Wuxia Zhao , Qiuying Yan , Lianfang Liu , Dahai Hou , Dongyang Xiang , Dongxin Tang , Liu Li , Weixing Shen , Weiwei Tao , Haibo Cheng , Dongdong Sun
{"title":"Curcumol promotes ferroptosis of colon cancer by targeting the ubiquitination and degradation of GPX4","authors":"Wuxia Zhao , Qiuying Yan , Lianfang Liu , Dahai Hou , Dongyang Xiang , Dongxin Tang , Liu Li , Weixing Shen , Weiwei Tao , Haibo Cheng , Dongdong Sun","doi":"10.1016/j.jtcme.2024.08.006","DOIUrl":"10.1016/j.jtcme.2024.08.006","url":null,"abstract":"<div><h3>Background and aim</h3><div>Colon cancer (CC) is one of the common malignant tumors in the digestive tract, the prognosis of CC patients has never been satisfying. A Ferrous-dependent form that regulates cell death, plays a key role in cancer development. As a core regulator of ferroptosis, GPX4 has become a potential molecular target for the development of antitumor drugs. Curcumol (Cur), a sesquiterpene natural product, it has significant anti-tumor effect. However, whether Cur mediates ferroptosis in colon cancer and its mechanism are still unclear. This study aimed to investigate the underlying mechanisms of Cur anti-tumor.</div></div><div><h3>Experimental procedure</h3><div>By investigating the Cancer Genome Atlas (TCGA) database and tissue immunofluorescence staining was also used to detect the levels of GPX4 protein in CC and matching paracancerous tissues. The anti-CC and pro-ferroptosis effects of Cur were detected in the <em>vivo</em> and <em>vitro</em> experiment. The interaction between Cur and GPX4 was predicted. In addition, the potential mechanism of Cur anti-CC was further discussed. Co-immunoprecipitation was used to confirm Cur-mediated GPX4 ubiquitination.</div></div><div><h3>Results and conclusion</h3><div>GPX4 was upregulated in CC tissue and was correlated with poor survival of patients. Cur inhibited the proliferation of CC cells, accompanied by regulating Fe<sup>2+</sup> overload, reactive oxygen species (ROS) formation, malondialdehyde (MDA) production and superoxide dismutase (SOD) consumption. Furthermore, GPX4 was predicted and verified as the direct target of Cur by molecular docking and structure-based virtual prediction. Meanwhile, Cur could promote the ubiquitination-mediated degradation of GPX4, induce ferroptosis in CC cells and regulate the expression of ferroptosis-related protein FTH1 and TfR1. In addition, when GPX4 was overexpressed (GPX4-OE), the inhibitory effect of Cur on the expression of GPX4 and ferroptosis-related protein FTH1 and the promotion of TfR1 expression were abolished. Cur could inhibit CC by increasing the ubiquitination degradation level of GPX4 to induce ferroptosis in CC cells.</div></div>","PeriodicalId":17449,"journal":{"name":"Journal of Traditional and Complementary Medicine","volume":"15 2","pages":"Pages 170-181"},"PeriodicalIF":3.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142078010","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}
Xujun Yu , Jingyi Zhang , Suyun Xu , Jing Zhou , Chenglin Zhuang , Junjun Li , Baojun Zhuang
{"title":"Guilingji capsules enhances erectile function by promoting testosterone-dependent angiogenesis in the corpus cavernosum","authors":"Xujun Yu , Jingyi Zhang , Suyun Xu , Jing Zhou , Chenglin Zhuang , Junjun Li , Baojun Zhuang","doi":"10.1016/j.jtcme.2024.06.009","DOIUrl":"10.1016/j.jtcme.2024.06.009","url":null,"abstract":"<div><h3>Background and aim</h3><div>Guilingji capsules (GLJC) have the effect of treating erectile dysfunction (ED). This study aims to explore the potential mechanisms of GLJC in treating ED.</div></div><div><h3>Experimental procedure</h3><div>We conducted network pharmacology analysis of ED-related targets with GLJC components reported in the TCMSP database and GLJC components reported in the literature, respectively. Molecular docking was employed to validate the binding affinity of these molecular targets. Animal experiments were conducted to validate the aforementioned results. The mechanism of GLJC in treating ED was studied using <span>d</span>-galactose-induced aging rats, and orchiectomized rats were used to investigate further whether the mechanism of GLJC in treating ED is related to androgen.</div></div><div><h3>Results and conclusions</h3><div>Two network pharmacology analyses indicated that Androgen receptor (AR) and fibroblast growth factor 2 (FGF2) are the candidate targets, suggesting that the mechanism of ED treatment by GLJC may be related to androgens and angiogenesis. Molecular docking further validated the effective binding of GLJC components to these two targets. In animal experiments, GLJC significantly increased the frequency of erections and elevated serum free testosterone levels and penile tissue AR expression in aged rats. GLJC also promoted angiogenesis and inhibited penile tissue fibrosis in aged rats by regulating the expression of FGF2, RICTOR/P-AKT/P-FOXO1. However, such regulation was not observed in orchiectomized rats. Therefore, GLJC increased testosterone utilization in <span>d</span>-galactose-induced aging rats and regulated FGF2, RICTOR/P-AKT/P-FOXO1 signaling pathway in a T-dependent manner, promoting corpus cavernosum survival and angiogenesis. This mechanism led to the inhibition of penile fibrosis.</div></div>","PeriodicalId":17449,"journal":{"name":"Journal of Traditional and Complementary Medicine","volume":"15 2","pages":"Pages 147-160"},"PeriodicalIF":3.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143428100","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}
Jun-Wei Wang , Hong Shao , You-Ni Zhang , Tong Ge , Xiao-Yi Chen , Xiao-Zhou Mou
{"title":"Traditional Chinese medicine as a protective strategy against chemotherapy-induced cardiotoxicity: An overview of the literature","authors":"Jun-Wei Wang , Hong Shao , You-Ni Zhang , Tong Ge , Xiao-Yi Chen , Xiao-Zhou Mou","doi":"10.1016/j.jtcme.2024.06.010","DOIUrl":"10.1016/j.jtcme.2024.06.010","url":null,"abstract":"<div><div>Cardiotoxicity refers to the damage caused to the heart or vascular system, which has become a significant cause of morbidity and mortality worldwide. Up to 20 % of adults undergoing cancer treatment may experience cardiotoxicity, with 7 %–10 % developing cardiomyopathy or heart failure. Cardiotoxic medications put patients at risk for a variety of heart conditions, including cardiac failure (HF), left ventricle (LV) systolic malfunction, cardiac arrhythmia, hypertension, coronary artery disease (CAD), and ischemia/myocardial infarction. These diseases may significantly impact the patient's quality of life and outcomes. Many conventional cancer chemotherapy agents have serious adverse effects. Anthracyclines, alkylating agents, taxanes, topoisomerase inhibitors, and antimetabolites are chemotherapeutic agents that induce cardiotoxicity. Recently, there has been an increasing focus on using traditional Chinese medicine (TCM) to treat chemotherapy-induced cardiotoxicity. TCM encompasses a range of practices, such as herbology, acupuncture, dietary therapy, and physical exercises like t'ai chi. These practices aim to enhance the flow of qi, which can alleviate symptoms of illness. Although the effectiveness of TCM has not been extensively researched and supported, scientists have begun utilizing scientific methods to gain a deeper understanding of the mechanisms underlying TCM. Ongoing research is being conducted to determine the safety and effectiveness of TCM treatments in reducing chemotherapy-induced toxicity. The present study aims to evaluate the protection and efficacy of various TCM treatments in chemotherapy-induced cardiotoxicity.</div></div>","PeriodicalId":17449,"journal":{"name":"Journal of Traditional and Complementary Medicine","volume":"15 2","pages":"Pages 107-118"},"PeriodicalIF":3.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143428089","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}
Zhengyang Zhu , Mingzhu Wang , Lin Huang , Zhixing He
{"title":"Jieduquyuziyin prescription attenuates the side effect of prednisone through regulating gut microbiota when in the combination with prednisone treat MRL/lpr mice","authors":"Zhengyang Zhu , Mingzhu Wang , Lin Huang , Zhixing He","doi":"10.1016/j.jtcme.2024.05.005","DOIUrl":"10.1016/j.jtcme.2024.05.005","url":null,"abstract":"<div><div>Jieduquyuziyin prescription (JP) is an empirical formula used to treat systemic lupus erythematosus (SLE). While JP has been shown to have synergistic and attenuated effects when combined with glucocorticoids (GCs) for SLE treatment, the precise mechanism remains unclear. This study utilized MRL/lpr mice to demonstrate the synergistic and attenuated effects of JP when combined with prednisone. Furthermore, a co-housing experiment was conducted to investigate whether JP-regulated gut microbiota had synergistic and attenuated effects in prednisone-treated MRL/lpr mice. The study found that JP exhibited synergistic effects only when combined with 5 mg/kg body weight prednisone, while its attenuated effects were observed with both 5 and 10 mg/kg body weight prednisone. Co-housing resulted in the transmission of gut microbiota between prednisone-treated and JP-treated MRL/lpr mice. However, co-housing did not enhance the therapeutic efficacy of prednisone; instead, it attenuated prednisone's adverse effects on liver inflammation (IL-6 and TNF-α) and serum cholesterol in MRL/lpr mice. The attenuated effects of JP may be associated with specific genera such as <em>Akkermansia</em>, <em>Parasutterella</em>, and <em>Alistipes</em>. These findings suggest that JP can mitigate the adverse effects of GCs by modulating gut microbiota during the treatment of SLE with GCs.</div></div>","PeriodicalId":17449,"journal":{"name":"Journal of Traditional and Complementary Medicine","volume":"15 2","pages":"Pages 119-127"},"PeriodicalIF":3.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141140178","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":"Potent anti-biofilm properties of plumbagin against fluconazole-resistant Candida auris","authors":"Hye-Won Jin , Yong-Bin Eom","doi":"10.1016/j.jtcme.2024.06.005","DOIUrl":"10.1016/j.jtcme.2024.06.005","url":null,"abstract":"<div><h3>Background and aim</h3><div>The escalation of fungal infections is driving an increase in disease and mortality rates. In particular, the emergence of <em>Candida auris</em> (<em>C. auris</em>), which shows powerful resistance to the antifungal drug fluconazole, is becoming a global concern. Furthermore, several biological hurdles need to be overcome by candidate therapeutics because <em>C. auris</em> has the ability to form biofilm. Therefore, this study aimed to investigate the antifungal and anti-biofilm effects of plumbagin, a natural extract, against fluconazole-resistant <em>C. auris</em> (FRCA).</div></div><div><h3>Experimental procedure</h3><div>The minimum inhibitory concentrations (MICs) of fluconazole and plumbagin were determined against clinically isolated <em>C. auris</em>. Inhibition of biofilm formation and eradication effects of plumbagin against FRCA were confirmed through minimum biofilm inhibition concentration (MBIC) and minimum biofilm eradication concentration (MBEC) assays. Additionally, the inhibition of metabolic activity in biofilm cells was verified through quantification by XTT reduction assay and visualization by confocal laser scanning microscopy (CLSM). The relative expression levels of the azole resistant gene <em>ERG11</em>, the efflux pump gene <em>CDR1</em>, and the extracellular matrix gene <em>KRE6</em>, were measured.</div></div><div><h3>Results and conclusion</h3><div>Plumbagin exhibits antifungal efficacy against <em>C. auris</em> and has been shown to effectively inhibit both the formation and eradication of biofilms produced by FRCA. Furthermore, the metabolic activity inhibition in biofilm cells was both quantified and visually observed. The downregulation of all genes (<em>ERG11</em>, <em>CDR1</em>, and <em>KRE6</em>) by plumbagin was confirmed. Taken together, this study demonstrates that plumbagin has antifungal and anti-biofilm efficacy against FRCA, indicating its potential as an alternative to antifungal agents and a valuable resource in combating FRCA infections.</div></div>","PeriodicalId":17449,"journal":{"name":"Journal of Traditional and Complementary Medicine","volume":"15 2","pages":"Pages 140-146"},"PeriodicalIF":3.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141403823","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}
Yuhao Teng , Ying Xing , Weiwei Xue , Yue Hu , Zirui Li , Jun Qian , Ruiping Wang
{"title":"Raddeanin A promotes the apoptosis of gastric cancer in conjunction with autophagy inhibitor Hydroxychloroquine via MAPK signaling pathway","authors":"Yuhao Teng , Ying Xing , Weiwei Xue , Yue Hu , Zirui Li , Jun Qian , Ruiping Wang","doi":"10.1016/j.jtcme.2024.07.004","DOIUrl":"10.1016/j.jtcme.2024.07.004","url":null,"abstract":"<div><h3>Purpose</h3><div>Gastric cancer (GC) is among the malignant cancers with the highest incidence and mortality worldwide. As GC is not very sensitive to current chemotherapy drugs, there is an urgent need to develop new effective drugs. Raddeanin A (RA) is extracted from the traditional Chinese medicine Anemone raddeana Regel, which has an anti-cancer effect. The purpose of this study was to explore the effects of RA on GC in vitro and in vivo.</div></div><div><h3>Methods</h3><div>We explored the targets of RA in GC through network pharmacology. MTT assay, flow cytometry, Western blotting, and other methods were used to detect the effects of RA on the proliferation, apoptosis, and autophagy of GC cells. After preconditioning with hydroxychloroquine (HCQ) and rapamycin, we observed the effects of RA-induced autophagy on apoptosis. We further verified the antitumor effect and safety of RA in vivo. Using SNU-1 xenograft tumor model in nude mice, tumor volume was observed and liver toxicity was observed by immunohistochemistry.</div></div><div><h3>Results</h3><div>Many cancer-related signaling pathways were visualized using Cytoscape software. Among them, the MAPK signaling pathway was one of the highest-ranked pathways. The MTT assay results suggested that RA could inhibit the proliferation of HGC-27 and SNU-1 cells effectively. Flow cytometry and Western blotting confirmed that RA could significantly induce apoptosis of HGC-27 and SNU-1 cells. Electron microscopy and Western blotting demonstrated that RA could induce autophagy of HGC-27 and SNU-1 cells. Further experiments suggested that HCQ, an autophagy inhibitor, could enhance the capacity of RA to induce apoptosis. In animal studies, we found that intraperitoneal injection of RA could effectively and safely inhibit gastric tumors.</div></div><div><h3>Conclusions</h3><div>RA significantly inhibited the proliferation and induced autophagy and apoptosis of GC cells. In combination with HCQ, RA-induced apoptosis increased in vitro. The combined application of RA and autophagy inhibitors may serve as an added approach to the treatment of GC, but the underlying mechanism needs further exploration. In vivo, it was observed that RA has a good antitumor effect without increasing liver toxicity.</div></div>","PeriodicalId":17449,"journal":{"name":"Journal of Traditional and Complementary Medicine","volume":"15 2","pages":"Pages 161-169"},"PeriodicalIF":3.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141842359","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}
Yuetong Li , Shifang Fu , Fanyi Li , Yan Guo , Yanbo Cao , Fengjiao Ren , Rongrong Li , Yanguo Wang , Mingchi Luo
{"title":"Pediatric tuina treatment for spleen deficiency diarrhea regulated through the skin-brain-gut axis and mast cell degranulation","authors":"Yuetong Li , Shifang Fu , Fanyi Li , Yan Guo , Yanbo Cao , Fengjiao Ren , Rongrong Li , Yanguo Wang , Mingchi Luo","doi":"10.1016/j.jtcme.2024.03.003","DOIUrl":"10.1016/j.jtcme.2024.03.003","url":null,"abstract":"<div><h3>Background</h3><div>Pediatric tuina is an effective alternative therapy for managing spleen deficiency diarrhea. The application of spleen-meridian and large-intestine-meridian points has been shown to alleviate symptoms and has garnered some support from evidence-based medicine. Nonetheless, there remains a dearth of research elucidating the biological effects of these specific acupoints. This study aimed to explore their effects by focusing on the material basis involving mast cells (MCs).</div></div><div><h3>Methods</h3><div>The experimental design induced spleen-deficiency diarrhea in Kunming mice through a 7-day administration of <em>Rheum officinale</em> extract through gavage. Following this induction, treatment was initiated, employing a combination of spleen-meridian and large-intestine-meridian points over 6 days. Efficacy was assessed using fecal scoring. Colonic structure was assessed through hematoxylin-eosin staining, while toluidine blue staining was employed to observe MC degranulation within the skin-brain-gut axis. Immunohistochemistry was performed to detect tryptase release from MCs.</div></div><div><h3>Results</h3><div>The treatment combining spleen-meridian and large-intestine-meridian points markedly ameliorated diarrhea symptoms and improved fecal scores in Kunming mice exhibiting spleen deficiency. Pediatric tuina treatment facilitated the restoration of the colonic barrier and reduction in MC counts within the skin acupoint-brain-gut axis, consequently affecting the biologically active substance tryptase.</div></div><div><h3>Conclusion</h3><div>This study reveals the biological mechanism underlying the efficacy of specific acupoints in pediatric tuina, employing a holistic perspective encompassing the skin-brain-gut axis and MCs. Our findings substantiate the scientific basis for the effectiveness of tuina therapy in managing diarrhea and offer a new avenue for fundamental research on specific acupoints within pediatric tuina.</div></div>","PeriodicalId":17449,"journal":{"name":"Journal of Traditional and Complementary Medicine","volume":"15 2","pages":"Pages 205-213"},"PeriodicalIF":3.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140280316","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":"Withdrawal notice to: “Knowledge and attitudes towards utilizing complementary and alternative medical (CAM) treatments by mental health practitioner from various disciplines” [J Tradit Complement Med 13 (6) (2023) 640]","authors":"Sharon Freeman Clevenger","doi":"10.1016/j.jtcme.2024.12.002","DOIUrl":"10.1016/j.jtcme.2024.12.002","url":null,"abstract":"","PeriodicalId":17449,"journal":{"name":"Journal of Traditional and Complementary Medicine","volume":"15 2","pages":"Page 214"},"PeriodicalIF":3.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143428016","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}
Xiangka Hu , Liuming Gui , Mushuang Qi , Wanjun Zhu , Ying Ren , Jin Li , Shuyu Yang , Chunmei Dai
{"title":"Study on the pharmacodynamics and related mechanism of Tangningtongluo tablet on prediabetes mice based on the theory of “liver controlling dispersion”","authors":"Xiangka Hu , Liuming Gui , Mushuang Qi , Wanjun Zhu , Ying Ren , Jin Li , Shuyu Yang , Chunmei Dai","doi":"10.1016/j.jtcme.2024.06.011","DOIUrl":"10.1016/j.jtcme.2024.06.011","url":null,"abstract":"<div><h3>Background and aim</h3><div>Prediabetes is an unavoidable process and a high risk factor for developing of type 2 diabetes. Tangningtongluo (TNTL) tablet is a kind of pure plant preparation in hospital and used for the diabetes (消渴病, xiāo kě bìng) caused by deficiency of both Qi and Yin (气阴两虚,qì yīn liǎng xū). However, the effect of TNTL tablet on prediabetes has not been reported for now. This study was aimed to investigate the effect and related mechanism of TNTL tablet on prediabetes.</div></div><div><h3>Experimental procedure</h3><div>Prediabetic mice induced by a high-sugar and high-fat diet combined with streptozotocin were treated with TNTL tablet, and the pharmacodynamics and related mechanism were studied.</div></div><div><h3>Results and conclusion</h3><div>Our results showed that TNTL tablet reduced body weight and regulated the disorder of glucose and lipid metabolism in prediabetic mice. The function and the pathological changes of liver and islet tissue were improved after TNTL tablet treated prediabetic mice. Additionally, TNTL tablet decreased the levels of MDA, TNF-α, IL-1β and IL-6 in serum, increased the contents of SOD and GSH-px, up-regulated the expression of p-PI3K and p-AKT protein, and down-regulated the expression of p-IKK and p-NF-κB p65 protein in liver tissue. This study revealed that TNTL tablet could improve insulin sensitivity and insulin resistance in prediabetic mice, and delay the procession of prediabetes to diabetes, which might be related to inhibiting IKK/NF-κB signaling pathway, exerting anti-inflammatory and antioxidant effects, and activating PI3K/AKT signaling pathway.</div></div>","PeriodicalId":17449,"journal":{"name":"Journal of Traditional and Complementary Medicine","volume":"15 2","pages":"Pages 182-191"},"PeriodicalIF":3.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143428014","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}
Fengxian Jiang , Pancen Ran , Liyin Pan , Jingjiang Lai , Junlei Zhang , Jing Zhao , Wei Xu , Jingliang Wang , Yang Shu , Yahui Wang , Rui Zhao , Weihao Wang , Jian Wei , Guobin Fu
{"title":"Mechanism of Atractylenolide Ⅲ alleviating pyrotinib-induced diarrhea by regulating AMPK/CFTR pathway through metabolite of gut microbiota","authors":"Fengxian Jiang , Pancen Ran , Liyin Pan , Jingjiang Lai , Junlei Zhang , Jing Zhao , Wei Xu , Jingliang Wang , Yang Shu , Yahui Wang , Rui Zhao , Weihao Wang , Jian Wei , Guobin Fu","doi":"10.1016/j.jtcme.2024.11.015","DOIUrl":"10.1016/j.jtcme.2024.11.015","url":null,"abstract":"<div><div>Atractylenolide III, a sesquiterpene extracted from the rhizome of Atractylodes macrocephala (Asteraceae), exhibits pharmacological effects, including improvement of gastrointestinal function, regulation of immune function, anti-inflammatory and antibacterial properties. Pyrotinib, a representative TKI originally developed in China, is classified as a Class 1.1 novel drug, exhibits superior efficacy compared to similar drugs. Notably, the overall incidence of pyrotinib-induced diarrhea stands at 95 %, with 40 % of cases classified as grade ≥3 diarrhea. Currently, the effect of Atractylenolide III on pyrotinib-induced diarrhea and the underlying mechanisms remain unclear. Therefore, in this study, we established a pyrotinib (80 mg/kg/day) Wistar rat diarrhea model to explore the effect of Atractylenolide III on pyrotinib-induced diarrhea. We exploded the potential mechanism of Atractylenolide III via MQAE chloride fluorescent probe, RT-qPCR, Western blot, 16S rRNA sequencing, metabolomics, etc. We found that Atractylenolide III demonstrated the ability to alleviate pyrotinib-induced diarrhea without compromising its anti-tumor effects, inhibited pyrotinib-induced chloride secretion, and the potential mechanism of action involved enhancing AMPK phosphorylation while decreasing CFTR protein expression. Additionally, Atractylenolide III alleviated pyrotinib-induced diarrhea by modulating intestinal flora structure and increasing lithocholic acid content. This study could provide potential novel traditional Chinese medicine targets for treating diarrhea caused by tyrosine kinase inhibitor drugs, such as pyrotinib. The study emphasizes the role of TCM in minimizing adverse effects during tumor treatment.</div></div>","PeriodicalId":17449,"journal":{"name":"Journal of Traditional and Complementary Medicine","volume":"15 2","pages":"Pages 192-204"},"PeriodicalIF":3.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143428015","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}