Frontiers in Pharmacology
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2021
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IF 5.811
Feng Huixia,Chen Guilin,Zhang Yongli,Guo Mingquan
Podophyllum sinense (P. sinense) has been used as a traditional herbal medicine for ages due to its extensive pharmaceutical activities, including antiproliferative, anti-inflammatory, antiviral, insecticidal effects, etc. Nevertheless, the specific bioactive constituents responsible for its antiproliferative, anti-inflammatory, and antiviral activities remain elusive, owing to its complicated and diversified chemical components. In order to explore these specific bioactive components and their potential interaction targets, affinity ultrafiltration with multiple drug targets coupled with high performance liquid chromatography/mass spectrometry (UF–HPLC/MS) strategy was developed to rapidly screen out and identify bioactive compounds against four well-known drug targets that are correlated to the application of P. sinense as a traditional medicine, namely, Topo I, Topo II, COX-2, and ACE2. As a result, 7, 10, 6, and 7 phytochemicals were screened out as the potential Topo I, Topo II, COX-2, and ACE2 ligands, respectively. Further confirmation of these potential bioactive components with antiproliferative and COX-2 inhibitory assays in vitro was also implemented. Herein, diphyllin and podophyllotoxin with higher EF values demonstrated higher inhibitory rates against A549 and HT-29 cells as compared with those of 5-FU and etoposide. The IC50 values of diphyllin were calculated at 6.46 ± 1.79 and 30.73 ± 0.56 μM on A549 and HT-29 cells, respectively. Moreover, diphyllin exhibited good COX-2 inhibitory activity with the IC50 value at 1.29 ± 0.14 μM, whereas indomethacin was 1.22 ± 0.08 μM. In addition, those representative constituents with good affinity on Topo I, Topo II, COX-2, or ACE2, such as diphyllin, podophyllotoxin, and diphyllin O-glucoside, were further validated with molecular docking analysis. Above all, the integrated method of UF–HPLC/MS with multiple drug targets rapidly singled out multi-target bioactive components and partly elucidated their action mechanisms regarding its multiple pharmacological effects from P. sinense, which could provide valuable information about its further development for the new multi-target drug discovery from natural medicines.
研究领域:
药理学
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药物化学
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传统医学
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药物发现
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
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2021
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IF 4.432
Feng Zhang,Keqing Zhao,Tao Tang,Yan Deng,Yun Zhang,Shuo Feng,Pu Feng,Mengyuan Guo,Xiaohui Li,Juan Cen
Neuroinflammation is considered as an important mechanism of vascular dementia (VaD). Our primary study showed that the bisindole analogue (2-(2-(bis(5-chloro-1H-indol-3-yl)methyl)phenoxy)aniline, compound 4ae ) had great anti-inflammation in zebrafish. Rat model of permanent occlusion of the bilateral common carotid arteries (2-vessel occlusion, 2VO) was utilized to evaluate the neuroprotective effect of 4ae . Our results showed that 4ae treatment effectively reduced Iba-1 positive microglia cells in cerebral cortex and hippocampus after cerebral ischemia . Compared with the model group, neuroinflammation characterized by Interleukin (IL)-6 and tumor necrosis factor (TNF)-α, oxidative stress characterized by reactive oxygen species (ROS) and superoxide dismutase (SOD) were both improved significantly after treatment with 4ae. Moreover, 4ae treatment significantly reversed ischemia-induced ACE enhancement, while notably increased the level of ACE2. To further elucidate the role of 4ae on neuroinflammation, we investigated the effects of 4ae on lipopolysaccharide (LPS)-induced inflammation in BV2 microglia cells, a kind of innate immune cells in central nervous system . The results demonstrated that the expressions of CD11b, TNFα and IL-6 and the level of ROS were up-regulated after treatment with LPS. More importantly, 4ae was able to block the activation of BV2 by reducing ROS production and the expression of inflammatory cytokines. In addition, our results suggested that 4ae inhibited the inflammatory response mediated by microglia cells by inhibiting NF-κB. This anti-inflammatory effect on microglia may be a potential mechanism for the neuroprotective effect of 4ae in VaD.
研究领域:
神经科学
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药理学
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炎症
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痴呆症
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神经保护
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产品关联
DOI
PubMed
高影响因子
Applied Materials Today
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2020
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IF 8.352
Fanyi Huang,Lingyu Sun,Cheng Zhao,Zeping Qiu,Yuanjin Zhao,Wei Jin
As a severe cardiovascular disease, acute myocardial infarction (AMI) has been attaching increasing attention and research for its high morbidity and mortality. In this paper, the novel protein microcapsules integrated hierarchical scaffold is designed for treating AMI model by using microfluidic templates. Based on advanced microfluidic electrospray technique, core-shell microspheres with controllable size are fabricated to build a double barrier for improving the stability of encapsulated drug. These microspheres are further combined with an electrospun polymer membrane to construct the desired hierarchical structure. Based on these designs, the microcapsules can realize long-term drug release while the polymer membrane scaffold exhibits anti-adhesive effect in vitro . By decreasing the level of Angiotensin Ⅱ and inhibiting the Renin-Angiotensin System (RAS) pathway, ACE2 can increase the concentration of Ang (1–7) and enhance its protective function. To evaluate the therapeutic effect, ACE2-encapsulted hierarchical scaffold is applied to AMI mice model, which achieves regional sustainable release and improves the severity of ischemic lesion, with an additional utility of preventing post-operative adhesion. Compared with injecting intramyocardially, implanting hierarchical scaffold avoids excess injury and shows more obvious therapeutic efficacy. These properties suggest that our hierarchical cardiac scaffolds provide a potential drug administration approach for local treatment of AMI.
研究领域:
心血管疾病
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生物材料
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药物递送系统
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组织工程
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产品关联
DOI
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
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2025
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IF 8
Chuan Liang,Yang Chen,Yunzhe Ling,Peirun Li,Jiahao Liu,Xuantian Li,Yanhua Xu,Zhiying Liu
Non-steroidal anti-inflammatory drugs (NSAIDs), though designed to target specific molecular pathways, pose significant environmental risks to non-target organisms, particularly marine fish. This study investigated the toxicity mechanisms and adaptive responses to diclofenac (DCF) and meloxicam (MEX) during the early life stages (ELS) of Oryzias melastigma at environmentally relevant concentrations over a 31-day period. Mechanistic investigations of sub-lethal effects were conducted using Enzyme-Linked Immunosorbent Assay (ELISA), RNA sequencing (RNA-Seq) and quantitative PCR (qPCR). The results revealed that cyclooxygenase (COX) inhibition disrupted the renin-angiotensin system, leading to an accumulation of angiotensin II and cardiovascular developmental defects. Additionally, downregulation of the pla2 gene reduced substrates essential for COX enzyme activity, exacerbating the effects. Although NSAIDs are known to affect the digestive system, no significant effects on developmental factors were observed. RNA-Seq and qPCR analyses revealed an adaptive upregulation of key genes, including ace2 and cyp7a1 , involved in cardiovascular and metabolic regulation. Furthermore, 16S rRNA sequencing identified shifts in the microbial community, particularly in g_Rubritalea and g_Sphingomonas genera. Both the upregulated genes and the altered microbial taxa likely played a role in mitigating toxic effects and promoting homeostasis. Moreover, molecular docking suggested that MEX exhibited stronger sub-lethal effects than DCF, likely due to its higher binding affinity to COX. These findings provide valuable insights into NSAID toxicity mechanisms in marine fish, highlighting the importance of adaptive responses in countering environmental stress and underscoring the long-term ecological risks of chronic NSAID exposure.
研究领域:
海洋毒理学
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环境科学
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药理学
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分子生物学
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发育生物学
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生态毒理学
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微生物学
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生物信息学
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药物发现
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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）