Pharmaceuticals
·
2024
·Vol. 17
·期 10
·1288
·
IF 4.3
Chunhua Liu,Yu He,Mingjin Wang,Jia Sun,Jie Pan,Ting Liu,Yueting Li,Meng Zhou,Yong Huang,Yongjun Li,Yanmin Zhang,Yuan Lu
Background: Polygonum orientale L. (PO) has demonstrated notable efficacy in treating coronary heart disease. Previous research identified eight key active components in PO for cardiomyocyte protection, but the underlying mechanisms remained unclear; Methods: Network pharmacology and molecular docking were used to identify potential target proteins of PO’s active components. Experimental models assessed the cardioprotective effects and mechanisms; Results: Network analysis and molecular docking revealed that the active components exhibited the highest binding affinity with SOD2, indicating it as a key element in the cardiac protection of PO. In vivo, PO extract improved myocardial structure and function, and increased SOD2 protein levels. In vitro, the active components of PO (Mixture) mitigated oxidative stress and apoptosis, upregulating SIRT3 and decreasing acetylated SOD2, leading to increased SOD2 and reduced ROS levels. The observed effects were reversed by a SIRT3 inhibitor, indicating the involvement of the SIRT3/SOD2 signaling pathway; Conclusions: This comprehensive approach elucidated the critical mechanisms underlying the cardioprotective properties of PO’s bioactive constituents, highlighting the regulation of the SIRT3/SOD2 signaling pathway as a new mechanism for PO’s anti-cardiovascular disease effects, and suggesting the Mixture’s potential as a promising drug candidate.
研究领域:
药理学
·
心血管病学
·
网络药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2023
·Vol. 28
·期 9
·3687
·
IF 4.6
Changli Fu,Mingjin Wang,Yuan Lu,Jie Pan,Yueting Li,Yongjun Li,Yonglin Wang,Aimin Wang,Yong Huang,Jia Sun,Chunhua Liu
AlthoughPolygonum orientaleL. (PO) has a beneficial effect on treatment of myocardial ischemia (MI), its mechanism remains unclear. This study aimed to explore the pharmacological mechanism of PO against MI through MAPK signaling pathways. Firstly, the therapeutic effect of PO was evaluated for treatment of MI mice. Using Western blot and immunohistochemistry, the influence of PO on MAPK signaling pathways and cell apoptosis was investigated. Subsequently, one key pathway (ERK) of MAPK signaling pathways was screened out, on which PO posed the most obvious impact. Finally, an inhibitor of ERK1/2 was utilized to further verify the regulatory effect of PO on the MAPK/ERK signaling pathway. It was found that PO could reduce the elevation of the ST segment; injury of heart tissue; the activity of LDH, CK, NOS, cNOS and iNOS and the levels of NO, BNP, TNF-α and IL-6. It is notable that PO could significantly modulate the protein content of p-ERK/ERK in mice suffering from MI but hardly had an effect on p-JNK/JNK and p-p38/p38. Additionally, the expressions of bax, caspase3 and caspase9 were inhibited in heart tissue in the PO-treated group. To evaluate whether ERK1/2 inhibitor (PD98059) could block the effect of PO on treatment of MI, both PO and PD98059 were given to mice with MI. It was discovered that the inhibitor indeed could significantly reverse the regulatory effects of PO on the above indicators, indicating that PO could regulate p-ERK/ERK. This study provides experimental evidence that PO extenuates MI injury, cardiomyocyte apoptosis and inflammation by activating the MAPK/ERK signaling pathway.Keywords:Polygonum orientaleL.;myocardial ischemia;MAPK signaling pathway
研究领域:
药理学
·
心脏病学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Natural Product Communications
·
2020
·
IF 0.468
Na Li,Ting Lv,Jie Pan,Chunhua Liu,Jia Sun,Yanyu Lan,Aimin Wang,Yongjun Li,Yonglin Wang,Yuan Lu
A simple, rapid, and selective ultra-performance liquid chromatography-mass spectrometry (MS)/MS method was established to investigate tissue distribution of 6 polyphenolic compounds of Polygonum orientale L. extract in normal and myocardial ischemia (MI) model rat tissues, including isoorientin, orientin, vitexin, quercitrin, astragalin, and protocatechuic acid. An Agilent Eclipse Plus C18 column was used. The mobile phase consisted of acetonitrile and water, both with 0.1% formic acid. Quantification was performed in negative ion multiple reaction monitoring mode. All the analysts had good linearity with r ≥ 0.9912. Accuracy ranged from 12.49% to −13.98% for the 6 compounds; within-day variation (precision) was ≤9.98% and interday precision was ≤11.88%. Extraction recovery of the analysts ranged from 80.55% to 99.92%; the matrix was 81.00%–98.73%. The analyst preparations were stable throughout. The 6 compounds were rapidly distributed in various tissues after oral administration, without accumulation over 12 hours. Compared with normal rats, distributions of 6 compounds in the heart, liver, spleen, lung, kidney, brain, stomach, and intestine in MI model rats were different from those in the normal group. The study provides an insight for further research of P. orientale L.
研究领域:
药理学
·
分析化学
·
心脏病学
✓ 已验证
产品关联
DOI
高影响因子
BIOMEDICAL CHROMATOGRAPHY
·
2025
·Vol. 39
·期 6
·e70089
·
IF 1.7
Chunhua Liu,Changli Fu,Luping Tang,Jieqi Li,Jia Sun,Yuan Lu,Jie Pan,Ting Liu,Yongjun Li,Yonglin Wang,Yong Huang,Yueting Li,Meng Zhou
Polygonum orientale L. (PO) represents significant bioactivities in treating myocardial ischemia (MI); however, its underlying mechanisms remain unclear. This study aims to elucidate PO's potential mechanisms in MI using an integrated approach that combines UHPLC–Q-Exactive Orbitrap HRMS, network pharmacology, and RNA-sequencing (RNA-seq). Initially, the chemical constituents of PO were identified using UHPLC–Q-Exactive Orbitrap HRMS. Subsequently, network pharmacology, molecular docking, and RNA-seq were employed to screen potential active components of PO targeting MI and predict their molecular mechanisms. Then, the molecular mechanisms were verified using western blotting and ELISA in MI mice. A total of 45 components were identified from PO, with 14 potential active compounds interacting with 204 MI-related genes. The findings suggest that PO could alleviate heart damage. The RNA-seq results indicated 244 potential targets regulated by PO. Integrating RNA-seq and network pharmacology analyses revealed that the toll-like receptor signaling pathway plays an important role, alongside the PI3K-Akt. Notably, PO reduced the expression of TLR4 and TLR2 while increasing p-Akt and p-PI3K levels in MI mice, leading to decreased inflammatory cytokines and apoptosis-related proteins. This study provides initial evidence that PO inhibits the toll-like signaling pathway and activates PI3K–Akt signaling pathway to exert protective effects against MI.
研究领域:
中药学
·
分子生物学
·
心血管病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICAL CHROMATOGRAPHY
·
2021
·Vol. 35
·期 10
·e5174
·
IF 1.902
Yuan Lu,Na Li,Xiaoqin Zhu,Jie Pan,Yonglin Wang,Yanyu Lan,Yongjun Li,Aimin Wang,Jia Sun,Chunhua Liu
Polygonum orientale L . is a traditional Chinese medicine having extensive pharmacological activities including antimyocardial ischemia (MI) injury properties. Isoorientin, orientin, vitexin, quercitrin, astragalin and protocatechuic acid are the main compounds in P. orientale extract. The aim of this study was to establish an ultra-performance liquid chromatography–tandem mass spectrometry method for the determination of the content of these compounds in urine, feces and bile samples simultaneously and application of the method in a comparative excretion study in normal and MI model rats after oral administration of P. orientale extract. Chromatographic seperation was conducted on an Agilent Eclipse Plus C 18 column with the mobile phase consisting of 0.1% formic acid–acetonitrile and 0.1% formic acid–water. Negative ion multiple reaction monitoring mode was used for quantification. The six compounds had good linearity ( r ≥ 0.9921) and acceptable accuracy ranging from 10.10 to −5.82% The relative standard deviations of within-day precision and inter-day precision were <10.45 and 13.44%, respectively. The extraction recovery of the six analytes ranged from 80.31 to 101.47% and the matrix effect was 82.56–102.88%, indicating that the preparations of sample collected form urine, feces and bile were stable throughout analysis. The excretion amount of the six analytes increased in both normal and MI model rats’ urine, feces and bile in a 24 h period and became stable between 36 and 48 h after administration. The total excretion rate of six compounds was <5% in urine, feces and bile of normal and MI model rats. The excretion peak period for all compounds in MI rats was slower than that in normal rats. This excretion study provides insights for further application and research on P. orientale .
研究领域:
药理学
·
分析化学
·
中药学
✓ 已验证
DOI
PubMed
高影响因子
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