PHYTOTHERAPY RESEARCH
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2025
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IF 6.3
Lin Cheng,Zhirui Du,Xueqiao Yan,Manju Che,Guoguo Zhi,Xiuying Ma,Funeng Geng,Baojie Li
Atopic dermatitis (AD) is a chronic inflammatory skin disorder with limited effective treatment. Sophora flavescens Aiton (Kushen) exhibits anti-inflammatory properties, but its key active components and mechanisms against AD remain unclear. This study aimed to identify its therapeutic compounds and the underlying molecular mechanisms. Network pharmacology and ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry were applied to screen for the potential bioactive compounds from Kushen, which were validated in AD mouse models. Formononetin (FMN) was topically administered to evaluate its curative efficacy through histopathological and immunofluorescent staining of skin lesions. Transcriptomic profiling explored the molecular mechanisms, with subsequent validation of neutrophil extracellular traps (NETs)-associated markers by immunofluorescent staining and western blotting. Co-treatment with PAD4 inhibitor GSK484 and molecular docking were used to study the underlying mechanisms. The study identified FMN as an important active component in Kushen, which showed therapeutic effects comparable to dexamethasone in AD models. FMN normalized cutaneous hyperplasia, reduced infiltration of CD3 + T cells, mast cells, and neutrophils, and suppressed inflammatory cytokine expression. Mechanistically, FMN inhibited NETs formation evidenced by decreased levels of citrullinated histone H3 (citH3), myeloperoxidase (MPO), and peptidylarginine deiminase 4 (PAD4). GSK484 co-treatment showed non-synergistic effects, suggesting that FMN suppresses NETs formation primarily through PAD4/MPO inhibition, which was confirmed by molecular docking. These findings highlight FMN as a primary anti-AD constituent of Kushen, therapeutically suppressing NETs-driven crosstalk of innate and adaptive immunity. FMN's multitarget mechanisms provide mechanistic insights and position it as a candidate for AD treatment.
研究领域:
药理学
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免疫学
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皮肤科学
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生物信息学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioactive Materials
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2025
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IF 20.3
Shuai Mao,Yubin Liang,Zikang Chen,Lei Wang,Quanfu Chen,Zhuting Fang,Qifan Zheng,Wen Ma,Hanping Zhang,Zhiqiang Yu,Ling Yu
Heart failure resulting from myocardial infarction (MI) is a leading global health concern. Current revascularization therapies cannot fully restore the infarcted myocardium or prevent maladaptive ventricular remodeling. Traditional Chinese medicine with its multitarget regulation and favorable biosafety shows a promising therapeutic potential. Tanshinone IIA (TIIA) and formononetin (FM), two bioactive compounds derived from Salvia miltiorrhiza and Astragalus membranaceus , respectively, exhibit antioxidant, anti-inflammatory, and proangiogenic effects. Herein, a neutrophil-targeted nanomedicine (TF-5NP) was developed to deliver TIIA and FM to the infarcted myocardium for mitigating oxidative damage and promoting angiogenesis. TF-5NP was synthesized by coassembling bis -5-hydroxytryptamine-modified 1,2-distearoyl-sn-glycero-3-phosphoethanolamine–polyethylene glycol–carboxylic acid with cholesterol and lipid 1,2-distearoyl-sn-glycero-3-phosphoglycerol, which binds to troponin in the infarcted myocardium. This nanomedicine reduces inflammation and cardiomyocyte damage and improves cardiac function in porcine MI models, with therapeutic effects lasting for ∼28 d. These findings suggest that TF-5NP use is a promising approach for treating post-MI maladaptive remodeling and heart failure.
研究领域:
纳米技术
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心脏病学
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药剂学
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传统中药学
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生物医学工程
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2023
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IF 5
Xufeng Yang,Yongrui Peng,Yu-e Wang,Yuxiu Zheng,Yiming He,Jiali Pan,Nan Liu,Yongxin Xu,Renhuan Ma,Junqiu Zhai,Yan Ma,Shixia Guan
Aimed to improve the absorption of Astragalus components (AC) via plant exosomes and demonstrate the synergistic mechanism of AC-loaded Curcumae Rhizoma Exosomes-like nanoparticles (AC-CELNs). CELNs with Curcumae Rhizoma active ingredients were extracted from the Curcumae Rhizoma by sucrose density gradient centrifugation method, and Formononetin , Astragaloside IV and Calycosin from Astragalus were loaded in CELNs by ultrasonic. AC-CELNs showed slow drug release in PBS (pH 7.4) compare to free AC, and encapsulation into CELNs helped to stabilize AC against simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). In addition, AC-CELNs exhibited superior uptake and transmembrane transport capacity on Caco-2 cell models and the endocytosis pathways related to the clathrin- and caveolin-dependent endocytosis ( P < 0.001 vs. free AC). MTT assay showed that AC-CELNs decreased the survival rate significantly against Caco-2 cells (42.58% at 48 h) and HeLa cells (33.34% at 48 h), and the inhibition was time-dependent and concentration-dependent. Furthermore, the pharmacokinetic parameters of Formononetin, Astragaloside IV, and Calycosin in rat plasma showed that CELNs could better promote the in vivo absorption of AC ( P < 0.05). The present study proposes that the CELNs are the potential and promising carriers to promote the absorption of AC in vitro or in vivo , and the combination of AC and CELNs is available for the enhancement of synergistic anti-tumor activity.
研究领域:
药理学
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纳米技术
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肿瘤学
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生物技术
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF CHROMATOGRAPHY A
·
2023
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IF 4.1
Jingtong Xia,Jiahao Zhou,Yanlong Liu,Na Yan,Xiaowen Hu,Lei Zhou,Qiaosheng Pu
Flavonoids are a class of natural polyphenolic compounds with great health benefits, and the development of methods for their analysis is of continuing interest. In this work, apigenin, kaempferol and formononetin were selected as the typical representatives of flavone, flavonol and isoflavone, three subclasses of flavonoids. Fluorescence studies revealed that tetraborate complexation could significantly sensitize the weak intrinsic fluorescence of flavonoids in solution, with a maximum of 137-fold for kaempferol. Subsequently, an integrated strategy of derivatization and separation was proposed for the universal analysis of flavonoids by capillary electrophoresis (CE) with 405 nm laser-induced fluorescence (LIF) detection. Using a running buffer consisting of 20 mM sodium tetraborate, 10 mM SDS and 10% methanol (pH 8.5), the dynamic derivatization was realized in the capillary, and the baseline separation was achieved within 10 min, with the detection limits of 0.92–35.46 nM (S/N=3) for the total of 9 flavonoids. The developed CE-LIF method was employed to the quantitative analysis of some flavonoids in Medicago sativa (alfalfa) plants and granulated alfalfa with the recoveries of 80.55–94.25%. Combined with the principal component analysis, the developed method was successfully applied to the non-destructive distinction of single seed for alfalfa and Melilotus officinalis (sweet clover), two forage grass seeds with very similar apparent morphology. Furthermore, this method was used to continuously monitor the substance metabolism during the soaking process at the level of single seed.
研究领域:
分析化学
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植物科学
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植物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Pharmaceutical Analysis
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2022
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IF 14.026
Xiaojuan Jiang,Yihua Lin,Yunlong Wu,Caixia Yuan,Xuli Lang,Jiayun Chen,Chunyan Zhu,Xinyi Yang,Yu Huang,Hao Wang,Caisheng Wu
Glycyrrhizae Radix et Rhizoma, a traditional Chinese medicine also known as Gan Cao (GC), is frequently included in clinical prescriptions for the treatment of pneumonia. However, the pharmacological components of GC for pneumonia treatment are rarely explored. Gan An He Ji oral liquid (GAHJ) has a simple composition and contains GC liquid extracts and paregoric, and has been used clinically for many years. Therefore, GAHJ was selected as a compound preparation for the study of GC in the treatment of pneumonia. We conducted an in vivo study of patients with pneumonia undergoing GAHJ treatments for three days. Using the intelligent mass spectrometry data-processing technologies to analyze the metabolism of GC in vivo, we obtained 168 related components of GC in humans, consisting of 24 prototype components and 144 metabolites, with 135 compounds screened in plasma and 82 in urine. After analysis of the metabolic transformation relationship and relative exposure, six components (liquiritin, liquiritigenin, glycyrrhizin, glycyrrhetinic acid, daidzin, and formononetin) were selected as potential effective components. The experimental results based on two animal pneumonia models and the inflammatory cell model showed that the mixture of these six components was effective in the treatment of pneumonia and lung injury and could effectively downregulate the level of inducible nitric oxide synthase (iNOS). Interestingly, glycyrrhetinic acid exhibited the strongest inhibition on iNOS and the highest exposure in vivo. The following molecular dynamic simulations indicated a strong bond between glycyrrhetinic acid and iNOS. Thus, the current study provides a pharmaceutical basis for GC and reveals the possible corresponding mechanisms in pneumonia treatment.
研究领域:
药理学
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中药学
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质谱学
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炎症
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分子动力学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Bioscience
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2023
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IF 5.2
Yaoyao Qi,Leyi Xie,Zeyuan Deng,Bing Zhang,Hongyan Li
The stability and antioxidant activity changes of 10 phytochemicals (isoflavones: genistein, genistin, daidzein, daidzin, formononetin, and anthocyanidins: delphinidin, cyanidin, pelargonidin, malvidin, petunidin) and food representatives (soybeans and blueberries) during in vitro digestion were investigated. Results indicated that the stability of isoflavones and anthocyanidins decreased with digestion. Among the isoflavones, the loss rate of formononetin was the largest, reaching 98.24%, and that of daidzein was the smallest (22.78%). And after intestinal digestion, anthocyanidins degraded into phenolic acids and other compounds, and the loss rate was above 95%. The loss of phenolic compounds in food extract was smaller than the standards, and the loss rate of phenolic compounds in hydrolyzed blueberry extracts (90.66%–96.04%) was higher than that of soybean extract (31.22%–59.74%). Moreover, the antioxidant activity of isoflavones and anthocyanidins decreased after the oral phase. During the gastrointestinal phase, the ABTS, DPPH and FRAP of isoflavones increased, while the ORAC and CAA decreased. The antioxidant activity of anthocyanidins increased in the gastric digestion and decreased in the intestinal phase. The glucoside linkage in the A ring and the hydroxyl methoxylation in the B ring weakened the antioxidant activity of isoflavones, while the hydroxylation and methoxylation of B rings of anthocyanidins could enhance thier antioxidant activity. The changes in antioxidant activity of the two food extracts were consistent with their contents.
研究领域:
食品科学
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营养学
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生物化学
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药理学
✓ 已验证
产品关联
DOI
高影响因子
Frontiers in Immunology
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2022
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IF 8.786
Bochen Song,Peng Li,Shaojia Yan,Yan Liu,Mingkun Gao,Huiyuan Lv,Zengpeng Lv,Yuming Guo
This study aimed to investigate the effects of dietary astragalus polysaccharide (APS) supplementation on the immune function, gut microbiota and metabolism of broiler chickens challenged with necrotic enteritis (NE). Two hundred forty Arbor Acres broiler chicks (one day old) were randomly assigned using a 2 × 2 factorial arrangement into two groups fed different levels of dietary APS (0 or 200 ppm of diet) and two disease challenge groups (control or NE challenged). The results showed that NE infection significantly increased FCR, mortality rate, Th17/Treg (Th17 cells% in blood and ileum, Th17/Treg, IL-17 and IL-17/IL-10 in blood), NO, lysozyme activity and IL-1β in blood, intestinal immune cell proportion and activity (Tc%, Treg% and monocyte phagocytic activity in ileum), intestinal inflammatory cytokines (TLR2, NF-κB, TNF-α and IL- 6) gene expression levels, and the number of Clostridium perfringens in cecum. NE infection significantly reduced body weight gain, thymus index, lymphocyte proliferation activity in blood and ileum, villus height and V/C in jejunum, Th cells% and Mucin2 gene expression in ileum. Dietary APS supplementation significantly increased body weight, feed intake, proportion of immune cells (T cells in blood and Tc, Treg in ileum), lymphocyte proliferation activity, V/C in jejunum, and ZO-1 gene expression in ileum. Dietary APS supplementation significantly reduced FCR and mortality rate, Th17/Treg, Th17%, intestinal pathology scores, intestinal inflammatory cytokine gene expression levels, and the number of Clostridium perfringens in cecum. In addition, broilers challenged with NE significantly increased Staphylococcus and Turicibacte r and reduced α diversity of microbiota in ileum. Dietary APS supplementation significantly increased α diversity, Romboutsia , Halomonas , propionic acid, butyric acid, formononetin, taurine, cholic acid and equol and downregulated uric acid, L-arginine and serotonin in ileum. Spearman’s correlation analysis revealed that Romboutsia, Turicibacter, Staphylocpccus, Halomonas, Streptococcus, Escherichia-Shigella, Prevotella , uric acid, L-arginine, jerivne, sodium cholate and cholic acid were related to inflammation and Th17/Treg balance. In conclusion, APS alleviated intestinal inflammation in broilers challenged with NE probably by regulating intestinal immune, Th17/Treg balance, as well as intestinal microbiota and metabolites.
研究领域:
动物科学
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免疫学
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微生物学
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营养学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Maoxing Pan,Yuanjun Deng,Yebei Qiu,Dajin Pi,Chuiyang Zheng,Zheng Liang,Jianwei Zhen,Wen Fan,Qingliang Song,Jinyue Pan,Yuanyou Li,Haizhen Yan,Qinhe Yang,Yupei Zhang
Background Non-alcoholic fatty liver disease (NAFLD) has emerged as a burgeoning health problem worldwide, but no specific drug has been approved for its treatment. Shenling Baizhu powder (SL) is extensively used to treat NAFLD in Chinese clinical practice. However, the therapeutic components and pharmacological mechanisms of SL against NAFLD have not been thoroughly investigated. Purpose This study aimed to investigate the pharmacological impact and molecular mechanism of SL on NAFLD. Methods First, we established an animal model of NAFLD by high-fat diet (HFD) feeding, and evaluated the therapeutic efficacy of SL on NAFLD by physiological, biochemical, pathological, and body composition analysis. Next, the effect of SL on autophagic flow in NAFLD rats was evaluated by ultrastructure, immunofluorescence staining, and western blotting. Moreover, an integrated strategy of targeted energy metabolomics and network pharmacology was performed to characterize autophagy-related genes and explore the synergistic effects of SL active compounds. UPLC-MS/MS, molecular docking combined with in vivo and in vitro experiments were conducted to verify the key compounds and genes. Finally, a network was established among SL-herb-compound-genes-energy metabolites-NAFLD, which explains the complicated regulating mechanism of SL on NAFLD. Results We discovered that SL decreased hepatic lipid accumulation, hepatic steatosis, and insulin resistance, and improved systemic metabolic disorders and pathological abnormalities. Subsequently, an integrated strategy of targeted energy metabolomics and network pharmacology identified quercetin, ellagic acid, kaempferol, formononetin, stigmasterol, isorhamnetin and luteolin as key compounds; catalase (CAT), AKT serine/threonine kinase 1 (AKT), nitric oxide synthase 3 (eNOS), NAD(P)H quinone dehydrogenase 1 (NQO1), heme oxygenase 1 (HO-1) and hypoxia-inducible factor 1 subunit alpha (HIF-1α) were identified as key genes; while nicotinamide adenine dinucleotide phosphate (NADP) and succinate emerged as key energy metabolites. Mechanistically, we revealed that SL may exert its anti-NAFLD effect by inducing autophagy activation and forming a comprehensive regulatory network involving key compounds, key genes, and key energy metabolites, ultimately alleviating oxidative stress, endoplasmic reticulum stress, and mitochondrial dysfunction. Conclusion Our study demonstrated the therapeutic effect of SL in NAFLD models, and establishes a basis for the development of potential products from SL plant materials for the treatment of NAFLD.
研究领域:
药理学
·
分子生物学
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代谢组学
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营养学
✓ 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）