Mechanism of platelet activation and potential therapeutic effects of natural drugs

Zhou, Yongfeng; Zhang, Dingkun; Tan, Peng; Xian, Bin; Jiang, Huajuan; Wu, Qinghua; Huang, Xulong; Zhang, Ping; Xiao, Xiaohe; Pei, Jin

doi:10.1016/j.phymed.2022.154463

Cited by 9 publications

(11 citation statements)

References 108 publications

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“…Furthermore, the draft guidance “Guidelines for R&D in the Botanical Drug Industry,” released by the US Food and Drug Administration (FDA) in 2016, underscores the importance of incorporating bioassays to gauge the biological potency of TCM and botanicals in the realm of quality control (Wang et al, 2017). Hence, a bioactive method was developed to assess the antiplatelet aggregation effect of PY, grounded in its primary efficacy and contemporary pharmacological insights (Qian et al, 2012; Zhao, 2016; Zhou et al, 2023). The outcomes demonstrated excellent reproducibility, affirming the method's suitability for evaluating the biological activity of PY from various sources.…”

Section: Discussionmentioning

confidence: 99%

Multimodal integrated strategy for the discovery and identification of antiplatelet aggregation Q‐markers in Paris polyphylla var. yunnanensis

Li,

Wen,

Yang

et al. 2024

Biomedical Chromatography

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To enhance the quality evaluation and control of traditional Chinese medicine (TCM) and ensure the safety and efficacy of clinical medication, it is imperative to establish a comprehensive quality assessment method aligned with TCM efficacy. This study uses a representative Chinese medicine with multi‐origin and multi‐efficacy, Paris polyphylla var. yunnanensis (PY), as an illustrative example. Surprisingly, despite the high fingerprint similarity among the 12 batches of PY samples collected from various regions in Yunnan, a notable variation in the composition and content of components was observed. The chromatographic analysis identified seven common peaks, namely, polyphyllin I, polyphyllin II, polyphyllin V, polyphyllin VI, polyphyllin VII, polyphyllin H, and polyphyllin D. In the bioactivity evaluation, an in vitro antiplatelet aggregation model induced by adenosine diphosphate was established, showcasing excellent stability. The maximum antiplatelet aggregation inhibition rate for all PY samples consistently remained stable at 73.1%–99.1%. However, the 50% inhibitory concentration (IC50) values exhibited a range from 1.615 to 18.200 mg/mL. This approach not only meets high‐throughput screening requirements but also demonstrates remarkable discrimination. The results of chemical and bioactivity evaluations were analyzed using hierarchical cluster analysis and canonical correlation analysis. Polyphyllin I, polyphyllin II, polyphyllin VII, polyphyllin H, and polyphyllin D were identified as the Q‐markers for antiplatelet aggregation in PY samples. Validation of the bioactivity for these monomer components aligned with the previously mentioned findings. Notably, this study established a spectrum–effect model for PY samples, enhancing the scientific robustness of the quality evaluation method. Furthermore, these findings offer valuable research insights for improving the quality assessment of other TCMs.

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Section: Discussionmentioning

confidence: 99%

Multimodal integrated strategy for the discovery and identification of antiplatelet aggregation Q‐markers in Paris polyphylla var. yunnanensis

Li,

Wen,

Yang

et al. 2024

Biomedical Chromatography

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“…Natural products can regulate the dynamic balance of coagulation and anticoagulation through different pathways and different targets, and their bi‐directional regulation is beneficial to reduce their adverse effects, which has broad application prospects in antithrombotic therapy (Zhou et al, 2023). In recent years, the antiplatelet and anticoagulant activities of natural products and their mechanisms have been extensively investigated, but only a few natural products have been found to promote fibrinolysis and their mechanisms are still unclear.…”

Section: Discussionmentioning

confidence: 99%

“…The activation of the PI3K/Akt pathway is important for granule secretion, integrin "outside-in" signaling, stable platelet adhesion, and the amplification of GPCR signaling (Estevez & Du, 2017). In humans, platelets express different isoforms of PI3K, of which PI3Kβ plays an essential role in the signaling amplification networks of platelet activation (Zhou et al, 2023). Agonists promote the activation of PI3K and the generation of phosphatidylinositol 3,4,5-triphosphate (PIP 3 ), which induces the phosphorylation and activation of protein kinase B (Akt).…”

Section: Pi3k/akt Pathwaymentioning

confidence: 99%

Therapeutic effects and molecular mechanisms of natural products in thrombosis

Yuan,

Zhong,

Wang

et al. 2024

Phytotherapy Research

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Thrombotic disorders, such as myocardial infarction and stroke, are the leading cause of death in the global population and have become a health problem worldwide. Drug therapy is one of the main antithrombotic strategies, but antithrombotic drugs are not completely safe, especially the risk of bleeding at therapeutic doses. Recently, natural products have received widespread interest due to their significant efficacy and high safety, and an increasing number of studies have demonstrated their antithrombotic activity. In this review, articles from databases, such as Web of Science, PubMed, and China National Knowledge Infrastructure, were filtered and the relevant information was extracted according to predefined criteria. As a result, more than 100 natural products with significant antithrombotic activity were identified, including flavonoids, phenylpropanoids, quinones, terpenoids, steroids, and alkaloids. These compounds exert antithrombotic effects by inhibiting platelet activation, suppressing the coagulation cascade, and promoting fibrinolysis. In addition, several natural products also inhibit thrombosis by regulating miRNA expression, anti‐inflammatory, and other pathways. This review systematically summarizes the natural products with antithrombotic activity, including their therapeutic effects, mechanisms, and clinical applications, aiming to provide a reference for the development of new antithrombotic drugs.

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“…Blood stasis syndrome is accompanied by pathological changes such as increased blood viscosity, increased hematocrit, and increased platelet aggregation. Some studies believe that in addition to the above-mentioned pathological abnormalities, blood stasis syndrome is also related to vascular endothelial cell damage, atherosclerosis, ischemia, and hypoxia, thrombosis, microcirculation disorders, inflammatory pathological processes, and other pathological changes [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Exploring the mechanism of Taohong Siwu Decoction on the treatment of blood deficiency and blood stasis syndrome by gut microbiota combined with metabolomics

Jiang

et al. 2023

Chin Med

Self Cite

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Background Taohong Siwu Decoction (THSWD) is a prescription which included in the “List of Ancient Classic Prescriptions (First Batch)” issued by the National Administration of Traditional Chinese Medicine (TCM) and the National Medical Products Administration of the People’s Republic of China. THSWD is effective and widely applied clinically for many diseases caused by blood deficiency and stasis syndrome in TCM, such as primary dysmenorrhea, menopausal syndrome, coronary heart disease, angina pectoris, and diabetes. Methods The TCM model of blood deficiency and blood stasis syndrome was prepared by ice water bath combined with cyclophosphamide, and the rats were randomly divided into control group, blood deficiency, and blood stasis model group, positive group, and THSWD treatment group. Pharmacodynamics measured the blood routine, blood coagulation, and other related indexes in rats. UHPLC-MS technology was used to analyze the changes in the fingerprints of metabolites in the plasma of rats with blood deficiency and blood stasis syndrome, and combined with mass spectrometry information and public database retrieval, to find potential biomarkers for screening metabolites. At the same time, 16S rDNA sequencing technology was used to identify intestinal flora, and statistical analysis was used to find differences in strain diversity between groups. Results THSWD administration can significantly improve the physical signs, blood routine, and hematopoietic factors caused by the blood deficiency and blood stasis syndrome model, and improve the symptoms of blood deficiency. The results of the general pharmacological studies showed THSWD groups improved changes in blood plasma viscosity and coagulation-related factors caused by modeling, and improved coagulation function significantly. The metabolomic analysis found that compared to the model group, THSWD exerted better effects on β-alanine, taurine, l-tyrosine, l-arginine, Eugenol, sodium deoxycholate, and deethylatrazine. Twenty-three potential differential metabolites showed intervention effects, mainly involved in eight metabolic pathways, including amino acid metabolism, taurine and hypotaurine metabolism, vitamin metabolism, and nucleotide metabolism. Gut microbiota data showed that, compared to the control group, the relative abundance and value of Firmicutes and Bacteroidota of the blood deficiency and blood stasis model group was significantly reduced, while the relative abundance of Actinobacteria, Spirochaetota, Proteobacteria, Campilobacterota, and other pathogenic bacteria was significantly increased. Following THSWD intervention, the abundance of beneficial bacteria increased, and the abundance of pathogenic bacteria decreased. Correlation analysis between the gut microbiota and differential metabolites showed that the two are closely related. THSWD affected the host blood system through mutual adjustment of these two factors, and improved blood deficiency and blood stasis syndrome in rats. Conclusion The blood deficiency and blood stasis syndrome model of TCM disease caused by ice bath combined with cyclophosphamide lead to changes in the pharmacology, metabolomics, and gut microbiota. The intervention of THSWD can improve the symptoms caused by blood deficiency and blood stasis. The mechanism is mainly through the regulation of platelet function and amino acid metabolism.

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Mechanism of platelet activation and potential therapeutic effects of natural drugs

Cited by 9 publications

References 108 publications

Multimodal integrated strategy for the discovery and identification of antiplatelet aggregation Q‐markers in Paris polyphylla var. yunnanensis

Multimodal integrated strategy for the discovery and identification of antiplatelet aggregation Q‐markers in Paris polyphylla var. yunnanensis

Therapeutic effects and molecular mechanisms of natural products in thrombosis

Exploring the mechanism of Taohong Siwu Decoction on the treatment of blood deficiency and blood stasis syndrome by gut microbiota combined with metabolomics

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