1.Traditional Chinese Medicine in Treatment of Chronic Atrophic Gastritis by Regulating PI3K/Akt Signaling Pathway:A Review
Yuxue DING ; Zhiwei SU ; Juan XUE ; Jun SUN ; Chunyan JI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(6):307-315
Chronic atrophic gastritis (CAG) is a digestive system disease characterized by the reduction and atrophy of the intrinsic glands of the gastric mucosa. This disease is closely related to risk factors such as Helicobacter pylori (Hp) infection,long-term unhealthy eating habits and lifestyle. As CAG is a key link in the development of gastric cancer,effectively preventing its deterioration is of great significance for the prevention of gastric cancer. At present,Western medicine mainly uses symptomatic treatments such as eradicating Hp,protecting gastric mucosa, and promoting gastrointestinal motility. However, long-term use is prone to drug resistance and cannot reverse limitations such as gland atrophy, making it urgent to explore new intervention strategies. In recent years,with the deepening of CAG mechanism research,the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway,as one of the classic signaling pathways,plays a significant role in the occurrence and development of CAG,while its systematic summary is still blank. Based on the regulatory advantages of "multi-target,multi-pathway,and low toxicity",traditional Chinese medicine can improve the pathological process of CAG by intervening in key nodes of the PI3K/Akt pathway. In this paper,the research progress of traditional Chinese medicine regulating PI3K/Akt pathway to improve CAG was systematically reviewed for the first time. The expression of PI3K/Akt signaling pathway in CAG was discussed,including the regulation of inflammation and oxidative stress,cell proliferation and apoptosis,and autophagy. The traditional Chinese medicine flavonoids,alkaloids,terpenoids and other compounds that regulate this pathway were summarized. The traditional Chinese medicine compounds mainly include classic famous prescriptions such as Xiaochaihu Tang,Banxia Xiexin Tang,Morodan concentrated pills,Elian granules and other traditional Chinese patent medicines,as well as empirical prescriptions such as modified Leweiyin formula,and Qiling prescription. This study aims to give full play to the advantages of traditional Chinese medicine and lay a solid foundation for the wide application and further development of CAG treatment,and provide new ideas for clinical research and drug research on CAG.
2.Mechanism of Huazhuo Sanjie Chubi Presciption in Regulating Macrophage Polarization and Improving Low-grade Inflammation in Rats with Chronic Gouty Arthritis
Yuwan LI ; Yingjie ZHANG ; Siyuan LIN ; Xiaohua CHEN ; Qianglong CHEN ; Fan YANG ; Jun LIU ; Bingyan CHEN ; Peng CHEN ; Jiemei GUO ; Youxin SU ; Yan XIAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(7):93-104
ObjectiveTo evaluate the therapeutic effect of Huazhuo SanJie Chubi presciption (HSCD) on chronic gouty arthritis (CGA) rats with low-grade inflammation and to explore the underlying mechanism with a focus on macrophage polarization. MethodsThe 41 male 6-week-old SD rats were randomly allocated, using the random number table, to a normal group (n=8) and a model group (n =33). CGA with low-grade inflammation was induced in the model group by daily gavage of potassium oxonate (250 mg·kg-1·d-1) and hypoxanthine (300 mg·kg-1·d-1), combined with intra-articular injection of a monosodium urate (MSU) crystal suspension (50 μL, 25 g·L-¹) into the left ankle twice weekly. After 4 weeks of modeling, 3 rats were randomly selected from each group for model validation. The remaining successfully modeled rats were randomly divided into a model group, an HSCD group (10.35 g·kg-1·d-1, gavage once daily), an M1 polarization agonist group (L-methionine sulfoximine, 300 mg·kg-1, subcutaneous injection every other day), an M1 polarization agonist + HSCD group, an M2 polarization inhibitor group (PD0325901, 10 mg·kg-1·d-1, gavage once daily), and M2 polarization inhibitor + HSCD group. The corresponding drug or drug combination was administered according to group assignment, whereas rats in the normal and model groups received 0.5% carboxymethyl cellulose sodium (CMC-Na) vehicle (10.35 g·kg-1·d-1, gavage once daily). All interventions were continued for four weeks. During the intervention period, except for the normal group, potassium oxonate (250 mg·kg⁻¹) and hypoxanthine (300 mg·kg-1) were co-administered by gavage every other day to maintain the model. At the end of treatment, serum uric acid (SUA), ankle joint diameter and joint swelling index were measured. The levels of high-sensitivity C-reactive protein (hs-CRP), interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), chemokine C-C motif ligand 2 (CCL2), S100 calcium-binding protein A8/A9 (S100A8/A9), interleukin-10 (IL-10) and arginase-1 (Arg-1) in serum and joint fluid were determined by enzyme-linked immunosorbent assay (ELISA). High-frequency ultrasound was used to assess MSU deposition in the ankle joint. Hematoxylin-eosin (HE) staining was performed to evaluate synovial histopathological changes. Quantitative Real-time PCR and immunofluorescence were used to detect the mRNA and protein expression of the M1 macrophage polarization markers inducible nitric oxide synthase (iNOS) and the M2 macrophage polarization marker scavenger receptor cysteine-rich type 1 protein M130 (CD163) in synovial tissue. ResultsCompared with the normal group, the model group showed significantly elevated SUA level and joint swelling index, and increased levels of pro-inflammatory cytokines, CCL2, and S100A8/A9 in both serum and joint fluid (P<0.05), accompanied by MSU deposition and synovial inflammation in the ankle joint. The mRNA and protein expression levels of macrophage polarization M1/M2 markers iNOS and CD163 in synovial tissues were also significantly up-regulated (P<0.05). Compared with model group, rats in HSCD group had significantly lower SUA levels, attenuated joint swelling, reduced serum levels of pro-inflammatory cytokines, and decreased levels of CCL2 and S100A8/A9 in both serum and joint fluid, accompanied with alleviated MSU deposition and synovial inflammation (P<0.05). HSCD markedly downregulated the mRNA and protein expression of M1 marker iNOS (P<0.05), whereas it had no significant effect on the expression of M2 marker CD163. Compared with the M1 polarization agonist group, the M1 polarization agonist + HSCD group showed significantly reduced joint swelling, lower serum levels of pro-inflammatory cytokines, and decreased levels of CCL2 and S100A8/A9 in joint fluid (P<0.05). In addition, synovial inflammatory cell infiltration and angiogenesis were attenuated, and iNOS mRNA and protein expression levels were significantly reduced (P<0.05). Compared with the M2 polarization inhibitor group, the M2 polarization inhibitor + HSCD group exhibited reduced joint swelling, decreased levels of CCL2 and S100A8/A9 in joint fluid and ameliorated synovial inflammation (P<0.05), whereas the levels of anti-inflammatory mediators (IL-10, Arg-1) and CD163 mRNA and protein expression were not significantly increased. ConclusionHSCD alleviates low-grade inflammation in CGA rats, at least in part, by inhibiting macrophage polarization toward the M1 phenotype.
3.Effect and Action Mechanism of Huazhuo Sanjie Chubi Prescription on Gouty Bone Erosion Model Rats Based on PI3K/Akt Signaling Pathway
Zhuoming ZHENG ; Jun LIU ; Meiling WANG ; Xiaohua CHEN ; Yuwan LI ; Siwei PENG ; Yingjie ZHANG ; Ruifang YANG ; Youxin SU ; Yan XIAO ; Jiemei GUO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(7):105-117
ObjectiveThis paper aims to observe the effect of Huazhuo Sanjie Chubi prescription (HSCD) on the gouty bone erosion model rats and investigate its action mechanism. MethodsThirty-six two-month-old male SD rats were randomly divided into the blank group with nine rats and the modeling group with 27 rats. The rats in the modeling group were administered hypoxanthine solution at 300 mg·kg-1·d-1 and potassium oxonate solution at 250 mg·kg-1·d-1, combined with intra-articular injection of 200 μL monosodium urate (MSU) crystal suspension at 25 g·L-1 into the right ankle joint (joint injection once every three days), so as to induce the gouty bone erosion model. After four weeks of modeling, three rats were selected from these two groups to validate the model. The modeled 24 rats were randomly divided into the model group, HSCD group (10.35 g·kg-1·d-1), allopurinol group (20 mg·kg-1·d-1), and inhibitor group (LY294002, 10 mg·kg-1·d-1), with six rats per group. Except for the blank group, rats in all other groups continued to receive hypoxanthine solution at 300 mg·kg-1 and potassium oxonate solution at 250 mg·kg-1 via gavage concurrently with administration to maintain modeling intervention. The rats in the HSCD group and allopurinol group received administration by gavage at the above doses. The rats in the inhibitor group received an intraperitoneal injection at the above dose. The rats in the blank group and model group received saline (10.35 g·kg-1·d-1) by gavage for four consecutive weeks. After administration, ankle joint swelling of the rats in all groups was observed, and the diameters were measured. Bone volume fraction (BV/TV) and bone surface area to bone volume (BS/BV) were observed and quantitatively analyzed by Micro-CT. Histopathological changes in the ankle joint were observed by hematoxylin-eosin (HE) staining and safranin O-fast green staining. The uric acid in the rats' serum was determined by enzyme colorimetry. The levels of inflammatory factors, including tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 were measured by enzyme-linked immunosorbent assay (ELISA). The protein expressions of receptor activator of nuclear factor-κB ligand (RANKL) and phosphorylated (p)-phosphatidylinositol-3-kinase (PI3K) in ankle joint tissues of rats were detected by immunofluorescence staining. The mRNA levels of the proteins related to the bone erosion, including RANKL, tartrate-resistant acid phosphatase
4.Multi-component Quality Consistency Evaluation of Leonuri Herba Granules Based on HPLC-DAD-CAD Multi-detector Technique and Chemometrics
Shuangyan LI ; Jun ZHANG ; Cong GUO ; Siyuan LI ; Jipeng DI ; Jiangmin SU ; An LIU ; Xiaodi KOU ; Yan LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):174-181
ObjectiveTo systematically evaluate the content differences of 4 components in Leonuri Herba granules, reveal the quality fluctuation patterns of products from the same and different manufacturers, providing scientific basis for the optimization of production process and quality control. MethodsHigh performance liquid chromatography-diode array detector-charged aerosol detector(HPLC-DAD-CAD) was employed to determine the contents of 4 components(syringic acid, leonurine hydrochloride, ferulic acid, and stachydrine hydrochloride) in samples from 19 manufacturers(53 batches, 159 boxes). Additionally, fingerprint profiles were constructed, and the fingerprint dissimilarity(PS) and relative standard deviation(RSD) of different samples from the same manufacturer were calculated. A principal component analysis(PCA) model was established with PS and the RSD values of the 4 components as variables to classify the manufacturers. Finally, samples from 5 manufacturers(M1-M5) covering three consistency groups were selected to calculate three quality consistency parameters, namely intra-batch consistency(PA), inter-batch consistency(PB), and PS. Then, PCA was performed with PA, PB, and PS of these 5 manufacturers as variables. ResultsThe average total content of the 4 index components per bag across the 19 manufacturers ranged from 41.10 mg to 97.54 mg. Among them, the content of stachydrine hydrochloride(a pharmacopoeial quality control component) was 32.46-72.70 mg per bag, all meeting the requirements of the 2025 edition of the Pharmacopoeia of the People's Republic of China, with RSD of 1.7%-17.1%. The content ranges of the other 3 components were as follows:syringic acid of 1.43-41.92 mg per bag, leonurine hydrochloride of 0.67-11.85 mg per bag, and ferulic acid of 0.11-3.81 mg per bag. Notably, leonurine hydrochloride exhibited the most significant content fluctuation among samples from the same manufacturer(RSD of 4.8%-59.2%). PCA results showed that the 19 manufacturers could be classified into 3 categories. Samples from 8 manufacturers(M2, M6, M7, M8, M10, M15, M17, M18) demonstrated relatively high consistency, five manufacturers(M3, M9, M12, M13, M14) showed moderate consistency, six manufacturers(M1, M4, M5, M11, M16, M19) exhibited low consistency. The two methods yielded consistent classification results for the 5 representative manufacturers, verifying the reliability of the proposed method. Among these, manufacturer M2 showed the best quality consistency and the highest total content of indicator components among M1-M5. ConclusionThe HPLC-DAD-CAD multi-detector hyphenation technology established in this study enables the accurate detection of 4 components in Leonuri Herba granules. Significant differences in the total content of these four components are observed among products from 19 manufacturers. The application of 2 consistency evaluation methods combined with PCA can effectively classify their consistency into 3 categories, and the classification results of the 2 methods are highly consistent. This study provides scientific basis for the process optimization and quality standard improvement of Leonuri Herba granules.
5.Multi-component Quality Consistency Evaluation of Leonuri Herba Granules Based on HPLC-DAD-CAD Multi-detector Technique and Chemometrics
Shuangyan LI ; Jun ZHANG ; Cong GUO ; Siyuan LI ; Jipeng DI ; Jiangmin SU ; An LIU ; Xiaodi KOU ; Yan LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):174-181
ObjectiveTo systematically evaluate the content differences of 4 components in Leonuri Herba granules, reveal the quality fluctuation patterns of products from the same and different manufacturers, providing scientific basis for the optimization of production process and quality control. MethodsHigh performance liquid chromatography-diode array detector-charged aerosol detector(HPLC-DAD-CAD) was employed to determine the contents of 4 components(syringic acid, leonurine hydrochloride, ferulic acid, and stachydrine hydrochloride) in samples from 19 manufacturers(53 batches, 159 boxes). Additionally, fingerprint profiles were constructed, and the fingerprint dissimilarity(PS) and relative standard deviation(RSD) of different samples from the same manufacturer were calculated. A principal component analysis(PCA) model was established with PS and the RSD values of the 4 components as variables to classify the manufacturers. Finally, samples from 5 manufacturers(M1-M5) covering three consistency groups were selected to calculate three quality consistency parameters, namely intra-batch consistency(PA), inter-batch consistency(PB), and PS. Then, PCA was performed with PA, PB, and PS of these 5 manufacturers as variables. ResultsThe average total content of the 4 index components per bag across the 19 manufacturers ranged from 41.10 mg to 97.54 mg. Among them, the content of stachydrine hydrochloride(a pharmacopoeial quality control component) was 32.46-72.70 mg per bag, all meeting the requirements of the 2025 edition of the Pharmacopoeia of the People's Republic of China, with RSD of 1.7%-17.1%. The content ranges of the other 3 components were as follows:syringic acid of 1.43-41.92 mg per bag, leonurine hydrochloride of 0.67-11.85 mg per bag, and ferulic acid of 0.11-3.81 mg per bag. Notably, leonurine hydrochloride exhibited the most significant content fluctuation among samples from the same manufacturer(RSD of 4.8%-59.2%). PCA results showed that the 19 manufacturers could be classified into 3 categories. Samples from 8 manufacturers(M2, M6, M7, M8, M10, M15, M17, M18) demonstrated relatively high consistency, five manufacturers(M3, M9, M12, M13, M14) showed moderate consistency, six manufacturers(M1, M4, M5, M11, M16, M19) exhibited low consistency. The two methods yielded consistent classification results for the 5 representative manufacturers, verifying the reliability of the proposed method. Among these, manufacturer M2 showed the best quality consistency and the highest total content of indicator components among M1-M5. ConclusionThe HPLC-DAD-CAD multi-detector hyphenation technology established in this study enables the accurate detection of 4 components in Leonuri Herba granules. Significant differences in the total content of these four components are observed among products from 19 manufacturers. The application of 2 consistency evaluation methods combined with PCA can effectively classify their consistency into 3 categories, and the classification results of the 2 methods are highly consistent. This study provides scientific basis for the process optimization and quality standard improvement of Leonuri Herba granules.
6.Characteristics and outcomes of portal vein thrombosis in patients with inflammatory bowel disease in Korea
Ki Jin KIM ; Su-Bin SONG ; Jung-Bin PARK ; June Hwa BAE ; Ji Eun BAEK ; Ga Hee KIM ; Min-Jun KIM ; Seung Wook HONG ; Sung Wook HWANG ; Dong-Hoon YANG ; Byong Duk YE ; Jeong-Sik BYEON ; Seung-Jae MYUNG ; Suk-Kyun YANG ; Chang Sik YU ; Yong-Sik YOON ; Jong-Lyul LEE ; Min Hyun KIM ; Ho-Su LEE ; Sang Hyoung PARK
The Korean Journal of Internal Medicine 2025;40(2):243-250
Background/Aims:
Portal vein thrombosis (PVT) frequently occurs in patients with inflammatory bowel disease (IBD), particularly when influenced by factors such as abdominal infections, IBD flare-ups, or surgical procedures. The implications of PVT range from immediate issues such as intestinal ischemia to long-term concerns including portal hypertension and its complications. However, there is a notable gap in comprehensive studies on PVT in IBD, especially with the increasing incidence of IBD in Asia. This research aimed to evaluate the clinical features and outcomes of PVT in patients with IBD at a leading hospital in South Korea.
Methods:
This retrospective analysis reviewed adult patients diagnosed with both IBD and PVT from 1989 to 2021 at a renowned South Korean medical center. The study focused on patient characteristics, specifics of PVT, administered treatments, and outcomes, all confirmed through enhanced CT scans.
Results:
A total of 78 patients met the study’s criteria. Notably, only 20.5% (16/78) were treated with oral anticoagulants; however, a vast majority (96.2%; 75/78) achieved complete radiographic resolution (CRR). When comparing patients receiving anticoagulants to those who did not, a significant preference for anticoagulant use was observed in cases where the main portal vein was affected, as opposed to just the left or right veins (p = 0.006). However, multivariable analysis indicated that neither anticoagulant use nor previous surgeries significantly impacted CRR.
Conclusions
Patients with IBD and PVT generally had favorable outcomes, regardless of anticoagulant use.
7.Immunologic Response and Effects of COVID-19Vaccines in Patients with Antineutrophil Cytoplasmic Antibody-Associated Vasculitis
Ki Hyun LEE ; Hyunsue DO ; Jun Yong CHOI ; Yong-Beom PARK ; Sinyoung KIM ; Sang-Won LEE ; Su Jin JEONG
Yonsei Medical Journal 2025;66(5):259-268
Purpose:
The immunological response and adverse effects of antineutrophil cytoplasmic antibody-associated vasculitis (AAV) in patients receiving coronavirus disease-2019 (COVID-19) vaccines remain unclear. We aimed to evaluate the effects of these vaccines on AAV disease activity.
Materials and Methods:
We reviewed the medical records of 52 patients with AAV who had received at least second doses of the COVID-19 vaccine and evaluated their immunogenicity by measuring the anti-spike (S) antibody (Ab) titer levels using the Roche Elecsys® immunoassay. Responses to the Birmingham Vasculitis Activity Score (BVAS) tool and 36-Item Short Form Survey before and after vaccination were obtained to assess AAV disease activity. Vaccine reactivity was measured using a standardized questionnaire.
Results:
We enrolled 52 patients with AAV. No differences were found between those who received second and third doses of vaccination in terms of AAV type, disease activity, vaccine type, or the use of immunosuppressive agents, including steroids. The median anti-S Ab titer was 3967.0 after third doses compared to 419.0 after second doses (p=0.001). Except for mycophenolate mofetil (MMF), when immunosuppressants were administered in conjunction with steroids, the Ab titer was higher after the third vaccination than that after the second dose. The BVAS remained unchanged before and after second and third doses. No life-threatening adverse events were reported.
Conclusion
Although COVID-19 vaccine may not produce sufficient antibodies in patients taking MMF, the vaccine did not exacerbate disease activity or cause severe side effects. Therefore, COVID-19 vaccines should be considered in patients with AAV.
8.Precise application of O-arm navigation system in thoracolumbar fractures with developmental pedicle stenosis
Lintao SU ; Jianfeng JIANG ; Jun MA ; Liangliang HUANG ; Changyu LEI ; Yaozheng HAN ; Hui KANG
Chinese Journal of Tissue Engineering Research 2025;29(9):1855-1862
BACKGROUND:For thoracolumbar spine fractures with developmental stenosis of the vertebral arch,accurate nail placement is difficult using traditional fluoroscopy-assisted techniques.O-arm navigation assistance systems offer higher precision in general vertebral arch nail placement,but there is scarce literature on the application of O-arm navigation-assisted nail placement in thoracolumbar spine fractures with developmental stenosis of the vertebral arch both domestically and abroad. OBJECTIVE:To explore the accuracy of percutaneous vertebral arch nail placement assisted by O-arm navigation in patients with thoracolumbar spine fractures complicated by developmental stenosis of the vertebral arch. METHODS:A retrospective analysis was conducted on 53 patients who underwent percutaneous vertebral arch screw fixation surgery at Department of Orthopedics,General Hospital of Central Theater Command of PLA for thoracolumbar spine fractures complicated by developmental stenosis of the vertebral arch from January 2021 to March 2023.Totally 208 cases of vertebral arch developmental stenosis were found(cases with multiple vertebral arch developmental stenosis were counted separately).Based on the surgical approach,the patients were divided into two groups:O-arm navigation group(n=98)and C-arm fluoroscopy group(n=110).Postoperative imaging data were compared between the two groups,including anatomical perforation score,functional perforation score,actual vs.expected nail trajectory in the horizontal plane,and sagittal plane angle differences. RESULTS AND CONCLUSION:(1)There was no significant difference in the narrowest width of the pedicle isthmus(pow)between the two groups of patients(P>0.05).The proportions of different degrees of narrowing(mild:6 mm≤pow<7 mm,moderate:5 mm≤pow<6 mm,severe:pow<5 mm)were also not significantly different between the two groups(P>0.05).(2)The overall grade and scores of anatomical perforation and functional perforation were lower in the O-arm group compared to the C-arm group,and these differences were statistically significant(P<0.001).In terms of the angular deviation between the actual and planned screw trajectories,the O-arm group had smaller deviations,and these differences were statistically significant(P<0.05).(3)In the mild and moderate narrowing groups,the O-arm group showed significant advantages in anatomical perforation,functional perforation,and angular deviation between actual and planned screw trajectories,and these differences were statistically significant(P<0.001).(4)The O-arm group demonstrated better performance in anatomical perforation and functional perforation,especially in the T12-L2 segment,with more significant advantages.Additionally,the O-arm group had better angular deviations in actual and planned screw trajectories in all segments compared to the C-arm group.(5)Therefore,the use of O-arm navigation-assisted percutaneous screw placement for the treatment of thoracolumbar fractures with developmental pedicle isthmal narrowing provides higher accuracy and safer surgery.
9.Traditional Chinese Medicine Intervenes in Non-alcoholic Fatty Liver Disease by Regulating TLR4 Signaling Pathway: A Review
Zhiwei SU ; Juan XUE ; Jun SUN ; Heng FAN ; Rui ZHU ; Chunyan JI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):291-299
Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease closely related to metabolism, which is mainly characterized by abnormal lipid deposition in hepatocytes. In recent years, with the increasing prevalence of obesity and metabolic syndrome, NAFLD has become one of the most common chronic diseases in the world. The pathogenesis of NAFLD is complex and varied, involving the cross-regulation of multiple signaling pathways such as glucose-lipid metabolism, oxidative stress, and inflammation. The TLR4 signaling pathway plays a key role in the development and progression of NAFLD, and abnormal activation of this pathway accelerates the deterioration of NAFLD by promoting the release of pro-inflammatory cytokines, inducing oxidative stress, and exacerbating insulin resistance. Studies have shown that traditional Chinese medicine (TCM) can regulate the TLR4 signaling pathway to alleviate the symptoms and pathological features of NAFLD. The present review summarizes the experimental research progress in the TCM regulation of the TLR4 signaling pathway in treating NAFLD in the past 5 years, covering a wide range of TCM active ingredients (such as polysaccharides, terpenoids, alkaloids, flavonoids) and compound prescriptions. The active ingredients and compound prescriptions of TCM can effectively ameliorate lipid metabolism disorders, reduce insulin resistance, regulate intestinal flora, and inhibit inflammation and oxidative stress by regulating the TLR4 signaling pathway via multiple targets and pathways, thus slowing down the progression of NAFLD. Through in-depth analysis of the pathological mechanisms of NAFLD and exploration of the potential of TLR4 signaling pathway as a therapeutic target, we can provide theoretical support for the application of TCM in the treatment of NAFLD, as well as new perspectives and directions for future clinical research and new drug development, thereby promoting the innovation and development of therapeutic strategies for NAFLD.
10.The Ferroptosis-inducing Compounds in Triple Negative Breast Cancer
Xin-Die WANG ; Da-Li FENG ; Xiang CUI ; Su ZHOU ; Peng-Fei ZHANG ; Zhi-Qiang GAO ; Li-Li ZOU ; Jun WANG
Progress in Biochemistry and Biophysics 2025;52(4):804-819
Ferroptosis, a programmed cell death modality discovered and defined in the last decade, is primarily induced by iron-dependent lipid peroxidation. At present, it has been found that ferroptosis is involved in various physiological functions such as immune regulation, growth and development, aging, and tumor suppression. Especially its role in tumor biology has attracted extensive attention and research. Breast cancer is one of the most common female tumors, characterized by high heterogeneity and complex genetic background. Triple negative breast cancer (TNBC) is a special type of breast cancer, which lacks conventional breast cancer treatment targets and is prone to drug resistance to existing chemotherapy drugs and has a low cure rate after progression and metastasis. There is an urgent need to find new targets or develop new drugs. With the increase of studies on promoting ferroptosis in breast cancer, it has gradually attracted attention as a treatment strategy for breast cancer. Some studies have found that certain compounds and natural products can act on TNBC, promote their ferroptosis, inhibit cancer cells proliferation, enhance sensitivity to radiotherapy, and improve resistance to chemotherapy drugs. To promote the study of ferroptosis in TNBC, this article summarized and reviewed the compounds and natural products that induce ferroptosis in TNBC and their mechanisms of action. We started with the exploration of the pathways of ferroptosis, with particular attention to the System Xc--cystine-GPX4 pathway and iron metabolism. Then, a series of compounds, including sulfasalazine (SAS), metformin, and statins, were described in terms of how they interact with cells to deplete glutathione (GSH), thereby inhibiting the activity of glutathione peroxidase 4 (GPX4) and preventing the production of lipid peroxidases. The disruption of the cellular defense against oxidative stress ultimately results in the death of TNBC cells. We have also our focus to the realm of natural products, exploring the therapeutic potential of traditional Chinese medicine extracts for TNBC. These herbal extracts exhibit multi-target effects and good safety, and have shown promising capabilities in inducing ferroptosis in TNBC cells. We believe that further exploration and characterization of these natural compounds could lead to the development of a new generation of cancer therapeutics. In addition to traditional chemotherapy, we discussed the role of drug delivery systems in enhancing the efficacy and reducing the toxicity of ferroptosis inducers. Nanoparticles such as exosomes and metal-organic frameworks (MOFs) can improve the solubility and bioavailability of these compounds, thereby expanding their therapeutic potential while minimizing systemic side effects. Although preclinical data on ferroptosis inducers are relatively robust, their translation into clinical practice remains in its early stages. We also emphasize the urgent need for more in-depth and comprehensive research to understand the complex mechanisms of ferroptosis in TNBC. This is crucial for the rational design and development of clinical trials, as well as for leveraging ferroptosis to improve patient outcomes. Hoping the above summarize and review could provide references for the research and development of lead compounds for the treatment for TNBC.

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