主要目的：观测流感发热患者的体温复常时间，评价连翘苷胶囊相较于安慰剂治疗流感相关发热症状消退时间方面的有效性。次要目的：（1）通过观测流感发热患者体温复常后的发热复发率、即刻退热时间、流感临床痊愈时间、流感症状缓解时间、流感症状改善程度、流感病毒转阴率、血清细胞因子-白细胞介素6（IL-6）水平，进一步评估连翘苷胶囊与安慰剂相比的有效性；（2）通过观测流感发热患者的不良事件等安全性评价指标，评估连翘苷胶囊的安全性和耐受性；（3）探索连翘苷胶囊治疗流感引起发热的最适剂量。

开始日期2020-01-04

申办/合作机构

大连富生天然药物开发有限公司

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CTR20170565 / Completed临床1期

健康志愿者单次和多次口服连翘苷胶囊或安慰剂的随机、双盲、剂量递增的耐受性、药代动力学和食物影响的研究

观察在健康人中单次和多次口服不同剂量连翘苷胶囊的安全性和耐受性特征，并观察在设定剂量组中可能出现的剂量限制性毒性（DLT）和最大耐受剂量（MTD）；考察单次和多次连续口服连翘苷胶囊在人体内的药代动力学参数；观察高脂饮食对连翘苷胶囊药物代谢的影响；药物代谢产物分析和代谢转化研究。

开始日期2017-06-21

申办/合作机构

大连富生天然药物开发有限公司

[+1]

100 项与大连富生天然药物开发有限公司相关的临床结果

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0 项与大连富生天然药物开发有限公司相关的专利（医药）

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项与大连富生天然药物开发有限公司相关的文献（医药）

2024-11-01·Phytomedicine

Phillyrin and its metabolites exert antipyretic effects by targeting the NAD+ binding domain of GAPDH, MDH2 and IDH2

Article

作者: Li, Junjie ; Xu, Sihan ; Wang, Yixu ; Fu, Li ; Li, Jiawei ; Liu, Wenjuan ; Jiang, Min ; Bai, Gang ; Wang, Shou

BACKGROUNDFever is one of the main pathophysiological reactions that occurs during the acute phase of various diseases. Excessive body temperature can lead to various adverse consequences such as brain tissue damage and abnormal immune responses. Phillyrin (Phr) is the main active ingredient in Forsythia suspensa (Thunb.) Vahl (Lian Qiao) and has antipyretic effects; however, its antipyretic mechanism of action remains unclear.PURPOSEThis study aimed to explore the antipyretic mechanisms of Phr and provide a new treatment plan for fever.METHODSThe antipyretic effects of Phr were evaluated using a mouse model of pneumonia fever. The main metabolites of Phr involved in its antipyretic function were identified using a mitochondrial temperature-sensitive probe. Further synthesis of the main metabolite, phillygenin (Phg), an alkynylated probe, was performed, and chemical proteomics was used to capture and analyze its direct target for antipyretic effects. The mechanism of action of Phg and its antipyretic targets was explored using metabolomics and various molecular biology methods.RESULTSPhr showed significant antipyretic and anti-inflammatory effects in a mouse model of lipopolysaccharide-induced fever. Phg reversibly targeted the nicotinamide adenine dinucleotide (NAD⁺) binding domain of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), malate dehydrogenase 2 (MDH2), and isocitrate dehydrogenase 2 (IDH2) to inhibit their enzymatic activity. In-depth analysis of cellular metabolomics and mitochondrial stress testing indicated that inhibition of GAPDH, MDH2, and IDH2 enzyme activity by Phg led to a decrease in cellular energy supply and heat production regulated by glycolysis, tricarboxylic acid cycle, and oxidative phosphorylation signaling pathways. Phg specifically targeted macrophages and inhibited LPS-induced macrophage activation by downregulating GAPDH enzyme activity, thereby exerting anti-inflammatory effects. In vivo experiments also confirmed that the antipyretic effect of Phr in LPS-induced fever model mice was related to its main metabolites, Phg and Phg-sulfonate (Phg-S), which directly targeted the NAD⁺ binding domain of GAPDH, IDH2, and MDH2, inhibiting the activity of these enzymes, thereby reducing energy supply and regulating febrile-related inflammatory factors.CONCLUSIONThis study reported for the first time that the antipyretic effect of Phr is produced by targeting GAPDH, IDH2, and MDH2 to regulate energy supply and febrile-related inflammatory factors through its main metabolites Phg and Phg-S. This study not only provides potential drugs for fever treatment but also provides new ideas for improving clinical fever treatment plans.

2024-10-01·Journal of Ethnopharmacology

Phillyrin and its metabolites treat pulmonary embolism by targeting PLCβ3 to inhibit platelet activation

Article

作者: Fu, Li ; Xu, Sihan ; Wang, Shou ; Wang, Yixu ; Bai, Gang ; Liu, Wenjuan ; Li, Jiawei ; Jiang, Min ; Li, Junjie

ETHNOPHARMACOLOGICAL RELEVANCELian 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 STUDYThis 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 METHODSAn 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 Ca²⁺ 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.RESULTSLQ 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-Ca²⁺ signaling pathway, effectively hindering platelet activation and therefore playing an anticoagulant role.CONCLUSIONThis 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.

2024-01-01·Journal of Ethnopharmacology

Mechanism difference of ginseng medicines with different natures on hyperthyroidism

Article

作者: Liu, Linlin ; Fu, Li ; Han, Xueying ; Shan, Guoshun ; Dou, Deqiang

ETHNOPHARMACOLOGICAL RELEVANCEMedicinal nature is a unique index in traditional Chinese medicine (TCM) to measure the efficacy of Chinese medicines. Hyperthyroidism, qi-Yin deficiency syndrome in TCM was regarded as the classic heat syndrome category in Chinese medicine. Moreover, it is extensively employed to evaluate the medicinal nature of herbs within the framework of the 'hot/cold' nature theory. Ginseng, red and black ginseng (GS, RG, and BG, respectively), and ginseng leaves (GL) are qi-tonifying herbs with different medicinal natures and were just right used to examine the underlying mechanisms between the nature of ginseng medicines and their tonifying effect.AIM OF THE STUDYTo examine the different mechanisms between different natures of ginseng medicines and their qi-tonifying action by comparison of their effects on hyperthyroidism and elucidate the nature of BG.MATERIALS AND METHODSThe hyperthyroidism model was induced through the oral administration of Euthyrox. Steroids belonging to hypothalamus pituitary adrenal (HPA) and hypothalamic pituitary gonadal (HPG) axes were determined with an ultra-performance liquid chromatography-triple quadrupole tandem mass spectrometry (UPLC-QqQ-MS/MS) method. Furthermore, the biochemical indexes associated with energy metabolism, including the serum cyclic nucleotide system and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling pathways were examined. Additionally, the gut microbiota was subjected to 16 S rDNA sequencing, followed by gas chromatography-mass spectrometry (GC-MS) analysis of short-chain fatty acids (SCFAs).RESULTSGS, RG, and BG could treat hyperthyroidism rats by regulating the hypothalamus pituitary thyroid (HPT) axis. The RG also had a strong regulatory effect on the HPA and HPG axis. The BG has a regulatory effect on the HPG axis. GL had a strong regulatory effect on HPA, HPG, and HPT axes. GS had the ability to regulate Firmicutes/Bacteroides of the intestinal flora, and GS, RG, and BG ameliorated the decrease of SCFAs induced by hyperthyroidism. According to PCA, BG is similar to GS, indicating a mild-warm nature.CONCLUSIONThe nature of BG was attributable to mild-warm and the GL with cold nature is best for the treatment of hyperthyroidism based on PCA analysis with all the bio-indices. In addition, the mechanism study indicated that the qi-tonifying effects of ginseng medicines are involved in HPT, HPA, and HPG axes to alleviate hyperthyroidism. In addition, the primary indexes reflected different natures of ginseng medicines are cyclic adenosine monophosphate (cAMP)/cyclic guanosine monophosphate (cGMP), AchE, and substance metabolism associated with Na⁺-K⁺-ATPase and PI3K/AKT signaling pathways, which are potential biomarkers for evaluation on the natures of qi-tonifying medicines.

100 项与大连富生天然药物开发有限公司相关的药物交易

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100 项与大连富生天然药物开发有限公司相关的转化医学

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