Chinese Medicine最新文献

{"title":"Metabolomics and proteomics analyses of Chrysanthemi Flos: a mechanism study of changes in proteins and metabolites by processing methods.","authors":"Wei Zhang, Yu-Wen Qin, Yang-Fei Ding, Jun-Wei Xiong, Xiang-Wei Chang, Hong-Su Zhao, Cheng-Kai Xia, Jiu-Ba Zhang, Yu Li, Chun-Qin Mao, Tu-Lin Lu, De-Ling Wu","doi":"10.1186/s13020-024-01013-w","DOIUrl":"https://doi.org/10.1186/s13020-024-01013-w","url":null,"abstract":"<p><strong>Background: </strong>Chrysanthemi Flos is a traditional Chinese medicine with a long history of medicinal use. Prior research suggests that the intrinsic composition of Chrysanthemi Flos is affected by shade-drying and oven-drying methods. Nevertheless, the effects of these methods on the proteins and metabolites of Chrysanthemi Flos have not been extensively studied.</p><p><strong>Methods: </strong>The TMT (tandem mass tag) quantitative proteomics method and the LC-MS/MS (liquid chromatography-tandem mass spectrometry) non-targeted metabolomics method were used to systematically study the differences in the proteins and metabolites during the process of drying Chrysanthemi Flos in the shade and an oven.</p><p><strong>Results: </strong>Differentially accumulated metabolites and abundant proteins were primarily enriched in the purine metabolism, pyrimidine metabolism, cyanogenic amino acid metabolism, phenylpropanoid biosynthesis, and starch and sucrose metabolism pathways. Primary metabolites, such as guanine, xanthine, cytidine 5'-diphosphate serine, L-isoleucine, stearidonic acid, alginate, and inulin, play a crucial role in providing energy for Chrysanthemi Flos to withstand desiccation stress. The upregulation of ferulate-5- hydroxylase (F5H), shikimate O hydroxycinnamoyltransferase (HCT), caffeoyl-CoA O-methyltransferase (CCoAOMT), and chalcone isomerase (CHI) enzymes promotes the synthesis of flavonoids, including sinapic acid, caffeoyl shikimic acid, and naringenin chalcone, which possess antioxidant properties. Despite the notable improvements in energy metabolism and antioxidant capacity, these enhancements proved insufficient in halting the senescence and ultimate demise of Chrysanthemi Flos. Moreover, the shade-drying method can inhibit protein expression and promote the accumulation of bioactive components, but the drying efficiency is low, while the oven-drying method exhibits rapid drying efficiency, it does not effectively preserve the components.</p><p><strong>Conclusion: </strong>Our study offers a comprehensive explanation for the changes in protein expression and metabolite conversion observed in shade-dried and oven-dried Chrysanthemi Flos, also providing a foundation for optimizing the drying process of Chrysanthemi Flos.</p>","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"19 1","pages":"160"},"PeriodicalIF":5.3,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Taraxerone inhibits M1 polarization and alleviates sepsis-induced acute lung injury by activating SIRT1.","authors":"Lang Deng, Weixi Xie, Miao Lin, Dayan Xiong, Lei Huang, Xiaohua Zhang, Rui Qian, Xiaoting Huang, Siyuan Tang, Wei Liu","doi":"10.1186/s13020-024-01002-z","DOIUrl":"10.1186/s13020-024-01002-z","url":null,"abstract":"<p><strong>Background: </strong>Acute lung injury (ALI) is the most lethal disease associated with sepsis, and there is a lack of effective drug treatment. As the major cells of sepsis-induced ALI, macrophages polarize toward the proinflammatory M1 phenotype and secrete multiple inflammatory cytokines to accelerate the disease process through nuclear factor kappa-B (NF-κB) and NLR family pyrin domain containing 3 (NLRP3) inflammasome signaling pathways. Taraxerone, the main component of the Chinese medicinal Sedum, possesses numerous biological activities. However, uncertainty remains regarding the potential of taraxerone to protect against sepsis-induced ALI. This study aimed to investigate the effects and mechanisms of taraxerone against ALI.</p><p><strong>Methods: </strong>An animal model for ALI was established by cecal ligation and puncture and treated with taraxerone via intraperitoneal administration. The protective effect of taraxerone on the lungs was analyzed using H&E staining, dihydroethidium staining, ELISA kits, cell counting, myeloperoxidase kit, malondialdehyde kit, glutathione kit, superoxide dismutase kit and flow cytometry. Western blotting, RT-PCR, flow cytometry, co-immunoprecipitation, and immunofluorescence were used to investigate the regulatory of taraxerone on SIRT1.</p><p><strong>Results: </strong>Our study demonstrates for the first time that taraxerone can activate SIRT1 in macrophages, promoting SIRT1 activity. This activation inhibited the NF-κB signaling pathway primarily through the dephosphorylation and deacetylation of p65. Simultaneously, taraxerone disrupted the NLRP3 inflammasome signaling pathway, thereby alleviating M1 polarization of macrophages and mitigating sepsis-induced pulmonary inflammation and oxidative stress. In vivo, EX527 was used to validate the anti-inflammatory and anti-oxidative stress effects of taraxerone mediated by SIRT1.</p><p><strong>Conclusion: </strong>SIRT1-mediated anti-inflammatory and anti-oxidative stress effects may be important targets for taraxerone in treating ALI.</p>","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"19 1","pages":"159"},"PeriodicalIF":5.3,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11566926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616019","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 integrated approach for studying exposure, metabolism, and disposition of traditional Chinese medicine using PATBS and MDRB tools: a case study of semen Armeniacae Amarum.","authors":"Dandan Zhang, Junyu Zhang, Simian Chen, Hairong Zhang, Yuexin Yang, Shan Jiang, Yun Hong, Mingshe Zhu, Qiang Xie, Caisheng Wu","doi":"10.1186/s13020-024-01031-8","DOIUrl":"10.1186/s13020-024-01031-8","url":null,"abstract":"<p><strong>Background: </strong>Deciphering the in vivo processes of traditional Chinese medicine (TCM) is crucial for identifying new pharmacodynamic substances and new drugs. Due to the complexity and diversity of components, investigating the exposure, metabolism, and disposition remains a major challenge in TCM research. In recent years, a number of non-targeted smart mass-spectrometry (MS) techniques, such as precise-and-thorough background-subtraction (PATBS) and metabolomics, have realized the intelligent identification of in vivo components of TCM. However, the metabolites characterization still largely relies on manual identification in combination with online databases.</p><p><strong>Results: </strong>We developed a scoring approach based on the structural similarity and minimal mass defect variations between metabolites and prototypes. The current method integrates three dimensions of mass spectral data including m/z, mass defect of MS1 and MS2, and the similarity of MS2 fragments, which was sequentially analyzed by a R-based mass dataset relevance bridging (MDRB) data post-processing technique. The MDRB technology constructed a component relationship network for TCM, significantly improving metabolite identification efficiency and facilitating the mapping of translational metabolic pathways. By combining MDRB with PATBS through this non-targeted identification technology, we developed a comprehensive strategy for identification, characterization and bridging analysis of TCM metabolite in vivo. As a proof of concept, we adopted the proposed strategy to investigate the process of exposure, metabolism, and disposition of Semen Armeniacae Amarum (CKXR) in mice.</p><p><strong>Significance: </strong>The currently proposed analytical approach is universally applicable and demonstrates its effectiveness in analyzing complex components of TCMs in vitro and in vivo. Furthermore, it enables the correlation of in vitro and in vivo data, providing insights into the metabolic transformations among components sharing the same parent nucleus structure. Finally, the developed MDRB platform is publicly available for ( https://github.com/933ZhangDD/MDRB ) for accelerating TCM research for the scientific community.</p>","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"19 1","pages":"158"},"PeriodicalIF":5.3,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11566643/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616012","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":"Periplaneta americana L. extract exerts neuroprotective effects by inhibiting endoplasmic reticulum stress via AKT-dependent pathway in experimental models of Parkinson's disease.","authors":"Ting Cao, Xue-Lian Wang, Jiang-Yan Rao, Hui-Feng Zhu, Hong-Yi Qi, Zhen Tian","doi":"10.1186/s13020-024-01029-2","DOIUrl":"10.1186/s13020-024-01029-2","url":null,"abstract":"<p><strong>Background: </strong>Parkinson's disease (PD) is a chronic neurodegenerative disorder that currently has no curable strategies. More and more evidence suggests that endoplasmic reticulum (ER) stress plays an essential role in PD pathogenesis. Periplaneta americana L. (P. americana) is a traditional Chinese medicine with diverse therapeutic properties. This study aims to investigate the neuroprotective effect and underlying mechanism of P. americana in in vitro and in vivo PD models.</p><p><strong>Methods: </strong>The exposure of SH-SY5Y cells to 1-methyl-4-phenyl-pyridinium (MPP⁺) was used as the in vitro PD model. MTT assay, Hoechst staining, Calcein AM-PI staining and flow cytometry were performed to measure the cell viability and apoptosis. DCFH-DA and JC-1 assay were used to measure the intracellular ROS and mitochondrial membrane potential (Δψm), respectively. Western-blot and immunostaining were conducted to detect the expression of key molecules related with ER stress. For the in vivo PD model induced by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydro-pyridine (MPTP), the motor function of mice was assessed by behavioral tests, the level of TH was examined by western-blot and immunostaining, the expression of key molecules related with ER stress was measured by western-blot.</p><p><strong>Results: </strong>Periplaneta americana ethanol extract (PAE) concentration-dependently inhibited MPP⁺-induced cell loss and increased cell viability. PAE also remarkably attenuated ROS accumulation, the decline of Δψm as well as the excessive ER stress. The neuroprotective effects of PAE could be blocked by ROS inducer trimethylamine N-Oxide or ER stress activator tunicaymycin, while the antioxidant N-Acetyl-L-cysteine or ER stress inhibitor sodium 4-phenylbutyrate mimicked the effects of PAE. Furthermore, we found that PAE could activate AKT/GSK3β/β-catenin pathway. The effect of PAE on ROS production, Δψm and ER stress was blocked by AKT inhibitor MK-2206. In in vivo model, PAE significantly improved motor function, prevented dopaminergic neuronal loss and attenuated ER stress in substantia nigra and striatum of MPTP-treated mice. Similarly, the effects of PAE on MPTP-treated mice were also abolished by MK-2206.</p><p><strong>Conclusions: </strong>Our results suggest that P. americana exerts neuroprotective effects through inhibiting ER stress via AKT-dependent pathway. Periplaneta americana may represent a promising therapeutic agent for PD treatment and is worthy of further being exploited.</p>","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"19 1","pages":"157"},"PeriodicalIF":5.3,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11562093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616018","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":"Electroacupuncture alleviates neuropathic pain in a rat model of CCD via suppressing P2X3 expression in dorsal root ganglia.","authors":"Yu Zheng, Minjian Jiang, Zhouyuan Wei, Hengyu Chi, Yurong Kang, Siyi Li, Yinmu Zheng, Xiaofen He, Xiaomei Shao, Jianqiao Fang, Yongliang Jiang","doi":"10.1186/s13020-024-01030-9","DOIUrl":"10.1186/s13020-024-01030-9","url":null,"abstract":"<p><strong>Background: </strong>Sciatica and low back pain are prevalent clinical types of neuropathic pain that significantly impair patients' quality of life. Conventional therapies often lack effectiveness, making these conditions challenging to treat. Electroacupuncture (EA) is an effective physiotherapy for pain relief. Prior research has demonstrated a relationship between the frequency of neuropathic pain and the analgesic impact of EA stimulation. This work aimed to assess the analgesic effects of EA in a rat model of chronic compression of the dorsal root ganglion (CCD) and to understand the underlying processes.</p><p><strong>Methods: </strong>We established a rat CCD model to simulate sciatica and low back pain. EA was applied to rats with CCD at various frequencies (2 Hz, 100 Hz, and 2/100 Hz). The paw withdrawal threshold (PWT) was measured to assess analgesic effects. Additionally, protein levels of the purinergic receptor P2X3 (P2X3) and the expression of nociceptive neuronal markers were analyzed using immunohistochemistry and western blot (WB) techniques. The study also measured levels of proinflammatory cytokines TNF-α and IL-1β in the dorsal root ganglion (DRG). The involvement of P2X3 receptors was further investigated using the P2X3 agonist, α,β-methylene ATP (α,β-meATP).</p><p><strong>Results: </strong>CCD rats developed pronounced mechanical allodynia. EA stimulation at all tested frequencies produced analgesic effects, with 2/100 Hz showing superior efficacy compared to 2 Hz and 100 Hz. The expression of P2X3 was increased in ipsilateral DRG of CCD model rats. P2X3 were co-labeled with isolectin B4 (IB4) and transient receptor potential vanilloid (TRPV1), indicating their role in nociception. 2/100 Hz EA treatment significantly reduced mechanical allodynia and inhibited the overexpression of P2X3, TRPV1, substance P (SP), and calcitonin gene-related peptide (CGRP) in the ipsilateral DRG of CCD model rats. Additionally, EA reduced the levels of proinflammatory cytokines TNF-α and IL-1β in the ipsilateral DRG, indicating an anti-inflammatory effect. The P2X3 agonist α,β-me ATP attenuated the analgesic effect of 2/100 Hz EA in CCD rats. The WB and immunofluorescence results consistently demonstrated P2X3 inhibition contributed to the analgesic effects of 2/100 Hz EA on CCD-induced neuropathic pain.</p><p><strong>Conclusions: </strong>Our findings suggest that 2/100 Hz EA alleviates neuropathic pain in rats by inhibiting the upregulation of P2X3 receptors in the ipsilateral DRG. This study backs up EA as a viable treatment option for sciatica and low back pain in clinical settings.</p>","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"19 1","pages":"156"},"PeriodicalIF":5.3,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11552355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616017","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":"Clinical efficacy of DSA-based features in predicting outcomes of acupuncture intervention on upper limb dysfunction following ischemic stroke.","authors":"Yuqi Tang, Sixian Hu, Yipeng Xu, Linjia Wang, Yu Fang, Pei Yu, Yaning Liu, Jiangwei Shi, Junwen Guan, Ling Zhao","doi":"10.1186/s13020-024-01026-5","DOIUrl":"10.1186/s13020-024-01026-5","url":null,"abstract":"<p><strong>Background and objectives: </strong>This study aimed to employ machine learning techniques to predict the clinical efficacy of acupuncture as an intervention for patients with upper limb motor dysfunction following ischemic stroke, as well as to assess its potential utility in clinical practice.</p><p><strong>Methods: </strong>Medical records and digital subtraction angiography (DSA) imaging data were collected from 735 ischemic stroke patients with upper limb motor dysfunction who were treated with standardized acupuncture at two hospitals. Following the initial screening, 314 patient datasets that met the inclusion criteria were selected. We applied three deep-learning algorithms (YOLOX, FasterRCNN, and TOOD) to develop the object detection model. Object detection results pertaining to the cerebral vessels were integrated into a clinical efficacy prediction model (random forest). This model aimed to classify patient responses to acupuncture treatment. Finally, the accuracies and discriminative capabilities of the prediction models were assessed.</p><p><strong>Results: </strong>The object detection model achieved an optimal recognition rate, The mean average precisions of YOLOX, TOOD, and FasterRCNN were 0.61, 0.7, and 0.68, respectively. The prediction accuracy of the clinical efficacy model reached 93.6%, with all three-treatment response classification area under the curves (AUCs) exceeding 0.95. Feature extraction using the prediction model highlighted the significant influence of various cerebral vascular stenosis sites within the internal carotid artery (ICA) on prediction outcomes. Specifically, the initial and C1 segments of the ICA had the highest predictive weights among all stenosis sites. Additionally, stenosis of the middle cerebral, anterior cerebral, and posterior cerebral arteries exerted a notable influence on the predictions. In contrast, the stenosis sites within the vertebral artery exhibited minimal impact on the model's predictive abilities.</p><p><strong>Conclusions: </strong>Results underscore the substantial predictive influence of each cerebral vascular stenosis site within the ICA, with the initial and C1 segments being pivotal predictors.</p>","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"19 1","pages":"155"},"PeriodicalIF":5.3,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11550517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616016","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":"Ren-Shen-Bu-Qi decoction alleviates exercise fatigue through activating PI3K/AKT/Nrf2 pathway in mice.","authors":"Yangyang Chen, Tinghui Gao, Jing Bai, Wenjing Zhang, Yutong Zhou, Ruichang Zhao, Youhui Deng, Xiaogang Liu, Zhangjun Huang, Songtao Wang, Caihong Shen, Sijing Liu, Jinlin Guo","doi":"10.1186/s13020-024-01027-4","DOIUrl":"10.1186/s13020-024-01027-4","url":null,"abstract":"<p><strong>Background: </strong>Fatigue is a prevalent issue that can lead individuals to a sub-health condition, impacting their work efficiency and quality of life. There are limited effective treatment options available for fatigue. Ren-Shen-Bu-Qi decoction (RSBQD) is a proprietary herbal remedy that is designed to address fatigue. However, the specific pharmacological mechanisms and basis of RSBQD are not yet fully understood.</p><p><strong>Purpose: </strong>This study aimed to investigate the pharmacological effects and mechanisms of RSBQD in a mouse model of exercise fatigue.</p><p><strong>Materials and methods: </strong>UPLC-Q-Orbitrap HRMS was used to analyze the chemical composition of RSBQD. The pharmacological basis and molecular mechanism of RSBQD on exercise fatigue were predicted using network pharmacology analysis. Subsequently, an exercise fatigue mouse model was established and used to analysis the effects of RSBQD. The potential mechanisms were verified by hematoxylin-eosin (HE) staining, real-time fluorescence quantitative PCR (RT-qPCR), Western blot (WB) and molecular docking.</p><p><strong>Results: </strong>The results showed that 88 main components of RSBQD were identified, which have mainly belonged to flavonoids and carboxylic acid compounds. The network pharmacology analysis indicated that RSBQD ameliorate fatigue through PI3K/AKT signaling pathway. Notably, RSBQD prolonged the swimming time and diminished body weight loss of exercise fatigue mice (P < 0.05). Meanwhile, RSBQD significantly alleviated the injury of liver and kidney induced by exhaustive exercise, and decreasing the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea and BUN levels (P < 0.05). In addition, RSBQD was found could relieve exercise fatigue by decreasing the content of creatine kinase (CK), lactate dehydrogenase (LDH), and lactic acid (LA), but increasing the blood glucose (GLU) and liver glycogen (HG) levels (P < 0.05). RSBQD also significantly increased the hepatic superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) but decreased hepatic malondialdehyde (MDA) levels. Moreover, RSBQD was able to upregulate protein level of activated Nrf2 and PI3K/AKT signaling pathways.</p><p><strong>Conclusions: </strong>RSBQD mitigates exercise fatigue by reversing metabolic changes and reducing oxidative damage through the PI3K/AKT/Nrf2 signaling pathway. This study offers pharmacological support for the utilization of RSBQD in exercise fatigue treatment.</p>","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"19 1","pages":"154"},"PeriodicalIF":5.3,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11539552/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582145","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":"Efficacy and safety of Shengjiang Xiexin decoction on irinotecan-induced diarrhea in small cell lung cancer patients: a multicenter, randomized, double-blind, placebo-controlled trial.","authors":"Chao Deng, Qing Liu, Meng Yang, Hui-Juan Cui, Yang Ge, Qin Li, Shi-Jie Zhu, Guo-Wang Yang, Zhi-Guo Zhang, Yu Gao, Yan-Ni Lou, Li-Qun Jia","doi":"10.1186/s13020-024-01025-6","DOIUrl":"10.1186/s13020-024-01025-6","url":null,"abstract":"<p><strong>Background: </strong>Irinotecan is a standard chemotherapeutic agent in small cell lung cancer (SCLC), however, as a common adverse reaction, diarrhea limits the use of irinotecan. Shengjiang Xiexin decoction (SXD) has been used in various gastrointestinal diseases in China two thousand years ago. We designed this clinical trial to supply more evidences on the use of SXD as prophylaxis for irinotecan-induced diarrhea, especially for high-risk population predicted by gene testing of uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1).</p><p><strong>Methods: </strong>In this clinical trial, 120 patients with SCLC were recruited from six hospitals in China. They received two cycles of chemotherapy, meanwhile they were randomized to receive SXD or placebo for 14 days of oral administration in each cycle of chemotherapy. The primary outcome is the incidence of diarrhea. And secondary outcomes include the the degree of diarrhea and neutropenia, the number of chemotherapy cycles with diarrhea, first occurrence time and duration of diarrhea. To evaluate the effect of SXD on the intestine, a rat model with delayed-onset diarrhea induced by irinotecan was established, and the expression of inflammatory factors including IL-1β, IL-6 and TNF-α, anti-inflammatory factors including IL-10, TGF- β in jejunal tissue was detected by ELISA.</p><p><strong>Results: </strong>101 patients (53 in SXD group, 48 in placebo group) completed the trial. The incidence of diarrhea in SXD group and placebo group were 26.42% (14/53) and 52.08% (25/48), respectively (P < 0.05), and the degree of diarrhea also had significant differences (P < 0.05). In UGT1A1 high-risk population, the incidence of diarrhea in two groups were 9.09% and 66.67% (P < 0.05), but there was no significant differences in UGT1A1 low-risk population. The incidence of neutropenia with degree 1-3 between two groups was 20.75% vs 20.83%, 13.21% vs 18.57%, 9.43% vs 20.83% (P < 0.05). No severe adverse events were reported in any group. And animal studies had shown SXD reduced content of IL-1β, IL-6, TNF-α, increased content of IL-10, TGF-β in jejunum tissue.</p><p><strong>Conclusions: </strong>SXD had a prophylactic effect in the diarrhea induced by irinotecan, especially for UGT1A1 high-risk population, and this effect from SXD appeared to be maintained the completion of chemotherapy schedule. The mechanism of action of SXD was related to the regulation of inflammatory factors. Trial registration Chinese Clinical Trial Register: ChiCTR1800018490. Registered on 20 September 2018. https://www.chictr.org.cn/showproj.html?proj=25250 . The preliminary protocol of this clinical study has been published in the journal \"Trials\" in the form of protocol before this paper (Deng et al. in Trials 21:370, 2020).</p>","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"19 1","pages":"153"},"PeriodicalIF":5.3,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11536713/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142575491","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":"Protective effect of Huashi Baidu formula against AKI and active ingredients that target SphK1 and PAI-1.","authors":"Yute Zhong, Xia Du, Ping Wang, Weijie Li, Cong Xia, Dan Wu, Hong Jiang, Haiyu Xu, Luqi Huang","doi":"10.1186/s13020-024-01024-7","DOIUrl":"10.1186/s13020-024-01024-7","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Huashi Baidu Formula (HBF) is a clinical formula known for its efficacy against coronavirus disease 2019 (COVID-19). HBF may reduce the number of patients with abnormal serum creatinine while improving respiratory symptoms, suggesting that this formula may have potential for treating acute kidney injury (AKI). However, the protective effect of HBF on AKI has not been definitively confirmed, and the mechanism remains unclear. Therefore, the present study explored the renoprotective effects and molecular mechanisms of HBF and screened for its active ingredients to identify new potential applications of renoprotection by HBF.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The present study first assessed the protective effects of HBF on AKI in a DOX-induced mouse model. Then, RNA-seq and bioinformatics analyses were used to explore the related pathological processes and potential molecular mechanisms, which were subsequently validated using qRT-PCR and Western blotting. Furthermore, candidate compounds with potential binding affinity to two pivotal targets, sphingosine kinase 1 (SphK1) and plasminogen activator inhibitor-1 (PAI-1), were screened from the 29 constituents present in the blood using Microscale Thermophoresis (MST). Finally, to identify the active ingredients, the candidate components were re-screened using the SphK1 kinase activity detection system or the uPA/PAI-1 substrate colorimetric assay system.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;In the DOX-induced AKI mouse model, therapeutic administration of HBF significantly reduced the levels of CRE, BUN, TNF-α, IL-1β, IL-6, and UA in plasma and the levels of MDA, T-CHO, and TG in kidney tissue. Additionally, the levels of TP and Alb in plasma and SOD and CAT in the kidney tissue were significantly increased. Histopathological assessment revealed that HBF reduced tubular vacuolation, renal interstitial inflammatory cell infiltration, tubular atrophy, and positive staining of renal interstitial collagen. RNA-seq and bioinformatics analyses showed that oxidative stress, the immune-inflammatory response, and extracellular matrix (ECM) formation could be the pathological processes that HBF targets to exerts its renoprotective effects. Furthermore, HBF regulated the APJ/SPHK1/NF-κB and APJ/PAI-1/TGFβ signaling axes and reduced the phosphorylation levels of NF-κB p65 and SMAD2 and the expression of cytokines and the ECM downstream of the axis. Finally, six SphK1 inhibitors (paeoniflorin, astragalin, emodin, glycyrrhisoflavone, quercetin, and liquiritigenin) and three PAI-1 inhibitors (glycyrrhisoflavone, licochalcone B, and isoliquiritigenin) were identified as potentially active ingredients in HBF.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;In brief, our investigation underscores the renoprotective effect of HBF in a DOX-induced AKI model mice, elucidating its mechanisms through distinct pathological processes and identifying key bioactive compounds. These findings offer new insights for br","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"19 1","pages":"152"},"PeriodicalIF":5.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11529477/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142563988","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":"Suppression of ferroptosis through the SLC7A11/glutathione/glutathione peroxidase 4 axis contributes to the therapeutic action of the Tangshenning formula on diabetic renal tubular injury.","authors":"Xiao-Meng Shan, Chun-Wei Chen, Da-Wei Zou, Yan-Bin Gao, Yin-Ying Ba, Jia-Xin He, Zhi-Yao Zhu, Jia-Jun Liang","doi":"10.1186/s13020-024-01007-8","DOIUrl":"10.1186/s13020-024-01007-8","url":null,"abstract":"<p><strong>Background: </strong>Tangshenning (TSN) is a safe and effective formula to treat diabetic nephropathy (DN), and clinical studies have demonstrated that its therapeutic effects are related to oxidative stress improvements in patients. Herein, this study aims to explore the potential mechanism of how TSN alleviates diabetic renal tubular injury.</p><p><strong>Methods: </strong>The ultrahigh pressure liquid chromatography-quadrupole-time of flight mass spectrometry (UPLC-QTOF/MS) was used to identify the chemical composition and serum components of TSN. KK-Ay mice served to investigate the protective effects and regulatory mechanisms of TSN on tubular damage in DN. Furthermore, inhibitors and inducers of ferroptosis were employed in high glucose-cultured tubular epithelial cells (TECs) to verify the potential mechanisms of TSN. The expressions of proteins related to renal tubular injury, ferroptosis and solute carrier family 7, member 11 (SLC7A11)/glutathione (GSH)/glutathione peroxidase 4 (GPX4) axis were analyzed by western blot and immunofluorescence. Mitochondrial ultrastructure was observed in kidney tissues and TECs by a transmission electron microscope. Pathological changes in the renal tissues were observed by HE, PAS, and Prussian blue staining. Ferroptosis-related reactive oxygen species (ROS), malondialdehyde (MDA), ferrous ion, the intake of cystine, GSH, and oxidized glutathione (GSSG) were evaluated and contrasted in vivo or in vitro.</p><p><strong>Results: </strong>51 compounds of TSN powder and 11 components in TSN-containing serum were identified by UPLC-QTOF/MS method. Administration of TSN ameliorated the elevated levels of proteinuria, serum creatinine, blood urea nitrogen, abnormal expression of renal tubular injury markers, and pathological damage to the renal tubules in DN mice model. Intriguingly, a strong inhibition of ferroptosis after TSN treatment occurred in both DN mice model and high glucose-cultured TECs. Notably, induction of ferroptosis by erastin attenuated the protective effect of TSN in high glucose-cultured TECs, while the ferroptosis inhibition by ferrostatin-1 treatment protected renal tubular, which was similar to TSN, suggesting the contribution of TSN-mediated by the inhibition of ferroptosis in DN progression. Mechanistically, TSN upregulated the SLC7A11/GSH/GPX4 axis to inhibit ferroptosis.</p><p><strong>Conclusion: </strong>TSN may delay the DN progression and attenuate the renal tubular injury by inhibiting the ferroptosis regulated by the SLC7A11/GSH/GPX4 axis.</p>","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"19 1","pages":"151"},"PeriodicalIF":5.3,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11523893/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544087","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}