JOURNAL OF ETHNOPHARMACOLOGY
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2022
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IF 5.195
Min Hao,Zhouhui Yao,Mengting Zhao,Ziyan Chen,Pingping Wang,Xianan Sang,Qiao Yang,Kuilong Wang,Xin Han,Gang Cao
Ethnopharmacological relevance Curcumae Rhizoma-Sparganii Rhizoma (CR-SR) is a classic herbal pair to promote blood circulation and remove blood stasis in ancient China. However, the molecular mechanism is still unclear. Aim of study To screen out the anti-liver fibrosis active ingredients in CR-SR. Moreover, preliminary exploration the molecular mechanism of CR-SR to ameliorates liver fibrosis . Materials and methods In this research, plant taxonomy has been confirmed in the “The Plant List” database ( www.theplantlist.org ). The chemical components of CR-SR were analysed by ultra-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (UPLC-Q/TOF-MS). “Component-Target-Pathway-Disease” network of CR-SR components were built by network pharmacology . Then, the interaction between primary components and predicted protein targets based on network pharmacology were validated by molecular docking. The pharmacological actions of CR-SR were verified by blood biochemical indexes, histopathologic examination of CCL 4 induced rats’ model. The core protein targets were verified by Western blot . The effects of screened active components by molecular autodocking were verified by HSC-T6 cell experiment. Results The result shows that 57 chemical constituents in CR-SR herbal pair were identified by UPLC-Q/TOF-MS, in which, 27 compounds were closely connected with liver fibrosis related protein targets. 55 protein targets screened out by “component-target-pathway-disease network” maybe the underlying targets for CR-SR to cure liver fibrosis. Moreover, the 55 protein targets are mainly related to RNA transcription, apoptosis , and signal transduction. The molecular autodocking predicted that ten components can bond well with PTGS2 and RELA protein targets. The blood biochemical indexes, histopathologic examination of CCL 4 induced rats experiment showed that CR-SR has well intervention effect of liver fibrosis. The Western blot analysis indicated that CR-SR could significantly inhibit RELA, PTGS2, IL-6, SRC, and AKT1 protein expression to exert the anti-fibrosis effect. The HSC-T6 cell experiment indicated that both formononetin (FNT) and curdione could significantly inhibit the activation of HSC and reduce the expression of PTGS2, and p-AKT1 which was accordance with the molecular autodocking results. Conclusion This study proved the molecular mechanism of CR-SR multi-component and multi-target anti-liver fibrosis effect through mass spectrometry, network pharmacology, and western blotting technology. The research provides a theoretical evidence for the development and utilization of CR-SR herbal pair.
研究领域:
药理学
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分子生物学
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网络药理学
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中药学
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肝病
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DOI
PubMed
高影响因子
Food & Function
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2020
·Vol. 11
·期 12
·10568-10579
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IF 4.171
Jing Xu,Shan Jin,Fei Gan,Hui Xiong,Zhinan Mei,Yu Chen,Guangzhong Yang
The fruits of Garcinia xanthochymus can be eaten raw or processed into jams, preserves and vinegar. They provide not only vitamin and protein nutrients, but also pharmacologically active compounds, among which polycyclic polyprenylated acylphloroglucinols (PPAPs) are a major class. According to the literature, PPAPs exhibited good anti-cancer effects. This study investigated the antitumor effects and the underlying mechanism of S1 (the regioisomeric mixture of xanthochymol and guttiferone E) and S2 (the regioisomeric mixture of isoxanthochymol and cycloxanthochymol) isolated from the fruits of G. xanthochymus. In an H22 allograft mouse model, S1 and S2 could suppress the liver tumor growth and phosphorylation of STAT3. Computational modeling showed that S1 and S2 could form hydrogen bonds with the SH2 domain of STAT3. In HepG2 and MCF-7 cell lines, S1 and S2 downregulated the expression of p-STAT3Tyr705. Moreover, S1 and S2 inhibited the phosphorylation of JAK2 and Src, which are the upstream kinases of STAT3, and the expression of various STAT3-regulated genes, including anti-apoptotic (Bcl-XL, Mcl-1 and survivin), proliferative (cyclin D1) and angiogenic (VEGF) genes. As a result, S1 and S2 arrested the cell cycle and induced cell apoptosis, which were proved by the activation of cleaved caspase-3 and caspase-8. These results demonstrated that S1 and S2 from G. xanthochymus exhibited antitumor effects through the inactivation of STAT3, and could be promising candidates for cancer treatment.
研究领域:
药理学
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肿瘤学
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分子生物学
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生物化学
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DOI
PubMed
高影响因子
Chinese Medicine
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2021
·Vol. 16
·期 1
·1-21
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IF 5.455
Li Qiaofeng,Lan Taijin,He Songhua,Chen Weiwei,Li Xiaolan,Zhang Weiquan,Liu Ying,Zhang Qiuping,Chen Xin,Han Yaoyao,Su Zhiheng,Zhu Dan,Guo Hongwei
Background Lei-gong-gen formula granule (LFG) is a folk prescription derived from Zhuang nationality, the largest ethnic minority among 56 nationalities in China. It consists of three herbs, namely Eclipta prostrata (L.) L., Smilax glabra Roxb, and Centella asiatica (L.) Urb. It has been widely used as health protection tea for hundreds of years to prevent hypertension in Guangxi Zhuang Autonomous Region. The purpose of this study is to validate the antihypertensive effect of LFG on the spontaneously hypertensive rat (SHR) model, and to further identify the effective components and anti-hypertension mechanism of LFG.Methods The effects of LFG on blood pressure, body weight, and heart rate were investigated in vivo using the SHR model. The levels of NO, ANG II, and ET-1 in the serum were measured, and pathological changes in the heart were examined by H&E staining. The main active components of LFG, their corresponding targets, and hypertension associated pathways were discerned through network pharmacology analysis based on the Traditional Chinese Medicine Systems Pharmacology (TCMSP), Traditional Chinese Medicine Integrated Database (TCMID), and the Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM). Then the predicted results were further verified by molecular biology experiments such as RT-qPCR and western blot. Additionally, the potential active compounds were predicted by molecular docking technology, and the chemical constituents of LFG were analyzed and identified by UPLC-QTOF/MS technology. Finally, an in vitro assay was performed to investigate the protective effects of potential active compounds against hydrogen peroxide (H2O2) induced oxidative damage in human umbilical vein endothelial cells (HUVEC).Results LFG could effectively reduce blood pressure and increase serum NO content in SHR model. Histological results showed that LFG could ameliorate pathological changes such as cardiac hypertrophy and interstitial inflammation. From network pharmacology analysis, 53 candidate active compounds of LFG were collected, which linked to 765 potential targets, and 828 hypertension associated targets were retrieved, from which 12 overlapped targets both related to candidate active compounds from LFG and hypertension were screened and used as the potential targets of LFG on antihypertensive effect. The molecular biology experiments of the 12 overlapped targets showed that LFG could upregulate the mRNA and protein expressions of NOS3 and proto-oncogene tyrosine-protein kinase SRC (SRC) in the thoracic aorta. Pathway enrichment analysis showed that the PI3K-AKT signaling pathway was closely related to the expression of NOS3 and SRC. Moreover, western blot results showed that LFG significantly increased the protein expression levels of PI3K and phosphorylated AKT in SHR model, suggesting that LFG may active the PI3K-AKT signaling pathway to decrease hypertension. Molecular docking study further supported that p-hydroxybenzoic acid, cedar acid, shikimic acid, salicylic acid, nicotinic acid, linalool, and histidine can be well binding with NOS3, SRC, PI3K, and AKT. UPLC-QTOF/MS analysis confirmed that p-hydroxybenzoic acid, shikimic acid, salicylic acid, and nicotinic acid existed in LFG. Pre-treatment of HUVEC with nicotinic acid could alleviate the effect on cell viability induced by H2O2 and increase the NO level in cell supernatants.Conclusion sLFG can reduce the blood pressure in SHR model, which might be attributed to increasing the NO level in serum for promoting vasodilation via upregulating SRC expression level and activating the PI3K-AKT-NOS3 signaling pathway. Nicotinic acid might be the potential compound for LFG antihypertensive effect.
研究领域:
药理学
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分子生物学
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中药学
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心血管疾病
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DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2025
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IF 6.1
Zichen Cui,Tian He,Shuo Zhang
Polylactic acid (PLA), as a bioplastic, is extensively utilized in bone tissue engineering for its biocompatibility, adaptability and affordability. However, the toxicological research of PLA is still limited. The hydrolysis products of PLA induced inflammatory response which caused inflammatory osteolysis mediated by oxidative damage through the recruitment of macrophages and the accumulation of foreign body multinucleated giant cells, ultimately leading to the failure of bone tissue regeneration. The lack of effective treatments highlights the importance of finding new therapies. This study systematically investigated the potential molecular mechanisms of PLA-induced inflammatory osteolysis by employing network toxicology and molecular docking techniques. We first conducted a network toxicology-based assessment according to the molecular structure of PLA. The result from integrating and screening targets from multiple databases identified 126 potential targets associated with PLA-induced inflammatory osteolysis, and then an interaction network diagram of the targets was constructed. Gene ontology (GO)/KEGG enrichment analysis clarified that PLA may cause inflammatory osteolysis via metabolic pathways and pathways in cancer, as well as lipid and atherosclerosis. Further analysis by STRING and Cytoscape software screened 25 core targets including HSP90AA1, AKT1, SRC, STAT1 and FYN. We found that the enriched highly correlated pathways covered 18 of the 25 core targets, supporting the scientific hypothesis that PLA induces inflammatory osteolysis. Moreover, the results of molecular docking confirmed that PLA displayed a strong binding ability with the core targets and formed stable binding. Taken together, this study not only revealed the potential biological mechanism of PLA-induced inflammatory osteolysis, but also provided new evidence for the future prevention and treatment of PLA-induced inflammation.
研究领域:
生物医学工程
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毒理学
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分子生物学
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生物信息学
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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）