Chinese Medicine
·
2025
·Vol. 20
·期 1
·1-20
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IF 5.7
Liu Changtong,Guo Rui,Zhou Yue,Zhu Miao,Shao Li,Wang Yingchao,Zhao Lu
Background Cardiac hypertrophy, characterized by the thickening of the heart muscle, arises from factors such as hypertension and genetic mutations, often leading to adverse outcomes like heart failure and arrhythmias. Guanxinning tablets (GXNT), a botanical drug composed of the blood-activating herbs Salvia miltiorrhiza Bunge. and Ligusticum striatum DC., are widely used in the treatment of cardiovascular diseases. However, the active ingredients and their molecular mechanisms are yet to be fully understood. Methods We evaluated the anti-hypertrophic effects of GXNT and screened its active substances via cardiac function live-imaging on an aristolochic acid A-stimulated zebrafish cardiac hypertrophy model, and through F-actin immunostaining on a phenylephrine-induced hypertrophic NRCMs model. Additionally, the protective effects of GXNT’s active substances were analyzed in a mouse model of cardiac hypertrophy using echocardiography, histopathology analysis, and western blotting. Results The anti-hypertrophic effects of GXNT were assessed using an aristolochic acid A-stimulated zebrafish model and phenylephrine-induced hypertrophic NRCMs. GXNT demonstrated significant anti-hypertrophic effects in both models. Phenotypic screening identified Senkyunolide I (Sen I) from Ligusticum striatum as the active component in the zebrafish model, while Salvianolic acid B (Sal B) and Rosmarinic acid from Salvia miltiorrhiza emerged as the key anti-hypertrophic compound in NRCMs. In a mouse model of isoproterenol-induced cardiac hypertrophy, Sal B and Sen I showed synergistic effects, improving cardiac function, reducing oxidative stress, and suppressing inflammation. Mechanistically, transcriptomic sequencing highlighted cooperative modulation of MAP3K1 signaling by the two compounds. Notably, siRNA-mediated knockdown of MAP3K1 in cardiomyocytes attenuated the hypertrophic phenotype, supporting its essential role in the pathological process. Molecular docking and dynamic simulations further supported their binding potential to MAP3K1. Conclusion These findings underscore GXNT’s potent anti-hypertrophic effects, possibly driven by the synergistic actions of Sal B and Sen I, and offer insights into its therapeutic potential through MAP3K1 signaling regulation.
研究领域:
心血管药理学
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分子药理学
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中药学
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信号转导
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转化医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Arabian Journal of Chemistry
·
2023
·
IF 6
Qingrong Han,Fei Liu,Chengjiu Wang,Zhentao Tang,Cheng Peng,Yuzhu Tan
In recent years, the quality and safety issues of Chinese medicinal herbs have received great attention worldwide. Thereinto, heavy metal contamination has been one of the most serious concerns. Compared to the wide research in the analysis of heavy metals in medicinal herbs, the studies on the removal of heavy metals are relatively limited. In this study, polyethylene glycol functionalized Fe 3 O 4 @MIL-101(Cr) (Fe 3 O 4 @MIL-101(Cr)@PEG) was designed and synthesized to remove heavy metals from the decoction of Ligusticum chuanxiong Hort. The in-house fabricated Fe 3 O 4 @MIL-101(Cr)@PEG was characterized by a porous structure and a large specific surface area. Then, the efficiency of the material for the removal of five heavy metals was tested under optimal adsorption conditions. Meanwhile, the content of Senkyunolide A, Senkyunolide I, and Ferulic acid, the solid content, and the HPLC fingerprints similarity were used as the quality monitoring indicators of Ligusticum chuanxiong Hort decoction before and after the heavy metal removal. Results showed that the magnetic nanomaterial had excellent removal efficiency for As 5+ (81.4 %), Cd 2+ (88.19 %), and Pb 2+ (83.79 %) and certain removal efficiency for Ni 2+ (51.59 %) and Zn 2+ (55.4 %) under the spiked concentration of 50 μg/mL. The content of Senkyunolide A, Senkyunolide I, and Ferulic acid were decreased by less than 8.00 % after the removal of heavy metals. Besides, the loss rate of solid content was only 0.18 %, and the fingerprints similarity was over 99.9 %. The results indicated that Fe 3 O 4 @MIL-101(Cr)@PEG could efficiently and selectively remove heavy metals from Ligusticum chuanxiong Hort without affecting its effective components. Due to the advantages of low-cost, simple manipulation, and good efficiency, the material can be recommended for heavy metals removal from the aqueous solutions of medicinal herbs, providing a new and promising application for the removal of exogenous contaminants in medicinal herbs.
研究领域:
药学
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环境科学
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材料科学
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分析化学
✓ 已验证
产品关联
DOI
高影响因子
FREE RADICAL BIOLOGY AND MEDICINE
·
2024
·
IF 7.1
Qi Wei,Fuxia He,Jiangyan Rao,Xiaoxia Xiang,Li Li,Hongyi Qi
Given the substantial risks associated with ultraviolet B radiation (UVB)-induced solar dermatitis, enhancing current strategies to combat UVB regarding skin diseases is imperative. The cross-talk between ferroptosis and inflammation has been proven to be an essential factor in UVB-induced skin inflammation, whereas detailed process of how their interaction contributes to this remains unclear. Therefore, further investigation of ferroptosis-mediated processes and identification of corresponding inhibitory approaches hold promise for repairing skin damage. Senkyunolide I (Sen I), a bioactive component mainly extracted from the traditional Chinese medicinal plants, Ligusticum chuanxiong Hort. and Angelica sinensis (Oliv.) Diels, has demonstrated efficacy in combating oxidative stress and inflammation. In this study, we utilized UVB-irradiated HaCaT cells as an in vitro model and C57BL/6J mice as an in vivo model of solar dermatitis. Our findings revealed the pivotal roles of autophagy and ferroptosis in inducing skin inflammation, particularly emphasizing the activation of ferroptosis through macroautophagy. Surprisingly, this mechanism operated independently of ferritinophagy, a classical autophagy-driven ferroptosis pathway. Instead, our results highlighted Transferrin Receptor 1 (TfR1), tightly controlled by autophagy, as a crucial mediator of ferroptosis execution and amplifier of subsequent lethal signals. Furthermore, extracellular High Mobility Group Box 1 protein (HMGB1), released following UVB-induced ferroptotic cells from activated autophagic flux, initiated a feedback loop with TfR1, propagating ferroptosis to neighboring cells and exacerbating damage. Remarkably, Sen I administration showed a significant protective effect against UVB damage in both in vitro and in vivo models by interrupting this cascade. Consequently, we have illuminated a novel therapeutic pathway post-UVB exposure and identified Sen I as a potent natural molecule that safeguarded against UVB-induced solar dermatitis by suppressing the autophagy-ferroptosis-HMGB1-TfR1 axis, highlighting a new frontier in photoprotection.
研究领域:
药理学
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皮肤病学
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分子生物学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2021
·
IF 5.811
Li Jun,Liu Hao,Yang Zhenzhong,Yu Qingqing,Zhao Lu,Wang Yi
Thrombosis is a key pathological event in cardiovascular diseases, and is also the most important targeting process for their clinical management. New drug development in thrombosis treatment is still in great demand. According to the traditional Chinese medicine (TCM) theory, thrombosis belongs to the syndrome of blood stasis. Salvia miltiorrhiza Bunge and Ligusticum striatum DC. are two common TCM herbs with long-term documented function in promoting blood circulation and inhibiting thrombosis, especially when used together. Guanxinning Tablet, a modern Chinese drug which contains extracts of the two herbs, also showed strong therapeutic effects in coronary heart disease. However, the pharmacological mechanism is still lacking for the compatibility of the two herbs. Here, through zebrafish-based in vivo fluorescence screening, we demonstrated the synergistic effects between S. miltiorrhiza Bunge and L. striatum DC. in regulating endogenous thrombosis. Moreover, combined with high-resolution mass spectrometry, the main compounds of the botanical drugs were analyzed and screened in our model system. Interestingly, cryptotanshinone and senkyunolide I, two representative compounds, respectively derived from the two herbs, also showed synergistic antithrombotic effects. Further analysis suggested that they may regulate thrombi formation at different levels via multiple signaling pathways, including oxidative stress, platelet activation and coagulation cascade. Taken together, our findings provided solid biological supports toward the drug compatibility theory of TCM, and suggested cryptotanshinone and senkyunolide I as promising drug candidates in thrombosis management.
研究领域:
药理学
·
心血管疾病
·
传统中药
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斑马鱼模型
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药物开发
✓ 已验证
DOI
PubMed
高影响因子
Drug Design Development and Therapy
·
2024
·
IF 4.7
Yule Wang,Yiran Li,Yue Zhou,Yue Gao,Lu Zhao
Background Currently, ischemic stroke (IS) continues to significantly contribute to functional deterioration and reduced life quality. Regrettably, the choice of neuro-rehabilitation interventions to enhance post-IS outcomes is limited. Guanxinning tablet (GXNT), a multi-component medicine composed of Danshen and Chuanxiong, has demonstrated neuroprotective potential against ischemic brain injury and diabetic encephalopathy. However, the therapeutic impact of GXNT on post-IS functional outcomes and pathological injury, as well as the underlying molecular mechanisms and anti-IS active substances, remain unclear.Methods To answer the above questions, neurological and behavioral assessment, cerebral lesions, and blood-brain barrier (BBB) integrity were combined to comprehensively investigate GXNT’s pharmacodynamic effects against post-IS injury. The possible molecular mechanisms were revealed through transcriptome sequencing coupled with experimental verification. Furthermore, the brain tissue distribution of main components in GXNT, behavioral changes of IS zebrafish, and molecular docking were integrated to identify the anti-IS active compounds.Results Treatment with GXNT significantly mitigated the functional deficits, cerebral cortex lesions, and BBB disruption following IS. Transcriptome sequencing and bioinformatics analysis suggested that complement and coagulation cascades as well as inflammation might play crucial roles in the GXNT’s therapeutic effects. Molecular biology experiments indicated that GXNT administration effectively normalized the abnormal expression of mRNA and protein levels of key targets related to complement and coagulation cascades (eg C3 and F7) and inflammation (eg MMP3 and MMP9) in the impaired cortical samples of IS mice. The locomotor promotion in IS zebrafish as well as favorable affinity with key proteins (C3, F7, and MMP9) highlighted anti-IS activities of brain-permeating constituents (senkyunolide I and protocatechuic acid) of GXNT.Conclusion Taken together, these intriguing findings indicate that GXNT intervention exerts a beneficial effect against post-IS injury via regulating the complement and coagulation cascades pathway and mobilizing inflammatory network. Senkyunolide I and protocatechuic acid show promise as anti-IS active compounds.
研究领域:
神经科学
·
药理学
·
分子生物学
·
转化医学
✓ 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）