EXPERIMENTAL ANIMALS
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2023
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IF 2.4
Ce XU,Jiahui HAN,Di JIA,Jimin CAI,Jianming YUAN,Xin GE
Increasing studies have suggested that oxidative stress and inflammation play momentous roles in acute pulmonary embolism (APE). Honokiol, a bioactive biphenolic phytochemical substance, is known for its strong anti-oxidative and anti-inflammatory effects and here serves as an activator of sirtuin3 (SIRT3). The purposes of the study are to explore the effects of Honokiol on APE rats, and investigate whether the function of Honokiol is mediated by SIRT3 activation. In this study, the rats received a right femoral vein injection with dextran gel G-50 particles (12 mg/kg) to establish the APE model, which were administrated with Honokiol and/or selective SIRT3 inhibitor 3- (1H-1, 2, 3-triazol-4-yl) pyridine (3-TYP; 5 mg/kg) intraperitoneally. The data showed that SIRT3 activation by Honokiol attenuated the loss in lung function, ameliorated inflammatory response and oxidative damage as well as inhibited apoptosis in lung tissues of the rats with APE, which was reversed by 3-TYP. In addition, we found AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway might be activated by Honokiol but restrained by 3-TYP. These results indicated that Honokiol was capable of suppressing APE’s adverse effects, which was diminished by SIRT3 suppression, implying that activation of SIRT3 might serve as a therapeutic method for APE.
研究领域:
药理学
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肺科学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2024
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IF 4.8
Junjie Li,Yixu Wang,Jiawei Li,Sihan Xu,Shou Wang,Wenjuan Liu,Li Fu,Min Jiang,Gang Bai
Ethnopharmacological relevance Lian Qiao (LQ), the dried fruit of Forsythia suspensa (Thunb.) Vahl, is a well-documented traditional Chinese medicine known for its detoxifying and heat-clearing properties. Clinically, compounds containing LQ are widely used to treat thrombotic diseases, indicating that it may have antithrombotic effects. However, its exact mechanism of action remains unknown. Aim of the study This study aimed to verify the antithrombotic effect of LQ and further explore the material basis and target mechanism of its antithrombotic effect using various biological methods. Materials and methods An epinephrine-collagen-thrombin-induced mouse model of acute pulmonary embolism (APE) was established to study the effects of LQ on thrombus development. A UPLC/Q/TOF-MS screening and identification system based on the inhibition of platelet aggregation and Ca 2+ antagonism was established to determine the pharmacodynamic components of LQ that inhibit platelet activation. The inhibitory effect of active ingredients on platelet activation, and the determination of the target of their inhibitory effect on platelet activation have been studied using chemical proteomics. Furthermore, based on the structure and function of the target protein, a multidisciplinary approach was adopted to analyze the molecular mechanism of active ingredient binding to target proteins and to evaluate the effects of active ingredients on the downstream signaling pathways of target proteins. Results LQ showed significant anticoagulant effects in APE model mice. Phillyrin and phillygenin were the antiplatelet-activating components of LQ. PLCβ3 was identified as a target for inhibiting platelet activation by phillyrin and its metabolites. The mechanism underlying the effect involves phillyrin and its metabolites inhibiting PLCβ3 activity by blocking the binding of PLCβ3 to Gαq through non-covalently targeting the ASN260 of PLCβ3, thus inhibiting the downstream Gαq-PLCβ3-Ca 2+ signaling pathway, effectively hindering platelet activation and therefore playing an anticoagulant role. Conclusion This study not only proposes and validates the antithrombotic effect of LQ for the first time but also finds that phillyrin and phillygenin are the main pharmacological substances through which LQ exerts antithrombotic activity and reveals a novel mechanism by which they exert antiplatelet activity by directly targeting and inhibiting PLCβ3 activity. These findings significantly contribute to our understanding of the therapeutic potential of phillyrin and provide important clues for the discovery and development of new antiplatelet drugs.
研究领域:
药理学
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传统中药
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分子生物学
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生物化学
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血栓研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2024
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IF 5.4
Ning Yang,Weikun Li,Zhicheng Qian,Xin Tan,Zonghao Liu,Feiling Feng,Ling Liu,Liqin Ge
Pulmonary embolism remains the third leading cause of human mortality after malignant tumors and myocardial infarction. Commonly available thrombolytic therapeutic agents suffer from the limitations of very short half-life, inadequate targeting, limited clot penetration, and a propensity for severe bleeding. Inspired by the trident, we developed the armor-piercing microcapsule (MC), fucoidan-urokinase-S-nitrosoglutathione-polydopamine@MC (FUGP@MC), which exhibited a triple combination of photothermal, mechanical and pharmacological thrombolysis for the therapeutic treatment of acute pulmonary embolism (APE). Briefly, the outermost fucoidan layer was utilized for targeting to the APE area. Programmed APE treatment was triggered by near-infrared (NIR) light irradiation. Photothermal thrombolytic therapy was carried out by photothermal conversion of polydopamine. The photothermal conversion broke the S-nitroso bond in S-nitrosoglutathione (GSNO) and produced large amounts of nitric oxide (NO) for mechanical thrombolysis, which subsequently disrupted the interfacial structure of microcapsule to stimulate the release of the urokinase (UK), leading to a triple synergistic thrombolytic effect. The results demonstrated that the embolization residual rate of FUGP@MC (contained ≈ 1452.5 IU/kg UK) group was significantly lower than that of UK (10,000 IU/kg) group (6.35 % VS 16.78 %). Remarkably, FUGP@MC demonstrated a reliable in vivo biosafety proficiency. In summary, trident-inspired armor-piercing microcapsule FUGP@MC reveals a potential avenue for advancing pulmonary embolism therapeutics and promises to be a safer alternative candidate to current drug approaches.
研究领域:
药学
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生物医学工程
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治疗技术
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材料科学
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纳米技术
✓ 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）