JOURNAL OF ETHNOPHARMACOLOGY
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2025
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IF 5.4
Qimeng Tian,Hong Jiang,Yajun Luan,Jingge Sun,Yihang Sui,Ling Chen,Yongxiang Wang,Ninghua Tan
Ethnopharmacological relevance Suhuang antitussive capsule (SH) is the only clinically approved traditional Chinese patent medicine for the treatment of post-infectious cough (PIC). During the past decade, our lab has conducted intensive researches on SH, including its efficacy and mechanism on PIC, and determined that SH has favorable anti-inflammatory, antitussive, expectorant, and anti-asthmatic pharmacological effects. Recently, we found that vicenin-2 (VIC-2) could be detected in SH and showed activity in vitro primary screening on PIC. Aim of the study To investigate the therapeutic effects of VIC-2 on PIC and its potential mechanisms, and want to elucidate VIC-2 as one of the efficacious components of SH. Materials and methods The PIC mouse model was established with lipopolysaccharide (LPS)-induced combined cigarette smoke (CS)-exposed ICR mice, while the in vitro assay was constructed to induce BEAS-2B cells with cigarette smoke extract (CSE). The therapeutic effects of VIC-2 on PIC in vitro and in vivo were assessed by pathological sections, cough assay, immune cell counting, and quantitative-polymerase chain reaction (Q-PCR). The mechanisms of VIC-2 on ferroptosis and mitophagy in PIC were further explored by cell viability assay, Prussian blue staining, lipid peroxidation assessment, confocal laser scanning microscopy, and western blotting. Subsequently, virtual docking, cellular thermal shift assay (CETSA), and drug affinity responsive target stability (DARTS) verified the target relationship between VIC-2 and LDL receptor-related protein 1 (LRP1). In addition, the link between LRP1 and mitophagy-dependent ferroptosis was explored by knocking down LRP1. Results VIC-2 significantly improved lung inflammation, oxidative stress, and airway remodeling in PIC and inhibited mitophagy-dependent ferroptosis, confirming that it is one of the antitussive components of SH for the treatment of PIC. LRP1 is one of the pharmacological targets of VIC-2, in which VIC-2 exerted the above effects through up-regulating LRP1 by influencing the LRP1-Parkin interaction. The blockade of LRP1 reversed the both in vitro and in vivo pharmacological activities of VIC-2 . Furthermore, our results showed for the first time that defects in LRP1 lead to ferroptosis. Conclusion This study demonstrates that VIC-2 inhibits mitophagy-dependent ferroptosis via LRP1 for the treatment of PIC, constituting one of the antitussive components of SH.
研究领域:
药理学
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分子生物学
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传统中药研究
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DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
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2021
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IF 9.381
Fei He,Shihai Zhang,Yanan Li,Xia Chen,Zhenyun Du,Chenghao Shao,Kan Ding
The fruit of Lycium ruthenicum Murr is used as traditional medicine and functional food . Previously we reported that one RG-I pectin from this fruit might inhibit pancreatic cancer cells growth. We further hypothesized that there might be other type of polysaccharides in this fruit also have anti-tumor effect. Here, we showed novel structure of a homogeneous polysaccharide named LRP1-S2 from this fruit and its anti-pancreatic cancer effect. Structure analyses suggested that LRP1-S2 was a novel arabinogalactan with the molecular weight ( Mw ) of 17.0 kDa. Bioactivity test showed that LRP1-S2 might attenuate the proliferation of pancreatic cancer cells in vitro and in vivo without significant cytotoxicity to normal pancreatic HPDE6-C7 cells and LO2 liver cells. Mechanism study indicated that it might induce apoptosis of BxPC-3 by inactivating P38 MAPK/NF-κB and GSK-3β/β-Catenin signaling pathways . These results suggested that LRP1-S2 could be a potential anti-tumor leading compound for functional food and new drug development. Chemical compounds arabinogalactan, pectin, galactan , arabinan , RN-1, HH1-1, LRP1-S2, LRP3-S1.
研究领域:
药理学
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癌症研究
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分子生物学
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植物学
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DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2020
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IF 4.545
Wen-Qiao Qiu,Rong Pan,Yong Tang,Xiao-Gang Zhou,Jian-Ming Wu,Lu Yu,Betty Yuen-Kwan Law,Wei Ai,Chong-Lin Yu,Da-Lian Qin,An-Guo Wu
Emerging evidence indicates that the enhancement of microglial autophagy inhibits the NLRP3 inflammasome mediated neuroinflammation in Alzheimer's disease (AD). Meanwhile, low density lipoprotein receptor-related protein 1 (LRP1) highly expressed in microglia is able to negatively regulate neuroinflammation and positively regulate autophagy. In addition, we have previously reported that an active lychee seed fraction enriching polyphenol (LSP) exhibits anti-neuroinflammation in Aβ-induced BV-2 cells. However, its molecular mechanism of action is still unclear. In this study, we aim to investigate whether LSP inhibits the NLRP3 inflammasome mediated neuroinflammation and clarify its molecular mechanism in Aβ-induced BV-2 cells and APP/PS1 mice. The results showed that LSP dose- and time-dependently activated autophagy by increasing the expression of Beclin 1 and LC3II in BV-2 cells, which was regulated by the upregulation of LRP1 and its mediated AMPK signaling pathway. In addition, both the Western blotting and fluorescence microscopic results demonstrated that LSP could significantly suppress the activation of NLRP3 inflammasome by inhibiting the expression of NLRP3, ASC, the cleavage of caspase-1, and the release of IL-1β in Aβ(1-42)-induced BV-2 cells. In addition, the siRNA LRP1 successfully abolished the effect of LSP on the activation of AMPK and its mediated autophagy, as well as the inhibition of NLRP3 inflammasome. Furthermore, LSP rescued PC-12 cells which were induced by the conditioned medium from Aβ(1-42)-treated BV-2 cells. Moreover, LSP improved the cognitive function and inhibited the NLRP3 inflammasome in APP/PS1 mice. Taken together, LSP inhibited the NLRP3 inflammasome-mediated neuroinflammation in the in vitro and in vivo models of AD, which was closely associated with the LRP1/AMPK-mediated autophagy. Thus, the findings from this study further provide evidences for LSP serving as a potential drug for the treatment of AD in the future.
研究领域:
神经科学
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药理学
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分子生物学
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PubMed
高影响因子
PHYSIOLOGY & BEHAVIOR
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2019
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IF 2.635
Hui Wang,Ling Xiao,Huiling Wang,Gaohua Wang
Low-density lipoprotein receptor-related protein 1 (LRP1) and tau play an important role in developing Alzheimer's disease. This study aimed to explore the involvement of LRP1 in microtubule dynamic and depressive-like behavior in a depressive-like rat model. It also investigated whether fluoxetine blocked the change induced by chronic unpredictable mild stress (CUMS). Sprague–Dawley rats (200–250 g) were exposed to CUMS and fluoxetine for 4 weeks respectively. The body weight was determined, and behavior tests, including sucrose preference test, forced swimming test and open field test were performed. Western blot analysis was conducted to determine the protein levels of LRP1, tubulin, Acet-tub, Tyr-tub and PI3K/Akt/GSK-3β. Real-time quantitative polymerase chain reaction was used for mRNA expression levels of LRP1. Immunohistochemical staining was applied for LRP1 and immunofluorescence staining for the co-location of p-tau (404,262) and Acet-tub. The CUMS group presented a decreased body weight and depressive-like behavior, which was improved by fluoxetine. The protein and mRNA expression levels of LRP1 were elevated in the CUMS group. The levels of Acet-tub increased following CUMS, accompanied by elevated levels of p-tau (404,262). The binding of p-tau and Acet-tub significantly decreased in depressive-like rats, and fluoxetine attenuated microtubule instability. Finally, the inhibition of CUMS-induced PI3K/Akt activated GSK-3β, and fluoxetine reversed the change in the signaling pathway. Hence, LRP1 might impair the microtubule dynamics accompanied by depressive-like behavior via the PI3K/ Akt /GSK3β pathway in adult depressive-like rats, and hippocampal LRP1 might be involved in the development of depression.
研究领域:
神经科学
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药理学
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行为科学
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产品关联
DOI
PubMed
高影响因子
Advanced Science
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2026
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IF 14.1
Jie Miao,Jing Wang,Yankun Li,Haipei Zhang,Yanli Zhang,Qingnian Li,Bo Xiao,Wenhu Zhou,Junhong Guo
Alzheimer's disease (AD) is characterized by amyloid‐β (Aβ) accumulation, neuroinflammation, and vascular dysfunction, yet effective therapies remain limited. Impaired Aβ clearance across the blood–brain barrier (BBB) is a key contributor to AD pathogenesis. Two sequential barriers to Aβ clearance are identified: proprotein convertase subtilisin/kexin type 9 (PCSK9) upregulation in cerebrovascular endothelial cells compromises low‐density lipoprotein receptor‐related protein 1 (LRP1)‐mediated Aβ efflux, whereas increased intracellular Aβ handling after PCSK9 silencing induces tribbles pseudokinase 3 (TRIB3) upregulation and exposes an autophagy blockade restricting intracellular Aβ degradation. PCSK9 silencing restores LRP1 expression and enhances Aβ uptake and efflux, whereas TRIB3 knockdown restores autophagic flux and facilitates Aβ degradation. SITR (siPCSK9/siTRIB3@TPN‐RAP), a RAP‐modified siRNA nanodelivery system based on tea polyphenol nanoparticles (TPNs), enables brain‐enriched co‐delivery of siPCSK9 and siTRIB3. SITR enhances BBB penetration and preferentially accumulates in cerebrovascular endothelial cells and microglia. In APP/PS1 mice, SITR improves cognitive performance, reduces Aβ and cerebral amyloid angiopathy burden, preserves vascular and neuronal homeostasis, and suppresses neuroinflammation, while showing no overt short‐term systemic toxicity under a 6‐week regimen. These findings establish PCSK9 and TRIB3 as complementary therapeutic targets and support SITR as an effective nanoplatform integrating enhanced Aβ efflux with restored autophagic degradation for AD intervention. PCSK9 upregulation in cerebrovascular endothelial cells and microglia destabilizes the Aβ transporter LRP1, while TRIB3‐associated autophagy blockade further limits intracellular Aβ degradation. A RAP‐modified tea‐polyphenol nanoparticle co‐delivers siPCSK9 and siTRIB3 to restore LRP1‐mediated Aβ efflux and autophagy‐dependent degradation, reducing Aβ deposition, cerebral amyloid angiopathy, BBB disruption, and neuroinflammation in APP/PS1 mice.
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PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
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2026
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IF 8.3
Panyi Hu,Liping Su,Jinfeng Liu,Rui Zhao,Dong Wang,Jiahan Cheng,Xiaohe Tian
Reliable visualization of lipid droplet (LD) remodeling remains challenging because conventional LD probes often suffer from background fluorescence and limited photostability in lipid-rich cellular environments. Here, we developed LD-TTP, an LD-targeting fluorescent probe integrating aggregation-induced emission (AIE) and intramolecular charge transfer (ICT) properties. LD-TTP exhibits strong fluorescence activation, high selectivity, and excellent photostability, enabling robust imaging and quantitative analysis of LD dynamics in cell-based steatotic models. Using staged steatotic HepG2 cells, we found that LD remodeling was accompanied by stage-dependent changes in the spatial distribution of the amyloid-β (Aβ)-associated receptor low-density lipoprotein receptor–related protein 1 (LRP1). In early steatosis, LRP1 expression increased and became enriched around LDs, coinciding with enhanced uptake of exogenous Cy5-labeled Aβ. As steatosis progressed, LRP1 expression declined, and its LD-associated localization was lost, paralleling reduced Aβ uptake. A diacylglycerol acyltransferase 1 (DGAT1) inhibitor partially restored Aβ uptake in moderate-to-severe steatotic HepG2 cells. These findings provide cellular-level evidence for a stage-dependent relationship among LD remodeling, LRP1 alteration, and Aβ uptake in hepatocytes. Although the present results offer mechanistic clues at the cellular level, they do not fully capture the influence of the physiological microenvironment in vivo . Further animal studies will be required to determine whether these LD–LRP1–Aβ-associated changes are maintained under physiological conditions.
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高影响因子
Advanced Science
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2025
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IF 14.1
Miao Wei,Yujia Huo,Jingchang Yuan,Xiao Fan,Xiaochen Wang,Sisi Tan,Xi Gao,Ruotong Ouyang,Hong Li
Glaucoma is a leading cause of irreversible blindness, characterized by progressive retinal ganglion cells (RGCs) loss. Increasing evidence links microglial activation and lipid metabolism dysregulation to neurodegeneration. However, the role of microglial lipid metabolic reprogramming in disease pathogenesis remains unclear. This study finds that microglia in an acute ocular hypertension (AOH) model exhibit abnormal lipid droplet accumulation, downregulation of low-density lipoprotein receptor-related protein 1 (LRP1), and a shift toward a pro-inflammatory M1 phenotype. Importantly, serum samples from glaucoma patients reveal significantly reduced LRP1 levels compared to controls. To restore lipid homeostasis, this study develops alpinetin-loaded PLGA nanoparticles (AlpNPs), which demonstrate efficient microglial uptake and sustained release. AlpNPs reduced intracellular lipid accumulation, promoted M2 polarization, and suppressed microglial proliferation and migration. Mechanistically, AlpNPs directly bind to LRP1 and enhance its interaction with PPARγ, thereby activating the downstream LXRα-ABCA1 pathway, which is pivotal for cholesterol efflux and anti-inflammatory responses. Knockdown of LRP1 abolished the protective effects of AlpNPs, confirming its essential role in mediating metabolic reprogramming. In vivo, intravitreal injection of AlpNPs significantly attenuates retinal inflammation and preserves RGCs in AOH. These findings identify microglial lipid metabolic dysfunction as a key driver in glaucoma and highlight LRP1-targeted nanotherapy as a promising strategy for neuroprotection.
研究领域:
眼科学
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神经科学
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纳米医学
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免疫代谢
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分子生物学
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PubMed
高影响因子
International Journal of Biological Sciences
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2022
·Vol. 18
·期 16
·6008-6019
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IF 10.75
Li Chao,Lv Li-fang,Qi-Li Mu-ge,Yang Rui,Wang Yu-jing,Chen Shuang-shuang,Zhang Ming-xiu,Li Tian-yu,Yu Tong,Zhou Yu-hong,Liang Hai-hai,Shan Hong-li,Li Xue-lian
Cardiac fibrosis is one of the common pathological processes in many cardiovascular diseases characterized by excessive extracellular matrix deposition. SerpinE2 is a kind of protein that inhibits peptidase in extracellular matrix and up-regulated tremendously in mouse model of cardiac fibrosis induced by pressure-overloaded via transverse aortic constriction (TAC) surgery. However, its effect on cardiac fibroblasts (CFs), collagen secretion and the underlying mechanism remains unclear. In this study, DyLight® 488 green fluorescent dye or His-tagged proteins were used to label the exogenous serpinE2 protein. It was showed that extracellular serpinE2 translocated into CFs by low-density lipoprotein receptor-related protein 1 (LRP1) and urokinase plasminogen activator receptor (uPAR) of cell membrane through endocytosis. Knockdown of LRP1 or uPAR reduced the level of serpinE2 in CFs and down-regulated the collagen expression. Inhibition of the endocytosis of serpinE2 could inhibit ERK1/2 and β-catenin signaling pathways and subsequently attenuated collagen secretion. Knockdown of serpinE2 attenuates cardiac fibrosis in TAC mouse. We conclude that serpinE2 could be translocated into cardiac fibroblasts due to endocytosis through directly interact with the membrane protein LRP1 and uPAR, and this process activated the ERK1/2, β-catenin signaling pathways, consequently promoting collagen production.
研究领域:
心血管疾病
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细胞生物学
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分子生物学
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病理学
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产品关联
DOI
PubMed
高影响因子
Science Advances
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2025
·Vol. 11
·期 3
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IF 12.5
Zhi Li,Shaoping Jiang,Jie Wang,Wenpei Li,Jun Yang,Weimin Liu,Huile Gao,Yuanyu Huang,Shaobo Ruan
The prevalent tumor-supporting glioblastoma-associated macrophages (GAMs) promote glioblastoma multiforme (GBM) progression and resistance to multiple therapies. Repolarizing GAMs from tumor-supporting to tumor-inhibiting phenotype may troubleshoot. However, sufficient accumulation of drugs at the GBM site is restricted by blood-brain barrier (BBB). Herein, we designed peptide-drug conjugates (PDCs) by conjugating camptothecin or resiquimod to a tandem peptide composed of matrix metalloproteinase 2–responsive peptide and angiopep-2 via disulfonyl-ethyl carbonate/carbamate (MAPDCs). The mixed self-assembly MAPDCs could recognize low-density lipoprotein receptor–related protein 1 (LRP1) to facilitate BBB transport. Once reaching the GBM site, the responsive peptide would be cleaved to shed the angiopep-2, blocking abluminal LRP1-mediated brain-to-blood efflux and enhancing drug retention. Sequentially, drugs are released under the high level of intracellular glutathione. In vivo studies demonstrated that MAPDCs repolarized GAMs, boosted immune response, and resensitized chemotherapeutic toxicity, offering a much-improved anti-GBM effect. The effectiveness of MAPDCs validates GAMs as therapeutic target and PDCs as versatile brain delivery system with high design flexibility.
研究领域:
肿瘤学
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药学
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神经科学
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免疫学
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产品关联
DOI
PubMed
高影响因子
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