{"title":"Angelicin improves osteoporosis in ovariectomized rats by reducing ROS production in osteoclasts through regulation of the KAT6A/Nrf2 signalling pathway.","authors":"Xiao-Feng Liu, Yi-Tao Liao, Jia-Hao Shao, Dan-Dan He, Zhi-Hong Fan, Ye-Nan Xu, Chao Li, Xian Zhang","doi":"10.1186/s13020-024-00961-7","DOIUrl":"10.1186/s13020-024-00961-7","url":null,"abstract":"<p><strong>Background: </strong>Angelicin, which is found in Psoralea, can help prevent osteoporosis by stopping osteoclast formation, although the precise mechanism remains unclear.</p><p><strong>Methods: </strong>We evaluated the effect of angelicin on the oxidative stress level of osteoclasts using ovariectomized osteoporosis model rats and RAW264.7 cells. Changes in the bone mass of the femur were investigated using H&E staining and micro-CT. ROS content was investigated by DHE fluorescence labelling. Osteoclast-related genes and proteins were examined for expression using Western blotting, immunohistochemistry, tartrate-resistant acid phosphatase staining, and real-time quantitative PCR. The influence of angelicin on osteoclast development was also evaluated using the MTT assay, double luciferin assay, chromatin immunoprecipitation, immunoprecipitation and KAT6A siRNA transfection.</p><p><strong>Results: </strong>Rats treated with angelicin had considerably higher bone mineral density and fewer osteoclasts. Angelicin prevented RAW264.7 cells from differentiating into osteoclasts in vitro when stimulated by RANKL. Experiments revealed reduced ROS levels and significantly upregulated intracellular KAT6A, HO-1, and Nrf2 following angelicin treatment. The expression of genes unique to osteoclasts, such as MMP9 and NFATc1, was also downregulated. Finally, KAT6A siRNA transfection increased intracellular ROS levels while decreasing KAT6A, Nrf2, and HO-1 protein expression in osteoclasts. However, in the absence of KAT6A siRNA transfection, angelicin greatly counteracted this effect in osteoclasts.</p><p><strong>Conclusions: </strong>Angelicin increased the expression of KAT6A. This enhanced KAT6A expression helps to activate the Nrf2/HO-1 antioxidant stress system and decrease ROS levels in osteoclasts, thus inhibiting oxidative stress levels and osteoclast formation.</p>","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"19 1","pages":"91"},"PeriodicalIF":5.3,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11218408/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141491121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chinese MedicinePub Date : 2024-07-02DOI: 10.1186/s13020-024-00964-4
Ting Zhang, Wenqiao An, Shengjie You, Shilin Chen, Sanyin Zhang
{"title":"G protein-coupled receptors and traditional Chinese medicine: new thinks for the development of traditional Chinese medicine.","authors":"Ting Zhang, Wenqiao An, Shengjie You, Shilin Chen, Sanyin Zhang","doi":"10.1186/s13020-024-00964-4","DOIUrl":"10.1186/s13020-024-00964-4","url":null,"abstract":"<p><p>G protein-coupled receptors (GPCRs) widely exist in vivo and participate in many physiological processes, thus emerging as important targets for drug development. Approximately 30% of the Food and Drug Administration (FDA)-approved drugs target GPCRs. To date, the 'one disease, one target, one molecule' strategy no longer meets the demands of drug development. Meanwhile, small-molecule drugs account for 60% of FDA-approved drugs. Traditional Chinese medicine (TCM) has garnered widespread attention for its unique theoretical system and treatment methods. TCM involves multiple components, targets and pathways. Centered on GPCRs and TCM, this paper discusses the similarities and differences between TCM and GPCRs from the perspectives of syndrome of TCM, the consistency of TCM's multi-component and multi-target approaches and the potential of GPCRs and TCM in the development of novel drugs. A novel strategy, 'simultaneous screening of drugs and targets', was proposed and applied to the study of GPCRs. We combine GPCRs with TCM to facilitate the modernisation of TCM, provide valuable insights into the rational application of TCM and facilitate the research and development of novel drugs. This study offers theoretical support for the modernisation of TCM and introduces novel ideas for development of safe and effective drugs.</p>","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"19 1","pages":"92"},"PeriodicalIF":5.3,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11218379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141491122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chinese MedicinePub Date : 2024-07-02DOI: 10.1186/s13020-024-00936-8
Yijie Gao, Baofu Wang, Gaofeng Qin, Shichao Liang, Jiajie Yin, Hong Jiang, Mengru Liu, Xianlun Li
{"title":"Therapeutic potentials of allicin in cardiovascular disease: advances and future directions.","authors":"Yijie Gao, Baofu Wang, Gaofeng Qin, Shichao Liang, Jiajie Yin, Hong Jiang, Mengru Liu, Xianlun Li","doi":"10.1186/s13020-024-00936-8","DOIUrl":"10.1186/s13020-024-00936-8","url":null,"abstract":"<p><p>Cardiovascular disease (CVD) remains the predominant cause of mortality and disability worldwide. Against this backdrop, finding effective drugs for the pharmacological treatment of CVD has become one of the most urgent and challenging issues in medical research. Garlic (Allium sativum L.) is one of the oldest plants and is world-renowned for its dietary and medicinal values. Allicin (diallyl thiosulfinate) is one of the primary natural active ingredients in garlic, which has been proven to have powerful cardioprotective effects and mediate various pathological processes related to CVD, such as inflammatory factor secretion, myocardial cell apoptosis, oxidative stress, and more. Therefore, allicin holds a promising application prospect in the treatment of CVD. This review summarized the biological functions of allicin and its potential mechanisms in CVD, including antioxidation, anti-inflammation, and anti-apoptosis effects. Reckoning with these, we delved into recent studies on allicin's cardioprotective effects concerning various CVDs, such as atherosclerosis, hypertension, myocardial infarction, arrhythmia, cardiac hypertrophy, heart failure, and cardiotoxicity. Further, considering the tremendous advancement in nanomedicine, nanotechnology-based drug delivery systems show promise in addressing limitations of allicin's clinical applications, including improving its solubility, stability, and bioavailability. Through this review, we hope to provide a reference for further research on allicin in cardioprotection and drug development.</p>","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"19 1","pages":"93"},"PeriodicalIF":5.3,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11218272/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141491123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"An optimal combination of four active components in Huangqin decoction for the synergistic sensitization of irinotecan against colorectal cancer.","authors":"Hongyan Zhou, Dingxin Hu, Xian Zhao, Siyuan Qin, Qiyao Nong, Yuan Tian, Zunjian Zhang, Haijuan Dong, Pei Zhang, Fengguo Xu","doi":"10.1186/s13020-024-00967-1","DOIUrl":"10.1186/s13020-024-00967-1","url":null,"abstract":"<p><strong>Background: </strong>Irinotecan (CPT-11) is a first-line treatment for advanced colorectal cancer (CRC). Four components (baicalin, baicalein, wogonin, and glycyrrhizic acid) derived from Huangqin Decoction (HQD) have been proven to enhance the anticancer activity of CPT-11 in our previous study.</p><p><strong>Objective: </strong>This study aimed to determine the optimal combination of the four components for sensitizing CPT-11 as well as to explore the underlying mechanism.</p><p><strong>Methods: </strong>The orthogonal design method was applied to obtain candidate combinations (Cmb1-9) of the four components. The influence of different combinations on the anticancer effect of CPT-11 was first evaluated in vitro by cell viability, wound healing ability, cloning formation, apoptosis, and cell cycle arrest. Then, a CRC xenograft mice model was constructed to evaluate the anticancer effect of the optimal combination in vivo. Potential mechanisms of the optimal combination exerting a sensitization effect combined with CPT-11 against CRC were analyzed by targeted metabolomics.</p><p><strong>Results: </strong>In vitro experiments determined that Cmb8 comprised of baicalin, baicalein, wogonin, and glycyrrhizic acid at the concentrations of 17 μM, 47 μM, 46.5 μM and 9.8 μM respectively was the most effective combination. Importantly, the cell viability assay showed that Cmb8 exhibited synergistic anticancer activity in combination with CPT-11. In in vivo experiments, this combination (15 mg/kg of baicalin, 24 mg/kg of baicalein, 24 mg/kg of wogonin, and 15 mg/kg of glycyrrhizic acid) also showed a synergistic anticancer effect. Meanwhile, inflammatory factors and pathological examination of the colon showed that Cmb8 could alleviate the gastrointestinal damage induced by CPT-11. Metabolic profiling of the tumors suggested that the synergistic anticancer effect of Cmb8 might be related to the regulation of fatty acid metabolism.</p><p><strong>Conclusion: </strong>The optimal combination of four components derived from HQD for the synergistic sensitization of CPT-11 against CRC was identified.</p>","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"19 1","pages":"94"},"PeriodicalIF":5.3,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11218176/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141491040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chinese MedicinePub Date : 2024-06-29DOI: 10.1186/s13020-024-00963-5
Lan Wang, Qian Zhang, Peng Zhang, Bowen Wu, Jun Chen, Jiamin Gong, Kaiqiang Tang, Shiyu Du, Shao Li
{"title":"Development of an artificial intelligent model for pre-endoscopic screening of precancerous lesions in gastric cancer.","authors":"Lan Wang, Qian Zhang, Peng Zhang, Bowen Wu, Jun Chen, Jiamin Gong, Kaiqiang Tang, Shiyu Du, Shao Li","doi":"10.1186/s13020-024-00963-5","DOIUrl":"10.1186/s13020-024-00963-5","url":null,"abstract":"<p><strong>Background: </strong>Given the high cost of endoscopy in gastric cancer (GC) screening, there is an urgent need to explore cost-effective methods for the large-scale prediction of precancerous lesions of gastric cancer (PLGC). We aim to construct a hierarchical artificial intelligence-based multimodal non-invasive method for pre-endoscopic risk screening, to provide tailored recommendations for endoscopy.</p><p><strong>Methods: </strong>From December 2022 to December 2023, a large-scale screening study was conducted in Fujian, China. Based on traditional Chinese medicine theory, we simultaneously collected tongue images and inquiry information from 1034 participants, considering the potential of these data for PLGC screening. Then, we introduced inquiry information for the first time, forming a multimodality artificial intelligence model to integrate tongue images and inquiry information for pre-endoscopic screening. Moreover, we validated this approach in another independent external validation cohort, comprising 143 participants from the China-Japan Friendship Hospital.</p><p><strong>Results: </strong>A multimodality artificial intelligence-assisted pre-endoscopic screening model based on tongue images and inquiry information (AITonguequiry) was constructed, adopting a hierarchical prediction strategy, achieving tailored endoscopic recommendations. Validation analysis revealed that the area under the curve (AUC) values of AITonguequiry were 0.74 for overall PLGC (95% confidence interval (CI) 0.71-0.76, p < 0.05) and 0.82 for high-risk PLGC (95% CI 0.82-0.83, p < 0.05), which were significantly and robustly better than those of the independent use of either tongue images or inquiry information alone. In addition, AITonguequiry has superior performance compared to existing PLGC screening methodologies, with the AUC value enhancing 45% in terms of PLGC screening (0.74 vs. 0.51, p < 0.05) and 52% in terms of high-risk PLGC screening (0.82 vs. 0.54, p < 0.05). In the independent external verification, the AUC values were 0.69 for PLGC and 0.76 for high-risk PLGC.</p><p><strong>Conclusion: </strong>Our AITonguequiry artificial intelligence model, for the first time, incorporates inquiry information and tongue images, leading to a higher precision and finer-grained pre-endoscopic screening of PLGC. This enhances patient screening efficiency and alleviates patient burden.</p>","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"19 1","pages":"90"},"PeriodicalIF":5.3,"publicationDate":"2024-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11218324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141476050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chinese MedicinePub Date : 2024-06-22DOI: 10.1186/s13020-024-00960-8
Qiqi He, Julie Meneely, Irene R Grant, Jason Chin, Séamus Fanning, Chen Situ
{"title":"Phytotherapeutic potential against MRSA: mechanisms, synergy, and therapeutic prospects.","authors":"Qiqi He, Julie Meneely, Irene R Grant, Jason Chin, Séamus Fanning, Chen Situ","doi":"10.1186/s13020-024-00960-8","DOIUrl":"10.1186/s13020-024-00960-8","url":null,"abstract":"<p><strong>Background: </strong>Rising resistance to antimicrobials, particularly in the case of methicillin-resistant Staphylococcus aureus (MRSA), represents a formidable global health challenge. Consequently, it is imperative to develop new antimicrobial solutions. This study evaluated 68 Chinese medicinal plants renowned for their historical applications in treating infectious diseases.</p><p><strong>Methods: </strong>The antimicrobial efficacy of medicinal plants were evaluated by determining their minimum inhibitory concentration (MIC) against MRSA. Safety profiles were assessed on human colorectal adenocarcinoma (Caco-2) and hepatocellular carcinoma (HepG2) cells. Mechanistic insights were obtained through fluorescence and transmission electron microscopy (FM and TEM). Synergistic effects with vancomycin were investigated using the Fractional Inhibitory Concentration Index (FICI).</p><p><strong>Results: </strong>Rheum palmatum L., Arctium lappa L. and Paeonia suffructicosaas Andr. have emerged as potential candidates with potent anti-MRSA properties, with an impressive low MIC of 7.8 µg/mL, comparable to the 2 µg/mL MIC of vancomycin served as the antibiotic control. Crucially, these candidates demonstrated significant safety profiles when evaluated on Caco-2 and HepG2 cells. Even at 16 times the MIC, the cell viability ranged from 83.3% to 95.7%, highlighting their potential safety. FM and TEM revealed a diverse array of actions against MRSA, such as disrupting the cell wall and membrane, interference with nucleoids, and inducing morphological alterations resembling pseudo-multicellular structures in MRSA. Additionally, the synergy between vancomycin and these three plant extracts was evident against MRSA (FICI < 0.5). Notably, aqueous extract of R. palmatum at 1/4 MIC significantly reduced the vancomycin MIC from 2 µg/mL to 0.03 µg/mL, making a remarkable 67-fold decrease.</p><p><strong>Conclusions: </strong>This study unveil new insights into the mechanistic actions and pleiotropic antibacterial effectiveness of these medicinal plants against resistant bacteria, providing robust evidence for their potential use as standalone or in conjunction with antibiotics, to effectively combat antimicrobial resistance, particularly against MRSA.</p>","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"19 1","pages":"89"},"PeriodicalIF":5.3,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11193263/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141440224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chinese MedicinePub Date : 2024-06-19DOI: 10.1186/s13020-024-00947-5
Guiyun Wang, Weixi Xie, Lang Deng, Xiaoting Huang, Mei Sun, Wei Liu, Siyuan Tang
{"title":"Nrf2 mediates the effects of shionone on silica-induced pulmonary fibrosis.","authors":"Guiyun Wang, Weixi Xie, Lang Deng, Xiaoting Huang, Mei Sun, Wei Liu, Siyuan Tang","doi":"10.1186/s13020-024-00947-5","DOIUrl":"10.1186/s13020-024-00947-5","url":null,"abstract":"<p><strong>Background: </strong>Extended contact with silica particles can lead to Silicosis, a chronic lung condition lacking established treatment protocols or clear mechanisms of development. The urgency for innovative treatments arises from the unavailability of effective treatment methodologies. The origin of silica-induced pulmonary fibrosis includes essential processes such as macrophage activation and the conversion of fibroblasts into myofibroblasts, with oxidative stress playing a pivotal role. Shionone (SHI), a triterpenoid extracted from the Aster tataricus plant, is recognized for its extensive health benefits. This study explores the capability of SHI to alleviate the effects of silica-induced lung fibrosis in mice.</p><p><strong>Methods: </strong>This investigation explored the impact of SHI on lung inflammation and fibrosis at different stages (early and late) triggered by silica in mice, focusing specifically on the initial and more developed phases. It comprised an analysis of isolated peritoneal macrophages and fibroblasts extracted from mice to elucidate SHI's therapeutic potential and its underlying mechanism. The methodology employed encompassed quantitative PCR, immunofluorescence, flow cytometry, and western blotting to examine macrophage activity and their transition into myofibroblasts. The activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway by SHI was confirmed via immunofluorescence and western blot studies. SHI's antioxidative properties were evidenced by the measurement of reactive oxygen species (ROS) and mitochondrial ROS within both macrophages and fibroblasts, using 2', 7'-dichlorodihydrofluorescein diacetate and MitoSOX, respectively. The relevance of SHI was further underscored by applying ML385 and Nrf2 siRNA to gauge its effectiveness.</p><p><strong>Results: </strong>Starting SHI treatment early countered the harmful effects of lung inflammation and fibrosis caused by silica, while initiating SHI at a later phase decelerated the advancement of fibrosis. SHI's action was linked to the activation of the Nrf2 signaling pathway, a boost in antioxidant enzyme levels, and a decrease in oxidative stress and inflammation in macrophages affected by silica. Furthermore, SHI prevented the conversion of fibroblasts into myofibroblasts prompted by TGF-β, along with the resultant oxidative stress. The beneficial outcomes of SHI were negated when ML385 and Nrf2 siRNA were applied, highlighting the pivotal role of the Nrf2 pathway in SHI's efficacy.</p><p><strong>Conclusion: </strong>SHI plays a significant role in stimulating the Nrf2 pathway, thereby defending against silica-induced oxidative stress and inflammatory reactions in macrophages, and inhibiting the conversion of fibroblasts to myofibroblasts due to TGF-β. This suggests that SHI is a viable option for treating lung inflammation and fibrosis in mice suffering from silicosis.</p>","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"19 1","pages":"88"},"PeriodicalIF":5.3,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11188511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141426445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chinese MedicinePub Date : 2024-06-15DOI: 10.1186/s13020-024-00958-2
Jianhua Zhen, Yini Li, Yunan Zhang, Yali Zhou, Lu Zhao, Guangrui Huang, Anlong Xu
{"title":"Shaoyao Decoction reduced T lymphocyte activation by regulating of intestinal flora and 5-hydroxytryptamine metabolism in ulcerative colitis.","authors":"Jianhua Zhen, Yini Li, Yunan Zhang, Yali Zhou, Lu Zhao, Guangrui Huang, Anlong Xu","doi":"10.1186/s13020-024-00958-2","DOIUrl":"10.1186/s13020-024-00958-2","url":null,"abstract":"<p><strong>Background: </strong>Shaoyao Decoction (SYD) is a widely recognized herbal formula utilized in traditional Chinese medicine for the treatment of diarrhea. Although it has demonstrated significant effectiveness in clinical practice for treating ulcerative colitis, the precise mechanisms by which it operates remain largely elusive.</p><p><strong>Methods: </strong>The active ingredients of SYD were obtained by ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS), which were used to explore the potential pharmacological mechanism based on TCMSP (Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform) and PANTHER (Protein Analysis Through Evolutionary Relationships) classification system. In a mouse model of dextran sulfate sodium (DSS)-induced colitis, mRNA sequencing, 16S rDNA sequencing and targeted metabolomics techniques were used to elucidate the mechanisms of SYD, and immunohistochemistry, immunofluorescence, enzyme linked immunosorbent assay, real time quantitative polymerase chain reaction and western blot were used to test the key targets. In addition, QGP-1 and H9 cells were performed to validate the discoveries from the animal experiments.</p><p><strong>Results: </strong>In the mouse model of DSS-induced colitis, SYD effectively alleviated symptoms such as bloody stool, tissue damage, inflammation, intestinal flora dysbiosis and abnormal gene expression. Analyses of both differential expressed genes in colonic tissue and predicted 16S rDNA genes, as well as the analyses of targeted genes from TCMSP based on the active ingredients in UPLC-MS/MS of SYD, uncovered the enrichment of pathways involved in the biosynthesis and degredation of 5-hydroxytryptamine (5-HT). Interestingly, SYD suppressed the relative abundance of key genes in 5-HT synthesis, Tph1(Tryptophan hydroxylase 1) and Ddc (Dopa decarboxylase), in faeces from DSS-induced mice, leading to a reduction in the concentration of fecal 5-HT. Moreover, SYD augmented the production of butyric acid. Subsequently, increasing butyric acid influenced the metabolism of 5-HT in the organism through G protein-coupled receptor 43 by impeding its synthesis, facilitating its transport and degredation. These findings were additionally corroborated in a model utilizing enterochromaffin cell (QGP-1 cells). Furthermore, reduced levels of 5-HT hindered the activation of T lymphocytes (H9 cells) via the PKC (Protein kinase C) and NF-κB (Nuclear factor kappa-B) signaling pathways, by means of HTR1A (5-HT receptor 1A) and HTR3 (5-HT receptor 3). Additionally, diminished secretion of 5-HT resulted in reduced secretion of associated cytokines, thereby alleviating inflammation in the colon.</p><p><strong>Conclusion: </strong>Through modulation of T lymphocyte activation mediated by 5-HT metabolism in the local colon via the intestinal flora and its metabolite, SYD effectively mitigated colonic inflammation in DSS-induced mice.</p>","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"19 1","pages":"87"},"PeriodicalIF":4.9,"publicationDate":"2024-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11180410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141327273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chinese MedicinePub Date : 2024-06-15DOI: 10.1186/s13020-024-00946-6
Qiong Zhao, Lu Chen, Xin Zhang, Hua Yang, Yi Li, Ping Li
{"title":"β-elemene promotes microglial M2-like polarization against ischemic stroke via AKT/mTOR signaling axis-mediated autophagy.","authors":"Qiong Zhao, Lu Chen, Xin Zhang, Hua Yang, Yi Li, Ping Li","doi":"10.1186/s13020-024-00946-6","DOIUrl":"10.1186/s13020-024-00946-6","url":null,"abstract":"<p><strong>Background: </strong>Resident microglia- and peripheric macrophage-mediated neuroinflammation plays a predominant role in the occurrence and development of ischemic stroke. Microglia undergo polarization to M1/M2-like phenotype under stress stimulation, which mediates intracellular inflammatory response. β-elemene is a natural sesquiterpene and possesses potent anti-inflammatory activity. This study aimed to investigate the anti-inflammatory efficacy and mechanism of β-elemene in ischemic stroke from the perspective of balancing microglia M1/M2-like polarization.</p><p><strong>Methods: </strong>The middle cerebral artery occlusion (MCAO) model and photothrombotic stroke model were established to explore the regulation effect of β-elemene on the cerebral ischemic injury. The LPS and IFN-γ stimulated BV-2 cells were used to demonstrate the anti-inflammatory effects and potential mechanism of β-elemene regulating M1/M2-like polarization in vitro.</p><p><strong>Results: </strong>In C57BL/6 J mice subjected to MCAO model and photothrombotic stroke model, β-elemene attenuated neurological deficit, reduced the infarction volume and neuroinflammation, thus improving ischemic stroke injury. β-elemene promoted the phenotype transformation of microglia from M1-like to M2-like, which prevented neurons from oxygen and glucose deprivation/reoxygenation (OGD/R) injury by inhibiting inflammatory factor release, thereby reducing neuronal apoptosis. Mechanically, β-elemene prevented the activation of TLR4/NF-κΒ and MAPK signaling pathway and increased AKT/mTOR mediated-autophagy, thereby promoting M2-like polarization of microglia.</p><p><strong>Conclusions: </strong>These results indicated that β-elemene improved cerebral ischemic injury and promoted the transformation of microglia phenotype from M1-like to M2-like, at least in part, through AKT/mTOR-mediated autophagy. This study demonstrated that β-elemene might serve as a promising drug for alleviating ischemic stroke injury.</p>","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"19 1","pages":"86"},"PeriodicalIF":4.9,"publicationDate":"2024-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11179363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141327274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Liguzinediol potentiates the metabolic remodeling by activating the AMPK/SIRT3 pathway and represses Caspase-3/GSDME-mediated pyroptosis to ameliorate cardiotoxicity.","authors":"Weijie Zhu, Naqi Lian, Jia Wang, Fengming Zhao, Bowen Liu, Jiaxing Sheng, Chenyan Zhang, Xuan Zhou, Wenbai Gao, Chen Xie, Haoyu Gu, Yuxin Zhang, Mianli Bian, Miao Jiang, Yu Li","doi":"10.1186/s13020-024-00955-5","DOIUrl":"10.1186/s13020-024-00955-5","url":null,"abstract":"<p><strong>Background: </strong>Liguzinediol (Lig) has emerged as a promising candidate for mitigating Doxorubicin (DOX)-induced cardiotoxicity, a significant limitation in the clinical application of this widely used antineoplastic drug known for its efficacy. This study aimed to explore the effects and potential mechanisms underlying Lig's protective role against DOX-induced cardiotoxicity.</p><p><strong>Methods: </strong>C57BL/6 mice were treated with DOX. Cardiac function changes were observed by echocardiography. Cardiac structure changes were observed by HE and Masson staining. Immunofluorescence was applied to visualize the cardiomyocyte apoptosis. Western blotting was used to detect the expression levels of AMP-activated protein kinase (AMPK), sirtuin 3 (SIRT3), Caspase-3 and gasdermin E N-terminal fragment (GSDME-N). These experiments confirmed that Lig had an ameliorative effect on DOX-induced cardiotoxicity in mice.</p><p><strong>Results: </strong>The results demonstrated that Lig effectively countered myocardial oxidative stress by modulating intracellular levels of reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD). Lig reduced levels of creatine kinase (CK) and lactate dehydrogenase (LDH), while ameliorating histopathological changes and improving electrocardiogram profiles in vivo. Furthermore, the study revealed that Lig activated the AMPK/SIRT3 pathway, thereby enhancing mitochondrial function and attenuating myocardial cell apoptosis. In experiments with H9C2 cells treated with DOX, co-administration of the AMPK inhibitor compound C (CC) led to a significant increase in intracellular ROS levels. Lig intervention reversed these effects, along with the downregulation of GSDME-N, interleukin-1β (IL-1β), and interleukin-6 (IL-6), suggesting a potential role of Lig in mitigating Caspase-3/GSDME-mediated pyroptosis.</p><p><strong>Conclusion: </strong>The findings of this study suggest that Lig effectively alleviates DOX-induced cardiotoxicity through the activation of the AMPK/SIRT3 pathway, thereby presenting itself as a natural product with therapeutic potential for preventing DOX-associated cardiotoxicity. This novel approach may pave the way for the development of alternative strategies in the clinical management of DOX-induced cardiac complications.</p>","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"19 1","pages":"85"},"PeriodicalIF":4.9,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11179277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141320667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}