<div><h3>Background</h3><div>Qingfei Jiedu Huatan Formula (QJHF) has demonstrated efficacy in reducing the clinical stabilization time for pneumonia patients, decreasing ICU durations, and enhancing patients' quality of life.</div></div><div><h3>Objective</h3><div>Protecting the alveolar epithelial barrier is a proven strategy for improving pneumonia outcomes. This study aims to investigate the protective effects and underlying mechanisms of QJHF on the alveolar epithelial barrier in pneumonia.</div></div><div><h3>Methods</h3><div>A mouse model of pneumonia and acute lung injury was established via tracheal instillation of Klebsiella pneumoniae and LPS to evaluate the therapeutic effects of QJHF. Additionally, a TNF-α-induced alveolar epithelial cell barrier injury model was employed to explore the molecular mechanisms underlying QJHF's protective effects. Transcriptomics combined with network analysis was utilized to identify the active components and mechanisms of action for QJHF. Molecular docking and molecular dynamics analyses elucidated the binding interactions between Ginsenoside Rb1 (GRb1) and target proteins, while the application of Nrf2 inhibitor and siRNA clarified the role of Nrf2 activation in GRb1-mediated alveolar barrier protection.</div></div><div><h3>Results</h3><div>QJHF significantly ameliorates Klebsiella pneumoniae-induced pneumonia in mice by improving lung tissue damage, reducing inflammatory cell infiltration, and decreasing levels of pro-inflammatory factors such as TNF-α, IL-1β, and IL-6. Additionally, QJHF upregulates the expression of cell junction proteins ZO-1 and OCLN, thereby protecting the alveolar epithelial barrier. Similarly, QJHF mitigates LPS-induced lung damage, inflammation, and alveolar epithelial barrier dysfunction. Through integrating serum component profiling, network pharmacology, and lung transcriptomics revealed that 12 constituents in QJHF may interact with Nrf2 to modulate oxidative stress and apoptosis signaling pathways. Both in vitro and in vivo studies demonstrate that GRb1, one of the 12 components, significantly protects against TNF-α-induced alveolar epithelial cell barrier dysfunction and LPS-induced lung inflammation and alveolar barrier damage in mice. Furthermore, GRb1 can inhibit TNF-α-induced ROS levels and apoptosis in alveolar epithelial cells. Molecular dynamics stimulation and luciferase assays demonstrate that GRb1 can bind to and activate Nrf2, promoting its interaction with antioxidant response elements. Additionally, rotenone can counteract the protective effect against apoptosis in the alveolar epithelial cell barrier by increasing cellular ROS levels. Similarly, siRNA can significantly impair GRb1′s protective effects against TNF-α-induced damage to the alveolar epithelial cell barrier. Nrf2 inhibitors notably attenuated GRb1′s amelioration of LPS-induced lung inflammation and alveolar barrier damage in mice.</div></div><div><h3>Conclusion</h3><div>This study confirms that
{"title":"Qingfei Jiedu Huatan formula protects against pneumonia by activating Nrf2 to suppress alveolar epithelial apoptosis","authors":"Yuhang Jiang , Qin Zhang , Yumeng Cheng , Haiyang Cao , Xiaoxiang Xing , Baixi Shan , Peng Zhao , Jiansheng Li","doi":"10.1016/j.phymed.2026.157879","DOIUrl":"10.1016/j.phymed.2026.157879","url":null,"abstract":"<div><h3>Background</h3><div>Qingfei Jiedu Huatan Formula (QJHF) has demonstrated efficacy in reducing the clinical stabilization time for pneumonia patients, decreasing ICU durations, and enhancing patients' quality of life.</div></div><div><h3>Objective</h3><div>Protecting the alveolar epithelial barrier is a proven strategy for improving pneumonia outcomes. This study aims to investigate the protective effects and underlying mechanisms of QJHF on the alveolar epithelial barrier in pneumonia.</div></div><div><h3>Methods</h3><div>A mouse model of pneumonia and acute lung injury was established via tracheal instillation of Klebsiella pneumoniae and LPS to evaluate the therapeutic effects of QJHF. Additionally, a TNF-α-induced alveolar epithelial cell barrier injury model was employed to explore the molecular mechanisms underlying QJHF's protective effects. Transcriptomics combined with network analysis was utilized to identify the active components and mechanisms of action for QJHF. Molecular docking and molecular dynamics analyses elucidated the binding interactions between Ginsenoside Rb1 (GRb1) and target proteins, while the application of Nrf2 inhibitor and siRNA clarified the role of Nrf2 activation in GRb1-mediated alveolar barrier protection.</div></div><div><h3>Results</h3><div>QJHF significantly ameliorates Klebsiella pneumoniae-induced pneumonia in mice by improving lung tissue damage, reducing inflammatory cell infiltration, and decreasing levels of pro-inflammatory factors such as TNF-α, IL-1β, and IL-6. Additionally, QJHF upregulates the expression of cell junction proteins ZO-1 and OCLN, thereby protecting the alveolar epithelial barrier. Similarly, QJHF mitigates LPS-induced lung damage, inflammation, and alveolar epithelial barrier dysfunction. Through integrating serum component profiling, network pharmacology, and lung transcriptomics revealed that 12 constituents in QJHF may interact with Nrf2 to modulate oxidative stress and apoptosis signaling pathways. Both in vitro and in vivo studies demonstrate that GRb1, one of the 12 components, significantly protects against TNF-α-induced alveolar epithelial cell barrier dysfunction and LPS-induced lung inflammation and alveolar barrier damage in mice. Furthermore, GRb1 can inhibit TNF-α-induced ROS levels and apoptosis in alveolar epithelial cells. Molecular dynamics stimulation and luciferase assays demonstrate that GRb1 can bind to and activate Nrf2, promoting its interaction with antioxidant response elements. Additionally, rotenone can counteract the protective effect against apoptosis in the alveolar epithelial cell barrier by increasing cellular ROS levels. Similarly, siRNA can significantly impair GRb1′s protective effects against TNF-α-induced damage to the alveolar epithelial cell barrier. Nrf2 inhibitors notably attenuated GRb1′s amelioration of LPS-induced lung inflammation and alveolar barrier damage in mice.</div></div><div><h3>Conclusion</h3><div>This study confirms that","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"152 ","pages":"Article 157879"},"PeriodicalIF":8.3,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146113969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-24DOI: 10.1016/j.phymed.2026.157888
Qing Yin , Zhengqin Xiong , Xinya Wang , Tong-You Wade Wei , Jiayue Chao , Wu Jiang , Ying Chen , Ruijun Dong , Hu Zhang , Yi Yang , Kaizheng Gong , Hui Shen
Background
Pulmonary arterial hypertension (PAH) is characterized by vascular remodeling and right ventricular failure. Paeonol, a bioactive compound extracted from the root bark of Paeonia suffruticosa, exhibits anti-inflammatory, antioxidant, and anticancer effects. However, its efficacy on pulmonary vasculature in the context of PAH remains unknown.
Purpose
This study aims to evaluate the protective effects of paeonol in murine pulmonary hypertension (PH) model and identify its underlying molecular mechanism.
Methods
A murine PH model was used to assess the effect of paeonol on hemodynamics, echocardiography and pathology. In vitro, pulmonary arterial smooth muscle cells (PASMCs) proliferation and apoptosis were evaluated. RNA sequencing and network pharmacology were analyzed for pathway changes. Molecular docking and surface plasmon resonance (SPR) were employed to identify paeonol targets, which were further validated by Western blotting and immunofluorescence.
Results
Paeonol administration significantly reduced right ventricular systolic pressure (RVSP), right ventricular hypertrophy, and pulmonary vascular remodeling in PH mice. Echocardiography further demonstrated that paeonol preserved right ventricular structural and functional integrity. In vitro, paeonol inhibited PASMCs proliferation and promoted apoptosis. RNA sequencing and network pharmacology revealed that the drug effect was on the bone morphogenetic protein (BMP)/transforming growth factor-β (TGF-β) pathway. SPR analysis confirmed a high-affinity direct binding between paeonol and BRCA1/BRCA2-containing complex subunit 3 (BRCC3). Paeonol binding promotes the stability of BMP receptors and restores the BMP/TGF-β signaling balance.
Conclusion
Paeonol attenuates PH by rebalancing the BMP/TGF-β signaling through interacting with BRCC3 activation, thereby inhibiting vascular remodeling. These findings suggest that paeonol is a promising therapeutic candidate for PAH.
{"title":"Paeonol alleviates pulmonary arterial hypertension by activation of BRCC3","authors":"Qing Yin , Zhengqin Xiong , Xinya Wang , Tong-You Wade Wei , Jiayue Chao , Wu Jiang , Ying Chen , Ruijun Dong , Hu Zhang , Yi Yang , Kaizheng Gong , Hui Shen","doi":"10.1016/j.phymed.2026.157888","DOIUrl":"10.1016/j.phymed.2026.157888","url":null,"abstract":"<div><h3>Background</h3><div>Pulmonary arterial hypertension (PAH) is characterized by vascular remodeling and right ventricular failure. Paeonol, a bioactive compound extracted from the root bark of <em>Paeonia suffruticosa</em>, exhibits anti-inflammatory, antioxidant, and anticancer effects. However, its efficacy on pulmonary vasculature in the context of PAH remains unknown.</div></div><div><h3>Purpose</h3><div>This study aims to evaluate the protective effects of paeonol in murine pulmonary hypertension (PH) model and identify its underlying molecular mechanism.</div></div><div><h3>Methods</h3><div>A murine PH model was used to assess the effect of paeonol on hemodynamics, echocardiography and pathology. <em>In vitro,</em> pulmonary arterial smooth muscle cells (PASMCs) proliferation and apoptosis were evaluated. RNA sequencing and network pharmacology were analyzed for pathway changes. Molecular docking and surface plasmon resonance (SPR) were employed to identify paeonol targets, which were further validated by Western blotting and immunofluorescence.</div></div><div><h3>Results</h3><div>Paeonol administration significantly reduced right ventricular systolic pressure (RVSP), right ventricular hypertrophy, and pulmonary vascular remodeling in PH mice. Echocardiography further demonstrated that paeonol preserved right ventricular structural and functional integrity. <em>In vitro</em>, paeonol inhibited PASMCs proliferation and promoted apoptosis. RNA sequencing and network pharmacology revealed that the drug effect was on the bone morphogenetic protein (BMP)/transforming growth factor-β (TGF-β) pathway. SPR analysis confirmed a high-affinity direct binding between paeonol and BRCA1/BRCA2-containing complex subunit 3 (BRCC3). Paeonol binding promotes the stability of BMP receptors and restores the BMP/TGF-β signaling balance.</div></div><div><h3>Conclusion</h3><div>Paeonol attenuates PH by rebalancing the BMP/TGF-β signaling through interacting with BRCC3 activation, thereby inhibiting vascular remodeling. These findings suggest that paeonol is a promising therapeutic candidate for PAH.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"152 ","pages":"Article 157888"},"PeriodicalIF":8.3,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146119613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Acinetobacter baumannii is a Gram-negative bacterial pathogen responsible for severe nosocomial infections. Carbapenems, including meropenem and imipenem, are β-lactam antibiotics commonly used as a last-resort treatment for infections caused by A. baumannii. While it is recognized that green tea polyphenols can enhance the efficacy of carbapenems against A. baumannii, the underlying mechanisms of this synergy remain undefined.
Purpose
This study aims to investigate the synergistic actions of green tea aqueous extract and its key bioactive component, epigallocatechin gallate (EGCG), in combination with meropenem against A. baumannii BAA-1605 and to elucidate the associated mechanisms.
Methods
The synergism with meropenem was assessed using antibiotic susceptibility testing and fractional inhibitory concentration index (FICI) analysis. The mechanism study included β-lactamase activity, Hoechst dye accumulation, and DiOC₂(3) membrane potential measurements. The effect of meropenem and/or EGCG on purified penicillin-binding protein 2 (PBP2) was also evaluated by nuclear magnetic resonance (NMR) spectroscopy and scanning electron microscopy (SEM). Transcriptomic sequencing and bioinformatic analyses were performed to elucidate global gene expression changes of A. baumannii BAA-1605 following exposure to meropenem and/or EGCG.
Results
Green tea aqueous extract synergized with meropenem against A. baumannii BAA-1605 by lowering the minimum inhibitory concentration (MIC) by 4-fold (128 to 32 μg/mL). EGCG was determined as the primary synergistic component in the extract (FICI = 0.375). The mechanism study showed that EGCG does not influence β-lactamase production or meropenem-mediated PBP2 inhibition but contributes to overcoming resistance by inhibiting efflux pump activity. Furthermore, transcriptomic analysis revealed that EGCG may suppress the AdeABC efflux system and enhance meropenem influx via a YiaD-dependent porin pathway.
Conclusion
This study presents a dual role of efflux inhibition and influx facilitation by EGCG in restoring meropenem efficacy, supporting its potential as a promising adjuvant to restore β-lactam potency against A. baumannii or other Gram-negative bacteria harbouring homologs of AdeABC and YiaD proteins.
{"title":"Restoration of meropenem efficacy against multidrug-resistant Acinetobacter baumannii by green tea polyphenol EGCG: Dual targeting of efflux and porin pathways","authors":"Zijian Liang , Xiaoxu Chen , Ivanhoe K.H. Leung , Pangzhen Zhang","doi":"10.1016/j.phymed.2026.157871","DOIUrl":"10.1016/j.phymed.2026.157871","url":null,"abstract":"<div><h3>Background</h3><div><em>Acinetobacter baumannii</em> is a Gram-negative bacterial pathogen responsible for severe nosocomial infections. Carbapenems, including meropenem and imipenem, are β-lactam antibiotics commonly used as a last-resort treatment for infections caused by <em>A. baumannii</em>. While it is recognized that green tea polyphenols can enhance the efficacy of carbapenems against <em>A. baumannii</em>, the underlying mechanisms of this synergy remain undefined.</div></div><div><h3>Purpose</h3><div>This study aims to investigate the synergistic actions of green tea aqueous extract and its key bioactive component, epigallocatechin gallate (EGCG), in combination with meropenem against <em>A. baumannii</em> BAA-1605 and to elucidate the associated mechanisms.</div></div><div><h3>Methods</h3><div>The synergism with meropenem was assessed using antibiotic susceptibility testing and fractional inhibitory concentration index (FICI) analysis. The mechanism study included β-lactamase activity, Hoechst dye accumulation, and DiOC₂(3) membrane potential measurements. The effect of meropenem and/or EGCG on purified penicillin-binding protein 2 (PBP2) was also evaluated by nuclear magnetic resonance (NMR) spectroscopy and scanning electron microscopy (SEM). Transcriptomic sequencing and bioinformatic analyses were performed to elucidate global gene expression changes of <em>A. baumannii</em> BAA-1605 following exposure to meropenem and/or EGCG.</div></div><div><h3>Results</h3><div>Green tea aqueous extract synergized with meropenem against <em>A. baumannii</em> BAA-1605 by lowering the minimum inhibitory concentration (MIC) by 4-fold (128 to 32 μg/mL). EGCG was determined as the primary synergistic component in the extract (FICI = 0.375). The mechanism study showed that EGCG does not influence β-lactamase production or meropenem-mediated PBP2 inhibition but contributes to overcoming resistance by inhibiting efflux pump activity. Furthermore, transcriptomic analysis revealed that EGCG may suppress the AdeABC efflux system and enhance meropenem influx via a YiaD-dependent porin pathway.</div></div><div><h3>Conclusion</h3><div>This study presents a dual role of efflux inhibition and influx facilitation by EGCG in restoring meropenem efficacy, supporting its potential as a promising adjuvant to restore β-lactam potency against <em>A. baumannii</em> or other Gram-negative bacteria harbouring homologs of AdeABC and YiaD proteins.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"152 ","pages":"Article 157871"},"PeriodicalIF":8.3,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146080634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-23DOI: 10.1016/j.phymed.2026.157876
Fang Zhang , Haonan Xu , Yan Zuo , Ke Che , Yu Cui , Zhenhua Niu , Weiliang Cao , Tingting Sun , Yan Che , Hao Yu , Hao Chen
Background
Oligopeptides derived from dietary sources are regarded as ideal functional ingredients for nutritional interventions in diabetes due to their favorable bioavailability, target specificity, and safety profiles. Gynura divaricata (GD), a medicinal food plant, has shown hypoglycemic properties; however, the potential of GD-derived oligopeptides in glycemic control and their mechanistic underpinnings remain largely unexplored.
Purpose
This study aimed to investigate the anti-diabetic efficacy of GD oligopeptides and elucidate their mechanisms of action, particularly via the gut-microbiota-brain axis, in a streptozotocin (STZ)/high-fat diet-induced diabetic mouse model.
Methods
The therapeutic effects of GD oligopeptides were assessed through longitudinal blood glucose monitoring and systemic biochemical profiling. Organ-specific protection was evaluated via histopathological examination of the liver, pancreas, intestine, and brain. The influence on gluconeogenesis was analyzed by quantifying key glycogen metabolic proteins. Gut microbiota composition was assessed by sequencing, short-chain fatty acids (SCFAs) were measured, and appetite/energy metabolism regulators in the brain were detected. And a subset of diabetic mice was subjected to broad-spectrum antibiotic treatment to validate the effcst of gut microbes. Bioactive peptides were identified using LC-ESI-MS/MS, and molecular docking was performed to evaluate binding affinity to AKT.
Results
GD oligopeptides significantly ameliorated hyperglycemia, dyslipidemia, and insulin resistance in diabetic mice. They enhanced hepatic glycogen synthesis and suppressed gluconeogenesis through activation of the AKT/FoxO1 pathway, and reduced pancreatic apoptosis via modulation of Bcl-2/Bax expression. A total of 37 bioactive peptides were identified, with molecular docking confirming strong binding between GD oligopeptides and AKT. Importantly, GD oligopeptides restored intestinal barrier integrity, enriched SCFA-producing Lachnospiraceae, and promoted GPR43-dependent GLP-1 secretion, leading to hypothalamic GLP-1R activation, subsequent POMC upregulation, and NPY/AgRP suppression, collectively normalizing energy homeostasis. Crucially, all these therapeutic benefits were substantially reduced following antibiotic-induced microbiota depletion.
Conclusion
These findings underscore the potential of GD oligopeptides as a novel functional food ingredient for diabetes management by simultaneously targeting gluconeogenesis, gut microbiota, and central energy regulation, providing a mechanistic foundation for clinical translation.
{"title":"Oligopeptides from Gynura divaricata improve glycemic control via inhibition of gluconeogenesis and gut-brain axis regulation","authors":"Fang Zhang , Haonan Xu , Yan Zuo , Ke Che , Yu Cui , Zhenhua Niu , Weiliang Cao , Tingting Sun , Yan Che , Hao Yu , Hao Chen","doi":"10.1016/j.phymed.2026.157876","DOIUrl":"10.1016/j.phymed.2026.157876","url":null,"abstract":"<div><h3>Background</h3><div>Oligopeptides derived from dietary sources are regarded as ideal functional ingredients for nutritional interventions in diabetes due to their favorable bioavailability, target specificity, and safety profiles. Gynura divaricata (GD), a medicinal food plant, has shown hypoglycemic properties; however, the potential of GD-derived oligopeptides in glycemic control and their mechanistic underpinnings remain largely unexplored.</div></div><div><h3>Purpose</h3><div>This study aimed to investigate the anti-diabetic efficacy of GD oligopeptides and elucidate their mechanisms of action, particularly via the gut-microbiota-brain axis, in a streptozotocin (STZ)/high-fat diet-induced diabetic mouse model.</div></div><div><h3>Methods</h3><div>The therapeutic effects of GD oligopeptides were assessed through longitudinal blood glucose monitoring and systemic biochemical profiling. Organ-specific protection was evaluated via histopathological examination of the liver, pancreas, intestine, and brain. The influence on gluconeogenesis was analyzed by quantifying key glycogen metabolic proteins. Gut microbiota composition was assessed by sequencing, short-chain fatty acids (SCFAs) were measured, and appetite/energy metabolism regulators in the brain were detected. And a subset of diabetic mice was subjected to broad-spectrum antibiotic treatment to validate the effcst of gut microbes. Bioactive peptides were identified using LC-ESI-MS/MS, and molecular docking was performed to evaluate binding affinity to AKT.</div></div><div><h3>Results</h3><div>GD oligopeptides significantly ameliorated hyperglycemia, dyslipidemia, and insulin resistance in diabetic mice. They enhanced hepatic glycogen synthesis and suppressed gluconeogenesis through activation of the AKT/FoxO1 pathway, and reduced pancreatic apoptosis via modulation of Bcl-2/Bax expression. A total of 37 bioactive peptides were identified, with molecular docking confirming strong binding between GD oligopeptides and AKT. Importantly, GD oligopeptides restored intestinal barrier integrity, enriched SCFA-producing Lachnospiraceae, and promoted GPR43-dependent GLP-1 secretion, leading to hypothalamic GLP-1R activation, subsequent POMC upregulation, and NPY/AgRP suppression, collectively normalizing energy homeostasis. Crucially, all these therapeutic benefits were substantially reduced following antibiotic-induced microbiota depletion.</div></div><div><h3>Conclusion</h3><div>These findings underscore the potential of GD oligopeptides as a novel functional food ingredient for diabetes management by simultaneously targeting gluconeogenesis, gut microbiota, and central energy regulation, providing a mechanistic foundation for clinical translation.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"Article 157876"},"PeriodicalIF":8.3,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146192188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-23DOI: 10.1016/j.phymed.2026.157873
Xiaoyao Ma , Yang Zhang , Lishan Sun , Hongwei Zhao , Zihan Wang , Cui Hao , Wei Wang
Background
Influenza A virus (IAV) poses a serious threat to human health, and the increasing problem of drug resistance, along with the emergence of highly pathogenic strains, makes the development of new antiviral drugs urgent. Neferine, a dibenzylisoquinoline alkaloid derived from Nelumbo nucifera Gaertn plant, possesses multiple pharmacological activities, including anti-tumor, cardiovascular protection, neuroprotection, and anti-inflammatory effects.
Purpose
In this study, the anti-influenza A virus (IAV) activities and mechanisms of Neferine in vitro and in vivo were investigated in order to provide reference for the development of novel plant-derived anti-IAV drugs.
Methods
The antiviral activity of Neferine against IAV in vitro was evaluated using plaque reduction assay, RT-PCR, and western blot assay. The anti-IAV mechanisms of Neferine's were determined through mini-genome assay, DARTS assay, and SPR analysis. The in vivo anti-IAV effects of Neferine were investigated using a mouse pneumonia model combined with HE staining.
Results
Neferine exhibits broad-spectrum and highly effective antiviral activity against IAV at the cellular level. Neferine can "trap" the influenza virus in early endosomes, preventing its transport from early to late endosomes. Neferine primarily targets the NP protein of IAV to block its nuclear import and oligomerization. Neferine may bind to the Glu339 site of NP, which is a highly conserved. Additionally, it demonstrates significant protective effects against IAV infection in mice, notably improving the survival rates and accelerating weight recovery.
Conclusion
Neferine exhibits significant anti-IAV activity both in vitro and in vivo. It inhibits IAV infection by blocking the transport of IAV from early to late endosomes and inhibiting the functions of nucleoprotein (NP). These findings provide a substantial theoretical and experimental foundation for the development of Neferine as a novel anti-IAV agent.
{"title":"Inhibition of influenza a virus infection by natural isoquinoline alkaloid neferine targeting virus nucleoprotein","authors":"Xiaoyao Ma , Yang Zhang , Lishan Sun , Hongwei Zhao , Zihan Wang , Cui Hao , Wei Wang","doi":"10.1016/j.phymed.2026.157873","DOIUrl":"10.1016/j.phymed.2026.157873","url":null,"abstract":"<div><h3>Background</h3><div>Influenza A virus (IAV) poses a serious threat to human health, and the increasing problem of drug resistance, along with the emergence of highly pathogenic strains, makes the development of new antiviral drugs urgent. Neferine, a dibenzylisoquinoline alkaloid derived from <em>Nelumbo nucifera Gaertn</em> plant, possesses multiple pharmacological activities, including anti-tumor, cardiovascular protection, neuroprotection, and anti-inflammatory effects.</div></div><div><h3>Purpose</h3><div>In this study, the anti-influenza A virus (IAV) activities and mechanisms of Neferine <em>in vitro</em> and <em>in vivo</em> were investigated in order to provide reference for the development of novel plant-derived anti-IAV drugs.</div></div><div><h3>Methods</h3><div>The antiviral activity of Neferine against IAV <em>in vitro</em> was evaluated using plaque reduction assay, RT-PCR, and western blot assay. The anti-IAV mechanisms of Neferine's were determined through mini-genome assay, DARTS assay, and SPR analysis. The <em>in vivo</em> anti-IAV effects of Neferine were investigated using a mouse pneumonia model combined with HE staining.</div></div><div><h3>Results</h3><div>Neferine exhibits broad-spectrum and highly effective antiviral activity against IAV at the cellular level. Neferine can \"trap\" the influenza virus in early endosomes, preventing its transport from early to late endosomes. Neferine primarily targets the NP protein of IAV to block its nuclear import and oligomerization. Neferine may bind to the Glu339 site of NP, which is a highly conserved. Additionally, it demonstrates significant protective effects against IAV infection in mice, notably improving the survival rates and accelerating weight recovery.</div></div><div><h3>Conclusion</h3><div>Neferine exhibits significant anti-IAV activity both <em>in vitro</em> and <em>in vivo</em>. It inhibits IAV infection by blocking the transport of IAV from early to late endosomes and inhibiting the functions of nucleoprotein (NP). These findings provide a substantial theoretical and experimental foundation for the development of Neferine as a novel anti-IAV agent.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"152 ","pages":"Article 157873"},"PeriodicalIF":8.3,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146080630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-23DOI: 10.1016/j.phymed.2026.157877
Lingchen Wang , Yufeng Xing , Shengchun Liao , Yiting Zhou , Meng Wang , Chen Wang , Jing Wang
Background
Chronic kidney disease (CKD) is a significant risk factor for myocardial injury. Despite the proven clinical safety and efficacy of Shen Shuai II Recipe (SSR) in CKD management, and evidence of its renoprotective effects involving anti-inflammation and mitochondrial protection in experimental models, its potential to ameliorate CKD-related myocardial injury has not been investigated.
Purpose
We sought to determine whether SSR confers protection against CKD-induced myocardial injury by suppressing the IL-18/IL-18R1/MyD88 pathway.
Methods
A CKD model was established in rats by 5/6 (A/I) surgery. The rats were randomly assigned to receive daily gavage of normal saline, SSR, or Losartan potassium for 8 weeks. In vitro, IL-18-stimulated H9C2 cells were treated with different concentrations of SSR, or H9C2 cells were directly treated with different concentrations of 5/6 (A/I)+SSR rat serum. The effects of SSR and rat serum on the IL-18R1/MyD88-mediated inflammatory pathway and myocardial injury were investigated via immunoblotting, luminex chip assay, histopathology and fluorescence staining. Additionally, to further elucidate the mechanisms of SSR against myocardial injury, H9C2 cells were treated with 5/6 (A/I) or 5/6 (A/I)+SSR rat serum in the presence or absence of IL-18 neutralizing antibody. Next, we delivered IL-18R1 overexpression plasmid or MyD88 inhibitor into the IL-18-treated H9C2 cells with concomitant SSR administration. Finally, using a co-culture approach, we explored whether hypoxic renal tubular cells induced myocardial injury via the IL-18R1/MyD88 pathway.
Results
SSR inhibited IL-18R1/MyD88-mediated inflammatory response, decreased the expression of β-MHC and ANP hypertrophy marker proteins, and attenuated myocardial injury in myocardial tissues of 5/6 (A/I) rats or IL-18-treated H9C2 cells. The same effect was also observed in H9C2 cells treated with 5/6 (A/I)+SSR rat serum. Further investigation confirmed that SSR ameliorated myocardial injury through suppression of the IL-18R1/MyD88 inflammatory pathway. More crucially, co-culture experiments demonstrated that SSR alleviated crosstalk between hypoxic tubular cells and cardiomyocytes via IL-18/IL-18R1/MyD88 pathway, thereby mitigating myocardial injury.
Conclusion
SSR ameliorates CKD-induced myocardial injury through suppression of the IL-18/IL-18R1/MyD88 pathway.
{"title":"Shen-Shuai-Ⅱ Recipe ameliorates chronic kidney disease-induced myocardial injury via inhibition of the IL-18/IL-18R1/MyD88 pathway","authors":"Lingchen Wang , Yufeng Xing , Shengchun Liao , Yiting Zhou , Meng Wang , Chen Wang , Jing Wang","doi":"10.1016/j.phymed.2026.157877","DOIUrl":"10.1016/j.phymed.2026.157877","url":null,"abstract":"<div><h3>Background</h3><div>Chronic kidney disease (CKD) is a significant risk factor for myocardial injury. Despite the proven clinical safety and efficacy of Shen Shuai II Recipe (SSR) in CKD management, and evidence of its renoprotective effects involving anti-inflammation and mitochondrial protection in experimental models, its potential to ameliorate CKD-related myocardial injury has not been investigated.</div></div><div><h3>Purpose</h3><div>We sought to determine whether SSR confers protection against CKD-induced myocardial injury by suppressing the IL-18/IL-18R1/MyD88 pathway.</div></div><div><h3>Methods</h3><div>A CKD model was established in rats by 5/6 (A/I) surgery. The rats were randomly assigned to receive daily gavage of normal saline, SSR, or Losartan potassium for 8 weeks. <em>In vitro</em>, IL-18-stimulated H9C2 cells were treated with different concentrations of SSR, or H9C2 cells were directly treated with different concentrations of 5/6 (A/I)+SSR rat serum. The effects of SSR and rat serum on the IL-18R1/MyD88-mediated inflammatory pathway and myocardial injury were investigated via immunoblotting, luminex chip assay, histopathology and fluorescence staining. Additionally, to further elucidate the mechanisms of SSR against myocardial injury, H9C2 cells were treated with 5/6 (A/I) or 5/6 (A/I)+SSR rat serum in the presence or absence of IL-18 neutralizing antibody. Next, we delivered IL-18R1 overexpression plasmid or MyD88 inhibitor into the IL-18-treated H9C2 cells with concomitant SSR administration. Finally, using a co-culture approach, we explored whether hypoxic renal tubular cells induced myocardial injury via the IL-18R1/MyD88 pathway.</div></div><div><h3>Results</h3><div>SSR inhibited IL-18R1/MyD88-mediated inflammatory response, decreased the expression of β-MHC and ANP hypertrophy marker proteins, and attenuated myocardial injury in myocardial tissues of 5/6 (A/I) rats or IL-18-treated H9C2 cells. The same effect was also observed in H9C2 cells treated with 5/6 (A/I)+SSR rat serum. Further investigation confirmed that SSR ameliorated myocardial injury through suppression of the IL-18R1/MyD88 inflammatory pathway. More crucially, co-culture experiments demonstrated that SSR alleviated crosstalk between hypoxic tubular cells and cardiomyocytes via IL-18/IL-18R1/MyD88 pathway, thereby mitigating myocardial injury.</div></div><div><h3>Conclusion</h3><div>SSR ameliorates CKD-induced myocardial injury through suppression of the IL-18/IL-18R1/MyD88 pathway.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"152 ","pages":"Article 157877"},"PeriodicalIF":8.3,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146080568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-23DOI: 10.1016/j.phymed.2026.157882
Zhirui Zhang , Meijuan Zhang , Lili Chen , Wuqin Xu , Huifang Xu , Songsong Zou , Tao Wang , Lin Wang , Yingjie Zhao , Hao Jiao
Background
Renal fibrosis (RF) is a critical step in the progression of chronic kidney disease to end-stage renal failure, but its treatment remains highly challenging, highlighting the urgent clinical need for novel therapeutic strategies. Shikonin, a naturally derived compound, shows promise in attenuating the progression of RF. A thorough understanding of its specific molecular targets and mechanism of action is essential.
Purpose
This study elucidates the molecular mechanism through which Shikonin modulates HSPA1A to suppress ferroptosis and regulate lipid metabolism in RF.
Methods
A unilateral ureteral obstruction (UUO) mouse model was used to assess the antifibrotic effects of Shikonin. Efficacy was evaluated by analyzing renal pathomorphological changes and fibrosis indicators, and by using ELISA to detect the inflammation levels and kidney function. We integrated results from network pharmacology, transcriptomics, and non-targeted metabolomics to explore Shikonin's mechanism in renal fibrosis and verified it through experiments including qRT-PCR, immunofluorescence, western blot, transmission electron microscopy, ROS staining, and Bodipy staining. In vitro, human renal tubule epithelial cells (HK-2) were stimulated with TGF-β1 and then treated with Shikonin. Lipid-MS, CETSA, SPR, and molecular dynamics simulations were jointly employed to identify Shikonin's target. After knocking down this target in vivo using AAV, the effect of Shikonin on renal fibrosis was observed.
Results
Shikonin notably ameliorated histopathological lesions, renal dysfunction, pathological damage and fibrosis in UUO model. Transcriptomic and non-targeted metabolomics analyses indicated that lipid metabolism specifically the arachidonic acid (AA) pathway, is a key pathway through which Shikonin exerted its effects. Mechanistically, Shikonin directly bind to HSPA1A and, through this interaction, downregulated the expression of key AA-metabolizing enzymes ACSL4 and ALOX15, thereby suppressing lipid peroxidation and ferroptosis. This mechanism was confirmed both in vivo and in vitro. Crucially, the anti-fibrosis efficacy of Shikonin was abolished upon HSPA1A knockdown or inhibition, and could be functionally reversed by exogenous AA supplementation.
Conclusion
This study has revealed a novel mechanism by which Shikonin alleviates renal fibrosis: by targeting HSPA1A to reprogram AA metabolism and inhibit ferroptosis. These findings display the HSPA1A-AA metabolism-ferroptosis axis as a critical therapeutic pathway and provide a compelling mechanistic foundation for developing Shikonin as a promising candidate drug.
{"title":"Shikonin ameliorates renal fibrosis by targeting HSPA1A to regulate lipid metabolism and inhibit ferroptosis","authors":"Zhirui Zhang , Meijuan Zhang , Lili Chen , Wuqin Xu , Huifang Xu , Songsong Zou , Tao Wang , Lin Wang , Yingjie Zhao , Hao Jiao","doi":"10.1016/j.phymed.2026.157882","DOIUrl":"10.1016/j.phymed.2026.157882","url":null,"abstract":"<div><h3>Background</h3><div>Renal fibrosis (RF) is a critical step in the progression of chronic kidney disease to end-stage renal failure, but its treatment remains highly challenging, highlighting the urgent clinical need for novel therapeutic strategies. Shikonin, a naturally derived compound, shows promise in attenuating the progression of RF. A thorough understanding of its specific molecular targets and mechanism of action is essential.</div></div><div><h3>Purpose</h3><div>This study elucidates the molecular mechanism through which Shikonin modulates HSPA1A to suppress ferroptosis and regulate lipid metabolism in RF.</div></div><div><h3>Methods</h3><div>A unilateral ureteral obstruction (UUO) mouse model was used to assess the antifibrotic effects of Shikonin. Efficacy was evaluated by analyzing renal pathomorphological changes and fibrosis indicators, and by using ELISA to detect the inflammation levels and kidney function. We integrated results from network pharmacology, transcriptomics, and non-targeted metabolomics to explore Shikonin's mechanism in renal fibrosis and verified it through experiments including qRT-PCR, immunofluorescence, western blot, transmission electron microscopy, ROS staining, and Bodipy staining. In vitro, human renal tubule epithelial cells (HK-2) were stimulated with TGF-β1 and then treated with Shikonin. Lipid-MS, CETSA, SPR, and molecular dynamics simulations were jointly employed to identify Shikonin's target. After knocking down this target in vivo using AAV, the effect of Shikonin on renal fibrosis was observed.</div></div><div><h3>Results</h3><div>Shikonin notably ameliorated histopathological lesions, renal dysfunction, pathological damage and fibrosis in UUO model. Transcriptomic and non-targeted metabolomics analyses indicated that lipid metabolism specifically the arachidonic acid (AA) pathway, is a key pathway through which Shikonin exerted its effects. Mechanistically, Shikonin directly bind to HSPA1A and, through this interaction, downregulated the expression of key AA-metabolizing enzymes ACSL4 and ALOX15, thereby suppressing lipid peroxidation and ferroptosis. This mechanism was confirmed both in vivo and in vitro. Crucially, the anti-fibrosis efficacy of Shikonin was abolished upon HSPA1A knockdown or inhibition, and could be functionally reversed by exogenous AA supplementation.</div></div><div><h3>Conclusion</h3><div>This study has revealed a novel mechanism by which Shikonin alleviates renal fibrosis: by targeting HSPA1A to reprogram AA metabolism and inhibit ferroptosis. These findings display the HSPA1A-AA metabolism-ferroptosis axis as a critical therapeutic pathway and provide a compelling mechanistic foundation for developing Shikonin as a promising candidate drug.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"152 ","pages":"Article 157882"},"PeriodicalIF":8.3,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146080636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pelargonium sidoides DC. (Geraniaceae) has a long history of traditional use among indigenous peoples of Southern Africa for treating respiratory and gastrointestinal disorders. Its transformation into the modern pharmaceutical product Umckaloabo (EPs® 7630) exemplifies the transition from traditional medicine to evidence-based therapeutics.
Purpose
To provide a systematic analysis of P. sidoides, spanning from its botanical characteristics and ethnobotanical roots to its development as a regulated phytomedicine. The review focuses on the plant's unique phytochemical profile and provides a detailed synthesis of its molecular and systems-biological mechanisms of action, cultivation sustainability, and clinical efficacy in managing respiratory tract infections.
Study design and methods
A systematic search was conducted across PubMed, Scopus, and Cochrane Library up to December 2025 following PRISMA guidelines. Sources included scientific articles, pharmacopoeias, patents, and ethnobotanical records in English and Ukrainian.
Results
The systematic synthesis of identified records characterizes the chemical diversity of P. sidoides, focusing on specialized metabolites such as highly substituted benzopyranones, prodelphinidins, and unique coumarin sulfates. The review discusses modern cultivation practices, sustainability issues, and comparative extraction techniques, while analytical methods such as HPLC, LC-MS, and TLC for standardization are summarized. The pharmacological profile is defined by multi-target activity, encompassing immunomodulatory, antibacterial, and antiviral effects, including studies on SARS-CoV-2 and other respiratory pathogens. Analysis of available clinical data validates the therapeutic use of P. sidoides root preparations for managing acute bronchitis, rhinosinusitis, and tonsillopharyngitis.
Conclusion
This study demonstrates that the integration of P. sidoides into modern healthcare is supported by the synergy between traditional knowledge and molecular and clinical validation. By mapping the developmental trajectory — from wild harvesting to systems-biological evidence — this review identifies P. sidoides as a model for the pharmaceutical translation of ethnobotanical resources into standardized, evidence-based phytomedicines.
{"title":"Pelargonium sidoides - from ethnopharmacology to evidence-based medicine: a systematic review","authors":"Oksana Honchar , Olha Мykhailenko , Olha Holovchenko , Victoriya Georgiyants","doi":"10.1016/j.phymed.2026.157880","DOIUrl":"10.1016/j.phymed.2026.157880","url":null,"abstract":"<div><h3>Background</h3><div><em>Pelargonium sidoides</em> DC. (Geraniaceae) has a long history of traditional use among indigenous peoples of Southern Africa for treating respiratory and gastrointestinal disorders. Its transformation into the modern pharmaceutical product Umckaloabo (EPs® 7630) exemplifies the transition from traditional medicine to evidence-based therapeutics.</div></div><div><h3>Purpose</h3><div>To provide a systematic analysis of <em>P. sidoides</em>, spanning from its botanical characteristics and ethnobotanical roots to its development as a regulated phytomedicine. The review focuses on the plant's unique phytochemical profile and provides a detailed synthesis of its molecular and systems-biological mechanisms of action, cultivation sustainability, and clinical efficacy in managing respiratory tract infections.</div></div><div><h3>Study design and methods</h3><div>A systematic search was conducted across PubMed, Scopus, and Cochrane Library up to December 2025 following PRISMA guidelines. Sources included scientific articles, pharmacopoeias, patents, and ethnobotanical records in English and Ukrainian.</div></div><div><h3>Results</h3><div>The systematic synthesis of identified records characterizes the chemical diversity of <em>P. sidoides</em>, focusing on specialized metabolites such as highly substituted benzopyranones, prodelphinidins, and unique coumarin sulfates. The review discusses modern cultivation practices, sustainability issues, and comparative extraction techniques, while analytical methods such as HPLC, LC-MS, and TLC for standardization are summarized. The pharmacological profile is defined by multi-target activity, encompassing immunomodulatory, antibacterial, and antiviral effects, including studies on SARS-CoV-2 and other respiratory pathogens. Analysis of available clinical data validates the therapeutic use of <em>P. sidoides</em> root preparations for managing acute bronchitis, rhinosinusitis, and tonsillopharyngitis.</div></div><div><h3>Conclusion</h3><div>This study demonstrates that the integration of <em>P. sidoides</em> into modern healthcare is supported by the synergy between traditional knowledge and molecular and clinical validation. By mapping the developmental trajectory — from wild harvesting to systems-biological evidence — this review identifies <em>P. sidoides</em> as a model for the pharmaceutical tran<strong>s</strong>lation of ethnobotanical resources into standardized, evidence-based phytomedicines.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"Article 157880"},"PeriodicalIF":8.3,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146137824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-22DOI: 10.1016/j.phymed.2026.157868
Maciej Klimiuk , Małgorzata Jefimow , Hanna Kletkiewicz
Background
Perinatal hypoxia–ischemia is a major cause of long-term neurological impairments in newborns, with ferroptosis recognized as a key mechanism of injury. Cannabidiol (CBD) is a non-psychoactive phytocannabinoid with antioxidant and neuroprotective properties. CBD is a potential modulator of hypoxic–ischemic brain damage, however its effects on ferroptosis-related pathways remain unclear.
Purpose
In this study, we examined whether CBD can alleviate ferroptosis-associated damage in differentiated human neuroblastoma (neuron-like SH-SY5Y) cell model of hypoxic–ischemic injury.
Study Design
Differentiated human neuroblastoma cells were exposed to oxygen–glucose deprivation (OGD) to simulate hypoxic–ischemic conditions.
Methods
Neuron-like SH-SY5Y cells were subjected to OGD to induce hypoxic–ischemic injury. CBD was applied to assess its neuroprotective effects. Oxidative stress markers, antioxidant enzyme activity, transcription factor activation Nrf2 (nuclear factor erythroid 2-related factor 2), iron metabolism proteins (ferroportin), hypoxia-inducible factor 1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF) expression were evaluated.
Results
CBD application significantly reduced oxidative stress by improving antioxidant capacity and lowering total oxidant status. CBD also preserved the expression and enzymatic activity of glutathione peroxidase 4, a central enzyme protecting against lipid peroxidation, and enhanced the activation of Nrf2, a key regulator of antioxidant defence. Additionally, CBD prevented OGD-induced downregulation of ferroportin, potentially supporting iron efflux and reducing ferroptotic risk. HIF-1α and its downstream target VEGF were upregulated under hypoxic conditions, and CBD further enhanced VEGF expression.
Conclusion
CBD mitigates ferroptosis by modulating redox balance, antioxidant defence, and iron metabolism, supporting its potential role as a therapeutic strategy for neonatal hypoxic–ischemic brain injury.
{"title":"Ferroptosis under fire: cannabidiol mitigates iron-dependent injury in differentiated human neuroblastoma cells following oxygen-glucose deprivation","authors":"Maciej Klimiuk , Małgorzata Jefimow , Hanna Kletkiewicz","doi":"10.1016/j.phymed.2026.157868","DOIUrl":"10.1016/j.phymed.2026.157868","url":null,"abstract":"<div><h3>Background</h3><div>Perinatal hypoxia–ischemia is a major cause of long-term neurological impairments in newborns, with ferroptosis recognized as a key mechanism of injury. Cannabidiol (CBD) is a non-psychoactive phytocannabinoid with antioxidant and neuroprotective properties. CBD is a potential modulator of hypoxic–ischemic brain damage, however its effects on ferroptosis-related pathways remain unclear.</div></div><div><h3>Purpose</h3><div>In this study, we examined whether CBD can alleviate ferroptosis-associated damage in differentiated human neuroblastoma (neuron-like SH-SY5Y) cell model of hypoxic–ischemic injury.</div></div><div><h3>Study Design</h3><div>Differentiated human neuroblastoma cells were exposed to oxygen–glucose deprivation (OGD) to simulate hypoxic–ischemic conditions.</div></div><div><h3>Methods</h3><div>Neuron-like SH-SY5Y cells were subjected to OGD to induce hypoxic–ischemic injury. CBD was applied to assess its neuroprotective effects. Oxidative stress markers, antioxidant enzyme activity, transcription factor activation Nrf2 (nuclear factor erythroid 2-related factor 2), iron metabolism proteins (ferroportin), hypoxia-inducible factor 1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF) expression were evaluated.</div></div><div><h3>Results</h3><div>CBD application significantly reduced oxidative stress by improving antioxidant capacity and lowering total oxidant status. CBD also preserved the expression and enzymatic activity of glutathione peroxidase 4, a central enzyme protecting against lipid peroxidation, and enhanced the activation of Nrf2, a key regulator of antioxidant defence. Additionally, CBD prevented OGD-induced downregulation of ferroportin, potentially supporting iron efflux and reducing ferroptotic risk. HIF-1α and its downstream target VEGF were upregulated under hypoxic conditions, and CBD further enhanced VEGF expression.</div></div><div><h3>Conclusion</h3><div>CBD mitigates ferroptosis by modulating redox balance, antioxidant defence, and iron metabolism, supporting its potential role as a therapeutic strategy for neonatal hypoxic–ischemic brain injury.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"152 ","pages":"Article 157868"},"PeriodicalIF":8.3,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146047170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-22DOI: 10.1016/j.phymed.2026.157881
Yiming Li , Wenxin Zou , Yan Zhang , Zhongwen Qi , Qing Wang , Zijun Jia , Qingbing Zhou , Fengqin Xu
Background
Atherosclerosis (AS) is a chronic disease characterized by lipid deposition in the vascular intima. As the pathological basis of cardiovascular diseases, AS represents a major contributor to global morbidity and mortality. While Gualou Huoxue Jiedu Decoction (GHJD) has been widely used in clinical practice for the treatment of AS, the molecular mechanisms remain unclear.
Purpose
To investigate the anti-atherosclerotic effects and underlying mechanisms of GHJD.
Methods
Apoe-/- mice were treated with GHJD to evaluate its effects on plaque formation, lipid profiles, and inflammatory responses. The main compounds in GHJD were identified using UHPLC-Q-Orbitrap HRMS. Integrated analyses of network pharmacology, methyl-capture sequencing (MC-seq), and RNA-seq were performed to elucidate the molecular mechanisms of GHJD. In vitro experiments were conducted to validate its mechanism of action.
Results
GHJD alleviated plaque formation, improved lipid metabolism, and suppressed inflammation in vivo. Multi-omics analysis revealed that DNA methylation of Mfap4 could be a pivotal target of GHJD efficacy. In vitro assays confirmed that GHJD suppressed Mfap4 transcription and translation, leading to downregulation of integrin receptor family expression and inhibition of VSMC phenotypic switching.
Conclusion
GHJD exerts anti-atherosclerotic effects through epigenetic modulation of Mfap4 and downstream integrin/FAK signaling pathway, thereby inhibiting VSMC phenotypic switching. These findings provide pharmacological evidence supporting GHJD as a potential therapy for AS and, for the first time, validate MFAP4 as a pharmacological target, offering new insights into AS prevention and treatment.
{"title":"Gualou Huoxue Jiedu Decoction inhibits VSMC phenotypic switching to alleviate atherosclerosis via promoting Mfap4 DNA methylation","authors":"Yiming Li , Wenxin Zou , Yan Zhang , Zhongwen Qi , Qing Wang , Zijun Jia , Qingbing Zhou , Fengqin Xu","doi":"10.1016/j.phymed.2026.157881","DOIUrl":"10.1016/j.phymed.2026.157881","url":null,"abstract":"<div><h3>Background</h3><div>Atherosclerosis (AS) is a chronic disease characterized by lipid deposition in the vascular intima. As the pathological basis of cardiovascular diseases, AS represents a major contributor to global morbidity and mortality. While Gualou Huoxue Jiedu Decoction (GHJD) has been widely used in clinical practice for the treatment of AS, the molecular mechanisms remain unclear.</div></div><div><h3>Purpose</h3><div>To investigate the anti-atherosclerotic effects and underlying mechanisms of GHJD.</div></div><div><h3>Methods</h3><div>Apoe<sup>-/-</sup> mice were treated with GHJD to evaluate its effects on plaque formation, lipid profiles, and inflammatory responses. The main compounds in GHJD were identified using UHPLC-Q-Orbitrap HRMS. Integrated analyses of network pharmacology, methyl-capture sequencing (MC-seq), and RNA-seq were performed to elucidate the molecular mechanisms of GHJD. In vitro experiments were conducted to validate its mechanism of action.</div></div><div><h3>Results</h3><div>GHJD alleviated plaque formation, improved lipid metabolism, and suppressed inflammation in vivo. Multi-omics analysis revealed that DNA methylation of Mfap4 could be a pivotal target of GHJD efficacy. In vitro assays confirmed that GHJD suppressed <em>Mfap4</em> transcription and translation, leading to downregulation of integrin receptor family expression and inhibition of VSMC phenotypic switching.</div></div><div><h3>Conclusion</h3><div>GHJD exerts anti-atherosclerotic effects through epigenetic modulation of <em>Mfap4</em> and downstream integrin/FAK signaling pathway, thereby inhibiting VSMC phenotypic switching. These findings provide pharmacological evidence supporting GHJD as a potential therapy for AS and, for the first time, validate MFAP4 as a pharmacological target, offering new insights into AS prevention and treatment.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"Article 157881"},"PeriodicalIF":8.3,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146192189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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