1.Clinical Advantages of Traditional Chinese Medicine in Treatment of Childhood Simple Obesity: Insights from Expert Consensus
Qi ZHANG ; Yingke LIU ; Xiaoxiao ZHANG ; Guichen NI ; Heyin XIAO ; Junhong WANG ; Liqun WU ; Zhanfeng YAN ; Kundi WANG ; Jiajia CHEN ; Hong ZHENG ; Xinying GAO ; Liya WEI ; Qiang HE ; Qian ZHAO ; Huimin SU ; Zhaolan LIU ; Dafeng LONG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(6):238-245
Childhood simple obesity has become a significant public health issue in China. Modern medicine primarily relies on lifestyle interventions and often suffers from poor long-term compliance, while pharmacological options are limited and associated with potential adverse effects. Traditional Chinese Medicine (TCM) has a long history in the prevention and management of this condition, demonstrating eight distinct advantages, including systematic theoretical foundation, diversified therapeutic approaches, definite therapeutic efficacy, high safety profile, good patient compliance, comprehensive intervention strategies, emphasis on prevention, and stepwise treatment protocols. Additionally, TCM is characterized by six distinctive features: the use of natural medicinal substances, non-invasive external therapies, integration of medicinal dietetics, simple exercise regimens, precise syndrome differentiation, and diverse dosage forms. By combining internal and external treatments, TCM facilitates individualized regimen adjustment and holistic regulation, demonstrating remarkable effects in improving obesity-related metabolic indicators, regulating constitutional imbalance, and promoting healthy behaviors. However, challenges remain, such as inconsistent operational standards, insufficient high-quality clinical evidence, and a gap between basic research and clinical application. Future efforts should focus on accelerating the standardization of TCM diagnosis and treatment, conducting multicenter randomized controlled trials, and fostering interdisciplinary integration, so as to enhance the scientific validity and international recognition of TCM in the prevention and treatment of childhood obesity.
2.Research on Development Path and Strategy of Human Use Experience in Traditional Chinese Medicine Based on Bibliometrics and Thematic Analysis
Yundan WU ; Qun CHEN ; Jie CHEN ; Yuhang OU ; Jindong WU ; Yan XIAO ; Jiemei GUO ; Jing CAI ; Youxin SU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(7):118-128
ObjectiveThe development trend and knowledge structure of the research on human use experience (HUE) of traditional Chinese medicine (TCM) were systematically reviewed, and the core challenges and future directions were identified. This study aims to provide reference for the construction of a scientific and feasible research and development framework and evidence transformation system. MethodsLiterature related to "human use experience" published from January 1, 2019 to July 31, 2025 was retrieved from the China National Knowledge Infrastructure (CNKI), Wanfang, China Science and Technology Journal Database (VIP), and PubMed databases. Bibliometric visualization was conducted using Excel, VOSviewer, and CiteSpace, followed by in-depth reading and thematic summarization of core literature. ResultsA total of 181 papers were included for bibliometric analysis, with 45 articles used for in-depth thematic mining. The analysis showed that the number of publications on HUE research has increased in a stepwise manner over the past five years. Yang Zhongqi (24 times) was the core of the author network, the journal with the highest number of publications was China Journal of Chinese Materia Medica, the institutions publishing the most articles were mainly research institutions, regulatory agencies, hospitals, and universities, high-frequency keywords included "new TCM drugs", "real-world studies", and "clinical comprehensive evaluation", keyword clustering analysis formed three major clusters: Policy orientation, application fields, and methodological approaches. Thematic analysis reveals that HUE-based evaluation should be integrated throughout the research and development process, encompassing three dimensions: TCM theory, clinical value, and pharmaceutical fundamentals, with toxic herbs and compatibility contraindications being key foci. Data collection primarily relies on empirical data, while real-world data constitute the primary source for clinical research, with efficacy and safety as the shared core. Data management emphasizes quality control and statistical analysis; however, the management of bias and confounding remains a critical bottleneck in evidence transformation. In practice, HUE-based approaches have successfully supported the registration and evaluation of multiple categories of new TCM drugs. ConclusionThe research on HUE of TCM has formed a policy-driven pattern characterized by, rapid development and close link with regulatory practice. A technical framework covering the whole chain of research and development has been constructed with clinical value as the core, which provides methodological basis and strategy reference for the scientific transformation of HUE of TCM from "experience" to "evidence".
3.Effects and mechanism of Qiangxin decoction on mitochondrion of rats with chronic heart failure
Meiling MAO ; Jianqi LU ; Zhide ZHU ; Yan PANG ; Liyu XIE ; Jiayong CHEN ; Xinyu WU ; Xiang XIAO ; Junshen LU ; Weiqi SHI
China Pharmacy 2025;36(2):160-165
OBJECTIVE To investigate the effects and potential mechanism of Qiangxin decoction on mitochondrion of rats with chronic heart failure (CHF). METHODS The CHF model was established by ligating the left anterior descending branch of the coronary artery. Modeled rats were divided into model group, Qiangxin decoction low-dose and high-dose groups (12.25, 24.50 g/kg, calculated by crude drug), and chemical medicine group (Sacubitril valsartan sodium tablets, 10.42 mg/kg), with 10 rats in each group; control group was set up without treatment. Each group of rats was orally administered with the corresponding medication or normal saline twice a day for 28 consecutive days. After the last medication, the contents of N-terminal pro-brain natriuretic peptide (NT-proBNP) and adenosine triphosphate (ATP) in serum and phosphatidic acid (PA) and cardiolipin (CL) in myocardial tissue were all detected; the pathological damage and collagen fibrosis of rat myocardial tissue were observed; the apoptosis of myocardial cells was determined; the ultrastructure of myocardial tissue was observed; the protein expressions of mitofusin 1 (Mfn1), Mfn2, optic atrophy protein 1 (OPA1) and dynamin-related protein 1 (Drp1) were all detected in myocardial tissue. RESULTS Compared with control group,the serum content of NT-proBNP, apoptotic rate of myocardial cells, and relative expressions of S-OPA1 and Drp1 proteins were all increased significantly; serum content of ATP,contents of PA and CL, and relative expressions of Mfn1, Mfn2 and L-OPA1 proteins were all significantly reduced (P<0.05). There were abnormal membrane tissue structure in various layers of myocardial tissue, degeneration and necrosis of myocardial cells, and severe fibrosis; the mitochondria were swollen, with reduced or absent cristae, and uneven matrix density. After intervention with Qiangxin decoction, the levels of the aforementioned quantitative indicators in serum and myocardial tissue of rats (excluding CL content in the Qiangxin decoction low- dose group) were significantly reversed (P<0.05); the pathological damage of myocardial tissue had significantly improved, fibrosis had significantly reduced, mitochondrial morphology tended to be normal, cristae had increased, and matrix density was uniform. CONCLUSIONS Qiangxin decoction can regulate myocardial mitochondrial function and structural integrity of CHF rats, thereby improving myocardial energy metabolism and antagonizing myocardial fibrosis, the mechanism of which may be associated with activating PA/Mfn/CL signaling pathway.
4.Effects and mechanism of Qiangxin decoction on mitochondrion of rats with chronic heart failure
Meiling MAO ; Jianqi LU ; Zhide ZHU ; Yan PANG ; Liyu XIE ; Jiayong CHEN ; Xinyu WU ; Xiang XIAO ; Junshen LU ; Weiqi SHI
China Pharmacy 2025;36(2):160-165
OBJECTIVE To investigate the effects and potential mechanism of Qiangxin decoction on mitochondrion of rats with chronic heart failure (CHF). METHODS The CHF model was established by ligating the left anterior descending branch of the coronary artery. Modeled rats were divided into model group, Qiangxin decoction low-dose and high-dose groups (12.25, 24.50 g/kg, calculated by crude drug), and chemical medicine group (Sacubitril valsartan sodium tablets, 10.42 mg/kg), with 10 rats in each group; control group was set up without treatment. Each group of rats was orally administered with the corresponding medication or normal saline twice a day for 28 consecutive days. After the last medication, the contents of N-terminal pro-brain natriuretic peptide (NT-proBNP) and adenosine triphosphate (ATP) in serum and phosphatidic acid (PA) and cardiolipin (CL) in myocardial tissue were all detected; the pathological damage and collagen fibrosis of rat myocardial tissue were observed; the apoptosis of myocardial cells was determined; the ultrastructure of myocardial tissue was observed; the protein expressions of mitofusin 1 (Mfn1), Mfn2, optic atrophy protein 1 (OPA1) and dynamin-related protein 1 (Drp1) were all detected in myocardial tissue. RESULTS Compared with control group,the serum content of NT-proBNP, apoptotic rate of myocardial cells, and relative expressions of S-OPA1 and Drp1 proteins were all increased significantly; serum content of ATP,contents of PA and CL, and relative expressions of Mfn1, Mfn2 and L-OPA1 proteins were all significantly reduced (P<0.05). There were abnormal membrane tissue structure in various layers of myocardial tissue, degeneration and necrosis of myocardial cells, and severe fibrosis; the mitochondria were swollen, with reduced or absent cristae, and uneven matrix density. After intervention with Qiangxin decoction, the levels of the aforementioned quantitative indicators in serum and myocardial tissue of rats (excluding CL content in the Qiangxin decoction low- dose group) were significantly reversed (P<0.05); the pathological damage of myocardial tissue had significantly improved, fibrosis had significantly reduced, mitochondrial morphology tended to be normal, cristae had increased, and matrix density was uniform. CONCLUSIONS Qiangxin decoction can regulate myocardial mitochondrial function and structural integrity of CHF rats, thereby improving myocardial energy metabolism and antagonizing myocardial fibrosis, the mechanism of which may be associated with activating PA/Mfn/CL signaling pathway.
5.Research on software development and smart manufacturing platform incorporating near-infrared spectroscopy for measuring traditional Chinese medicine manufacturing process.
Yan-Fei WU ; Hui XU ; Kai-Yi WANG ; Hui-Min FENG ; Xiao-Yi LIU ; Nan LI ; Zhi-Jian ZHONG ; Ze-Xiu ZHANG ; Zhi-Sheng WU
China Journal of Chinese Materia Medica 2025;50(9):2324-2333
Process analytical technology(PAT) is a key means for digital transformation and upgrading of the traditional Chinese medicine(TCM) manufacturing process, serving as an important guarantee for consistent and controllable TCM product quality. Near-infrared(NIR) spectroscopy has become the core technology for measuring the TCM manufacturing process. By incorporating NIR spectroscopy into PAT and starting from the construction of a smart platform for the TCM manufacturing process, this paper systematically described the development history and innovative application of the combination of NIR spectroscopy with chemometrics in measuring the TCM manufacturing process by the research team over the past two decades. Additionally, it explored the application of a validation method based on accuracy profile(AP) in the practice of NIR spectroscopy. Furthermore, the software development progress driven by NIR spectroscopy supported by modeling technology was analyzed, and the prospect of integrating NIR spectroscopy in smart factory control platforms was exemplified with the construction practices of related platforms. By integrating with the smart platform, NIR spectroscopy could improve production efficiency and guarantee product quality. Finally, the prospect of the smart platform application in measuring the TCM manufacturing process was projected. It is believed that the software development for NIR spectroscopy and the smart manufacturing platform will provide strong technical support for TCM digitalization and industrialization.
Spectroscopy, Near-Infrared/methods*
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Drugs, Chinese Herbal/analysis*
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Software
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Medicine, Chinese Traditional
;
Quality Control
6.Mechanism of Quanduzhong Capsules in treating knee osteoarthritis from perspective of spatial heterogeneity.
Zhao-Chen MA ; Zi-Qing XIAO ; Chu ZHANG ; Yu-Dong LIU ; Ming-Zhu XU ; Xiao-Feng LI ; Zhi-Ping WU ; Wei-Jie LI ; Yi-Xin YANG ; Na LIN ; Yan-Qiong ZHANG
China Journal of Chinese Materia Medica 2025;50(8):2209-2216
This study aims to systematically characterize the targeted effects of Quanduzhong Capsules on cartilage lesions in knee osteoarthritis by integrating spatial transcriptomics data mining and animal experiments validation, thereby elucidating the related molecular mechanisms. A knee osteoarthritis model was established using Sprague-Dawley(SD) rats, via a modified Hulth method. Hematoxylin and eosin(HE) staining was employed to detect knee osteoarthritis-associated pathological changes in knee cartilage. Candidate targets of Quanduzhong Capsules were collected from the HIT 2.0 database, followed by bioinformatics analysis of spatial transcriptomics datasets(GSE254844) from cartilage tissues in clinical knee osteoarthritis patients to identify spatially specific disease genes. Furthermore, a "formula candidate targets-spatially specific genes in cartilage lesions" interaction network was constructed to explore the effects and major mechanisms of Quanduzhong Capsules in distinct cartilage regions. Experimental validation was conducted through immunohistochemistry using animal-derived biospecimens. The results indicated that Quanduzhong Capsules effectively inhibited the degenerative changes in the cartilage of affected joints in rats, which was associated with the regulation of Quanduzhong Capsules on the thioredoxin-interacting protein(TXNIP)-NOD-like receptor family pyrin domain containing 3(NLRP3)-bone morphogenetic protein receptor type 2(BMPR2)-fibronectin 1(FN1)-matrix metallopeptidase 2(MMP2) signal axis in the articular cartilage surface and superficial zones, subsequently inhibiting cartilage matrix degradation leading to oxidative stress and inflammatory diffusion. In summary, this study clarifies the spatially specific targeted effects and protective mechanisms of Quanduzhong Capsules within pathological cartilage regions in knee osteoarthritis, providing theoretical and experimental support for the clinical application of this drug in the targeted therapy on the inflamed cartilage.
Animals
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Osteoarthritis, Knee/metabolism*
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Drugs, Chinese Herbal/administration & dosage*
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Rats, Sprague-Dawley
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Rats
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Male
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Humans
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Capsules
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Female
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Disease Models, Animal
7.Mechanism of Euphorbiae Ebracteolatae Radix processed by milk in reducing intestinal toxicity.
Chang-Li SHEN ; Hao WU ; Hong-Li YU ; Hong-Mei WEN ; Xiao-Bing CUI ; Hui-Min BIAN ; Tong-la-Ga LI ; Min ZENG ; Yan-Qing XU ; Yu-Xin GU
China Journal of Chinese Materia Medica 2025;50(12):3204-3213
This study aimed to investigate the correlation between changes in intestinal toxicity and compositional alterations of Euphorbiae Ebracteolatae Radix(commonly known as Langdu) before and after milk processing, and to explore the detoxification mechanism of milk processing. Mice were intragastrically administered the 95% ethanol extract of raw Euphorbiae Ebracteolatae Radix, milk-decocted(milk-processed), and water-decocted(water-processed) Euphorbiae Ebracteolatae Radix. Fecal morphology, fecal water content, and the release levels of inflammatory cytokines tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β) in different intestinal segments were used as indicators to evaluate the effects of different processing methods on the cathartic effect and intestinal inflammatory toxicity of Euphorbiae Ebracteolatae Radix. LC-MS/MS was employed to analyze the small-molecule components in the raw product, the 95% ethanol extract of the milk-processed product, and the milky waste(precipitate) formed during milk processing, to assess the impact of milk processing on the chemical composition of Euphorbiae Ebracteolatae Radix. The results showed that compared with the blank group, both the raw and water-processed Euphorbiae Ebracteolatae Radix significantly increased the fecal morphology score, fecal water content, and the release levels of TNF-α and IL-1β in various intestinal segments(P<0.05). Compared with the raw group, all indicators in the milk-processed group significantly decreased(P<0.05), while no significant differences were observed in the water-processed group, indicating that milk, as an adjuvant in processing, plays a key role in reducing the intestinal toxicity of Euphorbiae Ebracteolatae Radix. Mass spectrometry results revealed that 29 components were identified in the raw product, including 28 terpenoids and 1 acetophenone. The content of these components decreased to varying extents after milk processing. A total of 28 components derived from Euphorbiae Ebracteolatae Radix were identified in the milky precipitate, of which 27 were terpenoids, suggesting that milk processing promotes the transfer of toxic components from Euphorbiae Ebracteolatae Radix into milk. To further investigate the effect of milk adjuvant processing on the toxic terpenoid components of Euphorbiae Ebracteolatae Radix, transmission electron microscopy(TEM) was used to observe the morphology of self-assembled casein micelles(the main protein in milk) in the milky precipitate. The micelles formed in casein-terpenoid solutions were characterized using particle size analysis, fluorescence spectroscopy, ultraviolet spectroscopy, and Fourier-transform infrared(FTIR) spectroscopy. TEM observations confirmed the presence of casein micelles in the milky precipitate. Characterization results showed that with increasing concentrations of toxic terpenoids, the average particle size of casein micelles increased, fluorescence intensity of the solution decreased, the maximum absorption wavelength in the UV spectrum shifted, and significant changes occurred in the infrared spectrum, indicating that interactions occurred between casein micelles and toxic terpenoid components. These findings indicate that the cathartic effect of Euphorbiae Ebracteolatae Radix becomes milder and its intestinal inflammatory toxicity is reduced after milk processing. The detoxification mechanism is that terpenoid components in Euphorbiae Ebracteolatae Radix reassemble with casein in milk to form micelles, promoting the transfer of some terpenoids into the milky precipitate.
Animals
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Mice
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Milk/chemistry*
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Drugs, Chinese Herbal/chemistry*
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Male
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Tumor Necrosis Factor-alpha/immunology*
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Intestines/drug effects*
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Interleukin-1beta/immunology*
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Tandem Mass Spectrometry
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Female
8.Establishment of different pneumonia mouse models suitable for traditional Chinese medicine screening.
Xing-Nan YUE ; Jia-Yin HAN ; Chen PAN ; Yu-Shi ZHANG ; Su-Yan LIU ; Yong ZHAO ; Xiao-Meng ZHANG ; Jing-Wen WU ; Xuan TANG ; Ai-Hua LIANG
China Journal of Chinese Materia Medica 2025;50(15):4089-4099
In this study, lipopolysaccharide(LPS), ovalbumin(OVA), and compound 48/80(C48/80) were administered to establish non-infectious pneumonia models under simulated clinical conditions, and the correlation between their pathological characteristics and traditional Chinese medicine(TCM) syndromes was compared, providing the basis for the selection of appropriate animal models for TCM efficacy evaluation. An acute pneumonia model was established by nasal instillation of LPS combined with intraperitoneal injection for intensive stimulation. Three doses of OVA mixed with aluminum hydroxide adjuvant were injected intraperitoneally on days one, three, and five and OVA was administered via endotracheal drip for excitation on days 14-18 to establish an OVA-induced allergic pneumonia model. A single intravenous injection of three doses of C48/80 was adopted to establish a C48/80-induced pneumonia model. By detecting the changes in peripheral blood leukocyte classification, lung tissue and plasma cytokines, immunoglobulins(Ig), histamine levels, and arachidonic acid metabolites, the multi-dimensional analysis was carried out based on pathological evaluation. The results showed that the three models could cause pulmonary edema, increased wet weight in the lung, and obvious exudative inflammation in lung tissue pathology, especially for LPS. A number of pyrogenic cytokines, inclading interleukin(IL)-6, interferon(IFN)-γ, IL-1β, and IL-4 were significantly elevated in the LPS pneumonia model. Significantly increased levels of prostacyclin analogs such as prostaglandin E2(PGE2) and PGD2, which cause increased vascular permeability, and neutrophils in peripheral blood were significantly elevated. The model could partly reflect the clinical characteristics of phlegm heat accumulating in the lung or dampness toxin obstructing the lung. The OVA model showed that the sensitization mediators IgE and leukotriene E4(LTE4) were increased, and the anti-inflammatory prostacyclin 6-keto-PGF2α was decreased. Immune cells(lymphocytes and monocytes) were decreased, and inflammatory cells(neutrophils and basophils) were increased, reflecting the characteristics of "deficiency", "phlegm", or "dampness". Lymphocytes, monocytes, and basophils were significantly increased in the C48/80 model. The phenotype of the model was that the content of histamine, a large number of prostacyclins(6-keto-PGE1, PGF2α, 15-keto-PGF2α, 6-keto-PGF1α, 13,14-D-15-keto-PGE2, PGD2, PGE2, and PGH2), LTE4, and 5-hydroxyeicosatetraenoic acid(5S-HETE) was significantly increased, and these indicators were associated with vascular expansion and increased vascular permeability. The pyrogenic inflammatory cytokines were not increased. The C48/80 model reflected the characteristics of cold and damp accumulation. In the study, three non-infectious pneumonia models were constructed. The LPS model exhibited neutrophil infiltration and elevated inflammatory factors, which was suitable for the efficacy study of TCM for clearing heat, detoxifying, removing dampness, and eliminating phlegm. The OVA model, which took allergic inflammation as an index, was suitable for the efficacy study of Yiqi Gubiao formulas. The C48/80 model exhibited increased vasoactive substances(histamine, PGs, and LTE4), which was suitable for the efficacy study and evaluation of TCM for warming the lung, dispersing cold, drying dampness, and resolving phlegm. The study provides a theoretical basis for model selection for the efficacy evaluation of TCM in the treatment of pneumonia.
Animals
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Disease Models, Animal
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Mice
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Pneumonia/genetics*
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Medicine, Chinese Traditional
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Male
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Humans
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Cytokines/immunology*
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Female
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Lipopolysaccharides/adverse effects*
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Lung/drug effects*
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Drugs, Chinese Herbal
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Ovalbumin
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Mice, Inbred BALB C
9.Polarized light microscopic mineral phase authentication and health risk assessment of raw and calcined fossil mineral Chinese medicinal material Draconis Os.
Yan-Qiong PAN ; Zheng LIU ; Li-Wen ZHENG ; Ying ZHANG ; Liu ZHOU ; Xi-Long QIAN ; Fang FANG ; Xiao WU ; Sheng-Jin LIU
China Journal of Chinese Materia Medica 2025;50(15):4238-4247
This study aims to investigate the polarized microscopic mineral phase characteristics, inorganic element content, and potential health risks associated with the intake of raw and calcined fossil mineral Chinese medicinal material Draconis Os. Microscopy was employed to observe the mineralogical characteristics of Draconis Os and compare the microscopic features and phase composition of raw and calcined Draconis Os under monochromatic and orthogonal polarized light. Inductively coupled plasma mass spectrometry(ICP-MS) was employed to determine the content of 30 inorganic elements. Health risk assessment was conducted by calculating the single pollution index(P_i), average daily intake of elements for adults(ADI), target hazard quotient(THQ), non-carcinogenic assessment method-hazard quotient(HQ), and the carcinogenic risk of elements(CR). The results indicated that under monochromatic polarized light, the Draconis Os powder sections exhibited light gray-brown to gray-brown irregular fragments, some with undulating textures that were slightly curved. Under crossed polarized light, they appeared dark gray, grayish-white, and yellowish-white. Clear apatite was visible in the ground sections of Draconis Os under crossed polarized light. P_i results indicated that Draconis Os samples were free from contamination and were of good quality. According to the maximum allowable limits of heavy metals stipulated in ISO Traditional Chinese Medicine: Determination of heavy metals in herbal medicines used in Traditional Chinese Medicine, ADI, THQ, HQ, and CR were taken as assessment indicators. Only the THQ value for As(arsenic) in raw Draconis Os was greater than 1, while the THQ values for other heavy metal elements in the Draconis Os samples were all less than 1. The study demonstrates that the primary mineral phase of raw and calcined Draconis Os is apatite, with some samples co-existing with calcite, which can serve as one of the means for quality control of Draconis Os. The elemental analysis results from ICP-MS provide scientific evidence for the safety assessment of Draconis Os, indicating that Draconis Os is safe in clinical application.
Drugs, Chinese Herbal/analysis*
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Risk Assessment
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Minerals/chemistry*
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Fossils
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Humans
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Drug Contamination
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Mass Spectrometry
10.Ursodeoxycholic acid inhibits the uptake of cystine through SLC7A11 and impairs de novo synthesis of glutathione.
Fu'an XIE ; Yujia NIU ; Xiaobing CHEN ; Xu KONG ; Guangting YAN ; Aobo ZHUANG ; Xi LI ; Lanlan LIAN ; Dongmei QIN ; Quan ZHANG ; Ruyi ZHANG ; Kunrong YANG ; Xiaogang XIA ; Kun CHEN ; Mengmeng XIAO ; Chunkang YANG ; Ting WU ; Ye SHEN ; Chundong YU ; Chenghua LUO ; Shu-Hai LIN ; Wengang LI
Journal of Pharmaceutical Analysis 2025;15(1):101068-101068
Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [15N2]-cystine and [13C5]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

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