Pub Date : 2025-01-31DOI: 10.1016/j.jep.2024.119165
Lishi Jie , Chaofeng Zhang , Yujiang Liu , Zeling Huang , Bo Xu , Zaishi Zhu , Yuwei Li , Peimin Wang , Xiaoqing Shi
Ethnopharmacological relevance
Quzhi Tang (QZT) is a compound formula consisting of six traditional Chinese medicinal herbs. It has achieved good clinical results in the treatment of knee osteoarthritis (KOA), and the potential drug mechanisms involved are worth exploring in depth.
Materials and methods
Using single-cell transcriptome analysis, this study identified the key target of senescence, GPNMB. Then, it investigated the mechanism by which QZT regulates the GPNMB/Nrf2/NF-κB signaling pathway to repair mitochondrial damage and ameliorate the process of chondrocyte senescence.
Results
We collected cartilage tissues from mice and identified GPNMB as a key target of chondrocyte senescence by combining transcriptomics, histopathology, molecular biology, and immunology methods. The effects of QZT on the level of chondrocyte senescence in mice and its ameliorative effect on KOA were studied. In in vivo experiments, we explored the mechanism of GPNMB in the development of senescence in detail and revealed that, after siRNA-GPNMB interference, chondrocytes exhibited reduced impairment of mitochondrial function and senescence under equal amounts of stimuli, increasing Nrf2 expression and reducing NF-κB expression. In addition, the level of oxidative stress increased in chondrocytes overexpressing GPNMB after lentiviral infiltration, aggravating the impairment of mitochondrial function. After treatment with QZT, chondrocytes overexpressing GPNMB were able to increase Nrf2 expression, decrease NF-κB expression, repair mitochondrial damage, and improve the degree of chondrocyte aging.
Conclusion
We concluded that the GPNMB/Nrf2/NF-κB signaling pathway plays an important role in chondrocyte senescence and that QZT was able to reduce intracellular oxidative stress and restore impaired mitochondrial function by regulating the expression level of the GPNMB/Nrf2/NF-κB signaling pathway, reducing the level of chondrocyte senescence in the KOA process.
{"title":"Mechanistic study of the regulation of mitochondrial function by the GPNMB/Nrf2/NF-κB signaling pathway mediated by Quzhi Tang to alleviate chondrocyte senescence","authors":"Lishi Jie , Chaofeng Zhang , Yujiang Liu , Zeling Huang , Bo Xu , Zaishi Zhu , Yuwei Li , Peimin Wang , Xiaoqing Shi","doi":"10.1016/j.jep.2024.119165","DOIUrl":"10.1016/j.jep.2024.119165","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Quzhi Tang (QZT) is a compound formula consisting of six traditional Chinese medicinal herbs. It has achieved good clinical results in the treatment of knee osteoarthritis (KOA), and the potential drug mechanisms involved are worth exploring in depth.</div></div><div><h3>Materials and methods</h3><div>Using single-cell transcriptome analysis, this study identified the key target of senescence, GPNMB. Then, it investigated the mechanism by which QZT regulates the GPNMB/Nrf2/NF-κB signaling pathway to repair mitochondrial damage and ameliorate the process of chondrocyte senescence.</div></div><div><h3>Results</h3><div>We collected cartilage tissues from mice and identified GPNMB as a key target of chondrocyte senescence by combining transcriptomics, histopathology, molecular biology, and immunology methods. The effects of QZT on the level of chondrocyte senescence in mice and its ameliorative effect on KOA were studied. In in vivo experiments, we explored the mechanism of GPNMB in the development of senescence in detail and revealed that, after siRNA-GPNMB interference, chondrocytes exhibited reduced impairment of mitochondrial function and senescence under equal amounts of stimuli, increasing Nrf2 expression and reducing NF-κB expression. In addition, the level of oxidative stress increased in chondrocytes overexpressing GPNMB after lentiviral infiltration, aggravating the impairment of mitochondrial function. After treatment with QZT, chondrocytes overexpressing GPNMB were able to increase Nrf2 expression, decrease NF-κB expression, repair mitochondrial damage, and improve the degree of chondrocyte aging.</div></div><div><h3>Conclusion</h3><div>We concluded that the GPNMB/Nrf2/NF-κB signaling pathway plays an important role in chondrocyte senescence and that QZT was able to reduce intracellular oxidative stress and restore impaired mitochondrial function by regulating the expression level of the GPNMB/Nrf2/NF-κB signaling pathway, reducing the level of chondrocyte senescence in the KOA process.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"340 ","pages":"Article 119165"},"PeriodicalIF":4.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142769294","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 : 2025-01-31DOI: 10.1016/j.jep.2024.119197
Jian-Cheng Liao , Jie Xiang , Wan-Yu Gui , Hui-Zhi Luo , Qing You , Qi-Rui He , Ming-Xia Lu , Shu-Yun Yang , Qiong Wang , Jian-Dong Zou , Chang-Yin Li
Ethnopharmacological relevance
Huangkui Capsule (HKC) is a traditional Chinese medicinal preparation. Numerous clinical studies have reported that HKC has a good nephroprotection effect. The clinical application of cisplatin is greatly limited by its nephrotoxicity, and HKC shows promise in preventing cisplatin-induced nephrotoxicity (CIN).
Aim of the study
To evaluate the effectiveness of HKC in alleviating CIN and explore its underlying action mechanisms.
Materials and methods
A rat model of CIN was established via single-dose injection of cisplatin. The effectiveness of HKC was evaluated by biochemical indices and pathological sections. Then, serum, kidney, and cecal endogenous metabolic profiles as well as the gut microbiota were characterized using lipidomics, metabolomics, and 16S rRNA high-throughput sequencing technique. Spearman's correlation analysis was carried out between gut microbiota, biomarkers, and biochemical indices. Finally, antibiotic treatment was performed to establish a pseudo-sterile rat model and validate the nephroprotection of HKC in a gut microbiota-dependent manner.
Results
HKC could significantly attenuate the abnormal elevation of serum creatinine and urea nitrogen, kidney index, and kidney injury score in CIN rats, remarkably alleviate the disturbance of metabolic profiles of serum, kidney, and cecal contents, corresponding to the endogenous metabolites such as fatty acids, phosphatidylcholines, amino acids, acylcarnitines, and short-chain fatty acids, and enrich the diversity of gut microbiota. Spearman's correlation analysis revealed that Clostridium_sensu_stricto_1 was positively correlated with the altered short-chain fatty acids in serum and negatively correlated with the altered acylcarnitine in the kidney. In the pseudo-sterile rat model, the attenuation effect of HKC on the abnormal elevation of serum creatinine and urea nitrogen, along with the alleviation of metabolic profile disorders, was greatly diminished or even abolished, demonstrating the nephroprotective effect of HKC in a gut microbiota-dependent manner.
Conclusions
HKC exerted the nephroprotective effect on CIN in a gut microbiota-dependent manner, mainly by regulating Clostridium_sensu_stricto_1 mediated metabolisms of phosphatidylcholines, acylcarnitines, fatty acids, tryptophan, and short-chain fatty acids, thereby reducing the inflammatory response. The present study could provide reliable scientific evidence for gut microbiota-dependent mechanisms of HKC in the treatment of kidney injury and may widen the clinical application of HKC in cisplatin-containing cancer therapy.
{"title":"Broad range lipidomics and metabolomics coupled with 16S rRNA sequencing to reveal the mechanisms of Huangkui Capsule against cisplatin-induced nephrotoxicity","authors":"Jian-Cheng Liao , Jie Xiang , Wan-Yu Gui , Hui-Zhi Luo , Qing You , Qi-Rui He , Ming-Xia Lu , Shu-Yun Yang , Qiong Wang , Jian-Dong Zou , Chang-Yin Li","doi":"10.1016/j.jep.2024.119197","DOIUrl":"10.1016/j.jep.2024.119197","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Huangkui Capsule (HKC) is a traditional Chinese medicinal preparation. Numerous clinical studies have reported that HKC has a good nephroprotection effect. The clinical application of cisplatin is greatly limited by its nephrotoxicity, and HKC shows promise in preventing cisplatin-induced nephrotoxicity (CIN).</div></div><div><h3>Aim of the study</h3><div>To evaluate the effectiveness of HKC in alleviating CIN and explore its underlying action mechanisms.</div></div><div><h3>Materials and methods</h3><div>A rat model of CIN was established via single-dose injection of cisplatin. The effectiveness of HKC was evaluated by biochemical indices and pathological sections. Then, serum, kidney, and cecal endogenous metabolic profiles as well as the gut microbiota were characterized using lipidomics, metabolomics, and 16S rRNA high-throughput sequencing technique. Spearman's correlation analysis was carried out between gut microbiota, biomarkers, and biochemical indices. Finally, antibiotic treatment was performed to establish a pseudo-sterile rat model and validate the nephroprotection of HKC in a gut microbiota-dependent manner.</div></div><div><h3>Results</h3><div>HKC could significantly attenuate the abnormal elevation of serum creatinine and urea nitrogen, kidney index, and kidney injury score in CIN rats, remarkably alleviate the disturbance of metabolic profiles of serum, kidney, and cecal contents, corresponding to the endogenous metabolites such as fatty acids, phosphatidylcholines, amino acids, acylcarnitines, and short-chain fatty acids, and enrich the diversity of gut microbiota. Spearman's correlation analysis revealed that <em>Clostridium_sensu_stricto_1</em> was positively correlated with the altered short-chain fatty acids in serum and negatively correlated with the altered acylcarnitine in the kidney. In the pseudo-sterile rat model, the attenuation effect of HKC on the abnormal elevation of serum creatinine and urea nitrogen, along with the alleviation of metabolic profile disorders, was greatly diminished or even abolished, demonstrating the nephroprotective effect of HKC in a gut microbiota-dependent manner.</div></div><div><h3>Conclusions</h3><div>HKC exerted the nephroprotective effect on CIN in a gut microbiota-dependent manner, mainly by regulating <em>Clostridium_sensu_stricto_1</em> mediated metabolisms of phosphatidylcholines, acylcarnitines, fatty acids, tryptophan, and short-chain fatty acids, thereby reducing the inflammatory response. The present study could provide reliable scientific evidence for gut microbiota-dependent mechanisms of HKC in the treatment of kidney injury and may widen the clinical application of HKC in cisplatin-containing cancer therapy.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"340 ","pages":"Article 119197"},"PeriodicalIF":4.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142780117","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 : 2025-01-31DOI: 10.1016/j.jep.2024.119246
Yanling Li , Zhongji Hu , Linli Xie , Tingting Xiong , Yanyan Zhang , Yang Bai , Huang Ding , Xiaoping Huang , Xiaodan Liu , Changqing Deng
Ethnopharmacological relevance
Buyang Huanwu Decoction (BYHWD) exerts its anti-cerebral ischemia effects through multiple pathways and targets, although its specific mechanisms remain unclear.
Aim of the study
Ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS) metabolomics and other methods were employed to investigate the role of BYHWD in inhibiting neuronal apoptosis following cerebral ischemia-reperfusion by modulating the RhoA/Rock2 pathway.
Methods
A rat model of exhaustion swimming combined with middle cerebral artery occlusion (ES + I/R) was established to evaluate the intervention effects of Buyang Huanwu Decoction on cerebral ischemia-reperfusion. This was assessed using neurological function scores, Qi deficiency and blood stasis syndrome scores, HE staining, Nissl staining and TT staining. Differential metabolites and metabolic pathways associated with cerebral ischemia-reperfusion were identified using UPLC-QTOF-MS metabolomics, with key differential metabolites validated through ELISA. Molecular docking techniques were employed to predict interactions between the key differential metabolite, hippuric acid, and its primary downstream pathways. Finally, the levels of neurocellular apoptosis, as well as key molecules in the RhoA/Rock2 signaling pathway and the mitochondrial apoptosis pathway, were measured.
Results
The results indicated that the primary differential metabolites associated with BYHWD's protective effects against ischemia-reperfusion injury were hippuric acid, lysophosphatidic acid, and lysophosphatidylethanolamine, with the main metabolic pathway being phenylalanine metabolism. Molecular docking studies demonstrated that malonic acid exhibited a strong affinity for proteins related to the RhoA/Rock2 signaling pathway and the mitochondrial apoptosis pathway.Furthermore, we found that BYHWD treatment significantly decreased the apoptosis rate of cells following cerebral ischemia-reperfusion and inhibited the expression of key molecules in both the RhoA/Rock2 signaling pathway and the mitochondrial apoptosis pathway in brain tissue.
Conclusion
BYHWD ameliorated brain tissue injury after cerebral ischemia/reperfusion in rats with qi deficiency and blood stasis. The underlying mechanism may involve BYHWD's inhibition of the RhoA/Rock2 signaling pathway activation through modulation of the phenylalanine metabolism pathway, thereby reducing neuronal apoptosis mediated by the mitochondrial apoptosis pathway.
{"title":"Buyang huanwu decoction inhibits the activation of the RhoA/Rock2 signaling pathway through the phenylalanine metabolism pathway, thereby reducing neuronal apoptosis following cerebral ischemia-reperfusion injury","authors":"Yanling Li , Zhongji Hu , Linli Xie , Tingting Xiong , Yanyan Zhang , Yang Bai , Huang Ding , Xiaoping Huang , Xiaodan Liu , Changqing Deng","doi":"10.1016/j.jep.2024.119246","DOIUrl":"10.1016/j.jep.2024.119246","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Buyang Huanwu Decoction (BYHWD) exerts its anti-cerebral ischemia effects through multiple pathways and targets, although its specific mechanisms remain unclear.</div></div><div><h3>Aim of the study</h3><div>Ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS) metabolomics and other methods were employed to investigate the role of BYHWD in inhibiting neuronal apoptosis following cerebral ischemia-reperfusion by modulating the RhoA/Rock2 pathway.</div></div><div><h3>Methods</h3><div>A rat model of exhaustion swimming combined with middle cerebral artery occlusion (ES + I/R) was established to evaluate the intervention effects of Buyang Huanwu Decoction on cerebral ischemia-reperfusion. This was assessed using neurological function scores, Qi deficiency and blood stasis syndrome scores, HE staining, Nissl staining and TT staining. Differential metabolites and metabolic pathways associated with cerebral ischemia-reperfusion were identified using UPLC-QTOF-MS metabolomics, with key differential metabolites validated through ELISA. Molecular docking techniques were employed to predict interactions between the key differential metabolite, hippuric acid, and its primary downstream pathways. Finally, the levels of neurocellular apoptosis, as well as key molecules in the RhoA/Rock2 signaling pathway and the mitochondrial apoptosis pathway, were measured.</div></div><div><h3>Results</h3><div>The results indicated that the primary differential metabolites associated with BYHWD's protective effects against ischemia-reperfusion injury were hippuric acid, lysophosphatidic acid, and lysophosphatidylethanolamine, with the main metabolic pathway being phenylalanine metabolism. Molecular docking studies demonstrated that malonic acid exhibited a strong affinity for proteins related to the RhoA/Rock2 signaling pathway and the mitochondrial apoptosis pathway.Furthermore, we found that BYHWD treatment significantly decreased the apoptosis rate of cells following cerebral ischemia-reperfusion and inhibited the expression of key molecules in both the RhoA/Rock2 signaling pathway and the mitochondrial apoptosis pathway in brain tissue.</div></div><div><h3>Conclusion</h3><div>BYHWD ameliorated brain tissue injury after cerebral ischemia/reperfusion in rats with qi deficiency and blood stasis. The underlying mechanism may involve BYHWD's inhibition of the RhoA/Rock2 signaling pathway activation through modulation of the phenylalanine metabolism pathway, thereby reducing neuronal apoptosis mediated by the mitochondrial apoptosis pathway.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"340 ","pages":"Article 119246"},"PeriodicalIF":4.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142837049","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 : 2025-01-31DOI: 10.1016/j.jep.2024.119231
Yin-Jing Jiang , Yong-Hong Cheng , Hao-Qing Zhu , Yan-Ling Wu , Ji-Xing Nan , Li-Hua Lian
Ethnopharmacological relevance
Palmatine (Pal), derived from Daemonorops margaritae (Hance) Becc and Phellodendron amurense Rupr. is a natural isoquinoline alkaloid widely used in clearing heat and drying dampness, purging the pathogenic fire and removing symptoms, detoxifying toxins and healing sores.
Aim of the study
Gout is a common metabolic inflammatory disease caused by the deposition of MSU crystals (MSU) in joints and non-articulation structures. Given the multiple toxic side effects of clinical anti-gout medications, there is a need to find a safe and effective alternative. We investigated the therapeutic effects of Pal on MSU crystal-induced acute gouty inflammation, targeting the NLRP3 inflammasome mediated pyroptosis.
Materials and methods
In vitro, mouse peritoneal macrophages (MPM) and rat articular chondrocytes were stimulated with LPS plus MSU in the presence or absence of Palmatine. In vivo, arthritis models include the acute gouty arthritis model by injecting MSU crystals in the paws of mice and the air pouch acute gout model by injecting MSU crystals into the mouse subcutaneous tissue of the back. Expression of NLRP3 inflammasome activation and NETosis formation was determined by Western blot, ELISA kit, immunohistochemistry, and immunofluorescence. In addition, the anti-cartilage damage of Palmatine on MSU-induced arthritis mice were also evaluated.
Results
Pal dose-dependently decreased levels of NLRP3 inflammasome activation related proteins NLRP3, ASC, caspase-1, IL-1β, HMGB1 and Cathepsin B. The NETosis protein levels of caspase-11, histone3, PR3 and PAD4 were remarkably reduced by Pal. Pal effectively blocked the activation of NLRP3 inflammasome, attenuated the caspase-11 mediated noncanonical NLRP3 inflammasome activation and intervened the formation of NETs, thereby inhibiting the pyroptosis. In vivo, Pal attenuated MSU-induced inflammation in gouty arthritis and protect the articular cartilage through inhibiting the pyroptosis of proteins NLRP3, ASC, caspase-1, IL-1β, HMGB1 and Cathepsin B, reducing levels of NETosis relevant proteins caspase-11, histone3, PR3 and PAD4 and up-regulating expression of protein MMP-3.
Conclusion
Palmatine ameliorated gouty inflammation by inhibiting pyroptosis via NLRP3 inflammasome.
{"title":"Palmatine, an isoquinoline alkaloid from Phellodendron amurense Rupr., ameliorated gouty inflammation by inhibiting pyroptosis via NLRP3 inflammasome","authors":"Yin-Jing Jiang , Yong-Hong Cheng , Hao-Qing Zhu , Yan-Ling Wu , Ji-Xing Nan , Li-Hua Lian","doi":"10.1016/j.jep.2024.119231","DOIUrl":"10.1016/j.jep.2024.119231","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Palmatine (Pal), derived from <em>Daemonorops margaritae</em> (Hance) Becc and <em>Phellodendron amurense Rupr.</em> is a natural isoquinoline alkaloid widely used in clearing heat and drying dampness, purging the pathogenic fire and removing symptoms, detoxifying toxins and healing sores.</div></div><div><h3>Aim of the study</h3><div>Gout is a common metabolic inflammatory disease caused by the deposition of MSU crystals (MSU) in joints and non-articulation structures. Given the multiple toxic side effects of clinical anti-gout medications, there is a need to find a safe and effective alternative. We investigated the therapeutic effects of Pal on MSU crystal-induced acute gouty inflammation, targeting the NLRP3 inflammasome mediated pyroptosis.</div></div><div><h3>Materials and methods</h3><div><em>In vitro</em>, mouse peritoneal macrophages (MPM) and rat articular chondrocytes were stimulated with LPS plus MSU in the presence or absence of Palmatine. <em>In vivo</em>, arthritis models include the acute gouty arthritis model by injecting MSU crystals in the paws of mice and the air pouch acute gout model by injecting MSU crystals into the mouse subcutaneous tissue of the back. Expression of NLRP3 inflammasome activation and NETosis formation was determined by Western blot, ELISA kit, immunohistochemistry, and immunofluorescence. In addition, the anti-cartilage damage of Palmatine on MSU-induced arthritis mice were also evaluated.</div></div><div><h3>Results</h3><div>Pal dose-dependently decreased levels of NLRP3 inflammasome activation related proteins NLRP3, ASC, caspase-1, IL-1β, HMGB1 and Cathepsin B. The NETosis protein levels of caspase-11, histone3, PR3 and PAD4 were remarkably reduced by Pal. Pal effectively blocked the activation of NLRP3 inflammasome, attenuated the caspase-11 mediated noncanonical NLRP3 inflammasome activation and intervened the formation of NETs, thereby inhibiting the pyroptosis. <em>In vivo</em>, Pal attenuated MSU-induced inflammation in gouty arthritis and protect the articular cartilage through inhibiting the pyroptosis of proteins NLRP3, ASC, caspase-1, IL-1β, HMGB1 and Cathepsin B, reducing levels of NETosis relevant proteins caspase-11, histone3, PR3 and PAD4 and up-regulating expression of protein MMP-3.</div></div><div><h3>Conclusion</h3><div>Palmatine ameliorated gouty inflammation by inhibiting pyroptosis via NLRP3 inflammasome.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"340 ","pages":"Article 119231"},"PeriodicalIF":4.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864400","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 : 2025-01-31DOI: 10.1016/j.jep.2024.119270
Yeke Wu , Min Liu , Jiawei Li , Ranran Gao , Qiongying Hu , Yunfei Xie , Hongling Zhou , Huijing Li , Xiang He , Li Li
Ethnopharmacological relevance
Diabetic periodontitis (DP) is a commonly co-occurring complication in diabetes patients characterized by advanced gum disease and bone resorption. Conventional treatment modalities often fail to adequately address the underlying biological disruptions caused by diabetes. The use of traditional medicinal formulas Kouqiangjie Formula (KQJF) potentially offers novel therapeutic approaches for DP, but its detailed regulatory mechanisms remain unclear.
Aim of the study
This study aims to investigate the impacts of KQJF on osteoblastic activity and inflammatory responses in a rat model and in vitro pre-osteoblast cultures under conditions mimicking DP, focusing on the involvement of the miR-29a-3p-Dkk-1/Wnt/β-catenin signaling pathway.
Materials and methods
Using network pharmacological analysis, micro-CT, histological staining, and an array of molecular biology methodologies including Western blotting, RT-qPCR, and immunofluorescence, we investigated the systemic and cellular responses to KQJF treatment. Both in vivo (rat model) and in vitro (MC3T3-E1 pre-osteoblasts) models subjected to high glucose and lipopolysaccharide (HG + LPS) stress were used to simulate DP conditions.
Results
Network pharmacological analyses, incorporating protein-protein interactions and pathway enrichment, disclosed that KQJF interacts with pathways crucial for inflammation and bone metabolism. Experimentally, KQJF significantly preserved alveolar bone architecture, reduced osteoclast activity, and dampened inflammatory cytokine production in DP rats. In pre-osteoblasts, KQJF enhanced cell viability, promoted cell cycle progression, and decreased apoptosis. At the molecular level, KQJF treatment upregulated miR-29a-3p and downregulated Dkk-1, thereby activating the Wnt/β-catenin pathway. The interventional studies with miR-29a-3p antagonists and Dkk-1 knockdown further confirmed the regulatory role of the miR-29a-3p/Dkk-1 axis in mediating the effects of KQJF.
Conclusion
KQJF mitigates the deleterious effects of DP by enhancing osteoblastic activity and reducing inflammatory responses, predominantly through the modulation of the miR-29a-3p-Dkk-1/Wnt/β-catenin signaling pathway. These discoveries underscore the therapeutic promise of KQJF in managing bone and inflammatory complications of DP, offering insights into its mechanism, and supporting its use in clinical settings.
{"title":"Kouqiangjie formula alleviates diabetic periodontitis by regulating alveolar bone homeostasis via miR-29a-3p-mediated Dkk-1/Wnt/β-catenin signaling pathway","authors":"Yeke Wu , Min Liu , Jiawei Li , Ranran Gao , Qiongying Hu , Yunfei Xie , Hongling Zhou , Huijing Li , Xiang He , Li Li","doi":"10.1016/j.jep.2024.119270","DOIUrl":"10.1016/j.jep.2024.119270","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Diabetic periodontitis (DP) is a commonly co-occurring complication in diabetes patients characterized by advanced gum disease and bone resorption. Conventional treatment modalities often fail to adequately address the underlying biological disruptions caused by diabetes. The use of traditional medicinal formulas Kouqiangjie Formula (KQJF) potentially offers novel therapeutic approaches for DP, but its detailed regulatory mechanisms remain unclear.</div></div><div><h3>Aim of the study</h3><div>This study aims to investigate the impacts of KQJF on osteoblastic activity and inflammatory responses in a rat model and <em>in vitro</em> pre-osteoblast cultures under conditions mimicking DP, focusing on the involvement of the miR-29a-3p-Dkk-1/Wnt/β-catenin signaling pathway.</div></div><div><h3>Materials and methods</h3><div>Using network pharmacological analysis, micro-CT, histological staining, and an array of molecular biology methodologies including Western blotting, RT-qPCR, and immunofluorescence, we investigated the systemic and cellular responses to KQJF treatment. Both <em>in vivo</em> (rat model) and <em>in vitro</em> (MC3T3-E1 pre-osteoblasts) models subjected to high glucose and lipopolysaccharide (HG + LPS) stress were used to simulate DP conditions.</div></div><div><h3>Results</h3><div>Network pharmacological analyses, incorporating protein-protein interactions and pathway enrichment, disclosed that KQJF interacts with pathways crucial for inflammation and bone metabolism. Experimentally, KQJF significantly preserved alveolar bone architecture, reduced osteoclast activity, and dampened inflammatory cytokine production in DP rats. In pre-osteoblasts, KQJF enhanced cell viability, promoted cell cycle progression, and decreased apoptosis. At the molecular level, KQJF treatment upregulated miR-29a-3p and downregulated Dkk-1, thereby activating the Wnt/β-catenin pathway. The interventional studies with miR-29a-3p antagonists and Dkk-1 knockdown further confirmed the regulatory role of the miR-29a-3p/Dkk-1 axis in mediating the effects of KQJF.</div></div><div><h3>Conclusion</h3><div>KQJF mitigates the deleterious effects of DP by enhancing osteoblastic activity and reducing inflammatory responses, predominantly through the modulation of the miR-29a-3p-Dkk-1/Wnt/β-catenin signaling pathway. These discoveries underscore the therapeutic promise of KQJF in managing bone and inflammatory complications of DP, offering insights into its mechanism, and supporting its use in clinical settings.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"340 ","pages":"Article 119270"},"PeriodicalIF":4.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872233","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 : 2025-01-31DOI: 10.1016/j.jep.2024.119258
Xinzhong Li , Junchi Wang , Jiahui Zhou , Haiyan Xiao , Lina Liu , Zheng Zhang , Jianyong Si , Chengmin Yang , Ming Wang , Jingxue Ye , Guibo Sun
<div><h3>Ethnopharmacological relevance</h3><div><em>Myristica fragrans</em> (Nutmeg) is a commonly used Chinese herbal medicine and edible spice. According to <em>Pharmacopoeia of People's Republic of China</em>, it has the effects of warming the middle and promoting qi, astringent intestines, and antidiarrheal. In the record of <em>Compendium of Materia Medica</em>, it is the myristica fragrans water extract (MFWE) that is utilized for therapeutic purposes of gastrointestinal disorders frequently.</div></div><div><h3>Research purpose</h3><div>This study is to investigate the pharmacodynamic material foundation and molecular mechanism of myristica fragrans on gastric ulcers using UHPLC-Q-Orbitrap-MS/MS with network pharmacology and experimental verification. This may provide theoretical guidance for the clinical use of myristica fragrans, and support a theoretical foundation for its future advancement into natural functional products that can relieve acute gastric ulcers.</div></div><div><h3>Materials and methods</h3><div>Using UHPLC/MS technology and network pharmacology, we identified possible active chemicals molecules, screened out core targets and core pathways, and simulated drug target binding through molecular docking situations. Acute gastric ulcer was caused by intragastric administration of absolute ethanol (0.075 ml/10g). Myristica fragrans water extract (182 mg/kg and 364 mg/kg) was administered orally 14 days in advance. The same method was used to distribute 0.5% carboxymethyl cellulose solution into the Model and Control group. The mice were murdered on the 15th day. Following the sacrifice, the gastric tissue was removed for histological analysis. The tissue needs to detect levels of IL-1β, TNF-α, IL-10, and IL-6 as well as the activity of SOD, GSH-Px, MDA, and MPO. In addition, H&E staining and the TUNEL method were used to observe the effect on the gastric mucosa of mice. Western blot was used to detect apoptosis, ferroptosis, and antioxidation-related proteins.</div></div><div><h3>Results</h3><div>A total of 10 chemical constituents were identified from MFWE using UHPLC-Q-Orbitrap MS/MS and TCMSP database. Through the network pharmacological analysis of these identified components, it was discovered that the protective effect is mainly carried out by six compounds, they are: Myristicin, Myrisligna, Ferulaldehyde, Dehydrodiisoeugenol, 7-Methoxy-4-methylcoumarin, 1,5-Bis(2,5-dimethoxyphenyl) pentane-1,5-dione. Furthermore, MFWE was found to significantly reduce TNF-α, IL-1β, and IL-6, increase IL-10, and alleviate the inflammation caused by alcoholic gastric ulcers. It can lower MDA and MPO, raise SOD and GSH-Px to relieve oxidative stress. Results from network pharmacology indicated that the Akt, JNK, and apoptosis signaling pathways were essential for the therapeutic effects of MFWE on gastric ulcers. Further literature research revealed that Nrf2 and ferroptosis signaling pathways may be related to the role of MFWE. Mole
{"title":"Myristica fragrans water extract modulates multiple biological processes to pre-protect anhydrous ethanol-induced gastric ulcers via Akt/JNK/Nrf2 pathway activation","authors":"Xinzhong Li , Junchi Wang , Jiahui Zhou , Haiyan Xiao , Lina Liu , Zheng Zhang , Jianyong Si , Chengmin Yang , Ming Wang , Jingxue Ye , Guibo Sun","doi":"10.1016/j.jep.2024.119258","DOIUrl":"10.1016/j.jep.2024.119258","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Myristica fragrans</em> (Nutmeg) is a commonly used Chinese herbal medicine and edible spice. According to <em>Pharmacopoeia of People's Republic of China</em>, it has the effects of warming the middle and promoting qi, astringent intestines, and antidiarrheal. In the record of <em>Compendium of Materia Medica</em>, it is the myristica fragrans water extract (MFWE) that is utilized for therapeutic purposes of gastrointestinal disorders frequently.</div></div><div><h3>Research purpose</h3><div>This study is to investigate the pharmacodynamic material foundation and molecular mechanism of myristica fragrans on gastric ulcers using UHPLC-Q-Orbitrap-MS/MS with network pharmacology and experimental verification. This may provide theoretical guidance for the clinical use of myristica fragrans, and support a theoretical foundation for its future advancement into natural functional products that can relieve acute gastric ulcers.</div></div><div><h3>Materials and methods</h3><div>Using UHPLC/MS technology and network pharmacology, we identified possible active chemicals molecules, screened out core targets and core pathways, and simulated drug target binding through molecular docking situations. Acute gastric ulcer was caused by intragastric administration of absolute ethanol (0.075 ml/10g). Myristica fragrans water extract (182 mg/kg and 364 mg/kg) was administered orally 14 days in advance. The same method was used to distribute 0.5% carboxymethyl cellulose solution into the Model and Control group. The mice were murdered on the 15th day. Following the sacrifice, the gastric tissue was removed for histological analysis. The tissue needs to detect levels of IL-1β, TNF-α, IL-10, and IL-6 as well as the activity of SOD, GSH-Px, MDA, and MPO. In addition, H&E staining and the TUNEL method were used to observe the effect on the gastric mucosa of mice. Western blot was used to detect apoptosis, ferroptosis, and antioxidation-related proteins.</div></div><div><h3>Results</h3><div>A total of 10 chemical constituents were identified from MFWE using UHPLC-Q-Orbitrap MS/MS and TCMSP database. Through the network pharmacological analysis of these identified components, it was discovered that the protective effect is mainly carried out by six compounds, they are: Myristicin, Myrisligna, Ferulaldehyde, Dehydrodiisoeugenol, 7-Methoxy-4-methylcoumarin, 1,5-Bis(2,5-dimethoxyphenyl) pentane-1,5-dione. Furthermore, MFWE was found to significantly reduce TNF-α, IL-1β, and IL-6, increase IL-10, and alleviate the inflammation caused by alcoholic gastric ulcers. It can lower MDA and MPO, raise SOD and GSH-Px to relieve oxidative stress. Results from network pharmacology indicated that the Akt, JNK, and apoptosis signaling pathways were essential for the therapeutic effects of MFWE on gastric ulcers. Further literature research revealed that Nrf2 and ferroptosis signaling pathways may be related to the role of MFWE. Mole","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"340 ","pages":"Article 119258"},"PeriodicalIF":4.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872240","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 : 2025-01-31DOI: 10.1016/j.jep.2024.119279
Manman Wang , Yong Zhang , Xueqin Fu , Xuhuan Zou , Jun Xiang , Rui Lan
Ethnopharmacological relevance
Xiao-xu-ming decoction (XXMD), a prominent traditional Chinese medicinal formula historically revered for stroke treatment, demonstrates pronounced efficacy in ameliorating ischemic stroke injury.
Aim of the study
This study aims to investigate the effects and mechanisms of XXMD on neuroprotection subsequent to cerebral ischemia/reperfusion in vivo and in vitro.
Materials and methods
Neurobehavioral test, TTC staining, HE staining and nissl staining were used to examine the neuroprotective effect of XXMD on cerebral ischemia-reperfusion injury induced by middle cerebral artery occlusion (MCAO) in rats. Additionally, we assessed cell viability and injury with CCK8 and lactate dehydrogenase (LDH) assays. The changes in neuronal ultra-structure were observed after oxygen-glucose deprivation and reoxygenation (OGD/R) by transmission electron microscopy (TEM). Network analysis combined with ultrahighperformance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS) predicted the mechanism of XXMD on ischemic stroke injury. Furthermore, the expression of neuroplasticity-related proteins neurofilament 200 (NF200), microtubule-associated protein 2 (MAP2), postsynaptic density protein 95 (PSD95), synaptophysin (SYN), phosphorylated Janus kinase2 (p-JAK2), and phosphorylated signal transduction and activator of transcription 3 (p-STAT3) was evaluated by immunofluorescence staining and Western blot analyses.
Results
XXMD significantly improved Ethology, infarct area and pathological changes after MCAO and reperfusion, reducing morphological and ultrastructural alterations and decreased cell viability in HT22 cells induced by OGD/R. Network pharmacology showed that 1153 compounds of XXMD were matched. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrated that XXMD treated ischemia stroke mainly regulating inflammation reaction-related signaling pathways, atherosclerosish-related signaling pathways. Molecular docking results showed that TP53, AKT1, STAT3, and IL6 are closely bound to the corresponding active ingredients. XXMD treatment significantly reversed the above alternations. XXMD or AG490 up-regulated the expression of neuroplasticity-associated proteins, and reduced phosphorylation of JAK2, STAT3 expression following OGD/R.
Conclusion
XXMD exerts neuroprotective effects by promoting neural plasticity via regulating the JAK2/STAT3 pathway, indicating a promising alternative therapeutic strategy for ischemic stroke.
{"title":"Xiaoxuming decoction enhanced neuroprotection after cerebral ischemia/reperfusion via the JAK2/STAT3 signaling pathway based on UPLC/HRMS, network pharmacology and experimental validation","authors":"Manman Wang , Yong Zhang , Xueqin Fu , Xuhuan Zou , Jun Xiang , Rui Lan","doi":"10.1016/j.jep.2024.119279","DOIUrl":"10.1016/j.jep.2024.119279","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Xiao-xu-ming decoction (XXMD), a prominent traditional Chinese medicinal formula historically revered for stroke treatment, demonstrates pronounced efficacy in ameliorating ischemic stroke injury.</div></div><div><h3>Aim of the study</h3><div>This study aims to investigate the effects and mechanisms of XXMD on neuroprotection subsequent to cerebral ischemia/reperfusion in vivo and in vitro.</div></div><div><h3>Materials and methods</h3><div><em>N</em>eurobehavioral test, TTC staining, HE staining and nissl staining were used to examine the neuroprotective effect of XXMD on cerebral ischemia-reperfusion injury induced by middle cerebral artery occlusion (MCAO) in rats. Additionally, we assessed cell viability and injury with CCK8 and lactate dehydrogenase (LDH) assays. The changes in neuronal ultra-structure were observed after oxygen-glucose deprivation and reoxygenation (OGD/R) by transmission electron microscopy (TEM). Network analysis combined with ultrahighperformance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS) predicted the mechanism of XXMD on ischemic stroke injury. Furthermore, the expression of neuroplasticity-related proteins neurofilament 200 (NF200), microtubule-associated protein 2 (MAP2), postsynaptic density protein 95 (PSD95), synaptophysin (SYN), phosphorylated Janus kinase2 (p-JAK2), and phosphorylated signal transduction and activator of transcription 3 (p-STAT3) was evaluated by immunofluorescence staining and Western blot analyses.</div></div><div><h3>Results</h3><div>XXMD significantly improved Ethology, infarct area and pathological changes after MCAO and reperfusion, reducing morphological and ultrastructural alterations and decreased cell viability in HT22 cells induced by OGD/R. Network pharmacology showed that 1153 compounds of XXMD were matched. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrated that XXMD treated ischemia stroke mainly regulating inflammation reaction-related signaling pathways, atherosclerosish-related signaling pathways. Molecular docking results showed that TP53, AKT1, STAT3, and IL6 are closely bound to the corresponding active ingredients. XXMD treatment significantly reversed the above alternations. XXMD or AG490 up-regulated the expression of neuroplasticity-associated proteins, and reduced phosphorylation of JAK2, STAT3 expression following OGD/R.</div></div><div><h3>Conclusion</h3><div>XXMD exerts neuroprotective effects by promoting neural plasticity via regulating the JAK2/STAT3 pathway, indicating a promising alternative therapeutic strategy for ischemic stroke.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"340 ","pages":"Article 119279"},"PeriodicalIF":4.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895005","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 : 2025-01-31DOI: 10.1016/j.jep.2024.119170
Yuanying Xu , Wenjun Sha , Jun Lu , Shanshan Yu , Xinyan Jin , Cheng Chen , Guangbo Ge , Tao Lei
<div><h3>Ethnopharmacological relevance</h3><div>Vascular endothelial dysfunction (VED) is recognized as a key triggering diabetic vascular complications. Danggui Liuhuang Decoction (DGLHD) has shown potential in mitigating these complications. However, the clinical efficacy of DGLHD in enhancing endothelial function, as well as the molecular mechanisms underlying its alleviation of Type 2 Diabetes-Related Vascular Endothelial Dysfunction (T2DM-VED), remains insufficiently understood.</div></div><div><h3>Aim of the study</h3><div>This study aims to validate the therapeutic efficacy of DGLHD in ameliorating T2DM-VED through clinical research. Furthermore it seeks to analyze the pharmacodynamic basis and molecular mechanisms of DGLHD, elucidating the biological processes through which DGLHD alleviates VED in type 2 diabetes mellitus (T2DM).</div></div><div><h3>Materials and methods</h3><div>Patients diagnosed with “Yin deficiency with hyperactive fire syndrome”, who are at a high risk for atherosclerotic cardiovascular disease (ASCVD) associated with T2DM, were recruited for this study. The effect of DGLHD on vascular endothelial function in T2DM was assessed by measuring the levels of pro-inflammatory factors through enzyme-linked immunosorbent assay (ELISA) and flow-mediated dilation (FMD). The primary components of DGLHD were analyzed using the UHPLC-Q-Exactive Orbitrap system. Potential therapeutic targets of DGLHD were predicted using network pharmacology and molecular docking analysis. To validate the mechanism of DGLHD on T2DM-VED, endothelial injury and inflammation cell models were established using human umbilical vein endothelial cells (HUVECs). A mouse model of diabetic endothelial injury was also developed to observe the effects of DGLHD on pro-inflammatory factors and vascular endothelial factors were observed through immunohistochemistry. Additionally, the effects on the janus kinase 2 (JAK2) / signal transducer and activator of transcription 3 (STAT3) signaling pathway were observed through Western blot experiments.</div></div><div><h3>Results</h3><div>DGLHD was found to contain 201 active components. Network pharmacology analysis indicated that the treatment of T2DM-VED with DGLHD is associated with modulation of the JAK2/STAT3 signaling pathway. Molecular docking analysis demonstrated that small molecules in DGLHD interact with JAK2 and STAT3. Our clinical study demonstrated that DGLHD significantly reduces the levels of pro-inflammatory factors and improves FMD readings in diabetic patients, thereby alleviating T2DM-VED. DGLHD was shown to inhibit the phosphorylation of JAK2 and STAT3, which blocks the JAK2/STAT3 signaling pathway transmission, reducing the release of pro-inflammatory and vascular endothelial growth factors, and preventing the inflammatory response <em>in vivo</em> and <em>in vitro</em>.</div></div><div><h3>Conclusion</h3><div>This study demonstrates the potential efficacy of DGLHD in improving endothelial functi
{"title":"Danggui Liuhuang Decoction ameliorates endothelial dysfunction by inhibiting the JAK2/STAT3 mediated inflammation","authors":"Yuanying Xu , Wenjun Sha , Jun Lu , Shanshan Yu , Xinyan Jin , Cheng Chen , Guangbo Ge , Tao Lei","doi":"10.1016/j.jep.2024.119170","DOIUrl":"10.1016/j.jep.2024.119170","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Vascular endothelial dysfunction (VED) is recognized as a key triggering diabetic vascular complications. Danggui Liuhuang Decoction (DGLHD) has shown potential in mitigating these complications. However, the clinical efficacy of DGLHD in enhancing endothelial function, as well as the molecular mechanisms underlying its alleviation of Type 2 Diabetes-Related Vascular Endothelial Dysfunction (T2DM-VED), remains insufficiently understood.</div></div><div><h3>Aim of the study</h3><div>This study aims to validate the therapeutic efficacy of DGLHD in ameliorating T2DM-VED through clinical research. Furthermore it seeks to analyze the pharmacodynamic basis and molecular mechanisms of DGLHD, elucidating the biological processes through which DGLHD alleviates VED in type 2 diabetes mellitus (T2DM).</div></div><div><h3>Materials and methods</h3><div>Patients diagnosed with “Yin deficiency with hyperactive fire syndrome”, who are at a high risk for atherosclerotic cardiovascular disease (ASCVD) associated with T2DM, were recruited for this study. The effect of DGLHD on vascular endothelial function in T2DM was assessed by measuring the levels of pro-inflammatory factors through enzyme-linked immunosorbent assay (ELISA) and flow-mediated dilation (FMD). The primary components of DGLHD were analyzed using the UHPLC-Q-Exactive Orbitrap system. Potential therapeutic targets of DGLHD were predicted using network pharmacology and molecular docking analysis. To validate the mechanism of DGLHD on T2DM-VED, endothelial injury and inflammation cell models were established using human umbilical vein endothelial cells (HUVECs). A mouse model of diabetic endothelial injury was also developed to observe the effects of DGLHD on pro-inflammatory factors and vascular endothelial factors were observed through immunohistochemistry. Additionally, the effects on the janus kinase 2 (JAK2) / signal transducer and activator of transcription 3 (STAT3) signaling pathway were observed through Western blot experiments.</div></div><div><h3>Results</h3><div>DGLHD was found to contain 201 active components. Network pharmacology analysis indicated that the treatment of T2DM-VED with DGLHD is associated with modulation of the JAK2/STAT3 signaling pathway. Molecular docking analysis demonstrated that small molecules in DGLHD interact with JAK2 and STAT3. Our clinical study demonstrated that DGLHD significantly reduces the levels of pro-inflammatory factors and improves FMD readings in diabetic patients, thereby alleviating T2DM-VED. DGLHD was shown to inhibit the phosphorylation of JAK2 and STAT3, which blocks the JAK2/STAT3 signaling pathway transmission, reducing the release of pro-inflammatory and vascular endothelial growth factors, and preventing the inflammatory response <em>in vivo</em> and <em>in vitro</em>.</div></div><div><h3>Conclusion</h3><div>This study demonstrates the potential efficacy of DGLHD in improving endothelial functi","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"340 ","pages":"Article 119170"},"PeriodicalIF":4.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142768108","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 : 2025-01-31DOI: 10.1016/j.jep.2024.119215
Ya Wang , Xingjiang Liao , Jinjuan Zhang , Yaxin Yang , Yanyan Gao , Chunlei Zhang , Xiaoli Guo , Qinfeng Zhu , Jing Li , Lingling Yu , Guobo Xu , Xiang Fang , Shang-Gao Liao
Ethnopharmacological relevance
The seeds of Hovenia acerba water extract (HAW) are used as an edible traditional Chinese medicine to treat diseases related to hyperuricemia (HUA).
Aim of the study
To evaluate HAW for its anti-HUA effect and to figure out their underlying mechanisms.
Materials and methods
The anti-HUA effects were evaluated on a mouse model by testing HAW's effects on the levels of serum uric acid (SUA), the biochemical indicators of liver and kidney function, and the histology of liver and kidney. Body weight and organ coefficients were determined for safety evaluation. RT-qPCR, Western blot and transcriptomic analysis was applied to investigate key mRNAs, proteins and signaling pathways.
Results
HAW significantly reduced the serum levels of UA, ALT, AST, and xanthine oxidase (XOD) and histologically alleviated the liver damage in HUA mice with no negative effect on body weight and organ coefficients. HAW markedly inhibited hepatic XOD activity and protein expression, significantly down-regulated mRNA and protein expressions of urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9), and up-regulated those of ATP transporter G2 (ABCG2) and renal organic anion transporter 1 (OAT1). RNA-seq analysis showed that 248 HUA-induced differential expression genes (DEGs) were reversed by HAW in the kidney. qRT-PCR analysis showed that regulation of the expressions of HUA-related inflammatory genes were involved.
Conclusion
HAW possessed remarkable anti-HUA effect. The mechanism involved XOD inhibition to reduce uric acid production, up-regulation of ABCG2 and OAT1 to increase uric acid excretion, and down-regulation of GLUT9 and URAT1 to inhibit uric acid reabsorption, and regulation of HUA-related inflammatory genes.
{"title":"Anti-hyperuricemic effects of the seeds of Hovenia acerba in hyperuricemia mice","authors":"Ya Wang , Xingjiang Liao , Jinjuan Zhang , Yaxin Yang , Yanyan Gao , Chunlei Zhang , Xiaoli Guo , Qinfeng Zhu , Jing Li , Lingling Yu , Guobo Xu , Xiang Fang , Shang-Gao Liao","doi":"10.1016/j.jep.2024.119215","DOIUrl":"10.1016/j.jep.2024.119215","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>The seeds of <em>Hovenia acerba</em> water extract (HAW) are used as an edible traditional Chinese medicine to treat diseases related to hyperuricemia (HUA).</div></div><div><h3>Aim of the study</h3><div>To evaluate HAW for its anti-HUA effect and to figure out their underlying mechanisms.</div></div><div><h3>Materials and methods</h3><div>The anti-HUA effects were evaluated on a mouse model by testing HAW's effects on the levels of serum uric acid (SUA), the biochemical indicators of liver and kidney function, and the histology of liver and kidney. Body weight and organ coefficients were determined for safety evaluation. RT-qPCR, Western blot and transcriptomic analysis was applied to investigate key mRNAs, proteins and signaling pathways.</div></div><div><h3>Results</h3><div>HAW significantly reduced the serum levels of UA, ALT, AST, and xanthine oxidase (XOD) and histologically alleviated the liver damage in HUA mice with no negative effect on body weight and organ coefficients. HAW markedly inhibited hepatic XOD activity and protein expression, significantly down-regulated mRNA and protein expressions of urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9), and up-regulated those of ATP transporter G2 (ABCG2) and renal organic anion transporter 1 (OAT1). RNA-seq analysis showed that 248 HUA-induced differential expression genes (DEGs) were reversed by HAW in the kidney. qRT-PCR analysis showed that regulation of the expressions of HUA-related inflammatory genes were involved.</div></div><div><h3>Conclusion</h3><div>HAW possessed remarkable anti-HUA effect. The mechanism involved XOD inhibition to reduce uric acid production, up-regulation of ABCG2 and OAT1 to increase uric acid excretion, and down-regulation of GLUT9 and URAT1 to inhibit uric acid reabsorption, and regulation of HUA-related inflammatory genes.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"340 ","pages":"Article 119215"},"PeriodicalIF":4.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792009","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}
Ceratonia siliqua L., is a species of significant nutritional and industrial interest with extensive traditional uses. This fabaceae is renowned for its medicinal properties, including the treatment of high blood pressure. Due to its chemical composition, carob exhibits several valuable therapeutic functions such as antioxidant, antidiarrheal, antidiabetic, and antibacterial actions.
Aim of the review
This study investigates the chemical composition of Ceratonia siliqua L. leaves aqueous extract (CsAE) and explores the vasorelaxant effect and its underlying mechanisms. Acute toxicity and antioxidant activity of CsAE were also examined.
Methods
The phytochemical profile was elucidated using TLC and UHPLC-MS. The vasorelaxant effect and mechanisms were studied on thoracic aortic rings from normotensive rats, using various antagonists. Acute toxicity was assessed by orally administering the extract to mice. Antioxidant activity was evaluated using β-carotene bleaching and DPPH.
Results
TLC analysis of CsAE reveals flavonoids and hydrolysable tannins. Gallic acid, myricitrin, quercitrin as well as galloylglucopyranoside derivatives were identified by UHPLC-MS. CsAE relaxed phenylephrine-precontracted aorta in a concentration-dependent manner. This response was reduced when the aorta was denuded or pretreated with L-NAME, hydroxocobalamin, ODQ, 4-AP, TEA, calmidazolium chloride, and thapsigargin. CsAE showed significant antioxidant activity with no observed toxicity in the experimental animals.
Conclusion
CsAE has a significant vasodilatory effect, mediated through the CaM/eNOS/sGC pathway, activation of Kca and Kv, and intracellular calcium mobilization into SERCA. It also exhibits strong antioxidant activity, with no observed toxicity in the experimental animals. These findings represent the first evidence of the vasorelaxant effect of Ceratonia siliqua L. leaves from Eastern Morocco.
{"title":"Carob leaves: Phytochemistry, antioxidant properties, vasorelaxant effect and mechanism of action","authors":"Widad Dahmani , Zachée Louis Evariste Akissi , Nabia Elaouni , Nour Elhouda Bouanani , Hassane Mekhfi , Mohamed Bnouham , Abdelkhaleq Legssyer , Sevser Sahpaz , Abderrahim Ziyyat","doi":"10.1016/j.jep.2024.119226","DOIUrl":"10.1016/j.jep.2024.119226","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Ceratonia siliqua</em> L., is a species of significant nutritional and industrial interest with extensive traditional uses. This fabaceae is renowned for its medicinal properties, including the treatment of high blood pressure. Due to its chemical composition, carob exhibits several valuable therapeutic functions such as antioxidant, antidiarrheal, antidiabetic, and antibacterial actions.</div></div><div><h3>Aim of the review</h3><div>This study investigates the chemical composition of <em>Ceratonia siliqua</em> L. leaves aqueous extract (CsAE) and explores the vasorelaxant effect and its underlying mechanisms. Acute toxicity and antioxidant activity of CsAE were also examined.</div></div><div><h3>Methods</h3><div>The phytochemical profile was elucidated using TLC and UHPLC-MS. The vasorelaxant effect and mechanisms were studied on thoracic aortic rings from normotensive rats, using various antagonists. Acute toxicity was assessed by orally administering the extract to mice. Antioxidant activity was evaluated using β-carotene bleaching and DPPH.</div></div><div><h3>Results</h3><div>TLC analysis of CsAE reveals flavonoids and hydrolysable tannins. Gallic acid, myricitrin, quercitrin as well as galloylglucopyranoside derivatives were identified by UHPLC-MS. CsAE relaxed phenylephrine-precontracted aorta in a concentration-dependent manner. This response was reduced when the aorta was denuded or pretreated with L-NAME, hydroxocobalamin, ODQ, 4-AP, TEA, calmidazolium chloride, and thapsigargin. CsAE showed significant antioxidant activity with no observed toxicity in the experimental animals.</div></div><div><h3>Conclusion</h3><div>CsAE has a significant vasodilatory effect, mediated through the CaM/eNOS/sGC pathway, activation of Kc<sub>a</sub> and K<sub>v</sub>, and intracellular calcium mobilization into SERCA. It also exhibits strong antioxidant activity, with no observed toxicity in the experimental animals. These findings represent the first evidence of the vasorelaxant effect of <em>Ceratonia siliqua</em> L. leaves from Eastern Morocco.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"340 ","pages":"Article 119226"},"PeriodicalIF":4.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801075","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}
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