PHYTOCHEMICAL ANALYSIS
·
2026
·
IF 2.9
Yu Xia,Xinyi Zhong,Chenggang Zhang
Background Hypoxia is a core pathological factor in myocardial injury and is involved in the development of various cardiovascular diseases. Although baicalein shows cardiovascular protective potential, its mechanism against hypoxic injury remains unclear. Methods H9c2 cardiomyocytes were exposed to sodium sulfite to establish a chemical hypoxia model. Network pharmacology, molecular docking, molecular dynamics simulation, and molecular biology assays were employed to predict the core target and investigate the underlying mechanism. Results Network pharmacology identified ESR1 as a core target, with stable binding to baicalein confirmed by molecular docking and dynamics simulations. Baicalein alleviated hypoxia-induced oxidative stress by elevating key antioxidant markers and reducing malondialdehyde levels. It also ameliorated energy metabolism disorders, reduced lactate dehydrogenase release, suppressed reactive oxygen species production, and decreased cell apoptosis. Furthermore, baicalein upregulated hypoxia-suppressed ESR1 protein expression and enhanced its co‑localization with the antiapoptotic protein BCL-XL. The cytoprotective effects were abolished by the ESR1 inhibitor fulvestrant. Conclusion These findings demonstrate that baicalein protects cardiomyocytes against hypoxic injury through an ESR1‑dependent mechanism by modulating the BCL‑XL/BAX apoptotic balance, mitigating oxidative stress, and improving energy metabolism.
✓ 已验证
DOI
PubMed
高影响因子
Theranostics
·
2026
·Vol. 16
·期 14
·7765
·
IF 14.9
Ying Zhao,Shijie Fan,Yu Fang,Qingqing Zhao,Qian Zhou,Zheng Xu,Hong Zhu,Guang Liang
Rationale Acute kidney injury (AKI) is a life-threatening clinical syndrome characterized by high mortality, in which tubular epithelial cell death represents a key pathological event. Emerging evidence underscores the importance of the ubiquitin system in the progression of AKI. Here, we focus on the function of YOD1 in AKI. Methods We generated tubular epithelial cells (TECs)-specific Yod1 knockout mice (YOD1CKO) by crossing Yod1 fl/fl mice and Ggt1-cre mice. Both YOD1CKO mice and Yod1 fl/fl littermates were subjected to cisplatin- or ischemia/reperfusion (I/R)-induced AKI models. Through co-immunoprecipitation (Co-IP) combined with LC-MS/MS analysis, we identified potential substrate proteins of YOD1. Results We observed that YOD1 is predominantly expressed in TECs and is upregulated during AKI injury. Renal tubular specific Yod1 knockout significantly alleviated tubular damage and apoptosis in AKI mice. Mechanistically, we identified the pro-apoptotic protein Bax as a direct substrate of YOD1. YOD1 removes K63-linked ubiquitin chains from Bax at lysine 128 via its catalytic cysteine residue C155, thereby promoting Bax activation, and mitochondrial translocation and subsequent apoptosis. YOD1 failed to promote apoptosis in Bax-deficient cells, confirming Bax as the essential downstream mediator. Conclusions Our study reveals a previously unrecognized YOD1-Bax regulatory axis that drives tubular apoptosis in AKI, and highlights YOD1 may hold therapeutic potential.
✓ 已验证
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2024
·
IF 10
Jabeen Farheen,M. Zubair Iqbal,Asim Mushtaq,Yike Hou,Xiangdong Kong
Triple-negative breast cancer (TNBC) is the most common primary tumor of the breast with limited effectual drug availability. Therefore, the aim of the study is to develop an innovative phyto-nanomedicine (PNM) to cure TNBC with the least genotoxicity. Hereinafter, the sea buckthorn’ extracted polyphenols (SBP), combine with metformin (MET), are synthesized as a novel PNM to evaluate its anti-tumor properties, effectiveness, and mechanism of action in TNBC in vitro and in vivo models. The SBP exhibits 16 new kinds of polyphenols that are been reported earlier which regulated cell development, proliferation, and programmed cell death (PCD) effectively. SBP-MET PNM inhibits MDA-MB-231 (47%), MDA-MB-436 (46%), and 4T1 (46%) cell proliferation but does not affect L929 normal murine cell development and successfully induce PCD (73.19%) in MDA-MB-231 cells. Mechanistically, in vivo SBP-MET proteome expression profiling reveals upregulation of proapoptotic Bax protein and activation of Fas signaling pathways convince downstream Daxx and FADD proteins, which further triggers Caspase-3 that prompts apoptosis in human TNBC cells by cleaving PARP-1 protein. Current findings establish innovative highly biocompatible phyto-nanomedicine that has significant potential to inhibit TNBC cell growth and induce regulated cell death (RCD) in vivo model, thereby opening a new arena for TNBC therapy.
研究领域:
肿瘤学
·
药理学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2016
·
IF 7.145
Shiwei Zhou,Yingying Wang,Jun-Jie Zhu
B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax) are often used to monitor the apoptosis of tumor cells and evaluate cancer drug effect. In this work, a novel sandwich-type dual-signal-marked electrochemical biosensor was fabricated for simultaneous detection of Bcl-2 and Bax proteins. Reduced graphene oxide (RGO) layers were used as substrate to immobilize Bcl-2 and Bax antibodies for further capturing target antigens. CdSeTe@CdS quantum dots (QDs) and Ag nanoclusters (NCs) with antibody modification and mesoporous silica amplification were used as signal probes, which were proportional to the amount of Bcl-2 and Bax antigens. Mesoporous SiO2 can provide a larger surface area, more effectively charged by ethylene imine polymer or poly(diallyldimethylammonium chloride) to adsorb more probes. The Bcl-2 and Bax proteins were determined indirectly by the detection of oxidation peak currents of Cd and Ag using anodic stripping voltammetry, showing a good linear relationship in the protein concentration range from 1 ng/mL to 250 ng/mL. The detection limit of trace protein level was ∼0.5 fmol. The biosensor was further introduced to investigate Bcl-2 and Bax expressions from nilotinib-treated chronic myeloid leukemia K562 cells. With the increase of drug dosage and incubation time, the up-regulation for Bax and down-regulation for Bcl-2 were observed, which indicated that the apoptosis level of K562 cells could be regulated by Bcl-2 family. The ratio of Bax/Bcl-2 was further calculated for evaluation of its drug effect and apoptosis level. The limited cell amount for detection reached less than 1 × 103 cells, much lower than traditional methods. Furthermore, completely independent detection step and stable acid solutions containing Ag+ and Cd2+ for long-time storage contribute to reducing the error from the sample differences and avoiding the potential errors from the photodegradation of fluorescent probes, enzymolysis of DNA, or inactivation of enzyme during an excess experimental period.
研究领域:
生物化学
·
生物技术
·
癌症研究
·
电化学
·
纳米技术
✓ 已验证
DOI
PubMed
高影响因子
NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL
·
2021
·
IF 2.9
Yonglu Li,Yaxuan Wang,Xin Yu,Ting Yu,Xiaodong Zheng,Qiang Chu
Lung cancer with high mortality is regarded as a challenging global problem with unsatisfied curative effects. Clinically, the chemotherapy drugs are often faced with side-effects and tumor resistance. Radix Tetrastigma (RT) is a traditional Chinese herb and now regarded as a kind of functional food. In this study, A549-bearing nude mice control was adopted to evaluate the anti-tumor capacity of RT. Results demonstrated that RT showed excellent anti-tumor ability with no side-effect on mice compared to chemotherapy drug (5-Fu).Further studies proved that RT down-regulated the proliferation-related proteins (PCNA, Ki67) and vascular endothelial growth factor (VEGF). Additionally, RT up-regulated the ratio of Bax/Bcl-2, which caused the over-expression of Caspase-9, leading to the activation of downstream protein caspase-3, eventually resulting in apoptosis of A549 in solid tumor. These results together suggest that RT inhibits the non-small cell lung cancer (NSCLC) via Bax/Bcl2/Caspase-9/Caspase-3 pathway. Furthermore, the anti-A549 abilities of the main flavonoid components from RT were compared, and kaempferol-3-O-rutinoside would play a role in RT’s outstanding anti-NSCLC ability.
研究领域:
肿瘤学
·
药理学
·
中药学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
CELL TRANSPLANTATION
·
2020
·
IF 3.341
Jing hui Bai,Jian Xu,Jian Zhao,Rui Zhang
Ganoderma lucidum is a popular traditional Chinese medicine used in China to improve health. Previous researches have revealed that the polysaccharide from G. lucidum could exert diversity activities, including immunomodulation, antioxidant, and antitumor effects. However, the effect of enzymatically hydrolyzed G. lucidum polysaccharide (EGLP) in colorectal cancer (CRC) progression remains unknown. The present research aimed to investigate the antitumor mechanism of EGLP in human colon cancer cells. For this purpose, the cytotoxic effects of EGLP were measured by the (3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) method. The apoptosis was evoked upon EGLP treatment, which was assayed using flow cytometry. The results indicated that EGLP may induce apoptosis in human colon cancer cell (HCT-116) cells via the upregulation of BCL-2 associated X protein (Bax), phospho-extracellular regulated protein kinases (P-ERK), and cleaved caspase-3 expression and downregulation of B-cell lymphoma-2 (Bcl-2), phospho-serine/threonine kinase 1 (p-Akt1), and cyclo-oxygen-ase (COX-2) expression. The obtained findings indicated EGLP as a new therapeutic agent in fighting CRC.
研究领域:
肿瘤学
·
药理学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Foods
·
2025
·Vol. 14
·期 6
·1026
·
IF 5.1
Qiuyan Li,Lu Jiang,Ni Chen,Xingzhi Wang,Jiajun Yao,Zhien Su,Suqing Zhao
Melanoma is one of the most lethal cancers originating from melanocytes. Its incidence and mortality have been rising rapidly for several decades and have posed a serious threat to human health. Current melanoma treatments are hindered by the scope of application, low efficiency, high cost, and toxic side effects. Due to their affordability and minimal side effects, natural bioactive compounds derived from plants are promising candidates for melanoma treatment. This study aims to delve into the isolation, purification, and characterization of potato proteins and to explore their potential in melanoma treatment. Two potato proteins, patatin PP-1 and aspartate protease inhibitor PP-2, were isolated and purified by a newly developed method in this work, and their physicochemical properties were systematically characterized. Both potato proteins showed great antiproliferative activities and migration inhibition effects on melanoma cells. Meanwhile, Western blotting results illustrated that they could induce endogenous cell apoptosis by regulating the Bax/Bcl-2 pathway. Notably, aspartate protease inhibitor PP-2 demonstrated the best performance in inhibiting the growth and migration of melanoma cells, which might be attributed to the combined effect of its significant antioxidative activity and the inhibition effect of certain necessary protease activities in melanoma. This study provides valuable insights for developing nutraceuticals and therapeutic strategies against melanoma, which can lead to breakthroughs in melanoma treatment.
研究领域:
肿瘤学
·
药理学
·
植物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Oncology Letters
·
2017
·Vol. 14
·期 3
·3006-3010
·
IF 1.39
Zhen Wu,Jing Wu,Ping Fang,Shifeng Kan
The present study investigated the effect of puerarin (Pu) on the sensitivity of HepG2 human hepatocellular carcinoma (HCC) cells to chemotherapeutic drugs to determine the possible mechanism. HepG2 cells were treated with different concentrations of Pu and cisplatin (CDDP), alone or in combination. MTT assay was used to determine the inhibitory effects of the different drugs on HepG2 cells. Cell morphology was observed by inverted microscopy. The expression of B-cell lymphoma 2 (Bcl-2) and Bax protein was measured by western blot analysis. Pu and CDDP, alone or in combination, inhibited the proliferation of HepG2 cells. The inhibitory effect of CDDP combined with Pu on HepG2 cells was significantly higher than that of the single drug treatments (p<0.01). In addition, compared with the single drug groups, cellular morphology was significantly altered and the apoptotic rate of cells and the expression of Bax protein were significantly increased (p<0.01). However, the expression of Bcl-2 protein was significantly decreased (p<0.01) in the combined drug group. In conclusion, Pu can increase the sensitivity of HCC to chemotherapeutic drugs, enhance the inhibitory effect of chemotherapeutic drugs on cell proliferation and synergistically induce apoptosis of HepG2 cells. The mechanism is likely related to the upregulation of Bax protein and the downregulation of Bcl-2 protein.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
Journal of the Taiwan Institute of Chemical Engineers
·
2016
·
IF 2.848
Xiao-Wen Zhu,Min-Ping Wei,De-Ping Xu,Ya-Hui Guo,Yun-Fei Xie,Wei-Rong Yao
This study evaluated the antitumor effect of some fractions extracted from Sapindus spp. on breast cancer. Four water-extracted fractions (I, II, III, IV) were isolated from the pericarp of Sapindus spp. using X-5 and AB-8 macroporous resin columns and MCI gel column. The in vitro effect was determined using the MTT assay. Our results indicated that fractions I-IV did not exhibit significant cytotoxic effects towards the normal cell MDA-kb2; Fraction II and IV inhibited the growth of MCF-7 (estrogen receptor positive), MDA-MB-231 (estrogen receptor negative), and MDA-MB-435 s human breast cancer cell lines; of these, MDA-MB-435 s cell line was the most sensitive, and the IC 50 of Fraction II and IV against this cell line were 33.11 and 30.06 µg/mL, respectively. In the in vivo experiment, Fraction II and IV showed a strong antitumor effect at a dose of 162.5 mg/kg/d, with inhibition rate of 40.43% and 38.77%. Fraction II and IV also induced apoptosis of tumor cells, activations of Bax (Fraction II) and inhibition of Bcl-2 (Fraction II and IV). Our results underscore the pharmacological potential of Sapindus spp. extracts.
研究领域:
药理学
·
肿瘤学
·
植物化学
✓ 已验证
产品关联
DOI
高影响因子
ACS Applied Bio Materials
·
2026
·
IF 5.6
Wenjing Zhang,Xiaoyang Chen,Ziyi Lin,Shangyang Pan,Zufa sabeel,Wenxin Li,Heyun Shen,Zhao Yang
Breast cancer (BC) remains the most prevalent and deadly malignancy among women worldwide. While photothermal therapy (PTT) and chemodynamic therapy (CDT) offer tumor-specific and minimally invasive advantages, their standalone efficacy is limited. Ligustilide (LIG) can exert antitumor effects by generating •O2–, but its bioavailability is poor, thus necessitating improved delivery strategies. Here, we reported a multifunctional nanoplatform (FeD@LIG) integrating PTT, CDT, and chemotherapy for the simultaneous elimination of breast cancer stem cells (BCSCs) and non-BCSCs. FeD@LIG was synthesized via one-step oxidative polymerization of dopamine, co-loading Fe3+ and LIG. The nanospheres exhibited excellent photothermal conversion efficiency (52.8%) and pH/GSH-responsive drug release. Upon near-infrared (NIR) irradiation, FeD@LIG triggered ROS generation via Fenton-like reactions and elevated local temperature, leading to enhanced oxidative stress, apoptosis, and LIG release. In vitro, FeD@LIG reduced cell viabilities of MCF-7 and MDA-MB-231 cells to 12.5 and 7.9%, respectively, and significantly inhibited BCSCs’ self-renewal. In vivo, FeD@LIG achieved a tumor inhibition rate of 92.8% with minimal toxicity. Mechanistic studies revealed activation of the BAX/BCL-2/Caspase-3 pathway and suppression of Hedgehog signaling. Overall, FeD@LIG represents a promising nanotherapeutic strategy for overcoming drug resistance and recurrence by inhibiting both BCSCs and non-BCSCs through multimodal synergistic therapy.
✓ 已验证
DOI
PubMed
高影响因子
Evidence-based Complementary and Alternative Medicine
·
2020
·
IF 1.813
Yuan-Yuan Li,Nan-Qu Huang,Fei Feng,Ying Li,Xiu-Mei Luo,Lin Tu,Jing-Qiu Qu,Yi-Man Xie,Yong Luo
Icaritin (ICT) is the main component in the traditional Chinese herb Epimedium, and it has been shown to have anti-Alzheimer’s disease (AD) effects, but its neuroprotective effects and the pharmacological mechanisms are unclear. In the present study, senescence-accelerated mouse prone 8 (SAMP8) mice were randomly divided into a model group and an ICT-treated group. Learning and memory abilities were detected by the Morris water maze assay, and the expression of amyloid beta protein (Aβ) and β-site APP cleavage enzyme 1 (BACE1) was determined by Western blotting and polymerase chain reaction (PCR). Histological changes in CA1 and CA3 were detected by hematoxylin-eosin staining (H&E staining), and the immunohistochemical analysis was used to detect the expression and localization of Bax and Bcl-2. The results showed that compared with the SAMP8 mice, the ICT-treated SAMP8 mice showed improvements in spatial learning and memory retention. In addition, the number of necrotic cells and the morphological changes in CA1 and CA3 areas were significantly alleviated in the group of ICT-treated SAMP8 mice, and the expression of BACE1, Aβ1-42 levels, and the Bax/Bcl-2 ratio in the hippocampus was obviously decreased in the ICT-treated group compared with the control group. The results demonstrated that ICT reduced BACE-1 levels, the contents of Aβ1-42, and the Bax/Bcl-2 ratio, suggesting that ICT might have potential therapeutic benefits by delaying or modifying the progression of AD.
研究领域:
神经科学
·
药理学
·
老年学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Jia-Wei Wu,Wei Gao,Li-Ping Shen,Yong-Lin Chen,Shi-Qing Du,Zhi-Yong Du,Xu-Dong Zhao,Xiao-Jie Lu
ABSTRACT Ethnopharmacological relevance Leonurus japonicus Houtt. (Labiatae), commonly known as Chinese motherwort, is a herbaceous flowering plant that is native to Asia. It is widely acknowledged in traditional medicine for its diuretic, hypoglycemic, antiepileptic properties and neuroprotection. Currently, Leonurus japonicus (Leo) is included in the Pharmacopoeia of the People's Republic of China. Traditional Chinese Medicine (TCM) recognizes Leo for its myriad pharmacological attributes, but its efficacy against ICH-induced neuronal apoptosis is unclear. Aims of the study This study aimed to identify the potential targets and regulatory mechanisms of Leo in alleviating neuronal apoptosis after ICH. Materials and methods The study employed network pharmacology, UPLC-Q-TOF-MS technique,molecular docking, pharmacodynamic studies, western blotting, and immunofluorescence techniques to explore its potential mechanisms. Results Leo was found to assist hematoma absorption, thus improving the neurological outlook in an ICH mouse model. Importantly, molecular docking highlighted JAK as Leo's potential therapeutic target in ICH scenarios. Further experimental evidence demonstrated that Leo adjusts JAK1 and STAT1 phosphorylation, curbing Bax while augmenting Bcl-2 expression. Conclusion Leo showcases potential in mitigating neuronal apoptosis post-ICH, predominantly via the JAK/STAT mechanism.
研究领域:
药理学
·
神经科学
·
传统中药
·
分子生物学
✓ 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）