JOURNAL OF CHROMATOGRAPHY A
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2025
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IF 4
Jiaming Yuan,Yuexiang Chang,Rongkai Gu,Zijian He,Ruining Zhang,Ann Van Schepdael,Tingting Zhang,Jincai Wang,Zhengjin Jiang
The highly conserved N -terminal domain of polymerase acidic endonuclease (PA N ) makes it an attractive target for the development of anti-influenza virus drugs. This study developed an innovative multi-detector based at-line nanofractionation platform by coupling an HPLC system containing triple-detector (diode array detector (DAD), charged aerosol detector (CAD) and MS) with fluorescence resonance energy transfer (FRET)-based bioassays to systematically identify potential PA N inhibitors from traditional Chinese medicine (TCM). A preliminary screening of 230 TCM extracts revealed an exceptional PA N inhibition by Terminalia chebula Retz. (IC 50 = 0.88 μg/mL). A time-resolved FRET bioassay in 384 well-plates with parallelized MS/MS analysis enabled real-time acquisition of both biological activity profiles and chemical information from Terminalia chebula Retz . extracts. HPLC-DAD-CAD analysis further elucidated the correlation between the content and bioactivity of the identified potential PA N -inhibitory compounds, addressing the limitations of traditional single UV-based detection. Remarkably, 31 bioactive compounds (including gallotannins, ellagitannins, and phenolic acids) were identified through this approach, with 75.9% exhibiting low abundance (CAD response < 1 pA·min), highlighting the unique capability of this platform in discovering low-abundant bioactive entities. Five verified compounds (ellagic acid, chebulinic acid, punicalagin, chebulagic acid, and 1,3,6-tri-O-galloyl- β -D-glucose) exhibited superior PA N inhibition (IC 50 = 0.52-1.00 μM) in comparison to baloxavir marboxil (IC 50 = 10.83 ± 1.46 μM). A molecular docking study elucidated their crucial PA N -binding interactions and fundamental mechanisms. Overall, this study not only identified several potential PA N inhibitors from Terminalia chebula Retz., but also offered a scalable at-line nanofractionation strategy to reveal the content-activity correlation of complex TCM extracts.
研究领域:
药物化学
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天然产物药理学
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抗病毒研究
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中药现代化
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分子药理学
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分析化学
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药物发现
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DOI
PubMed
高影响因子
Biomedicines
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2025
·Vol. 13
·期 11
·2584
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IF 3.9
Ting Cui,Xiaoqing Wang,Qi Wu,Ye Zhong,Fenglou Wang,Yue Zou,Yushu Wang,Shanshan Jiang,Gang Ma
Background/Objectives:Androgenetic alopecia (AGA) is the most common hair loss disorder in dermatological practice. Its primary pathogenesis involves the conversion of testosterone to dihydrotestosterone (DHT) by type II 5α-reductase upon reaching dermal papilla cells (DPCs). DHT impairs DPCs’ activity and inhibits hair growth. Although the FDA-approved drugs finasteride and minoxidil show certain efficacy, they are also associated with severe side effects. This study aims to explore the effects ofTerminalia chebulafruit extract (TCFE) on hair growth and its underlying molecular mechanisms.Methods: We investigated the therapeutic potential of TCFE in hair follicle regeneration, employing a multi-level experimental approach combining in vitro analyses of DPCs, in vivo animal models of AGA, and ex vivo cultures of human hair follicles and scalp tissue.Results: First, RNA-seq analysis and RT-PCR validation revealed that TCFE treatment activated the Wnt and TGF-β3 signaling pathways in DPCs, particularly upregulating the AKR1C gene family, which is involved in DHT metabolism. TCFE also potently inhibited type II 5α-reductase activity and mitigated DHT-induced damage to DPCs. In an AGA mouse model, TCFE reversed the AGA phenotype with efficacy comparable to finasteride. However, unlike finasteride, TCFE specifically enhanced the expression of AKR1C1 and AKR1C3, indicating a distinct mechanism. Finally, in ex vivo organ cultures, TCFE suppressed hair follicle cell apoptosis, promoted proliferation, and thereby stimulated hair growth.Conclusions: These findings suggest that TCFE is a promising natural treatment for AGA, likely acting through multiple mechanisms, including Wnt pathway activation, 5α-reductase inhibition, and enhanced DHT degradation.
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2023
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IF 5.4
Ling Ou,Heng-rui Liu,Xiao-yan Shi,Chang Peng,Yuan-jing Zou,Jun-wei Jia,Hui Li,Zhi-xiang Zhu,Yan-hua Wang,Bing-mei Su,Yu-qian Lai,Mei-yun Chen,Wei-xing Zhu,Zhong Feng,Gui-min Zhang,Mei-cun Yao
Ethnopharmacological relevance Terminalia chebula Retz. , known as the King of Traditional Tibetan Medicine, is widely used for treating various ailments, particularly stomach disorders . It exhibited inhibitory activity against helicobacter pylori . Aim of the study : The exact mechanism by which T. chebula combats H. pylori infection remains unclear. Therefore, this study aimed to investigate its mechanism of action and the key pathways and targets involved. Material and methods Minimum inhibitory concentration (MIC) assay, scanning electron microscope, and inhibiting kinetics curves were conducted. The mRNA expressions were measured by RNA-seq analysis and RT-QPCR. ELISA and Western blot were used to detect the changes in proteins. The main compounds were analyzed by High-performance Liquid Chromatography. The interaction between the compound and target was predicted by Molecular Docking. Results The study revealed that T. chebula disrupted the structure of H. pylori bacteria and inhibited Cag A protein expression. Additionally, T. chebula can reduce the expression of flaA, flaB , babA, alpA, alpB, ureE, and ureF genes. Furthermore, T. chebula demonstrated its effectiveness in inhibiting the H. pylori -induced inflammatory response by regulating the inflammasome signaling and ER-stress pathway. Moreover, the study discovered that chebulagic acid has anti-HP activity and inhibits the expression of Cag A protein. Conclusions T. chebula acts as a natural remedy for combating H. pylori infection. Its ability to disrupt the bacterial structure, inhibit key proteins, regulate inflammatory pathways, and the presence of chebulagic acid contribute to its anti- H. pylori activity.
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PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2026
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IF 6.8
Ling Ou,Bingyun Lu,Zhong Feng,Haobo Chen,Yuanjing Zou,Chuqiu Zhang,Qingchang Chen,Chang Peng,Meicun Yao,Ye Chen
Ethnopharmacological relevance Helicobacter pylori ( H. pylori ) infection is a leading risk factor for chronic gastritis, peptic ulcers, and gastric cancer. The escalating antibiotic resistance of H. pylori and adverse effects arising from standard antibiotic regimens have underscored an urgent need for natural, food-complementary therapeutic alternatives. Terminalia chebula Retz., commonly named “Hezi” in traditional Chinese medicine and “Haritaki” in Ayurveda, is a well-recognized edible fruit with a long history of use in alleviating gastrointestinal disorders. Aim of the study While it has been traditionally recognized for its anti-inflammatory and antimicrobial properties, its anti-adhesive efficacy against H. pylori and the metabolic mechanisms underlying its in vivo effects remain largely unexplored. Materials and methods This study adopted multiple analytical and experimental approaches: ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), RNA-seq, cell viability and adhesion assays, western blotting, hematoxylin and eosin (H&E) staining, enzyme-linked immunosorbent assay (ELISA), metabolomics, and proteomics. Results In this study, 15 primary compounds in T. chebula aqueous extract were identified, predominantly tannins. Multi-omics analyses (transcriptomics, metabolomics, and proteomics) revealed that T. chebula aqueous extract significantly inhibited H. pylori adhesion and enriched the lysine degradation pathway. Notably, N-alpha-acetyl-L-lysine was characterized as a key metabolite in fecal metabolomic profiling, which was associated with glycosphingolipid biosynthesis, ferroptosis, HIF-1 signaling, lysosomal function, and arginine metabolism. In vitro assays confirmed that N-alpha-acetyl-L-lysine reduced H. pylori adhesion to GES-1 cells, reversed H. pylori -induced cellular damage, and suppressed the secretion of pro-inflammatory cytokines (IL-6 and TNF-α). In vivo , T. chebula aqueous extract administration markedly alleviated H. pylori -induced gastric inflammation by downregulating IL-6, IL-1β, TNF-α, TGF-β, and IFN-γ. Collectively, these findings demonstrate that T. chebula aqueous extract exerts anti- H. pylori effects by regulating lysine metabolism, with N-alpha-acetyl-L-lysine serving as a key metabolite via fecal metabolomics. Conclusion These findings highlight T. chebula 's promising potential as a functional food ingredient or adjunctive therapy for H. pylori -related diseases, providing a natural, mechanism-based option for clinical intervention.
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高影响因子
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