JOURNAL OF FOOD BIOCHEMISTRY
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2022
·Vol. 46
·期 12
·e14460
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IF 3.654
Jing Guo,Jian-Kai Tang,Bai-Fang Wang,Wen-Rui Yan,Ting Li,Xue-Jian Guo,Lei Zhang,Tao Wang,Qian-Yun Sun,Li-Wei Zhang
Forsythia suspensa (Thunb.) Vahl (Oleaceae) leaves are valuable sources of phillygenin. This study aimed to isolate phillygenin from F. suspensa leaves and examine its analgesic and anti-inflammatory effects. Phillygenin was successfully extracted and isolated from F. suspensa leaves after fermentation. Phillygenin significantly reduced the number of writhing induced by acetic acid, prolonged the latency period in the hot plate test, and inhibited the xylene-induced ear edema and carrageenan-induced paw edema in mice. IL-6, TNF-α, IL-1β, NO, and PGE 2 levels in the carrageenan-induced paw edema were notably reduced after pretreatment with phillygenin. Phillygenin significantly decreased the iNOS and COX-2 protein expressions and the IκB-α and NF-κB p65 phosphorylation. This study demonstrated that phillygenin is a potential therapeutic candidate for managing pain and inflammation-mediated disorders. The study contributes to the comprehensive development and utilization of F. suspensa leaves for economic and health care. Practical applications Phillygenin is one of the major active ingredients in Forsythia suspensa . But the content of phillygenin in F. suspensa is very low which limits its application. Phillygenin has potential pharmacological activity and anti-inflammatory properties. However, the potential effects of phillygenin on analgesic activity have not been clarified. Furthermore, the data on its anti-inflammatory activity in vivo are relatively limited. This study evaluated the analgesic activity for the first time and the acute anti-inflammatory effect of phillygenin from F. suspensa leaves by fermentation, which indicated phillygenin is a potential therapeutic candidate for managing pain and inflammation-mediated disorders.
研究领域:
药理学
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炎症
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疼痛管理
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天然产物
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传统中药
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DOI
PubMed
高影响因子
Journal of Pharmaceutical Analysis
·
2024
·
IF 6.1
Huanhuan Xue,Peijie Li,Jing Guo,Tinggui Chen,Shifei Li,Liwei Zhang
Ulcerative colitis (UC) is an idiopathic, relapsing, and etiologically complicated chronic inflammatory bowel disease. Despite substantial progress in the management of UC, the outcomes of mucosal barrier repair are unsatisfactory. In this study, phillygenin (PHI) treatment alleviated the symptoms of chronic colitis in mice, including body weight loss, severe disease activity index scores, colon shortening, splenomegaly, oxidative stress, and inflammatory response. In particular, PHI treatment ameliorated the tight junction proteins (TJs) reduction, fibrosis, apoptosis, and intestinal stem cell activity, indicating that PHI exerted beneficial effects on the intestinal mucosal barrier in mice with chronic colitis. In the NCM460 cells damage model, dextran sulfate sodium triggered the sequential induction of TJs reduction, fibrosis, and apoptosis. Takeda G protein-coupled receptor-5 (TGR5) dysfunction mediated NCM460 cell injury. Moreover, PHI treatment enhanced TJs and suppressed fibrosis and apoptosis to maintain NCM460 cell function, depending on TGR5 activation. PHI promoted TGR5 activation and elevated intracellular cyclic adenosine monophosphate levels in HEK 293T cells transfected with TGR5 expression plasmids. Cellular thermal shift assay and molecular docking studies confirmed that PHI directly binds to TGR5, indicating that PHI is an agonist of TGR5. The process of PERK-eIF2α pathway-mediated endoplasmic reticulum Ca 2+ release was involved in NCM460 cell injury as well, which was associated with TGR5 dysfunction. When NCM460 cells were pretreated with PHI, the PERK-eIF2α pathway and elevated Ca 2+ levels were blocked. In conclusion, our study demonstrated a novel mechanism that PHI inhibited the PERK-eIF2α-Ca 2+ pathway through TGR5 activation to against DSS-induced TJs reduction, fibrosis, and apoptosis.
研究领域:
胃肠病学
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药理学
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细胞生物学
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炎症性肠病
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DOI
PubMed
高影响因子
Pharmaceutics
·
2020
·Vol. 12
·期 2
·130
·
IF 4.421
Lingzhi Wang,Wenrui Yan,Yurun Tian,Huanhuan Xue,Jiankai Tang,Liwei Zhang
Phillygenin, as an active ingredient ofForsythia suspensa, possesses a wide range of biological and pharmacological activity. However, its development and application are restricted due to its poor bioavailability and low solubility. Our work aimed to develop a self-microemulsifying drug delivery system to improve the oral bioavailability of phillygenin. The composition of the self-microemulsifying drug delivery system was preliminary screened by the pseudo-ternary phase diagram. Subsequently, the central composite design method was employed to optimize the prescription of the self-microemulsifying drug delivery system loaded with phillygenin. The prepared self-microemulsifying drug delivery system of phillygenin was characterized in terms of morphology, droplet size distribution, polydispersity index and stability. Then, the in vitro dissolution and the oral bioavailability were analyzed. The optimized self-microemulsifying drug delivery system of phillygenin consisted of 27.8% Labrafil M1944CS, 33.6% Cremophor EL, 38.6% polyethylene glycol 400 (PEG-400) and 10.2 mg/g phillygenin loading. The prepared self-microemulsifying drug delivery system of phillygenin exhibited spherical and uniform droplets with small size (40.11 ± 0.74 nm) and satisfactory stability. The in vitro dissolution experiment indicated that the cumulative dissolution rate of the self-microemulsifying drug delivery system of phillygenin was significantly better than that of free phillygenin. Furthermore, after oral administration in rats, the bioavailability of phillygenin was significantly enhanced by the self-microemulsifying drug delivery system. The relative bioavailability of the self-microemulsifying drug delivery system of phillygenin was 588.7% compared to the phillygenin suspension. These findings suggest that the self-microemulsifying drug delivery system of phillygenin can be a promising oral drug delivery system to improve the absorption of phillygenin.Keywords:phillygenin;self-microemulsifying drug delivery system;pharmacokinetics;oral bioavailability;in vitro dissolution
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DOI
PubMed
高影响因子
POULTRY SCIENCE
·
2026
·
IF 4.2
Bingbing Meng,Kang Zhang,Guowei Xu,Lei Wang,Zhiting Guo,Shuqi Liu,Xueyan Gu,Haiyu Chen,Jiyu Qian,Jingyan Zhang,Jianxi Li
Infectious bronchitis (IB) poses a significant global economic threat to the poultry industry. Phillygenin (PHI), a lignan compound possessing antiviral activity, has its clinical application limited by poor aqueous solubility and low oral bioavailability. To overcome these limitations, a self-nanoemulsifying drug delivery system loaded with PHI (PHI SNEDDS) was prepared. The resulting formulation exhibited uniform spherical nanoparticles with a size of 35.06 ± 0.64 nm, a zeta potential of -2.22 ± 0.27 mV, and a polydispersity index (PDI) of 0.180 ± 0.006, indicating high physical stability. In vitro release studies showed that PHI SNEDDS significantly enhanced both the rate and extent of drug release. A pharmacokinetic study in broilers revealed that the relative oral bioavailability of PHI SNEDDS reached 388.34% compared to the PHI suspension, accompanied by significantly increased maximum plasma concentration (C max ) and area under the curve (AUC 0-t ) ( P < 0.001), which confirms a substantial enhancement in absorption. In an IBV-infected broiler model, the SNEDDS formulation potentiated the antiviral efficacy of PHI. Compared to the IBV group and the PHI suspension group, PHI SNEDDS markedly enhanced antiviral efficacy, alleviating weight loss, clinical signs, and pathological damage in the trachea, lungs, and kidneys. It also significantly reduced viral load, virus shedding, and IBV-N protein expression ( P < 0.05), while increasing anti-IBV antibody levels ( P < 0.05), collectively indicating effective suppression of viral replication and enhancement of the host immune response. In conclusion, PHI SNEDDS effectively improved the solubility, bioavailability, and in vivo anti-IBV activity of PHI, demonstrating considerable potential as a therapeutic strategy for IB and offering a robust solution for administering hydrophobic active compounds.
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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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DOI
PubMed
高影响因子
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