Fan Wang, Hai-Qing Gao, Zhe Lyu, Xiao-Ming Wang, Hui Han, Yong-Xia Wang, Feng Lu, Bo Dong, Jun Pu, Feng Liu, Xiu-Guang Zu, Hong-Bin Liu, Li Yang, Shao-Ying Zhang, Yong-Mei Yan, Xiao-Li Wang, Jin-Han Chen, Min Liu, Yun-Mei Yang, Xiao-Ying Li
{"title":"Efficacy and Safety of Yangxue Qingnao Pills Combined with Amlodipine in Treatment of Hypertensive Patients with Blood Deficiency and Gan-Yang Hyperactivity: A Multicenter, Randomized Controlled Trial.","authors":"Fan Wang, Hai-Qing Gao, Zhe Lyu, Xiao-Ming Wang, Hui Han, Yong-Xia Wang, Feng Lu, Bo Dong, Jun Pu, Feng Liu, Xiu-Guang Zu, Hong-Bin Liu, Li Yang, Shao-Ying Zhang, Yong-Mei Yan, Xiao-Li Wang, Jin-Han Chen, Min Liu, Yun-Mei Yang, Xiao-Ying Li","doi":"10.1007/s11655-024-4001-4","DOIUrl":"10.1007/s11655-024-4001-4","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the clinical efficacy and safety of Yangxue Qingnao Pills (YXQNP) combined with amlodipine in treating patients with grade 1 hypertension.</p><p><strong>Methods: </strong>This is a multicenter, randomized, double-blind, and placebo-controlled study. Adult patients with grade 1 hypertension of blood deficiency and Gan (Liver)-yang hyperactivity syndrome were randomly divided into the treatment or the control groups at a 1:1 ratio. The treatment group received YXQNP and amlodipine besylate, while the control group received YXQNP's placebo and amlodipine besylate. The treatment duration lasted for 180 days. Outcomes assessed included changes in blood pressure, Chinese medicine (CM) syndrome scores, symptoms and target organ functions before and after treatment in both groups. Additionally, adverse events, such as nausea, vomiting, rash, itching, and diarrhea, were recorded in both groups.</p><p><strong>Results: </strong>A total of 662 subjects were enrolled, of whom 608 (91.8%) completed the trial (306 in the treatment and 302 in the control groups). After 180 days of treatment, the standard deviations and coefficients of variation of systolic and diastolic blood pressure levels were lower in the treatment group compared with the control group. The improvement rates of dizziness, headache, insomnia, and waist soreness were significantly higher in the treatment group compared with the control group (P<0.05). After 30 days of treatment, the overall therapeutic effects on CM clinical syndromes were significantly increased in the treatment group as compared with the control group (P<0.05). After 180 days of treatment, brachial-ankle pulse wave velocity, ankle brachial index and albumin-to-creatinine ratio were improved in both groups, with no statistically significant differences (P>0.05). No serious treatment-related adverse events occurred during the study period.</p><p><strong>Conclusions: </strong>Combination therapy of YXQNP with amlodipine significantly improved symptoms such as dizziness and headache, reduced blood pressure variability, and showed a trend toward lowering urinary microalbumin in hypertensive patients. These findings suggest that this regimen has good clinical efficacy and safety. (Registration No. ChiCTR1900022470).</p>","PeriodicalId":10005,"journal":{"name":"Chinese Journal of Integrative Medicine","volume":" ","pages":"195-205"},"PeriodicalIF":2.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647008","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":"Zedoarondiol Inhibits Neovascularization in Atherosclerotic Plaques of ApoE<sup>-/-</sup> Mice by Reducing Platelet Exosomes-Derived MiR-let-7a.","authors":"Bei-Li Xie, Bo-Ce Song, Ming-Wang Liu, Wei Wen, Yu-Xin Yan, Meng-Jie Gao, Lu-Lian Jiang, Zhi-Die Jin, Lin Yang, Jian-Gang Liu, Da-Zhuo Shi, Fu-Hai Zhao","doi":"10.1007/s11655-024-4003-2","DOIUrl":"10.1007/s11655-024-4003-2","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the effect of zedoarondiol on neovascularization of atherosclerotic (AS) plaque by exosomes experiment.</p><p><strong>Methods: </strong>ApoE<sup>-/-</sup> mice were fed with high-fat diet to establish AS model and treated with high- and low-dose (10, 5 mg/kg daily) of zedoarondiol, respectively. After 14 weeks, the expressions of anti-angiogenic protein thrombospondin 1 (THBS-1) and its receptor CD36 in plaques, as well as platelet activation rate and exosome-derived miR-let-7a were detected. Then, zedoarondiol was used to intervene in platelets in vitro, and miR-let-7a was detected in platelet-derived exosomes (Pexo). Finally, human umbilical vein endothelial cells (HUVECs) were transfected with miR-let-7a mimics and treated with Pexo to observe the effect of miR-let-7a in Pexo on tube formation.</p><p><strong>Results: </strong>Animal experiments showed that after treating with zedoarondiol, the neovascularization density in plaques of AS mice was significantly reduced, THBS-1 and CD36 increased, the platelet activation rate was markedly reduced, and the miR-let-7a level in Pexo was reduced (P<0.01). In vitro experiments, the platelet activation rate and miR-let-7a levels in Pexo were significantly reduced after zedoarondiol's intervention. Cell experiments showed that after Pexo's intervention, the tube length increased, and the transfection of miR-let-7a minics further increased the tube length of cells, while reducing the expressions of THBS-1 and CD36.</p><p><strong>Conclusion: </strong>Zedoarondiol has the effect of inhibiting neovascularization within plaque in AS mice, and its mechanism may be potentially related to inhibiting platelet activation and reducing the Pexo-derived miRNA-let-7a level.</p>","PeriodicalId":10005,"journal":{"name":"Chinese Journal of Integrative Medicine","volume":" ","pages":"228-239"},"PeriodicalIF":2.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142784233","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":"Research Progress of Vagal Nerve Regulation Mechanism in Acupuncture Treatment of Atrial Fibrillation.","authors":"Lu-Lu Cao, Hui-Rong Liu, Ya-Jie Ji, Yin-Tao Zhang, Bing-Quan Wang, Xiao-Hong Xue, Pei Wang, Zhi-Hui Luo, Huan-Gan Wu","doi":"10.1007/s11655-024-3660-5","DOIUrl":"10.1007/s11655-024-3660-5","url":null,"abstract":"<p><p>Atrial fibrillation (AF) is the most common arrhythmia in clinical practice. It has a high prevalence and poor prognosis. The application of antiarrhythmic drugs and even surgery cannot completely treat the disease, and there are many sequelae. AF can be classified into the category of \"palpitation\" in Chinese medicine according to its symptoms. Acupuncture has a significant effect on AF. The authors find that an important mechanism of acupuncture in AF treatment is to regulate the cardiac vagus nerve. Therefore, this article intends to review the distribution and function of vagus nerve in the heart, the application and the regulatroy effect for the treatment of AF.</p>","PeriodicalId":10005,"journal":{"name":"Chinese Journal of Integrative Medicine","volume":" ","pages":"281-288"},"PeriodicalIF":2.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141579120","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":"Shenmai Injection Reduces Cardiomyocyte Apoptosis Induced by Doxorubicin through miR-30a/Bcl-2.","authors":"Xiao-Nan Zhang, Yan-Yang Li, Shi-Chao Lyu, Qiu-Jin Jia, Jun-Ping Zhang, Long-Tao Liu","doi":"10.1007/s11655-025-4005-8","DOIUrl":"10.1007/s11655-025-4005-8","url":null,"abstract":"<p><strong>Objective: </strong>To explore the molecular mechanism of Shenmai Injection (SMI) against doxorubicin (DOX) induced cardiomyocyte apoptosis.</p><p><strong>Methods: </strong>A total of 40 specific pathogen-free (SPF) male Sprague Dawley (SD) male rats were divided into 5 groups based on the random number table, including the control group, the model group, miR-30a agomir group, SMI low-dose (SMI-L) group, and SMI high-dose (SMI-H) group, with 8 rats in each group. Except for the control group, the rats were injected weekly with DOX (2 mg/kg) in the tail vein for 4 weeks to induce myocardial injury, and were given different regimens of continuous intervention for 2 weeks. Cardiac function was detected by echocardiography and myocardial pathological changes were observed by Van Gieson (VG) staining. Myocardial injury serum markers, including creatine kinase (CK), lactate dehydrogenase (LDH), troponin T (cTnT), N-terminal pro-brain natriuretic peptide (NT-proBNP), soluble ST2 (sST2), and growth differentiation factor-15 (GDF-15) were detected by enzyme linked immunosorbent assay (ELISA). Cardiomyocyte apoptosis was observed by terminal deoxynucleotidyl transferase-mediated biotinylated dUTP triphosphate nick end labeling (TUNEL) and transmission electron microscopy, and the expressions of target proteins and mRNA were detected by Western blot and quantitative real time polymerase chain reaction (qRT-RCR), respectively.</p><p><strong>Results: </strong>The treatment with different doses of SMI reduced rat heart mass index and left ventricular mass index (P<0.05), significantly improved the left ventricular ejection fraction (P<0.05), decreased the levels of serum CK, LDH, cTnT, and NT-proBNP (P<0.05 or P<0.01), reduced the levels of serum sST2 and GDF-15 (P<0.05 or P<0.01), decreased the collagen volume fraction, reduced the expressions of rat myocardial type I and type III collagen (P<0.05 or P<0.01), and effectively alleviated myocardial fibrosis. And the study found that SMI promoted the expression levels of miR-30a and Bcl-2 in myocardium, and down-regulated the expression of Bax, which inhibited the activation of Caspase-3 and Caspase-9 (P<0.05 or P<0.01), and improved myocardial cell apoptosis.</p><p><strong>Conclusions: </strong>SMI can alleviate myocardial injury and apoptosis caused by DOX, and its mechanism possibly by promoting the targeted expression of myocardial Bcl-2 protein through miR-30a.</p>","PeriodicalId":10005,"journal":{"name":"Chinese Journal of Integrative Medicine","volume":" ","pages":"240-250"},"PeriodicalIF":2.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982758","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}
Xiao-Qian Sun, Xuan Li, Yan-Qin Li, Xiang-Yu Lu, Xiang-Ning Liu, Ling-Wen Cui, Gang Wang, Man Zhang, Chun Li, Wei Wang
{"title":"Qishen Granules Modulate Metabolism Flexibility Against Myocardial Infarction via HIF-1 α-Dependent Mechanisms in Rats.","authors":"Xiao-Qian Sun, Xuan Li, Yan-Qin Li, Xiang-Yu Lu, Xiang-Ning Liu, Ling-Wen Cui, Gang Wang, Man Zhang, Chun Li, Wei Wang","doi":"10.1007/s11655-024-3667-y","DOIUrl":"10.1007/s11655-024-3667-y","url":null,"abstract":"<p><strong>Objective: </strong>To assess the cardioprotective effect and impact of Qishen Granules (QSG) on different ischemic areas of the myocardium in heart failure (HF) rats by evaluating its metabolic pattern, substrate utilization, and mechanistic modulation.</p><p><strong>Methods: </strong>In vivo, echocardiography and histology were used to assess rat cardiac function; positron emission tomography was performed to assess the abundance of glucose metabolism in the ischemic border and remote areas of the heart; fatty acid metabolism and ATP production levels were assessed by hematologic and biochemical analyses. The above experiments evaluated the cardioprotective effect of QSG on left anterior descending ligation-induced HF in rats and the mode of energy metabolism modulation. In vitro, a hypoxia-induced H9C2 model was established, mitochondrial damage was evaluated by flow cytometry, and nuclear translocation of hypoxia-inducible factor-1 α (HIF-1 α) was observed by immunofluorescence to assess the mechanism of energy metabolism regulation by QSG in hypoxic and normoxia conditions.</p><p><strong>Results: </strong>QSG regulated the pattern of glucose and fatty acid metabolism in the border and remote areas of the heart via the HIF-1 α pathway, and improved cardiac function in HF rats. Specifically, QSG promoted HIF-1 α expression and entry into the nucleus at high levels of hypoxia (P<0.05), thereby promoting increased compensatory glucose metabolism; while reducing nuclear accumulation of HIF-1 α at relatively low levels of hypoxia (P<0.05), promoting the increased lipid metabolism.</p><p><strong>Conclusions: </strong>QSG regulates the protein stability of HIF-1 α, thereby coordinating energy supply balance between the ischemic border and remote areas of the myocardium. This alleviates the energy metabolism disorder caused by ischemic injury.</p>","PeriodicalId":10005,"journal":{"name":"Chinese Journal of Integrative Medicine","volume":" ","pages":"215-227"},"PeriodicalIF":2.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281143","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":"Mechanism and Application of Chinese Herb Medicine in Treatment of Peripheral Nerve Injury.","authors":"Yu-Qing Chen, Yan-Xian Zhang, Xu Zhang, Yong-Mei Lyu, Zeng-Li Miao, Xiao-Yu Liu, Xu-Chu Duan","doi":"10.1007/s11655-024-4004-1","DOIUrl":"10.1007/s11655-024-4004-1","url":null,"abstract":"<p><p>Peripheral nerve injury (PNI) encompasses damage to nerves located outside the central nervous system, adversely affecting both motor and sensory functions. Although peripheral nerves possess an intrinsic capacity for self-repair, severe injuries frequently result in significant tissue loss and erroneous axonal junctions, thereby impeding complete recovery and potentially causing neuropathic pain. Various therapeutic strategies, including surgical interventions, biomaterials, and pharmacological agents, have been developed to enhance nerve repair processes. While preclinical studies in animal models have demonstrated the efficacy of certain pharmacological agents in promoting nerve regeneration and mitigating inflammation, only a limited number of these agents have been translated into clinical practice to expedite nerve regeneration. Chinese herb medicine (CHM) possesses a longstanding history in the treatment of various ailments and demonstrates potential efficacy in addressing PNI through its distinctive, cost-effective, and multifaceted methodologies. This review critically examines the advancements in the application of CHM for PNI treatment and nerve regeneration. In particular, we have summarized the most commonly employed and rigorously investigated CHM prescriptions, individual herbs, and natural products, elucidating their respective functions and underlying mechanisms in the context of PNI treatment. Furthermore, we have deliberated on the prospective development of CHM in both clinical practice and fundamental research.</p>","PeriodicalId":10005,"journal":{"name":"Chinese Journal of Integrative Medicine","volume":" ","pages":"270-280"},"PeriodicalIF":2.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766623","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}
K H Anush Sheikh, Songthat William Haokip, B N Hazarika, Oinam Bidyalaxmi Devi, Hau Ngaih Lian, Tabalique Yumkhaibam, Linthoingambi Ningombam, Yengkhom Disco Singh
{"title":"Phyto-chemistry and Therapeutic Potential of Natural Flavonoid Naringin: A Consolidated Review.","authors":"K H Anush Sheikh, Songthat William Haokip, B N Hazarika, Oinam Bidyalaxmi Devi, Hau Ngaih Lian, Tabalique Yumkhaibam, Linthoingambi Ningombam, Yengkhom Disco Singh","doi":"10.1007/s11655-025-3826-9","DOIUrl":"https://doi.org/10.1007/s11655-025-3826-9","url":null,"abstract":"","PeriodicalId":10005,"journal":{"name":"Chinese Journal of Integrative Medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491019","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}
Hai-Min Ye, Zhuo-Yan Li, Peng Zhang, Zhen Kang, De-Sheng Zhou
{"title":"Exploring Mechanism of Electroacupuncture in Modulating Neuroinflammation Based on Intestinal Flora and Its Metabolites.","authors":"Hai-Min Ye, Zhuo-Yan Li, Peng Zhang, Zhen Kang, De-Sheng Zhou","doi":"10.1007/s11655-024-3766-9","DOIUrl":"10.1007/s11655-024-3766-9","url":null,"abstract":"<p><p>Neuroinflammatory responses play an important role in the pathogenesis of various diseases, particularly those affecting the central nervous system. Inhibition of neuroinflammation is a crucial therapeutic strategy for the management of central nervous system disorders. The intestinal microbial-gut-brain axis serves as a key regulatory pathway that modulates neuroinflammatory processes. Intestinal flora metabolites such as short-chain fatty acids, indoles and their derivatives, lipopolysaccharides, trimethylamine oxide, and secondary bile acids exert direct or indirect effects on neuroinflammation. Studies have shown that electroacupuncture (EA) modulates the composition of the intestinal microbiota and its metabolites, while also suppressing neuroinflammation by targeting the TLR4/NF- κ B, NLRP3/caspase-1, and microglial cell M2-type transformation pathways. This review discusses the mechanisms by which EA regulates neuroinflammation via intestinal microbiota and its metabolites, providing information and a foundation for further investigation of the precise therapeutic mechanisms of EA in neurological disorders.</p>","PeriodicalId":10005,"journal":{"name":"Chinese Journal of Integrative Medicine","volume":" ","pages":"183-192"},"PeriodicalIF":2.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141747477","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":"Mechanism of Asperosaponin VI Related to EGFR/MMP9/AKT/PI3K Pathway in Treatment of Rheumtoid Arthritis.","authors":"Jin-Fang Luo, Yang Yu, Jian-Xin Liu","doi":"10.1007/s11655-024-3767-8","DOIUrl":"10.1007/s11655-024-3767-8","url":null,"abstract":"<p><strong>Objective: </strong>To explore the mechanism of action of asperosaponin VI (AVI) in the treatment of rheumatoid arthritis (RA) and validate it in ex vivo experiments using network pharmacology and molecular docking methods.</p><p><strong>Methods: </strong>The predicted targets of AVI were obtained from PharmMaper, UniProt and SwissTarget Prediction platforms, the disease targets were collected from Online Mendelian Inheritance in Man, Therapeutic Target Database and GeneCards databases, the intersection targets of AVI and RA were obtained from Venny 2.1.0, and the protein-protein interaction (PPI) network was obtained from STRING database, which was analyzed by Cytoscape software and screened to obtain the core targets. Cytoscape software was used to analyze PPI network and screen the core targets. Based on the Database for Annotation, Visualization and Integrated Discovery database, Gene Ontology functional and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed, and Cytoscape software was used to construct the \"Disease-Pathway-Target-Drug\" network, which was finally verified by molecular docking and animal experiments.</p><p><strong>Results: </strong>Network pharmacological studies showed that AVI was able to modulate 289 targets, with 102 targets for the potential treatment of RA, with the core pathway being the AKT/PI3K signaling pathway, and the core targets being the epidermal growth factor receptor (EGFR) and matrix metalloproteinase 9 (MMP9). Molecular docking results showed that AVI could produce strong binding with both of the 2 core targets. In vitro cellular experiments showed that AVI reduced nitric oxide, prostaglandin E<sub>2</sub>, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-1 β levels (P<0.05) and inhibited cyclooxygenase-2, nitric oxide synthase, EGFR, MMP9, phosphorylated phosphoinositide 3-kinase (p-PI3K), and phosphorylated serine-threonine kinase (p-AKT) proteins (P<0.05). The results of in vivo studies showed that AVI improved RA score and foot swelling thickness and decreased TNF-α, IL-6, p-PI3K and p-AKT levels in RA rats (P<0.05).</p><p><strong>Conclusion: </strong>AVI exerts anti-inflammatory and anti-RA effects which might be related to the EGFR/MMP9/AKT/PI3K pathway.</p>","PeriodicalId":10005,"journal":{"name":"Chinese Journal of Integrative Medicine","volume":" ","pages":"131-141"},"PeriodicalIF":2.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582406","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}
Cheng-Xian Li, Xiao-He Xiao, Xin-Yu Li, Da-Ke Xiao, Yin-Kang Wang, Xian-Ling Wang, Ping Zhang, Yu-Rong Li, Ming Niu, Zhao-Fang Bai
{"title":"Stir-fried Semen Armeniacae Amarum Suppresses Aristolochic Acid I-Induced Nephrotoxicity and DNA Adducts.","authors":"Cheng-Xian Li, Xiao-He Xiao, Xin-Yu Li, Da-Ke Xiao, Yin-Kang Wang, Xian-Ling Wang, Ping Zhang, Yu-Rong Li, Ming Niu, Zhao-Fang Bai","doi":"10.1007/s11655-024-3809-2","DOIUrl":"10.1007/s11655-024-3809-2","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the protective effects of stir-fried Semen Armeniacae Amarum (SAA) against aristolochic acid I (AAI)-induced nephrotoxicity and DNA adducts and elucidate the underlying mechanism involved for ensuring the safe use of Asari Radix et Rhizoma.</p><p><strong>Methods: </strong>In vitro, HEK293T cells overexpressing Flag-tagged multidrug resistance-associated protein 3 (MRP3) were constructed by Lentiviral transduction, and inhibitory effect of top 10 common pairs of medicinal herbs with Asari Radix et Rhizoma in clinic on MRP3 activity was verified using a self-constructed fluorescence screening system. The mRNA, protein expressions, and enzyme activity levels of NAD(P)H quinone dehydrogenase 1 (NQO1) and cytochrome P450 1A2 (CYP1A2) were measured in differentiated HepaRG cells. Hepatocyte toxicity after inhibition of AAI metabolite transport was detected using cell counting kit-8 assay. In vivo, C57BL/6 mice were randomly divided into 5 groups according to a random number table, including: control (1% sodium bicarbonate), AAI (10 mg/kg), stir-fried SAA (1.75 g/kg) and AAI + stir-fried SAA (1.75 and 8.75 g/kg) groups, 6 mice in each group. After 7 days of continuous gavage administration, liver and kidney damages were assessed, and the protein expressions and enzyme activity of liver metabolic enzymes NQO1 and CYP1A2 were determined simultaneously.</p><p><strong>Results: </strong>In vivo, combination of 1.75 g/kg SAA and 10 mg/kg AAI suppressed AAI-induced nephrotoxicity and reduced dA-ALI formation by 26.7%, and these detoxification effects in a dose-dependent manner (P<0.01). Mechanistically, SAA inhibited MRP3 transport in vitro, downregulated NQO1 expression in vivo, increased CYP1A2 expression and enzymatic activity in vitro and in vivo, respectively (P<0.05 or P<0.01). Notably, SAA also reduced AAI-induced hepatotoxicity throughout the detoxification process, as indicated by a 41.3% reduction in the number of liver adducts (P<0.01).</p><p><strong>Conclusions: </strong>Stir-fried SAA is a novel drug candidate for the suppression of AAI-induced liver and kidney damages. The protective mechanism may be closely related to the regulation of transporters and metabolic enzymes.</p>","PeriodicalId":10005,"journal":{"name":"Chinese Journal of Integrative Medicine","volume":" ","pages":"142-152"},"PeriodicalIF":2.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141293215","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}