INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
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IF 8.5
Yijun Tu,Yijie Cai,Jiachuan Lei,Jianqing Yu
The programmed death-ligand 1 (PD-L1) protein plays a key role in immune responses. Scutellarin (SCU), as a flavonoid, has a variety of bioactivities. In this study, the human PD-L1 was obtained by expression and purification, and the interaction mechanisms between PD-L1 and SCU were revealed through multi-spectroscopy and computer simulation. Fluorescence data indicated that the quenching of PD-L1 by SCU was mainly static quenching, and primarily driven by hydrogen bonding and van der Waals forces. The binding constant (K a ) was decreased from 2.05 ± 0.55 × 10 4 L·mol −1 to 0.28 ± 0.08 × 10 4 L·mol −1 with increasing temperature. Meanwhile, the changes in the microenvironment of PD-L1 were revealed by the synchronous and the 3D fluorescence data. In addition, the melting temperature of PD-L1 increased by 1.67 °C after binding with SCU. Moreover, the circular dichroism data showed that SCU changed the secondary structure of PD-L1 by increasing α-helix content and decreasing β-sheet content. Furthermore, the binding modes between SCU and PD-L1 and the key residues involved in the interaction were revealed by molecular docking and molecular dynamics. These findings supported SCU as an alternative ICB therapeutic strategy and provided evidence for computer-based drug design strategies.
研究领域:
生物化学
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免疫学
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药物设计
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DOI
PubMed
高影响因子
CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY
·
2024
·Vol. 51
·期 4
·e13845
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IF 2.4
Wen-Cong Gao,Tie-Hua Yang,Bin-Bao Wang,Qian Liu,Qing Li,Xiao-Huan Zhou,Chang-Bo Zheng,Peng Chen
Abnormalities in vascular smooth muscle cells (VSMCs) are pivotal in the pathogenesis of cardiovascular pathologies such as atherosclerosis and hypertension. Scutellarin (Scu), a flavonoid derived from marigold flowers, exhibits a spectrum of biological activities including anti-inflammatory, antioxidant, antitumor, immunomodulatory and antimicrobial effects. Notably, Scu has demonstrated the capacity to mitigate vascular endothelial damage and prevent atherosclerosis via its antioxidative properties. Nevertheless, the influence of Scu on the formation of VSMC-derived foam cells remains underexplored. In this study, Scu was evidenced to efficaciously attenuate oleic acid (OA)-induced lipid accumulation and the upregulation of adipose differentiation-associated protein Plin2 in a dose- and time-responsive manner. We elucidated that Scu effectively diminishes OA-provoked VSMC foam cell formation. Further, it was established that Scu pretreatment augments the protein expression of LC3B-II and the mRNA levels of Map1lc3b and Becn1, concurrently diminishing the protein levels of the NLRP3 inflammasome compared to the OA group. Activation of autophagy through rapamycin attenuated NLRP3 inflammasome protein expression, intracellular lipid droplet content and Plin2 mRNA levels. Scu also counteracted the OA-induced decrement of LC3B-II levels in the presence of bafilomycin-a1, facilitating the genesis of autophagosomes and autolysosomes. Complementarily, in vivo experiments revealed that Scu administration substantially reduced arterial wall thickness, vessel wall cross-sectional area, wall-to-lumen ratio and serum total cholesterol levels in comparison to the high-fat diet model group. Collectively, our findings suggest that Scu attenuates OA-induced VSMC foam cell formation through the induction of autophagy and the suppression of NLRP3 inflammasome activation.
研究领域:
心血管疾病
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药理学
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细胞生物学
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炎症
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DOI
PubMed
高影响因子
PLoS One
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2025
·Vol. 20
·期 1
·e0318031
·
IF 2.6
Xiu-Ying He,Yui-Si Yang,Yue-Xiang Zheng,Qing-Jie Xia,Hong-Zhou Yu,Xiao-Ming Zhao,Ting-Hua Wang
Purpose
Glioma is the most common primary intracranial tumors. Although great achievements have been made in the treatment, the efficacy is still unsatisfactory, which imposes a hefty burden on patients and society. Therefore, the exploration of new and effective anti-glioma drugs is urgent.
Methods
Human glioma cell lines U251 and LN229 were included in the study. Cell proliferation was detected by cell counting kit-8 (CCK8), plate clone formation assay, EdU incorporation assay and xCELLigence real-time cell analyzer. Cell apoptosis was evaluated by TUNEL assay and flow cytometry. Then, transwell assay was used for assessing the migration. Moreover, tumor xenograft model was established to examine the effect of scutellarin (SCU) and lidocaine on the growth of glioma in vivo . Lastly, western blot was performed to detect the protein level of epidermal growth factor receptor (EGFR).
Results
In present study, we found that SCU and lidocaine suppressed the proliferation and migration, and induced the apoptosis of human glioma cell lines, including U251 and LN229 cells, in a dose-dependent manner in vitro . Moreover, the combination of SCU and lidocaine further restrained the proliferation and migration ability of U251 and LN229 cells, while induced their apoptosis in vitro . Additionally, SCU and lidocaine also inhibited the growth of glioma in vivo , and the effect of the combination was better. Above all, the toxicity of SCU and its combination with lidocaine was low to normal astrocytes and neurons. Mechanistically, the effect of SCU and its combination with lidocaine on glioma cells was partially associated with the repression of EGFR signaling.
Conclusions
Scutellarin and lidocaine exerted a synergistic effect on suppressing the proliferation and migration and inducing the apoptosis of glioma cells, which was partly associated with the repression of EGFR signaling.
研究领域:
肿瘤学
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分子生物学
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神经科学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2017
·Vol. 15
·期 1
·1-17
·
IF 4.946
Wang Jingnan,Tan Jiayun,Luo Jiahao,Huang Peilin,Zhou Wuyi,Chen Luming,Long Lingli,Zhang Li-ming,Zhu Banghao,Yang Liqun,Deng David Y. B.
Background Diabetic retinopathy is the most common complication in diabetic patients relates to high expression of VEGF and microaneurysms. Scutellarin (Scu) turned out to be effective against diabetes related vascular endothelial cell dysfunction. However, its clinical applications have been limited by its low bioavailability. In this study, we formulated and characterized a novel intestinal target nanoparticle carrier based on amphiphilic chitosan derivatives (Chit-DC-VB12) loaded with scutellarin to enhance its bioavailability and then evaluated its therapeutic effect in experimental diabetic retinopathy model.Results Chit-DC-VB12 nanoparticles showed low toxicity toward the human colon adenocarcinoma (Caco-2) cells and zebra fish within concentration of 250 μg/ml, owing to good biocompatibility of chitosan. The scutellarin-loaded Chit-DC-VB12 nanoparticles (Chit-DC-VB12-Scu) were then prepared by self-assembly in aqueous solution. Scanning electron microscopy and dynamic light scattering analysis indicated that the Chit-DC-VB12-Scu nanoparticles were spherical particles in the sizes ranging from 150 to 250 nm. The Chit-DC-VB12-Scu nanoparticles exhibited high permeation in Caco-2 cell, indicated it could be beneficial to be absorbed in humans. We also found that Chit-DC-VB12 nanoparticles had a high cellular uptake. Bioavailability studies were performed in Sprague–Dawley rats, which present the area under the curve of scutellarin of Chit-DC-VB12-Scu was two to threefolds greater than that of free scutellarin alone. Further to assess the therapeutic efficacy of diabetic retinopathy, we showed Chit-DC-VB12-Scu down-regulated central retinal artery resistivity index and the expression of angiogenesis proteins (VEGF, VEGFR2, and vWF) of retinas in type II diabetic rats.Conclusion sChit-DC-VB12 nanoparticles loaded with scutellarin have better bioavailability and cellular uptake efficiency than Scu, while Chit-DC-VB12-Scu nanoparticles alleviated the structural disorder of intraretinal neovessels in the retina induced by diabetes, and it also inhibited the retinal neovascularization via down-regulated the expression of angiogenesis proteins. In conclusion, the Chit-DC-VB12 nanoparticles enhanced scutellarin oral delivery efficacy and exhibited potential as small intestinal target promising nano-carriers for treatment of type II diabetes induced-retinopathy.
研究领域:
药学
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纳米技术
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糖尿病研究
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眼科学
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DOI
PubMed
高影响因子
Journal of Translational Medicine
·
2026
·Vol. 24
·期 1
·492
·
IF 9.7
Li Ze,Ling Yimin,Xiao Wei,Li JiaZheng,Rong JiaHui,Zhang Zewen,Wei Yan,Huo Zhongchao,Li Dong
Background Scutellarin (SCU) is a natural flavonoid compound exhibiting anti-tumor activity. This study aimed to elucidate the molecular mechanism underlying SCU’s therapeutic effects in liver cancer. Methods An integrated approach combining network pharmacology and transcriptomic analysis was employed to identify SCU-related targets, followed by the identification of core targets through protein–protein interaction (PPI) network construction and topological analysis using MCC and MCODE algorithms. A circular RNA (circRNA)-mediated competing endogenous RNA (ceRNA) regulatory network was constructed by integrating data from databases including miRWALK and circBANK with whole-transcriptome sequencing. Molecular interactions were experimentally validated using Western blotting, dual-luciferase reporter assays, and RNA immunoprecipitation (RIP). In Huh7 and HepG2 cells, overexpression and knockdown models of key RNAs were established to evaluate their functional roles, with cell proliferation, cell cycle distribution, and apoptosis assessed via CCK-8, colony formation, and flow cytometry assays. To investigate in vivo anti-tumor efficacy and associated mechanisms, a subcutaneous xenograft tumor model was established in nude mice. Results Integrated network pharmacology and transcriptomic analysis identified 11 core genes significantly enriched in the estrogen signaling pathway, among which ESR1 was validated as a key target. SCU downregulated ESR1 expression in a dose-dependent manner. Mechanistically, SCU upregulated miR-2682-5p while downregulating circSRBD1. Dual-luciferase reporter assays confirmed that miR-2682-5p directly binds to the 3′UTRs of both circSRBD1 and ESR1, supporting the existence of a circSRBD1/miR-2682-5p/ESR1 ceRNA regulatory axis. Functional studies demonstrated that overexpression of circSRBD1 attenuated SCU-induced cell cycle arrest, apoptosis, and suppression of proliferation, whereas silencing circSRBD1 enhanced these effects. Furthermore, SCU and fulvestrant exhibited synergistic anti-tumor activity both in vitro and in vivo. Conclusion This study identifies a novel circSRBD1/miR-2682-5p/ESR1 ceRNA regulatory axis that plays a critical role in mediating SCU’s inhibitory effects on liver cancer progression, highlighting the potential therapeutic value of combining SCU with fulvestrant. Clinical trial number Not applicable.
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产品关联
DOI
PubMed
高影响因子
Frontiers in Plant Science
·
2018
·
IF 3.677
Chen Ruibing,Chen Xianghui,Zhu Tingting,Liu Jianghua,Xiang Xing,Yu Jian,Tan Hexin,Gao Shouhong,Li Qing,Fang Yichao,Chen Wansheng,Zhang Lei,Huang Baokang
Scutellarin, a flavonoid 7-O-glucuronide, is an essential bioactive compound of Erigeron breviscapus (Vaniot) Hand.-Mazz. used for the treatment of cerebrovascular diseases. However, due to overexploitation and overuse, E. breviscapus is facing the problems of extinction and habitat degradation. In this study, a correlation analysis between the transcript and metabolite profiles of methyl jasmonate (MeJA)-treated E. breviscapus at different time points indicated that chalcone isomerase (EbCHI) was the primary contributor to scutellarin accumulation during flavonoid biosynthesis. EbCHI was then further characterized as a chalcone isomerase that efficiently converted chalcone to naringenin in vitro. Optimal parameters derived by comparing different culture conditions were successfully used to establish hairy root cultures of E. breviscapus with a maximum transformation rate of 60% in B5 medium. Furthermore, overexpression of EbCHI significantly enhanced scutellarin accumulation in E. breviscapus hairy roots with a maximum content of 2.21 mg g-1 (dw), 10-fold higher than that of natural roots (0.21 mg g-1 dw). This study sheds new light on a method of effective gene-based metabolic engineering by accurate and appropriate strategies and provides a protocol for hairy root cultures that accumulate high levels of scutellarin, providing a promising prospect for relieving the overexploitation and unavailability of E. breviscapus in the future.
研究领域:
植物生物技术
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植物化学
·
代谢工程
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DOI
PubMed
高影响因子
SEPARATION AND PURIFICATION TECHNOLOGY
·
2025
·
IF 9
Yongjing Liu,Dongting Huang,Lirong Chen,Huixin You,Hua Li,Wei Xu
In this study, a novel boronic acid-decorated Zinc-based metal–organic framework (Zn-PTA-BDBA MOF) was fabricated using Zinc nitrate as a metal unit as well as p-phthalic acid (PTA) and benzene diboronic acid (BDBA) as dual organic ligands. Herein, a dispersive solid-phase extraction (D-μSPE) method based on Zn-PTA-BDBA as adsorbent and deep eutectic solvents (DESs) as eluent was successfully proposed for highly efficient purification and enrichment of scutellarin. The morphology, structure, and thermal stability of Zn-PTA-BDBA MOF were systematically characterized. The effects of synthesis conditions, D-μSPE conditions, adsorption isotherms, adsorption kinetics, reproducibility, and reusability were evaluated in detail. Under the optimum condition, the Zn-PTA-BDBA MOF demonstrates outstanding adsorption performance for scutellarin with an adsorption capacity of 570.19 ± 14.44 mg/g. Furthermore, PEG 200/lactic acid (4:1) was ultimately selected as the optimal DES elution solvent with the desorption rate of scutellarin up to 94.77 ± 2.06 %. More importantly, the application of DES that is ecological, decomposable, and non-lethal makes the D-μSPE process more secure, aligning with green chemical principles. Finally, the established D-μSPE method was successfully applied to the purification and preparation of scutellarin in the traditional Chinese medicine Erigerontis Herba. As well as we employed the D-μSPE method combined with HPLC to establish a rapid, simple, efficient, and green method for the purification and determination of scutellarin in urine samples.
研究领域:
分析化学
·
中药学
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产品关联
DOI
高影响因子
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