毒理学
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分子生物学
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DOI
PubMed
高影响因子
Food Science & Nutrition
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2025
·Vol. 13
·期 10
·e71000
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IF 3.8
Zhou Ning,Chen Linlin,Zhang Xing,He Kunmiao,Xu Tiantian,Wang Hanshuo,Sun Jie,Yu Miao,Ren Hongtao,Wang Na
Proanthocyanidins play a crucial role in celiac disease (CD) through their antioxidant and anti-inflammatory properties, effectively regulating oxidative stress and inflammatory responses. However, the poor stability and low bioavailability of proanthocyanidins significantly limit their therapeutic applications. The aim of this study was to investigate the effects of lyoprotectants on proanthocyanidin nanoliposome freeze-dried powder (PCNL-FD), characterize its structural properties, evaluate its in vitro antioxidant capacity and explore its protective effects in a celiac disease cell model. The addition of 4% trehalose as a lyoprotectant effectively maintained the encapsulation efficiency and redispersion stability of PCNL-FD. FTIR and TEM analyses confirmed the successful incorporation of proanthocyanidins into the phospholipid bilayer. In vitro antioxidant assays showed that PCNL-FD exhibited significantly higher DPPH, ABTS, and hydroxyl radical scavenging activities compared to free proanthocyanidins. In the p31-43 peptide-induced celiac disease Caco-2 cell model, PCNL-FD significantly reduced oxidative stress by decreasing ROS and MDA levels while increasing GSH levels and antioxidant enzyme activities (SOD and CAT). The formulation showed anti-inflammatory effects by inhibiting pro-inflammatory cytokines (TNF-α, IL-6) and promoting anti-inflammatory cytokines (IL-4, IL-10). In addition, PCNL-FD activated the Keap1/Nrf2 signaling pathway and upregulated the expression of NQO-1 and HO-1. This nanoliposomal delivery system effectively overcame the bioavailability and stability limitations of free proanthocyanidins, providing new insights into the management of oxidative stress in inflammatory diseases such as celiac disease.
研究领域:
分子生物学
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药剂学
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免疫学
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消化病学
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营养学
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纳米医学
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氧化应激
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产品关联
DOI
PubMed
高影响因子
FISH & SHELLFISH IMMUNOLOGY
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2023
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IF 4.7
Shengnan Shi,Ju Wang,Changhong Liu,Lei Zheng
Quercetin is a kind of flavonoid substance extensively existing in the plant, which has antioxidant, anti-inflammatory, and anti-apoptosis effects. It was reported that the higher concentration of spores present in the environment could cause abnormal development in zebrafish larvae. Therefore, this study set out to investigate whether quercetin could reduce the zebrafish larvae damage caused by Botrytis cinerea exposure as well as to examine the molecular basis for this action. The findings demonstrated that 50 μM quercetin improved the developmental dysplasia of zebrafish larvae induced by 10 2 CFU/mL Botrytis cinerea spore suspension, reduced abnormal apoptosis, enhanced antioxidant system, relieved inflammation, reshaped intestinal morphology and recovered intestinal motility . At the molecular level, quercetin decreased the transcriptional abundance of pro-apoptotic factors ( bax , p53 , caspase3 , and caspase9 ) and up-regulated the anti-apoptotic gene ( bcl-2 ) expression to reduce apoptosis. Moreover, quercetin enhanced the activities of downstream antioxidant enzymes (SOD and CAT) to clear excess ROS and MDA due to Botrytis cinerea exposure by up-regulating the expression of antioxidant genes ( nrf2 , ho-1 , sod , and cat ) in the Keap1-Nrf2 pathway. Additionally, quercetin inhibited the elevation of TNF-α by regulating the gene expression of key targets ( jak3 , pi3k , pdk1 , akt , and ikk2 ) and the content of major proteins NF-κB (P65) and IκB in the NF-κB pathway. In conclusion, this work enriched the contents of the biological research of Botrytis cinerea and provided a new direction for the drug development and targeted therapy of quercetin.
研究领域:
药理学
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毒理学
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动物学
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分子生物学
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DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2018
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IF 3.457
Ji Ma,Maoru Li,Praveen Kumar Kalavagunta,Jiajing Li,Qiangqiang He,Yifan Zhang,Owais Ahmad,Hongli Yin,Tao Wang,Jing Shang
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease with a broad spectrum of liver injury. Oxidant stress is believed to be the pathogenesis of NAFLD as the “second hit”. Hydrogen peroxide is widely used as an oxidant reagent to induce the oxidant injury of cells and larval zebrafish. Recently, cichoric acid is being studied extensively for its obesity attenuating, hepatic steatosis reduction and anti-oxidant effects. In this study, to identify whether CRA could protect the H 2 O 2 induced oxidant injury via anti-oxidant impact by using L02 and HepG2 hepatocytes as in vitro and larval zebrafish as in vivo injury models, and evaluated the protective and anti-oxidant effects of CRA by pretreated it on both in vitro and in vivo models. CRA was found to reduce the production of ROS and MDA, activate the anti-oxidant enzymes SOD and GSH-px, and pathways Keap1-Nrf2 and HO-1. These results demonstrated that CRA might protect the liver injury by its anti-oxidant effect, which could be a potential therapeutic agent of NAFLD.
研究领域:
药理学
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毒理学
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细胞生物学
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斑马鱼模型
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肝脏疾病
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产品关联
DOI
PubMed
高影响因子
Advanced Science
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2024
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IF 14.3
Gaoxiang Yu,Yijie Chen,Ningning Yang,Haojie Zhang,Xuzi Zhang,Yibo Geng,Jiayi Zhao,Zhuliu Chen,Chengji Dong,Lidan Lin,Jianjun Qi,Xuanlong Zhang,Xiaoqiong Jiang,Weiyang Gao,Yuepiao Cai,Xiangyang Wang,Jian Ding,Jian Xiao,Kailiang Zhou
Preventing and treating avascular necrosis at the distal end of the flaps are critical to surgery success, but current treatments are not ideal. A recent study shows that apoptotic bodies (ABs) generated near the site of apoptosis can be taken up and promote cell proliferation. The study reveals that ABs derived from fibroblast-like cells in the subcutaneous connective tissue (FSCT cells) of skin flaps promoted ischaemic flap survival. It is also found that ABs inhibited cell death and oxidative stress and promoted M1-to-M2 polarization in macrophages. Transcriptome sequencing and protein level testing demonstrated that ABs promoted ischaemic flap survival in endothelial cells and macrophages by inhibiting ferroptosis via the KEAP1-Nrf2 axis. Furthermore, microRNA (miR) sequencing data and in vitro and in vivo experiments demonstrated that ABs inhibited KEAP1 by delivering miR-339-5p to exert therapeutic effects. In conclusion, FSCT cell-derived ABs inhibited ferroptosis, promoted the macrophage M1-to-M2 transition via the miR-339-5p/KEAP1/Nrf2 axis and promoted ischaemic flap survival. These results provide a potential therapeutic strategy to promote ischaemic flap survival by administering ABs.
研究领域:
外科手术
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细胞生物学
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分子生物学
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组织工程
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再生医学
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
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2026
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IF 11.3
Li Zhen,Jianhong Peng,Huimin Cui,Junhong Tao,Yaping Liu,Jianxin Cao,Hesham R El-Seedi,Guiguang Cheng,Zhengxuan Wang
Background The flowers of Rosa chinensis cv. ‘JinBian’ (RCF) has been utilized as a herbal tea for millennia to prevent aging-related diseases. RCF is enriched in flavonoids and exhibits significant antioxidant effects for anti-aging potential. However, the specific bioactive compounds and their underlying anti-aging mechanisms remain unclear. Purpose This study aimed to investigate the bioactive ingredients and neuroprotective mechanisms of RCF extracts. Methods The study obtained dichloromethane (RD), ethyl acetate (RE), n-butanol (RB), and residual water (RW) fractions from RCF after liquid-liquid extraction. It investigated their neuroprotective effect in in vitro and in vivo experiments. UHPLC-ESI-HRMS/MS analysis was used to identify phytochemicals in RE. In vitro assays included measuring phenolic and flavonoid contents, ABTS⁺ and DPPH + scavenging capacities, and effects on H₂O₂-induced SHSY-5Y cells. In vivo , D-galactose-induced mice were used and assessed through the Morris water maze test and the crucifixion anxiety test. Molecular pathways and gut microbiota were analyzed. Results Among the fractions, RE had the highest phenolic and flavonoid contents, the strongest ABTS⁺ and DPPH + scavenging capacities, and significantly inhibited ROS accumulation by increasing antioxidants (glutathione, catalase, superoxide dismutase) in H₂O₂-induced SHSY-5Y cells. UHPLC-ESI-HRMS/MS analysis identified 28 phytochemicals in RE, primarily gallic acid derivatives and flavonoid derivatives. In D-galactose-induced mice, RE alleviated memory impairment and anxiety-like behavior. RE ameliorated brain damage by activating the Keap1/Nrf2-regulated antioxidant pathway (increasing T-AOC, GSH, GPX4, NQO1, SOD1, HO-1), suppressing ferroptosis, inhibiting acetylcholinesterase activity, attenuating GSK-3β/Tau/Bcl-2 axis-regulated apoptosis, and modulating AMPK-regulated autophagy. Additionally, RE improved gut microbiota diversity, particularly increasing beneficial bacteria such as Lactobacillus and Bifidobacterium . Conclusions Therefore, RE could alleviate the cognitive deficit associated with age-related neurodegenerative diseases by targeting ferroptosis-related oxidative stress, apoptosis, and autophagy, as well as modulating the gut microbiota.
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PubMed
高影响因子
Toxins
·
2022
·Vol. 14
·期 12
·876
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IF 5.075
Yanan Wang,Jiayu Wu,Lingfeng Wang,Ping Yang,Zuhong Liu,Shahid Ali Rajput,Mubashar Hassan,Desheng Qi
Aflatoxin B1(AFB1) exists widely in feed and food with severe hazards, posing a serious threat to human and animal health. Epigallocatechin gallate (EGCG) and glutathione (GSH) have been reported as having anti-oxidative and other functions. The present study aimed to investigate the detoxification effect of EGCG and GSH alone or in combination on AFB1exposure in ducklings. Fifty one-day-old male ducklings were randomly assigned into five experimental groups (n= 10): 1. Control (CTR); 2. 0.3 mg/kg BW AFB1(AFB1); 3. 0.3 mg/kg BW AFB1+ 100 mg/kg BW EGCG (AFB1+ EGCG); 4. 0.3 mg/kg BW AFB1+ 30 mg/kg BW GSH (AFB1+ GSH); 5. 0.3 mg/kg BW AFB1+ 100 mg/kg BW EGCG + 30 mg/kg BW GSH (AFB1+ EGCG + GSH). The experiment lasted for seven days. Compared with the CTR group, AFB1reduced growth performance, total serum protein and albumin content, increased serum enzyme activity (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and γ-glutamyl transpeptidase), and caused pathological damage to the ducklings’ livers. AFB1exposure increased malondialdehyde content and decreased superoxide dismutase, total antioxidant capacity, catalase, glutathione peroxidase activities, and glutathione content in the liver. EGCG and GSH alone or in combination mitigated these adverse effects. Meanwhile, EGCG and GSH attenuate apoptosis of hepatocytes, and regulated AFB1-induced changes in the abundance of genes contained in the Keap1/Nrf2 signalling and apoptotic pathways. Collectively, these results suggest that EGCG and GSH alleviate the hepatocyte injury induced by AFB1by inhibiting oxidative stress and attenuating excessive mitochondria-mediated apoptosis.Keywords:aflatoxin B1;duckling;epigallocatechin gallate;glutathione;oxidative stress;Keap1/Nrf2 signalling;apoptosisKey Contribution:EGCG and GSH alleviate AFB1-induced liver injury in ducklings by increasing antioxidant capacity and antagonising apoptosis.
研究领域:
兽医学
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毒理学
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药理学
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产品关联
DOI
PubMed
高影响因子
Experimental and Therapeutic Medicine
·
2021
·Vol. 22
·期 6
·1-10
·
IF 2.447
Qian Li,Zhaoyan Qiu,Yan Wang,Chunyan Guo,Xu Cai,Yandong Zhang,Li Liu,Hongkun Xue,Jintian Tang
Tea polyphenols (TPs) are the major bioactive extract from green tea that have been extensively reported to prevent and treat oxidative stress damage. In previous studies, TPs have been demonstrated to protect cells against oxidative injury induced by hydrogen peroxide (H2O2). However, the underlying mechanism remains unclear. The aim of the current study was to investigate whether the protective and regulatory effects of TPs on oxidative stress damage were dependent on the mammalian STE20‑like protein kinase (Mst)/nuclear factor (erythroid‑derived 2)‑like 2 (Nrf2) axis and the Kelch‑like ECH‑associated protein 1 (Keap1)/Nrf2/heme oxygenase 1 (HO‑1) pathway in RAW264.7 cells, a murine macrophage cell line. Maintaining a certain range of intracellular reactive oxygen species (ROS) levels is critical to basic cellular activities, while excessive ROS generation can override the antioxidant capacity of the cell and result in oxidative stress damage. The inhibition of ROS generation offers an effective target for preventing oxidative damage. The results of the present study revealed that pretreatment with TPs inhibited the production of intracellular ROS and protected RAW264.7 cells from H2O2‑induced oxidative damage. TPs was also demonstrated to attenuate the production of nitric oxide and malondialdehyde and increase the levels of antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase). In addition, following TPs treatment, alterations in Mst1/2 at the mRNA and protein level inhibited the production of ROS and promoted the self‑regulation of antioxidation. TPs‑induced Keap1 gene downregulation also increased the expression of Nrf2 and HO‑1. Collectively, the results of the present study demonstrated that TPs provided protection against H2O2‑induced oxidative injury in RAW264.7 cells.
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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生物化学
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DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2025
·
IF 4.5
Yulu Wang,Minghao Yuan,Sihui Li,Jiamei Tang,Yan Wan,Xue Liang,Yiping Guo,Li Guo
Alcohol liver disease (ALD) is a chronic liver disorder resulting from long-term heavy alcohol consumption. The pathogenesis of ALD is multifactorial, and existing therapeutic agents primarily target specific aspects of the disease while presenting significant side effects, including drug-induced liver injury and hepatobiliary disease. Silibinin (SLB) has attracted widespread attention for its hepatoprotective effects and favorable safety profile. However, inherent limitations associated with SLB, such as poor solubility and bioavailability, have significantly limited its clinical application. Drug delivery systems, including liposomes, offer promising potential for the delivery of hydrophobic drugs. However, the selection of an appropriate delivery vehicle requires optimization. Ursodeoxycholic acid sodium (UAS) serves as a promising alternative to cholesterol in liposomal formulations, offering a potential strategy to mitigate the health risks associated with cholesterol. In this study, UAS was employed as the liposomal membrane material to prepare a UAS liposome loaded with SLB (SUL), and its efficacy and mechanism of action in alcoholic-induced liver injury were subsequently evaluated. The experimental results demonstrated that SUL exhibited a uniform particle size distribution, good stability, and an effective release profile in vitro. Following oral administration, SUL effectively inhibited alcohol-induced liver damage, oxidative stress, and fat accumulation. In addition, SUL regulated the expression of the kelch-1ike ECH- associated protein l (Keap1), nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase 1 (HO-1) proteins, thereby exerting antioxidative stress effects. Furthermore, it also modulated apoptosis-related factors, including B-cell lymphoma-2 (Bcl-2), BCL-2-associated X (Bax), cysteinyl aspartate specific proteinase-3 (Caspase-3), and cleaved caspase-3, to mitigate hepatocyte apoptosis. In summary, SUL demonstrates enhanced therapeutic efficacy against ALD, offering a novel approach for the clinical application of SLB in the prevention and treatment of ALD.
研究领域:
药理学
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肝病学
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药物递送系统
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）