Pub Date : 2025-03-02DOI: 10.1016/j.jep.2025.119568
Yuhe Zhou , Wen Su , Mengzhen Xu , Aijun Zhang , Shaoli Li , Hong Guo , Kai Gong , Kaihui Lu , Xin Yu , Jiang Zhu , Qingjun Zhu , Chuanguo Liu
Ethnopharmacological relevance
Maimendong decoction (MMDD) originates from the ancient Chinese medical text Synopsis of the Golden Chamber and is a well-established remedy for treating lung diseases. It has demonstrated efficacy in the long-term clinical management of idiopathic pulmonary fibrosis (IPF); however, its underlying mechanisms remain unclear.
Aim of the study
This study investigates whether MMDD alleviates IPF by reducing type 2 alveolar epithelial cell (AEC2) senescence and enhancing mitochondrial autophagy. It also explores whether these effects are mediated through the PTEN-induced putative kinase 1 (PINK1)/Parkinson juvenile disease protein 2 (Parkin) pathway.
Materials and methods
An IPF mouse model was established with bleomycin (BLM). Mice were administered MMDD, pirfenidone (PFD), or saline for 7 or 28 days. Body weight, lung coefficient, and lung appearance were monitored, and lung tissue pathology was assessed. The expression levels of p53, p21, p16, SA-β-gal activity, and senescence-associated secretory phenotype (SASP) markers were measured. Ultrastructural changes in AEC2 mitochondria were analyzed using transmission electron microscopy. Protein levels of autophagy markers sequestosome-1 and light chain 3 were assessed. The protein levels of PINK1, Parkin, and phosphorylated Parkin were further assessed using network pharmacology analysis and molecular docking technology.
Results
MMDD alleviated BLM-induced IPF by improving body weight, lung appearance, and histopathological features. It reduced AEC2 senescence markers, including p53, p21, p16, SA-β-gal, and SASP, while enhancing mitochondrial autophagy and repairing mitochondrial damage. Network pharmacology and molecular docking identified PINK1 as a major target, and Western blot (WB) analysis confirmed that MMDD regulates the PINK1/Parkin signaling pathway in the treatment of IPF.
Conclusions
MMDD regulates the PINK1/Parkin signaling pathway, alleviates AEC2 senescence, and enhances mitochondrial autophagy, providing significant therapeutic potential for IPF treatment.
{"title":"Maimendong decoction modulates the PINK1/Parkin signaling pathway alleviates type 2 alveolar epithelial cells senescence and enhances mitochondrial autophagy to offer potential therapeutic effects for idiopathic pulmonary fibrosis","authors":"Yuhe Zhou , Wen Su , Mengzhen Xu , Aijun Zhang , Shaoli Li , Hong Guo , Kai Gong , Kaihui Lu , Xin Yu , Jiang Zhu , Qingjun Zhu , Chuanguo Liu","doi":"10.1016/j.jep.2025.119568","DOIUrl":"10.1016/j.jep.2025.119568","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Maimendong decoction (MMDD) originates from the ancient Chinese medical text <em>Synopsis of the Golden Chamber</em> and is a well-established remedy for treating lung diseases. It has demonstrated efficacy in the long-term clinical management of idiopathic pulmonary fibrosis (IPF); however, its underlying mechanisms remain unclear.</div></div><div><h3>Aim of the study</h3><div>This study investigates whether MMDD alleviates IPF by reducing type 2 alveolar epithelial cell (AEC2) senescence and enhancing mitochondrial autophagy. It also explores whether these effects are mediated through the PTEN-induced putative kinase 1 (PINK1)/Parkinson juvenile disease protein 2 (Parkin) pathway.</div></div><div><h3>Materials and methods</h3><div>An IPF mouse model was established with bleomycin (BLM). Mice were administered MMDD, pirfenidone (PFD), or saline for 7 or 28 days. Body weight, lung coefficient, and lung appearance were monitored, and lung tissue pathology was assessed. The expression levels of p53, p21, p16, SA-β-gal activity, and senescence-associated secretory phenotype (SASP) markers were measured. Ultrastructural changes in AEC2 mitochondria were analyzed using transmission electron microscopy. Protein levels of autophagy markers sequestosome-1 and light chain 3 were assessed. The protein levels of PINK1, Parkin, and phosphorylated Parkin were further assessed using network pharmacology analysis and molecular docking technology.</div></div><div><h3>Results</h3><div>MMDD alleviated BLM-induced IPF by improving body weight, lung appearance, and histopathological features. It reduced AEC2 senescence markers, including p53, p21, p16, SA-β-gal, and SASP, while enhancing mitochondrial autophagy and repairing mitochondrial damage. Network pharmacology and molecular docking identified PINK1 as a major target, and Western blot (WB) analysis confirmed that MMDD regulates the PINK1/Parkin signaling pathway in the treatment of IPF.</div></div><div><h3>Conclusions</h3><div>MMDD regulates the PINK1/Parkin signaling pathway, alleviates AEC2 senescence, and enhances mitochondrial autophagy, providing significant therapeutic potential for IPF treatment.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"345 ","pages":"Article 119568"},"PeriodicalIF":4.8,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143548723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01DOI: 10.1016/j.jep.2025.119566
Qinwei Zheng , Yongming Zhou , Ming Han , Mengyuan Zhang , Nan Zhang , Shuangshuang Fang , Hongwei Wang , Hongmei Ni , Weiwei Hao , Shengquan Fang , Qilong Chen
<div><h3>Ethnopharmacological relevance</h3><div>Gastroesophageal reflux disease (GERD) is a common gastrointestinal disease Shugan-Hewei (SGHW) formula is an extensively used traditional herbal decoction for treating GERD, which can significantly improve the clinical symptoms, quality of life, anxiety and depression status, etc.</div></div><div><h3>Aim of the study</h3><div>To elucidate the potential targets and pathways of SGHW in treating GERD by employing an integrative approach involving transcriptomics-based analysis combined with accurate network pharmacology.</div></div><div><h3>Materials and methods</h3><div>First, we conducted animal experiments to investigate the effect of SGHW on GERD. Then, transcriptome sequencing was used to reveal the differentially expressed genes (DEGs). Meanwhile, the main ingredients of SGHW were identified by UPLC/Q-TOF MS, and the compound-target network was constructed. We integrated the DEGs with the compound-target network to identify core DEGs, which were used to establish a protein-protein interaction (PPI) network and GO/KEGG pathways. After that, we mapped the core PPI network and the core pathway to pinpoint the critical targets. Similarly, we mapped the critical targets and the compound-target network to discover core compound-target pairs and employed molecular docking techniques to elucidate the interactions between these pairs. Finally, key signaling pathways and their targets were validated by immunoblotting and immunofluorescence.</div></div><div><h3>Results</h3><div>The application of the SGHW resulted in a notable enhancement of the phenotype in the mixed reflux rat model. Transcriptomic analysis revealed a total of 1388 DEGs, among which 801 were upregulated and 587 were downregulated. According to Lipinski's “rule of 5”, 45 compounds were extracted from the SGHW samples using UPLC/Q-TOF MS. Through online database searches, we identified 1131 potential targets for the active compounds and constructed a compound-target network based on these potential targets. Subsequently, we mapped the DEGs associated with the compound-target network, identifying 29 compounds targeting 119 core DEGs. KEGG pathway analysis of these core DEGs highlighted the chemical carcinogenesis-reactive oxygen species (ROS) signaling pathway as one of the most prominent pathways involved. We then established a PPI network based on these core DEGs and mapped the core PPI network alongside ROS pathway-related targets, identifying HMOX1 and CYP1A1 as the critical targets. Further analysis pinpointed key compound-target pairs, including <em>Berberine</em> targeting CYP1A1, and <em>Honokiol, Tangeretin, α-Cyperone, 1-O-Acetylbritannilactone, Rotundine B, Cyperolone</em> targeting HMOX1. These findings were validated through immunoblotting and immunofluorescence assays conducted <em>in vivo</em>.</div></div><div><h3>Conclusion</h3><div>In this study, we identified the monomers recipe derived from SGHW, including <em>Berberine<
{"title":"A novel ingredients recipe derived from Shugan-Hewei Formula targeting chemical carcinogenesis-ROS signaling pathway treated gastroesophageal reflux disease","authors":"Qinwei Zheng , Yongming Zhou , Ming Han , Mengyuan Zhang , Nan Zhang , Shuangshuang Fang , Hongwei Wang , Hongmei Ni , Weiwei Hao , Shengquan Fang , Qilong Chen","doi":"10.1016/j.jep.2025.119566","DOIUrl":"10.1016/j.jep.2025.119566","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Gastroesophageal reflux disease (GERD) is a common gastrointestinal disease Shugan-Hewei (SGHW) formula is an extensively used traditional herbal decoction for treating GERD, which can significantly improve the clinical symptoms, quality of life, anxiety and depression status, etc.</div></div><div><h3>Aim of the study</h3><div>To elucidate the potential targets and pathways of SGHW in treating GERD by employing an integrative approach involving transcriptomics-based analysis combined with accurate network pharmacology.</div></div><div><h3>Materials and methods</h3><div>First, we conducted animal experiments to investigate the effect of SGHW on GERD. Then, transcriptome sequencing was used to reveal the differentially expressed genes (DEGs). Meanwhile, the main ingredients of SGHW were identified by UPLC/Q-TOF MS, and the compound-target network was constructed. We integrated the DEGs with the compound-target network to identify core DEGs, which were used to establish a protein-protein interaction (PPI) network and GO/KEGG pathways. After that, we mapped the core PPI network and the core pathway to pinpoint the critical targets. Similarly, we mapped the critical targets and the compound-target network to discover core compound-target pairs and employed molecular docking techniques to elucidate the interactions between these pairs. Finally, key signaling pathways and their targets were validated by immunoblotting and immunofluorescence.</div></div><div><h3>Results</h3><div>The application of the SGHW resulted in a notable enhancement of the phenotype in the mixed reflux rat model. Transcriptomic analysis revealed a total of 1388 DEGs, among which 801 were upregulated and 587 were downregulated. According to Lipinski's “rule of 5”, 45 compounds were extracted from the SGHW samples using UPLC/Q-TOF MS. Through online database searches, we identified 1131 potential targets for the active compounds and constructed a compound-target network based on these potential targets. Subsequently, we mapped the DEGs associated with the compound-target network, identifying 29 compounds targeting 119 core DEGs. KEGG pathway analysis of these core DEGs highlighted the chemical carcinogenesis-reactive oxygen species (ROS) signaling pathway as one of the most prominent pathways involved. We then established a PPI network based on these core DEGs and mapped the core PPI network alongside ROS pathway-related targets, identifying HMOX1 and CYP1A1 as the critical targets. Further analysis pinpointed key compound-target pairs, including <em>Berberine</em> targeting CYP1A1, and <em>Honokiol, Tangeretin, α-Cyperone, 1-O-Acetylbritannilactone, Rotundine B, Cyperolone</em> targeting HMOX1. These findings were validated through immunoblotting and immunofluorescence assays conducted <em>in vivo</em>.</div></div><div><h3>Conclusion</h3><div>In this study, we identified the monomers recipe derived from SGHW, including <em>Berberine<","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"344 ","pages":"Article 119566"},"PeriodicalIF":4.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01DOI: 10.1016/j.jep.2025.119574
Huan Wang , Ting Liu , Chao Liao , Fangqi Liang , Li Tian
Ethnopharmacological relevance
House dust mite (HDM)-induced allergic rhinitis (AR) is a significant global health issue, leading to considerable illness and disability worldwide. In traditional Chinese medicine, Modified Yupingfeng Nasal Spray (MYN) is believed to support defense systems, and regulate immune defense systems.
Aim of the study
Previous research has shown that both MYN and mometasone furoate nasal spray (MFN) can alleviate symptoms of HDM-induced AR. However, the safety and onset time of MYN compared to MFN for treating HDM-induced AR remain unclear. This study aimed to explore the onset time, safety, and potential mechanisms of MYN and MFN in the treatment of HDM-induced AR.
Methods
In a multicenter, randomized, open-label, parallel-arm trial, 207 patients with AR who tested positive for HDMs allergens (≥2+) were randomly assigned to receive either MYN or MFN treatment. The primary endpoint was the onset time of AR remission. Additionally, 9 patients were randomly selected from each group to investigate potential mechanisms.
Results
Compared to MFN (12.05 ± 1.07 days), MYN (21.56 ± 1.92 days) had a slower onset time in controlling AR symptoms. However, there was no significant difference in cumulative remission of AR between MYN and MFN after 77 days of treatment. At the end of the study, no significant difference in disease control rates was observed between MYN (89.00%) and MFN (96.04%) (P > 0.05). MYN treatment significantly increased PTEN mRNA levels in nasal mucosal epithelial cells and serum IL-10, while reducing NF-κΒ and TSLP levels in nasal lavage fluid, as well as serum IL-6 and TNF-α (P < 0.05).
Conclusions
Both MYN and MFN effectively reduce AR symptoms; however, MFN acts more quickly than MYN in relieving these symptoms, while MYN is associated with fewer side effects. The therapeutic effects of MYN may be linked to the regulation of the PTEN/NF-κB/TSLP signaling pathway.
{"title":"Safety and onset time of modified Yupingfeng nasal spray versus mometasone furoate nasal spray on house dust mites-induced moderate to severe allergic rhinitis: A prospective, multicenter, randomized, open-label, parallel-group clinical trial","authors":"Huan Wang , Ting Liu , Chao Liao , Fangqi Liang , Li Tian","doi":"10.1016/j.jep.2025.119574","DOIUrl":"10.1016/j.jep.2025.119574","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>House dust mite (HDM)-induced allergic rhinitis (AR) is a significant global health issue, leading to considerable illness and disability worldwide. In traditional Chinese medicine, Modified Yupingfeng Nasal Spray (MYN) is believed to support defense systems, and regulate immune defense systems.</div></div><div><h3>Aim of the study</h3><div>Previous research has shown that both MYN and mometasone furoate nasal spray (MFN) can alleviate symptoms of HDM-induced AR. However, the safety and onset time of MYN compared to MFN for treating HDM-induced AR remain unclear. This study aimed to explore the onset time, safety, and potential mechanisms of MYN and MFN in the treatment of HDM-induced AR.</div></div><div><h3>Methods</h3><div>In a multicenter, randomized, open-label, parallel-arm trial, 207 patients with AR who tested positive for HDMs allergens (≥2+) were randomly assigned to receive either MYN or MFN treatment. The primary endpoint was the onset time of AR remission. Additionally, 9 patients were randomly selected from each group to investigate potential mechanisms.</div></div><div><h3>Results</h3><div>Compared to MFN (12.05 ± 1.07 days), MYN (21.56 ± 1.92 days) had a slower onset time in controlling AR symptoms. However, there was no significant difference in cumulative remission of AR between MYN and MFN after 77 days of treatment. At the end of the study, no significant difference in disease control rates was observed between MYN (89.00%) and MFN (96.04%) (<em>P</em> > 0.05). MYN treatment significantly increased PTEN mRNA levels in nasal mucosal epithelial cells and serum IL-10, while reducing NF-κΒ and TSLP levels in nasal lavage fluid, as well as serum IL-6 and TNF-α (<em>P</em> < 0.05).</div></div><div><h3>Conclusions</h3><div>Both MYN and MFN effectively reduce AR symptoms; however, MFN acts more quickly than MYN in relieving these symptoms, while MYN is associated with fewer side effects. The therapeutic effects of MYN may be linked to the regulation of the PTEN/NF-κB/TSLP signaling pathway.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"344 ","pages":"Article 119574"},"PeriodicalIF":4.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-28DOI: 10.1016/j.jep.2025.119572
Keyan Chai , Wei Wang , Haojia Wang , Tong Zhang , Jiying Zhou , Jiaqi Li , Siyun Yang , Chuanqi Qiao , Xinjie Guo , Xiaomeng Zhang , Jiarui Wu
Ethnopharmacological relevance
Biyuan Tongqiao granules (BYTQ granules) is a commonly used traditional Chinese medicine for the treatment of allergic rhinitis (AR), made from 14 herbal ingredients. Studies have shown that this medicine can increase the permeability of nasal capillaries, inhibit inflammatory mediators, and help alleviate the symptoms of rhinitis, proving its effectiveness in treating AR.
Aim of the study
This study aimed to assess the effectiveness and safety of BYTQ granules as an adjunctive treatment for AR.
Materials and methods
Seven databases were searched to identify eligible randomized controlled trials (RCTs) involving the BYTQ granules therapy for AR until October 1, 2024. The primary outcome included the clinical efficacy, and the secondary outcomes were symptom scores and inflammatory cytokines. We assessed the risk of bias utilizing the Cochrane ROB2, performed the analysis using RevMan 5.3 software and assessed the quality of evidence through the GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology.
Results
The systematic review and meta-analysis comprised 38 RCTs with a total of 4228 participants. BYTQ granules paired with Western Medicine (WM) were superior to WM alone in individuals with AR, as showed by higher clinical efficacy (RR = 1.17, 95%CI: 1.14–1.20, P < 0.00001), more pronounced reductions in nasal symptom scores and greater decreases in inflammatory cytokines, including IL-4 (SMD = −1.30, 95%CI: −1.62 ∼ −0.98, P < 0.00001) and TNF-α levels. Moreover, the TSA analysis reinforced these findings by demonstrating a lower incidence of adverse reactions.
Conclusion
BYTQ granules with WM demonstrated superior efficacy in treating AR, including a lower recurrence rate based on the available results. Nonetheless, further RCTs are required to validate these results more conclusively.
{"title":"Efficacy and safety of biyuan tongqiao granules in the treatment of allergic rhinitis: A meta-analysis of randomized controlled trials","authors":"Keyan Chai , Wei Wang , Haojia Wang , Tong Zhang , Jiying Zhou , Jiaqi Li , Siyun Yang , Chuanqi Qiao , Xinjie Guo , Xiaomeng Zhang , Jiarui Wu","doi":"10.1016/j.jep.2025.119572","DOIUrl":"10.1016/j.jep.2025.119572","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Biyuan Tongqiao granules (BYTQ granules) is a commonly used traditional Chinese medicine for the treatment of allergic rhinitis (AR), made from 14 herbal ingredients. Studies have shown that this medicine can increase the permeability of nasal capillaries, inhibit inflammatory mediators, and help alleviate the symptoms of rhinitis, proving its effectiveness in treating AR.</div></div><div><h3>Aim of the study</h3><div>This study aimed to assess the effectiveness and safety of BYTQ granules as an adjunctive treatment for AR.</div></div><div><h3>Materials and methods</h3><div>Seven databases were searched to identify eligible randomized controlled trials (RCTs) involving the BYTQ granules therapy for AR until October 1, 2024. The primary outcome included the clinical efficacy, and the secondary outcomes were symptom scores and inflammatory cytokines. We assessed the risk of bias utilizing the Cochrane ROB2, performed the analysis using RevMan 5.3 software and assessed the quality of evidence through the GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology.</div></div><div><h3>Results</h3><div>The systematic review and meta-analysis comprised 38 RCTs with a total of 4228 participants. BYTQ granules paired with Western Medicine (WM) were superior to WM alone in individuals with AR, as showed by higher clinical efficacy (<em>RR</em> = 1.17, 95%<em>CI</em>: 1.14–1.20, <em>P</em> < 0.00001), more pronounced reductions in nasal symptom scores and greater decreases in inflammatory cytokines, including IL-4 (<em>SMD</em> = −1.30, 95%<em>CI</em>: −1.62 ∼ −0.98, <em>P</em> < 0.00001) and TNF-α levels. Moreover, the TSA analysis reinforced these findings by demonstrating a lower incidence of adverse reactions.</div></div><div><h3>Conclusion</h3><div>BYTQ granules with WM demonstrated superior efficacy in treating AR, including a lower recurrence rate based on the available results. Nonetheless, further RCTs are required to validate these results more conclusively.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"344 ","pages":"Article 119572"},"PeriodicalIF":4.8,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-28DOI: 10.1016/j.jep.2025.119549
Bingjie Luo , Ziwen Liang , Weiwen Lin , Yan Li , Wenqiang Zhong , Donghui Bai , Xueling Hu , Ji Xie , Xiaoyun Li , Panpan Wang , Xiaofeng Zhu , Ronghua Zhang , Li Yang
Ethnopharmacological relevance
Rehmanniae Radix Praeparata (RRP), a widely used traditional Chinese medicine and a processed form of Rehmannia glutinosa, is primarily utilized to supplement kidney function and promote bone health. Clinical evidence suggests that RRP exhibits significant efficacy in the treatment of osteoporosis (OP). However, the precise mechanisms underlying its therapeutic effects remain incompletely understood.
Aim of the study
OP is a systemic skeletal disorder characterized by reduced bone density and quality, leading to an increased risk of fractures. The aim of this study is to evaluate the effectiveness and underlying mechanisms of RRP in treating OP.
Materials and methods
Ovariectomized (OVX) rats were administered RRP aqueous extract via gavage for three months. After the treatment period, femoral microstructure and osteogenic protein levels were assessed to evaluate the efficacy of RRP. Serum exosomes (Exos) derived from different groups of rats were isolated and characterized. The levels of miR-29a-3p in serum-derived Exos and femoral tissue were quantified. Subsequently, Exos were co-cultured with rat bone marrow mesenchymal stem cells (rBMSCs) to investigate their role in promoting osteogenic differentiation and explore the molecular mechanisms underlying this process, particularly through the miR-29a-3p/NFIA/Wnt signaling pathway axis.
Results
OVX rats exhibited significant bone microdamage. In contrast, the RRP-treated OVX rats showed marked improvements in femoral bone microstructure and increased osteogenic protein expression. MiR-29a-3p levels were elevated in serum-derived Exos from the RRP-treated rats. Furthermore, rBMSCs treated with these Exos displayed an increase in miR-29a-3p expression. Further investigations revealed that miR-29a-3p promoted osteogenesis by inhibiting NFIA expression in both bone tissue and rBMSCs. Overexpression of NFIA reversed the osteogenic effects of miR-29a-3p, confirming NFIA as its direct target and suggesting that miR-29a-3p enhances osteogenesis by inhibiting NFIA. Additionally, NFIA was found to promote the transcription of SFRP1, an inhibitor of the Wnt signaling pathway. Our findings suggest that the RRP aqueous extract increases miR-29a-3p levels in serum Exos, which in turn inhibits NFIA and activates the Wnt signaling pathway, thereby promoting osteogenesis.
Conclusion
These findings suggest that the RRP aqueous extract improves bone health and mitigates bone microstructural damage caused by OP through the regulation of the miR-29a-3p/NFIA/Wnt signaling pathway axis.
{"title":"Aqueous extract of Rehmanniae Radix Praeparata improves bone health in ovariectomized rats by modulating the miR-29a-3p/NFIA/Wnt signaling pathway axis","authors":"Bingjie Luo , Ziwen Liang , Weiwen Lin , Yan Li , Wenqiang Zhong , Donghui Bai , Xueling Hu , Ji Xie , Xiaoyun Li , Panpan Wang , Xiaofeng Zhu , Ronghua Zhang , Li Yang","doi":"10.1016/j.jep.2025.119549","DOIUrl":"10.1016/j.jep.2025.119549","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Rehmanniae Radix Praeparata (RRP), a widely used traditional Chinese medicine and a processed form of Rehmannia glutinosa, is primarily utilized to supplement kidney function and promote bone health. Clinical evidence suggests that RRP exhibits significant efficacy in the treatment of osteoporosis (OP). However, the precise mechanisms underlying its therapeutic effects remain incompletely understood.</div></div><div><h3>Aim of the study</h3><div>OP is a systemic skeletal disorder characterized by reduced bone density and quality, leading to an increased risk of fractures. The aim of this study is to evaluate the effectiveness and underlying mechanisms of RRP in treating OP.</div></div><div><h3>Materials and methods</h3><div>Ovariectomized (OVX) rats were administered RRP aqueous extract via gavage for three months. After the treatment period, femoral microstructure and osteogenic protein levels were assessed to evaluate the efficacy of RRP. Serum exosomes (Exos) derived from different groups of rats were isolated and characterized. The levels of miR-29a-3p in serum-derived Exos and femoral tissue were quantified. Subsequently, Exos were co-cultured with rat bone marrow mesenchymal stem cells (rBMSCs) to investigate their role in promoting osteogenic differentiation and explore the molecular mechanisms underlying this process, particularly through the miR-29a-3p/NFIA/Wnt signaling pathway axis.</div></div><div><h3>Results</h3><div>OVX rats exhibited significant bone microdamage. In contrast, the RRP-treated OVX rats showed marked improvements in femoral bone microstructure and increased osteogenic protein expression. MiR-29a-3p levels were elevated in serum-derived Exos from the RRP-treated rats. Furthermore, rBMSCs treated with these Exos displayed an increase in miR-29a-3p expression. Further investigations revealed that miR-29a-3p promoted osteogenesis by inhibiting NFIA expression in both bone tissue and rBMSCs. Overexpression of NFIA reversed the osteogenic effects of miR-29a-3p, confirming NFIA as its direct target and suggesting that miR-29a-3p enhances osteogenesis by inhibiting NFIA. Additionally, NFIA was found to promote the transcription of SFRP1, an inhibitor of the Wnt signaling pathway. Our findings suggest that the RRP aqueous extract increases miR-29a-3p levels in serum Exos, which in turn inhibits NFIA and activates the Wnt signaling pathway, thereby promoting osteogenesis.</div></div><div><h3>Conclusion</h3><div>These findings suggest that the RRP aqueous extract improves bone health and mitigates bone microstructural damage caused by OP through the regulation of the miR-29a-3p/NFIA/Wnt signaling pathway axis.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"344 ","pages":"Article 119549"},"PeriodicalIF":4.8,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-28DOI: 10.1016/j.jep.2025.119531
Syeda Masooma Ali , Sania Atta , Iffat Naz , Humaira Fatima , Ihsan-ul Haq
Ethnopharmacological relevance
Artemisia roxburghiana Wall. ex Besser is a well-known remedy for treating fever and diabetes. Natives of the Himalayan region use it to treat malaria, dysentery, rheumatism, and viral hepatitis.
Aim
The current investigation aimed to evaluate the phytochemical profile, acute and sub-acute toxicity of the aqueous leaf extract of Artemisia roxburghiana.
Methods
Liquid chromatography coupled with mass spectrometry determined the phytochemical profile. The potential toxicity of A. roxburghiana was evaluated by executing acute and sub-acute toxicity according to guidelines 423 and 407 of OECD. A single dose of 2 g/kg body weight was gavaged orally in acute toxicity. Animals were observed for memory impairment, depressive/anxiogenic behavior, and mortality for 14 days. In sub-acute toxicity, 200, 400, and 600 mg/kg body weight of extract was given for 28 days. Body weights, relative organ weights, hematological, histological, biochemical parameters, and endogenous antioxidants were assessed and compared with control.
Results
LD50 was established to be > 2 g/kg body weight. No significant difference was observed between control and test groups for body weights, relative organ weights, behavioral, hematological, and biochemical studies in sub-acute toxicity. No signs of depletion of endogenous antioxidant enzymes and lipid peroxidation were observed. Histoarchitecture of the kidney, testes, ovaries, heart, liver, spleen and stomach of extract-treated groups was preserved and comparable to the control group.
Conclusion
The extract was rich in bioactive compounds with determinate therapeutic benefits. The plant was safe in repeated administration for 28 days which justifies its expansive use in traditional medicine systems.
{"title":"Toxicological assessment of standardized Artemisia roxburghiana wall. ex Besser aqueous leaf extract to acute and subacute exposure in Albino mice","authors":"Syeda Masooma Ali , Sania Atta , Iffat Naz , Humaira Fatima , Ihsan-ul Haq","doi":"10.1016/j.jep.2025.119531","DOIUrl":"10.1016/j.jep.2025.119531","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Artemisia roxburghiana</em> Wall. ex Besser is a well-known remedy for treating fever and diabetes. Natives of the Himalayan region use it to treat malaria, dysentery, rheumatism, and viral hepatitis.</div></div><div><h3>Aim</h3><div>The current investigation aimed to evaluate the phytochemical profile, acute and sub-acute toxicity of the aqueous leaf extract of <em>Artemisia roxburghiana</em>.</div></div><div><h3>Methods</h3><div>Liquid chromatography coupled with mass spectrometry determined the phytochemical profile. The potential toxicity of <em>A. roxburghiana</em> was evaluated by executing acute and sub-acute toxicity according to guidelines 423 and 407 of OECD. A single dose of 2 g/kg body weight was gavaged orally in acute toxicity. Animals were observed for memory impairment, depressive/anxiogenic behavior, and mortality for 14 days. In sub-acute toxicity, 200, 400, and 600 mg/kg body weight of extract was given for 28 days. Body weights, relative organ weights, hematological, histological, biochemical parameters, and endogenous antioxidants were assessed and compared with control.</div></div><div><h3>Results</h3><div>LD<sub>50</sub> was established to be > 2 g/kg body weight. No significant difference was observed between control and test groups for body weights, relative organ weights, behavioral, hematological, and biochemical studies in sub-acute toxicity. No signs of depletion of endogenous antioxidant enzymes and lipid peroxidation were observed. Histoarchitecture of the kidney, testes, ovaries, heart, liver, spleen and stomach of extract-treated groups was preserved and comparable to the control group.</div></div><div><h3>Conclusion</h3><div>The extract was rich in bioactive compounds with determinate therapeutic benefits. The plant was safe in repeated administration for 28 days which justifies its expansive use in traditional medicine systems.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"344 ","pages":"Article 119531"},"PeriodicalIF":4.8,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-27DOI: 10.1016/j.jep.2025.119525
Zelu Zheng , Xiaohan Wang , Baohong Mi , Jun Zhou , Yan Yan , Shuwen Li , Yuxin Luo , Kaiqiang Tang , Yawei Dong , Rui Quan , Jiaming Lin , Jiawen Zhang , Jiachun Liu , Yuhang Shi , Rongtian Wang , Yanqiong Zhang , Na Lin , Xisheng Weng , Weiheng Chen
Ethnopharmacological relevance
Chinese patent medicine Tenghuang Jiangu tablet (THJGT) is frequently used to treat knee osteoarthritis (KOA).
Aim
This prospective multicenter registry study investigated the effectiveness and safety of THJGT in treating KOA.
Materials and methods
Patients with KOA aged 50–75 years were preferentially treated with THJGT, other nonsurgical conventional treatments (CTs), or both. The treatment duration was 8 weeks, with follow-ups at weeks 4 and 8. The visual analog scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores were the efficacy assessments. Adverse events and drug reactions were evaluated to assess the safety of THJGT. Propensity score matching (PSM) was used for the subgroup analysis.
Results
From September 2019 to January 2021, a total of 2995 participants were included, with 1471 in THJGT group, 490 in CT group and 1034 in THJGT + CT group. After treatment, the VAS and WOMAC scores in the three groups improved significantly (P < 0.001). At week 8, the VAS scores in the THJGT group significantly improved, were lower than those in the CT group (P < 0.01), and were comparable to those in the THJGT + CT group (P = 0.623). The WOMAC scores significantly improved (P < 0.001), with no differences between groups (P > 0.05). The WOMAC pain and stiffness scores were better in the THJGT + CT than in the THJGT and CT groups. PSM revealed that the WOMAC pain and stiffness scores were significantly lower in the THJGT than in the nonsteroidal anti-inflammatory drugs (NSAID) group (P < 0.01 and 0.001). Adverse events were higher in the CT and THJGT + CT groups (P < 0.001).
Conclusion
THJGT is effective and safe for treating KOA, particularly in improving stiffness symptoms.
{"title":"Tenghuang Jiangu tablet in knee osteoarthritis therapy: A prospective multicenter registry study in China","authors":"Zelu Zheng , Xiaohan Wang , Baohong Mi , Jun Zhou , Yan Yan , Shuwen Li , Yuxin Luo , Kaiqiang Tang , Yawei Dong , Rui Quan , Jiaming Lin , Jiawen Zhang , Jiachun Liu , Yuhang Shi , Rongtian Wang , Yanqiong Zhang , Na Lin , Xisheng Weng , Weiheng Chen","doi":"10.1016/j.jep.2025.119525","DOIUrl":"10.1016/j.jep.2025.119525","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Chinese patent medicine Tenghuang Jiangu tablet (THJGT) is frequently used to treat knee osteoarthritis (KOA).</div></div><div><h3>Aim</h3><div>This prospective multicenter registry study investigated the effectiveness and safety of THJGT in treating KOA.</div></div><div><h3>Materials and methods</h3><div>Patients with KOA aged 50–75 years were preferentially treated with THJGT, other nonsurgical conventional treatments (CTs), or both. The treatment duration was 8 weeks, with follow-ups at weeks 4 and 8. The visual analog scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores were the efficacy assessments. Adverse events and drug reactions were evaluated to assess the safety of THJGT. Propensity score matching (PSM) was used for the subgroup analysis.</div></div><div><h3>Results</h3><div>From September 2019 to January 2021, a total of 2995 participants were included, with 1471 in THJGT group, 490 in CT group and 1034 in THJGT + CT group. After treatment, the VAS and WOMAC scores in the three groups improved significantly (<em>P</em> < 0.001). At week 8, the VAS scores in the THJGT group significantly improved, were lower than those in the CT group (<em>P</em> < 0.01), and were comparable to those in the THJGT + CT group (<em>P</em> = 0.623). The WOMAC scores significantly improved (<em>P</em> < 0.001), with no differences between groups (P > 0.05). The WOMAC pain and stiffness scores were better in the THJGT + CT than in the THJGT and CT groups. PSM revealed that the WOMAC pain and stiffness scores were significantly lower in the THJGT than in the nonsteroidal anti-inflammatory drugs (NSAID) group (<em>P</em> < 0.01 and 0.001). Adverse events were higher in the CT and THJGT + CT groups (<em>P</em> < 0.001).</div></div><div><h3>Conclusion</h3><div>THJGT is effective and safe for treating KOA, particularly in improving stiffness symptoms.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"345 ","pages":"Article 119525"},"PeriodicalIF":4.8,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-27DOI: 10.1016/j.jep.2025.119538
Xiaoqin Yang , Heng Zhang , Chenglin He , Di Wang , Jingjing Li , Chaomei Fu , Yitao Wang , Yihan Wu , Jinming Zhang
Ethnopharmacological relevance
Although several traditional Chinese medicine formulas have demonstrated remarkable outcomes in suppressing the severe gastrointestinal toxicity induced by irinotecan (CPT-11), few studies have investigated whether enhanced anti-cancer efficacy and reduced intestinal toxicity can be achieved through co-administration. CPT-11, as a first-line drug for treating colorectal cancer, has the side effect of intestinal toxicity. Previous studies have primarily focused on using traditional Chinese medicine to alleviate diarrhea caused by CPT-11. The combination of the classic Chinese medicine prescription Gegen Qinlian decoction (GQD) extract and CPT-11 can significantly reduce its intestinal toxicity. However, the mechanism by which it enhances anti-cancer effects remains to be elucidated.
Aim of study
To investigate the combined effects of GQD and CPT-11 on colorectal cancer progression and intestinal toxicity.
Materials and methods
The CT-26 xenograft tumor-bearing mouse model was established to evaluate the synergistic antitumor effects of GQD extract and CPT-11. Tumor size and tumor tissue changes were assessed, and flow cytometry was employed to analyze immune cell populations, thereby evaluating the impact of the combined treatment on tumor growth inhibition and immune modulation. Under anaerobic glycolysis conditions, glucose uptake and cell viability of CT26 cells were measured, and Western blotting analysis was used to determine the protein expression of PKM2 and GAPDH in tumors, assessing the metabolic impact of GQD extract on cancer cells. Flow cytometry was also used to assess the polarization of macrophages in colon tissue, and ELISA was employed to measure cytokine levels in colon tissue, evaluating the protective effect of GQD extract on the colon.
Results
The combination of GQD extract and CPT-11 significantly increased tumor growth suppression and decreased intestinal toxicity in the mouse model. The anti-cancer synergy was reduced Treg cell immunosuppression and increased CD4+ and CD8+ T cell populations. GQD extract regulated glucose uptake and cell viability in CT-26 cells under anaerobic glycolysis, potentially disrupting cancer cell glycolysis. GQD also alleviated intestinal toxicity by modulating cytokine levels and promoting macrophage polarization from M1 to M2 in colon tissues.
Conclusion
The study indicates that GQD extract improves CPT-11 efficacy in treating colorectal cancer and provides insights into the synergistic effects of TCM formulas in cancer treatment.
{"title":"Gegen Qinlian decoction remodels tumor immune microenvironment and inhibits aerobic glycolysis with the synergistic combination of CPT-11 chemotherapy in colorectal cancer therapy","authors":"Xiaoqin Yang , Heng Zhang , Chenglin He , Di Wang , Jingjing Li , Chaomei Fu , Yitao Wang , Yihan Wu , Jinming Zhang","doi":"10.1016/j.jep.2025.119538","DOIUrl":"10.1016/j.jep.2025.119538","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Although several traditional Chinese medicine formulas have demonstrated remarkable outcomes in suppressing the severe gastrointestinal toxicity induced by irinotecan (CPT-11), few studies have investigated whether enhanced anti-cancer efficacy and reduced intestinal toxicity can be achieved through co-administration. CPT-11, as a first-line drug for treating colorectal cancer, has the side effect of intestinal toxicity. Previous studies have primarily focused on using traditional Chinese medicine to alleviate diarrhea caused by CPT-11. The combination of the classic Chinese medicine prescription Gegen Qinlian decoction (GQD) extract and CPT-11 can significantly reduce its intestinal toxicity. However, the mechanism by which it enhances anti-cancer effects remains to be elucidated.</div></div><div><h3>Aim of study</h3><div>To investigate the combined effects of GQD and CPT-11 on colorectal cancer progression and intestinal toxicity.</div></div><div><h3>Materials and methods</h3><div>The CT-26 xenograft tumor-bearing mouse model was established to evaluate the synergistic antitumor effects of GQD extract and CPT-11. Tumor size and tumor tissue changes were assessed, and flow cytometry was employed to analyze immune cell populations, thereby evaluating the impact of the combined treatment on tumor growth inhibition and immune modulation. Under anaerobic glycolysis conditions, glucose uptake and cell viability of CT26 cells were measured, and Western blotting analysis was used to determine the protein expression of PKM2 and GAPDH in tumors, assessing the metabolic impact of GQD extract on cancer cells. Flow cytometry was also used to assess the polarization of macrophages in colon tissue, and ELISA was employed to measure cytokine levels in colon tissue, evaluating the protective effect of GQD extract on the colon.</div></div><div><h3>Results</h3><div>The combination of GQD extract and CPT-11 significantly increased tumor growth suppression and decreased intestinal toxicity in the mouse model. The anti-cancer synergy was reduced Treg cell immunosuppression and increased CD4<sup>+</sup> and CD8<sup>+</sup> T cell populations. GQD extract regulated glucose uptake and cell viability in CT-26 cells under anaerobic glycolysis, potentially disrupting cancer cell glycolysis. GQD also alleviated intestinal toxicity by modulating cytokine levels and promoting macrophage polarization from M1 to M2 in colon tissues.</div></div><div><h3>Conclusion</h3><div>The study indicates that GQD extract improves CPT-11 efficacy in treating colorectal cancer and provides insights into the synergistic effects of TCM formulas in cancer treatment.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"344 ","pages":"Article 119538"},"PeriodicalIF":4.8,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-27DOI: 10.1016/j.jep.2025.119571
Siqi Gao , Xingxing Wang , Qiuying Xu , Rongsheng Li , Lumeng Yao , Anna Zhang , Qun Zhou , Zhun Xiao , Shengsheng Li , Xiongyu Meng , Jianjun Wu , Luping Qin
<div><h3>Ethnopharmacological relevance</h3><div>Sanghuangporus, the dried fruiting body of <em>Sanghuangporus vaninii</em> (Ljub) L.W.Zhou et Y.C.Dai. As the main species of Sanghuang, it has been well-known and used commonly as a traditional medicinal and edible macrofungi for thousands of years in many countries, including China, Korea and Japan. Although it has good hepatoprotective activity, its potential efficacy and mechanism on liver fibrosis remain elusive.</div></div><div><h3>Aim of the study</h3><div>Total <em>Sanghuangporus vaninii</em> extract (TSH) was prepared by ethanol extraction to investigate its chemical components and to conduct an initial assessment of its efficacy and underlying mechanism in a murine model of liver fibrosis.</div></div><div><h3>Materials and methods</h3><div>The chemical components of TSH were initially analyzed by UHPLC-Q-Orbitrap HRMS. To elucidate the effects of TSH, an <em>in vivo</em> model of fibrosis was established in mice using carbon tetrachloride (CCl<sub>4</sub>), followed by assessments of serum liver function and histopathological analysis. Besides, indicators related to liver fibrosis, hepatic stellate cells (HSCs) activation, inflammation response and ferroptosis related indicators were detected by western blotting, immunohistochemistry and real-time quantitative PCR (RT-qPCR) analysis. Additionally, the 16S rDNA sequencing and untargeted metabolomics analysis of intestinal microbiota were employed to investigating the role of TSH in gut microbiome. <em>In vitro</em>, the human hepatocyte line L02 was stimulated with erastin and treated with or without TSH to elucidate its underlying mechanism.</div></div><div><h3>Results</h3><div>The administration of TSH significantly improved serum indicators of liver injury in CCl<sub>4</sub>-induced fibrosis mice, reduced HSCs activation and collagen deposition, while inhibiting the expressions of transforming growth factor-β1(TGF-β1)/Smad signaling pathway. Notably, TSH treatment attenuated hepatocyte ferroptosis and lipid peroxidation both <em>in vivo</em> and <em>in vitro</em>, as evidenced by a marked decrease in liver iron and malondialdehyde (MDA) contents. In particular, TSH was demonstrated to activate the nuclear factor erythroid 2-related factor 2 (Nrf2)-glutathione peroxidase 4 (GPX4) signaling pathway, thereby protecting hepatocytes from ferroptosis with a particular enhancement of Nrf2 nuclear transcription. Furthermore, TSH influenced gut microbiota composition and ameliorated intestinal metabolic disorders. The increased abundance of <em>Parasutterella</em> and <em>Olsenellas</em> due to TSH treatment was significantly positively correlated with elevated phosphatidylcholines involved in linoleic acid metabolism, and negatively correlated with the reduction of fatty acyls. And the enrichment of intestinal linoleic acid metabolism presented a negative correlation in liver fibrosis biomarkers.</div></div><div><h3>Conclusions</h3><div>Our fin
{"title":"Total Sanghuangporus vaninii extract inhibits hepatocyte ferroptosis and intestinal microbiota disturbance to attenuate liver fibrosis in mice","authors":"Siqi Gao , Xingxing Wang , Qiuying Xu , Rongsheng Li , Lumeng Yao , Anna Zhang , Qun Zhou , Zhun Xiao , Shengsheng Li , Xiongyu Meng , Jianjun Wu , Luping Qin","doi":"10.1016/j.jep.2025.119571","DOIUrl":"10.1016/j.jep.2025.119571","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Sanghuangporus, the dried fruiting body of <em>Sanghuangporus vaninii</em> (Ljub) L.W.Zhou et Y.C.Dai. As the main species of Sanghuang, it has been well-known and used commonly as a traditional medicinal and edible macrofungi for thousands of years in many countries, including China, Korea and Japan. Although it has good hepatoprotective activity, its potential efficacy and mechanism on liver fibrosis remain elusive.</div></div><div><h3>Aim of the study</h3><div>Total <em>Sanghuangporus vaninii</em> extract (TSH) was prepared by ethanol extraction to investigate its chemical components and to conduct an initial assessment of its efficacy and underlying mechanism in a murine model of liver fibrosis.</div></div><div><h3>Materials and methods</h3><div>The chemical components of TSH were initially analyzed by UHPLC-Q-Orbitrap HRMS. To elucidate the effects of TSH, an <em>in vivo</em> model of fibrosis was established in mice using carbon tetrachloride (CCl<sub>4</sub>), followed by assessments of serum liver function and histopathological analysis. Besides, indicators related to liver fibrosis, hepatic stellate cells (HSCs) activation, inflammation response and ferroptosis related indicators were detected by western blotting, immunohistochemistry and real-time quantitative PCR (RT-qPCR) analysis. Additionally, the 16S rDNA sequencing and untargeted metabolomics analysis of intestinal microbiota were employed to investigating the role of TSH in gut microbiome. <em>In vitro</em>, the human hepatocyte line L02 was stimulated with erastin and treated with or without TSH to elucidate its underlying mechanism.</div></div><div><h3>Results</h3><div>The administration of TSH significantly improved serum indicators of liver injury in CCl<sub>4</sub>-induced fibrosis mice, reduced HSCs activation and collagen deposition, while inhibiting the expressions of transforming growth factor-β1(TGF-β1)/Smad signaling pathway. Notably, TSH treatment attenuated hepatocyte ferroptosis and lipid peroxidation both <em>in vivo</em> and <em>in vitro</em>, as evidenced by a marked decrease in liver iron and malondialdehyde (MDA) contents. In particular, TSH was demonstrated to activate the nuclear factor erythroid 2-related factor 2 (Nrf2)-glutathione peroxidase 4 (GPX4) signaling pathway, thereby protecting hepatocytes from ferroptosis with a particular enhancement of Nrf2 nuclear transcription. Furthermore, TSH influenced gut microbiota composition and ameliorated intestinal metabolic disorders. The increased abundance of <em>Parasutterella</em> and <em>Olsenellas</em> due to TSH treatment was significantly positively correlated with elevated phosphatidylcholines involved in linoleic acid metabolism, and negatively correlated with the reduction of fatty acyls. And the enrichment of intestinal linoleic acid metabolism presented a negative correlation in liver fibrosis biomarkers.</div></div><div><h3>Conclusions</h3><div>Our fin","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"345 ","pages":"Article 119571"},"PeriodicalIF":4.8,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}