CYTOKINE
·
2024
·
IF 3.7
Chenggang Huang,Jiajia Teng,Wei Liu,Junzhe Wang,An Liu
Background Impaired wound healing in traumatic skin injuries remains a severe clinical challenge due to impaired re-vascularization, harmful bacteria infection, and inflammation dysregulation. Macrophages are recognized as prominent immune cells in tissue regeneration and wound healing. Consequently, the modulation of macrophages provides a promising therapeutic target for wound healing disorders. Here, we aimed to explore whether a novel constructed combination of thermosensitive hydrogel Pluronic F-127 (PF-127) and phillyrin (PH, the main active compound of forsythia suspensa) could improve skin wound healing. Methods Firstly, the biological effects of pH on the phenotype and inflammation of macrophages were assessed by flow cytometry and ELISA. The biocompatibility of the PF-127 plus PH combination was investigated on keratinocytes and red blood cells. The biological effect of PF-127/PH hydrogel on the migratory ability of keratinocytes in vitro was evaluated using the scratch and transwell migration assays. In addition, S. aureus and E. coli were employed to test the antibacterial properties of the PF-127 plus PH combination. Finally, PF-127 plus PH scaffold was applied to the full-thickness skin defect in mice. Histomorphological evaluation and immunochemistry were performed to explore the wound-healing activity of PF-127/PH hydrogel. Results PH can promote the polarization of macrophages from the M1 (pro-inflammatory) phenotype to the M2 (anti-inflammatory) phenotype. The PF-127/PH hydrogel was highly biocompatible and showed a potent stimulative effect on the migration of keratinocytes in vitro. The combination of PF-127 and PH exerted a pronounced antibacterial activity on S. aureus and E. coli in vitro. PF-127/PH hydrogel potently accelerates the healing of full-thickness skin defects by promoting skin cell proliferation, accelerating angiogenesis, and inhibiting inflammation. Conclusions Our study suggests that PF-127/PH hydrogel has excellent potential for treating traumatic skin defects.
研究领域:
医学
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生物材料学
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免疫学
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2021
·
IF 4.432
Xin Guo,Pingping Cao,Xiongfeng Lian,Meng Hu,Jingyi Zhao,Wenjing Shen,Haili Wang,Hailong Yu,Yingzhu Chen
Phillyrin, a natural plant extract, has significant antioxidant and anti-apoptotic effects. However, its effect on intracerebral hemorrhage (ICH) remains unclear. In this study, we investigated a potential role for phillyrin in the regulation of the oxidative stress and apoptosis induced by ICH. A model of ICH was induced by collagenase IV (0.2 U in 1 μl sterile normal saline) in male C57BL/6J (B6) mice and different doses of phillyrin (5, 15, or 30 mg/kg) were intraperitoneally (i.p.) injected at 30 min, 6 h, and 22 h after modeling. We found that phillyrin significantly reduced neural function and lesion volume, improved injury of white and grey matter around the lesion, decreased apoptosis and oxidative stress, increased the expression of nuclear factor-erythroid 2-related factor 2 (Nrf2), heme oxygenase 1(HO-1), NADPH quinone oxidoreductase 1 (NQO1) and Superoxide Dismutase-1(SOD-1) in vitro and in vivo , and protected neurons from the stimulation of hemin by promoting Nrf2 nuclear translocation. Treatment with ML385 (Nrf2 inhibitor) completely reversed the protective effects of phillyrin in vivo after ICH injury. Based on our findings, we conclude that phillyrin treatment alleviates ICH injury-induced apoptosis and oxidative stress via activation of the Nrf2 signaling pathway, highlighting a potential role for phillyrin as an ICH therapeutic.
研究领域:
神经科学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2025
·
IF 5.6
Feng Li,Xinrong Fan,Bohao Wang,Jingyang Tong,Menglai Ling,Haibin Tong,Yumei Huang
Acute lung injury (ALI) in neonates presents a grave threat to infant health, characterized by a heightened risk of mortality. Phillyrin, an extraordinary constituent derived from a traditional Chinese medicinal herb Forsythia suspensa , has garnered considerable attention for its pronounced anti-inflammatory properties. However, its therapeutic potential for acute inflammatory diseases in neonates remains unclear. Therefore, our current study endeavors to assess the protective effects of phillyrin against lipopolysaccharide (LPS)-induced ALI in neonates and elucidate the underlying mechanisms. Phillyrin exhibited significant amelioration of lung damage in neonatal rats with LPS-induced ALI, accompanied by reductions in the total cell counts, neutrophil counts, and total protein level in bronchoalveolar lavage fluid (BALF). Notably, phillyrin substantially attenuated proinflammatory cytokine secretion and suppressed NF-κB activation in the lungs of neonatal ALI rats; however, it demonstrated inefficacy in mitigating LPS-induced cytokine secretion and NF-κB activation in vitro . Notably, phillyrin effectively inhibited β2 integrin-mediated neutrophil adhesion, migration, and chemotaxis. Moreover, phillyrin robustly suppressed β2 integrin engagement-induced actin polymerization and the Vav1/Rac1/PAK1/LIMK1/cofilin pathway. From a mechanistic standpoint, phillyrin exhibited direct interaction with β2 integrin, effectively antagonizing its function and significantly disrupting its binding affinity to intercellular adhesion molecule 1 (ICAM-1). This investigation unveils the promising therapeutic prospects of phillyrin as a novel compound against neonatal ALI.
研究领域:
药理学
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免疫学
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呼吸病学
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Wenjuan Liu,Junjie Li,Sihan Xu,Yixu Wang,Jiawei Li,Shou Wang,Li Fu,Min Jiang,Gang Bai
ABSTRACT Background Fever 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. Purpose This study aimed to explore the antipyretic mechanisms of Phr and provide a new treatment plan for fever. Methods The 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. Results Phr 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. Conclusion This 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.
研究领域:
药理学
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生物化学
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分子生物学
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免疫学
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产品关联
DOI
PubMed
高影响因子
Evidence-based Complementary and Alternative Medicine
·
2022
·
IF 2.65
Geng Zhang,Ying Zhang,Cong Wang,Chenhe Zhou,Shigui Yan
Postmenopausal osteoporosis is a metabolic disease caused by an imbalance between osteoclasts and osteoblasts. At present, the drug strategy for treating postmenopausal osteoporosis has some limitations and is unable to satisfy the demands of patients. Phillyrin (Phil) is an herbal extract from Forsythiae Fructus, with an inhibitory effect on osteolysis. In this study, we described the role of Phil in ovariectomy-induced osteoporosis and its effect on osteoclast differentiation in vitro. Eighteen female C57BL/6 mice were randomly divided into three groups: sham group (sham surgery and injection with 0.9% normal saline), ovariectomized group (ovariectomy and injection with 0.9% normal saline), and Phil group (ovariectomy and injecting Phil with 100 mg/kg for 2 days). Mice were sacrificed after 6-week Phil administration and femurs were harvested for microcomputed tomography (micro-CT) and histomorphology analyses. In vitro, we used different concentrations of Phil to study its effect on osteoclastogenesis. The results showed that the BV/TV, Tb.Th, and Tb.N in trabecular bone were increased in the Phil group compared with the OVX group, and the trabecular bone mass was remarkably decreased in the OVX group compared with the sham group. The number of osteoclasts was increased in the OVX group compared to the sham group, and the number and area of osteoclasts were decreased in the Phil group compared to the control group. Compared with the OVX group, the number and area of osteoclasts were reduced in the Phil group. In conclusion, Phil could inhibit the formation of osteoclasts, promote the growth of bone trabecular, and relieve osteoporosis caused by ovariectomy, with a certain clinical adoption value.
研究领域:
药理学
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骨科
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内分泌学
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DOI
PubMed
高影响因子
ACS Omega
·
2025
·
IF 4.3
Shixi Li,Xuhua Liang,Jiale Xing,Min Cheng,Xue Liu,Rong Zheng,Ruya Feng
Phillyrin has many effects, such as reducing blood lipids, anti-inflammatory properties, lowering blood pressure, and decreasing tyrosinase activity. However, the bioavailability of phillyrin with oral administration is very low due to its poor water solubility. In order to overcome the bioavailability problems of phillyrin, a phillyrin self-microemulsion was prepared by changing the dosage form, the preparation process of which was optimized, and its characterizations were investigated. Based on a self-microemulsion administration system, appropriate ingredients were chosen first on the basis of a solubility test, and the range of application of each ingredient was determined by ternary phase diagrams. Second, the formula of the phillyrin self-microemulsion was optimized through the response surface method by using the mass percentage of ethyl oleate and Km value (the ratio between surfactant and cosurfactant) as independent variables and using the encapsulation efficiency (EE), grain size, and polydispersity index (PDI) as dependent variables. The average grain size, PDI, and encapsulation efficiency of the optimized microemulsion are 42.37 nm, 0.244, and 69.51%, respectively. Finally, the apparent properties, stability, and pharmic content of the prepared phillyrin self-microemulsion were characterized. Moreover, in vitro dissolution was analyzed by using the rotatory-basket method, proving the self-microemulsion could improve the in vitro dissolution of phillyrin. The above-mentioned results indicated that self-microemulsion could be used to improve the solubility and bioavailability of phillyrin, which might be a good alternative solution to improve the oral utilization of phillyrin.
研究领域:
药剂学
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药物递送
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分子药理学
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药物代谢
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纳米医学
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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2026
·
IF 2.5
Jin-Chan Liu,Ren-Ju Yang,Ya-Wen Liu,Fei He
Glucocorticoid-induced skeletal muscle atrophy is characterized by progressive loss of muscle mass and function, yet effective pharmacological interventions remain limited. Prostaglandin E 2 (PGE 2 ) plays an important role in maintaining muscle regeneration, and its degradation is primarily controlled by 15-hydroxyprostaglandin dehydrogenase (15-PGDH). Here we investigated whether phillyrin, a natural lignan compound, protects against dexamethasone (DEX)-induced muscle atrophy in mice. Phillyrin treatment significantly attenuated DEX-induced reductions in muscle mass and improved grip strength and motor endurance. Histological analysis showed that phillyrin alleviated myofiber atrophy and preserved mitochondrial ultrastructure. Mechanistically, phillyrin suppressed the upregulation of 15-PGDH and restored intramuscular PGE 2 levels, accompanied by recovery of EP4 signaling. These changes were associated with inhibition of FOXO3a-mediated proteolysis and partial restoration of mTOR and PGC-1α signaling in skeletal muscle. Collectively, these findings indicate that phillyrin protects against glucocorticoid-induced muscle atrophy, potentially through modulation of the 15-PGDH/PGE 2 pathway. These findings suggest that phillyrin may represent a potential therapeutic candidate for the treatment of glucocorticoid-induced skeletal muscle atrophy.
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DOI
PubMed
高影响因子
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
·
2024
·
IF 3.1
Duan Qiong,Li Ruochen,Wang Mingxiao,Cui Zhenting,Zhu Xia,Chen Fanghong,Han Feng,Ma Jianxin
Phillyrin (PHN), derived from the dried fruit of Forsythia suspensa (Thunb.) Vahl, is a kind of Chinese herbal medicine with the effect of clearing heat, and has been used in China for thousands of years in treating various tumors. However, the mechanism of its main components on non-small cell lung cancer (NSCLC) remains unclear. PHN is a distinct component extracted from Forsythia suspensa with promising anti-cancer activity against various tumor types. This study sought to elucidate the promising effects of PHN on NSCLC. Based on network pharmacology results, we identified potential PHN targets and pathways for NSCLC treatment. CCK-8 assay, wound healing assay, apoptosis assay, western blot, and in vivo experiments verified the inhibitory effect of PHN on NSCLC. Network pharmacology identified 160 potential PHN targets, 955 NSCLC-related targets, and 54 common targets, along with 132 pathways and 2 core genes. Biological experiments demonstrated that PHN significantly inhibited the growth and migration of A549 and LLC cells while promoting their apoptosis. Western blot analysis revealed down-regulation of AKT, HSP90AA1, and CDC37 expression, suggesting that PHN inhibits A549 and LLC cell proliferation by down-regulating the HSP90-AKT pathway. In vivo experiments confirmed that PHN significantly inhibited NSCLC growth with low toxicity. This study, using network pharmacology and biological experiments, verified the effectiveness of PHN against NSCLC through the HSP90-AKT pathway. These findings provide a foundation for further research and analysis.
研究领域:
肿瘤学
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药理学
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分子生物学
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中药学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
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
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产品关联
DOI
PubMed
高影响因子
Frontiers in Microbiology
·
2026
·
IF 5.8
Rongling Yang,Ziling Huang,Yuli Tong,Dong Xu,Xiaoyan Li,Yanjin Li,Chun Zhu,Xiangjie Zhao
Phillyrin is a critical bioactive constituent of Forsythiae Fructus, exhibiting multiple pharmacological properties, but suffers from poor membrane permeability and low oral bioavailability. In this study, we developed a novel, green method employing whole-cell biocatalysts and natural deep eutectic solvents (NADESs) for the cinnamoylation of phillyrin to improve its liposolubility and bioactivity. Aspergillus oryzae whole cells showed high catalytic activity and stability in co-solvent systems containing hydrophobic NADESs. The NADES-tetrahydrofuran (50%, v/v) mixture maintained a high conversion rate (97.32–99.00%) and excellent 6′-regioselectivity (>99%) under optimal conditions (20 mg·mL−1 whole-cell dosage, 15:1 vinyl cinnamate/phillyrin, at 50 °C). Crucially, Aspergillus oryzae whole-cell biocatalysts exhibited markedly enhanced operational stability across all tested NADES-tetrahydrofuran (50%, v/v) reaction systems, retaining 80.09–97.95% of their original activity after six consecutive batch cycles. This study successfully combined hydrophobic NADESs with a whole-cell biocatalytic system, achieving efficient and regioselective cinnamoylation of phillyrin.
✓ 已验证
DOI
高影响因子
Communications Chemistry
·
2026
·
IF 6.9
Yuan Yuan,Liu Yongze,He Lei,Ma Xiaofeng,Wang Heyan,Li Yuanchao,Zhang Zhaoxiang,Zhang Jun,Wu Yongjun,Gao Xia
Acute sinusitis, common across populations, worsens seasonally due to pollution and improper medication, increasing the risk of chronic disease and impairing quality of life. To improve treatment and limit antimicrobial resistance in acute sinusitis, we developed a natural injectable QACS/SA@Py@Ta 4 C 3 hydrogel. It integrates the traditional Chinese medicine phillyrin with Ta 4 C 3 quantum dots and natural polymers—quaternary chitosan and sodium alginate. The hydrogel is designed for NIR II–mediated treatment of acute sinusitis via combined photothermal and photodynamic therapy. It exhibited a photothermal conversion efficiency of 22.6% and generated transient ROS, as demonstrated in vitro. Bacteriostatic experiments revealed that the hydrogel inhibited S. aureus with an efficiency of 99.7%. Furthermore, cell studies showed that the hydrogel was minimally cytotoxic, modulated macrophage cytokine expression, and displayed anti-inflammatory and antioxidant activities. Finally, in a rabbit sinusitis model, hydrogel implantation at the treatment site significantly reduced bacterial burden and decreased inflammation after NIR II laser treatment, demonstrating promising therapeutic potential.
✓ 已验证
DOI
PubMed
高影响因子
MOLECULES
·
2025
·Vol. 30
·期 17
·3528
·
IF 4.6
Teng Wang,Zexi Zhang,Jiayu Wang,Yuanyuan Fu,Xiaolin Zou,Wei Li,Zhaolun Zhang,Youting Liu,Zhaojun Jia,Zhenguo Wen,Yong Chen
In this study, a green and efficient extraction methodology was developed by leveraging the unique properties of chitosan—namely its non-toxicity, biocompatibility, and adhesive nature—to enhance the recovery of bioactive ingredients fromForsythia suspensaleaves. The core mechanism involves the formation of complexes between chitosan and the target bioactive ingredients, which significantly boosts their extraction efficiency. To substantiate this mechanism, comprehensive characterization was performed using Powder X-ray Diffraction (PXRD), Fourier Transform Infrared Spectroscopy (FT-IR), Differential Scanning Calorimetry (DSC), Scanning Electron Microscopy (SEM), and molecular docking analyses. The results provided robust evidence of a strong interaction between chitosan and the bioactive ingredients, leading to a marked enhancement in both the stability and aqueous solubility of the target compounds. For process optimization, a multi-objective approach was implemented using the Non-dominated Sorting Genetic Algorithm II (NSGA-II) to simultaneously maximize the extraction yields of phillyrin and forsythoside A. The algorithm identified the optimal parameters as a leaf-to-chitosan mass ratio of 10:11.75, a solid-to-liquid ratio of 1:52 g/mL, a temperature of 80 °C, and a duration of 120 min. Under these optimized conditions, the corresponding extraction yields for phillyrin and forsythoside A were 1.68 ± 0.16% and 3.23 ± 0.27%, respectively. These findings collectively indicate that chitosan-assisted extraction represents a highly promising and advanced technology for the sustainable and effective extraction of bioactive ingredients from botanical sources.
研究领域:
植物学
·
分析化学
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药用植物学
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绿色提取技术
✓ 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）