KOREAN JOURNAL OF PHYSIOLOGY & PHARMACOLOGY
·
2025
·Vol. 29
·期 4
·487
·
IF 2.2
Tingting Yu,Zirui Yuan,Jiaona Yu,Lu Chen,Wei Hao,Xiaohui Xu
Melittin (MEL) is the main bioactive component of bee venom and has been reported to have various pharmacological effects. This study investigates the protective effect of MEL on MPP + -injured HT22 cells and the possible mechanisms involved. We treated the cells with 4 mM MPP + for 24 h to induce a cellular injury model. HT22 cells were pretreated with 0.1 µM MEL for 6 h and then exposed to 4 mM MPP + for 24 h. We measured cell viability, the expression of Bax, the indicators and protein levels associated with apoptosis and parthanatos, and the co-localisation of MEL and mitochondria, and mitochondrial function-related indices such as the mitochondrial membrane potential (MMP) and mito-SOX. We show that PAR protein expression was significantly increased in the MPP + -treated cell model and that the parthanatos inhibitor DPQ significantly reduced MPP + -induced cell death, suggesting that MPP + can cause PARP1-dependent cell death. MEL significantly inhibited cell death, increased cell viability as well as NAD+ and ATP levels, increased the expression of Bcl-2 and suppressed the activation of Bax, cleaved-caspase3, and cleaved-PARP1. Moreover, MEL was found to be localised on the mitochondria of HT22 cells and to improve mitochondrial functions including increased MMP and decreased mitochondrial reactive oxygen species. We speculate that MEL may protect neurons against MPP + -induced HT22 cell injury by inhibiting Bax activation, suppressing changes in mitochondrial permeability, and improving mitochondrial function, thereby preventing cell parthanatos and apoptosis.
研究领域:
神经生物学
·
药理学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
AAPS PHARMSCITECH
·
2023
·Vol. 24
·期 4
·1-18
·
IF 3.3
Cao Xia,Liu Qi,Adu-Frimpong Michael,Shi Wenwan,liu Kai,Deng Tianwen,Yuan Hui,Weng Xuedi,Gao Yihong,Yu Qingtong,Deng Wenwen,Yu Jiangnan,Wang Qilong,Xiao Gao,Xu Ximing
Glioma, in which a malignant tumor cell occurs in neural mesenchymal cells, has a rapid progression and poor prognosis, which is still far from desirable in clinical treatments. We developed a lab-on-a-chip (LOC) device for the rapid and efficient preparation of vitexin/indocyanine green (ICG) liposomes. Vitexin could be released from liposome to kill cancer cell, which can potentially improve the glioma therapeutic effect and reduce the treatment time through synergistic photodynamic/photothermal therapies (PDT/PTT). The vitexin/ICG liposome was fabricated via LOC and its physicochemical property and release in vitro were evaluated. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method and live/dead staining were used to examine the enhanced antitumor effect of vitexin/ICG liposome in cooperation with PDT/PTT, while the related mechanism was explored by flow cytometry and western blot. The results were as follows: (1) The prepared vitexin/ICG liposome was smaller in size, homogenous in particle size distribution with significant low polydispersity index (PDI), and enhanced cumulative release in vitro . (2) We found that the formulated liposome presented strong cancer cell inhibition and suppression of its migration in a dose-dependent manner. (3) Further mechanistic studies showed that liposome combined with near-infrared irradiation could significantly upregulate levels of B cell lymphoma 2-associated X (Bax) protein and decrease B cell lymphoma 2 (Bcl-2) at protein levels. The vitexin/ICG liposomes prepared based on a simple LOC platform can effectively enhance the solubility of insoluble drugs, and the combined effect of PTT/PDT can effectively increase their antitumor effect, which provides a simple and valid method for the clinical translation of liposomes. Graphical Abstract
研究领域:
肿瘤学
·
药学
·
生物医学工程
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
·
2023
·
IF 4.4
Wenyuan Zhang,Songjuan Zhuang,Hui Guan,Feng Li,Hui Zou,Dapeng Li
Excessive apoptosis can kill normal cells and lead to liver damage, heart failure and neurodegenerative diseases. Polyphenols are secondary metabolites of plants that can interact with proteins to inhibit toxins and disease-related apoptosis. Bax is the major pro-apoptotic protein that disrupts the outer mitochondrial membrane to induce apoptosis, but limited studies have focused on the interaction between polyphenols and Bax and the associated anti-apoptotic mechanisms, especially at the atomic level. In this article, we collected 69 common polyphenols for active ingredient screening targeting Bax. Polyphenols with better and worse molecular docking scores were selected, and their anti-apoptosis effects were compared using the H2O2-induced HepG2 cell model. The interactions between the selected polyphenols and Bax protein were analyzed using molecular dynamics simulation to explore the molecular mechanism underlying the anti-apoptosis effect. Secoisolariciresinol diglucoside (SDG) and Epigallocatechin-3-gallate (EGCG) with the best affinity for Bax (−6.76 and −6.52 kcal/mol) reduced the expression of cytochrome c and caspase 3, decreasing the apoptosis rate from 52 to 11% and 12%. Molecular dynamics simulation results showed that Bim unfolded the α1-α2 loop of Bax, and disrupted the non-bond interactions between the loop (Pro-43, Glu-44 and Leu-45) and surface (Ile-133, Arg-134 and Met-137) residues, with binding free energy changed from −15.0 to 0 kJ/mol. The hydrogen bonds and van der Waals interactions formed between polyphenols and Bax prevented the unfolding of the loop. Taken together, our results proved that polyphenols can inhibit apoptosis by maintaining the unactivated conformation of Bax to reduce outer mitochondrial membrane damage.Communicated by Ramaswamy H. Sarma
研究领域:
药理学
·
分子生物学
·
生物化学
·
细胞生物学
✓ 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）